ted

Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law

A Louisiana law that sought to post the Ten Commandments in every schoolroom in the state has been shelved by a federal judge. U.S. District Court Judge John W. deGravelles, […]

The post Obama-Appointed Federal Judge Temporarily Blocks Ten Commandments Law appeared first on The Western Journal.




ted

[4Fe-4S] cluster trafficking mediated by Arabidopsis mitochondrial ISCA and NFU proteins [Enzymology]

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.




ted

Reply to Sysel et al.: Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

In their comment (1) on our publication (2), the authors make two points: (i) they raise concerns about the possible effect of residual NONOate in our study, and (ii) they promote nitrosylcobalamin (NOCbl) supplied by their own company. Both points lack merit for the following reasons. The authors make the astonishing claim that the spectra of nitric oxide (NO•) and cobalamins overlap. Unlike NO•, cobalamin absorbs in the visible region, permitting unequivocal spectral assignment of NOCbl as reported (3). We demonstrated that whereas NOCbl is highly unstable in solution, it is stabilized by the B12 trafficking protein CblC. So even if present, residual NONOate (which is unstable at neutral pH and is removed during the work-up (3)) could not account for the observed difference.The authors then misrepresent our synthetic method, claiming that anaerobic conditions were used to generate nitrocobalamin (NO2Cbl), which results in the transient formation of NOCbl. We synthesized NO2Cbl aerobically using nitrite as described (4); NOCbl is not an intermediate in this ligand exchange reaction. The aerobic instability of NOCbl has been rigorously described by inorganic chemists (3, 5) and raises obvious questions about its purported biological effects as exemplified by the authors' own 2003 JBC publication, which was later withdrawn.As to promoting NOCbl from their company, the authors refer to a synthetic route from a mixture of NO• gas and aquocobalamin. The authors' method (6) has been described as “dubious” by chemists (5). Whereas DEAE NONOate used in our method is widely known as an NO• donor,...




ted

Comment on the importance of using nitric oxide gas in the synthesis of nitrosylcobalamin and ICH-validated methods to assess purity and stability [Letters to the Editor]

After a thorough read of this paper (1), we wish to clarify that the authors' anaerobic method of synthesis for the production of nitrocobalamin results in the transient formation of nitrosylcobalamin, an unstable intermediate upon exposure to air. We concur that the authors' method results in the production of nitrocobalamin based on the UV-visible data as shown. The authors' adapted anaerobic method consists of mixing hydroxocobalamin hydrochloride with diethylamine NONOate diethylammonium salt in aqueous solution. Of concern, the UV spectrum of nitric oxide overlaps that of all cobalamin species under anaerobic conditions, making any assignments of the binding of nitric oxide to hydroxocobalamin suspect (2). Additionally, the use of acetone to precipitate the authors' product causes precipitation of diethylamine NONOate, resulting in an impure product. As a result, its utility for drawing experimental conclusions is faulty.The product from the authors' anaerobic synthetic method has not been assessed for purity, and the synthetic method itself has not been validated using a stability-indicating method as required by the International Conference on Harmonization (ICH) (ICH Q2B, Validation of Analytical Procedures) methodology, which is a hallmark for analytical characterization. Our nitrosylcobalamin synthesis involves reacting nitric oxide gas with hydroxocobalamin acetate as a heterogeneous mixture in a non-electron-donating solvent followed by rotary evaporation. Our nitrosylcobalamin product is stable in air, releases nitric oxide gas in situ (3), and meets ICH stability guidelines (4). Additionally, our nitrosylcobalamin product demonstrates biological activity, which has not been observed for nitrocobalamin (3, 5).




ted

Disease-associated mutations in inositol 1,4,5-trisphosphate receptor subunits impair channel function [Molecular Bases of Disease]

The inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which form tetrameric channels, play pivotal roles in regulating the spatiotemporal patterns of intracellular calcium signals. Mutations in IP3Rs have been increasingly associated with many debilitating human diseases such as ataxia, Gillespie syndrome, and generalized anhidrosis. However, how these mutations affect IP3R function, and how the perturbation of as-sociated calcium signals contribute to the pathogenesis and severity of these diseases remains largely uncharacterized. Moreover, many of these diseases occur as the result of autosomal dominant inheritance, suggesting that WT and mutant subunits associate in heterotetrameric channels. How the in-corporation of different numbers of mutant subunits within the tetrameric channels affects its activities and results in different disease phenotypes is also unclear. In this report, we investigated representative disease-associated missense mutations to determine their effects on IP3R channel activity. Additionally, we designed concatenated IP3R constructs to create tetrameric channels with a predefined subunit composition to explore the functionality of heteromeric channels. Using calcium imaging techniques to assess IP3R channel function, we observed that all the mutations studied resulted in severely attenuated Ca2+ release when expressed as homotetramers. However, some heterotetramers retained varied degrees of function dependent on the composition of the tetramer. Our findings suggest that the effect of mutations depends on the location of the mutation in the IP3R structure, as well as on the stoichiometry of mutant subunits assembled within the tetrameric channel. These studies provide insight into the pathogenesis and penetrance of these devastating human diseases.




ted

The interconnected impacts of the Iraq war

The interconnected impacts of the Iraq war Expert comment LJefferson 22 March 2023

Relying on weak intelligence for invading Iraq has had a negative impact on US and UK credibility with several consequences that persist to this day.

20 years on from the fateful decision to invade Iraq, it is generally accepted that the US and UK governments overstated the evidence available for them to justify military action. The central claim to defend invading Iraq was that the country had continued its illicit nuclear weapons programme and had retained illegal stockpiles of biological and chemical weapons. None of these claims supported an imminent threat justification nor could any hidden caches of WMD be found by the US Iraq Survey Group after the invasion.  

In the US, President George W. Bush and Vice President Dick Cheney hinted at additional evidence which could not be shared publicly to suggest that if only people knew what the government knew, they would agree that Iraq posed a significant threat to the West and needed to be disarmed.

In the UK, the Blair government acted similarly, focusing on a narrow interpretation of the evidence provided by the intelligence services and ignoring many of the dire warnings offered by academics and other experts. The Chilcot Inquiry found that the Blair government greatly exaggerated the threat Iraq posed to the UK, and that government arguments were based on the prime minister’s personal beliefs, as well as his promise to President Bush to support the US invasion. 

Relying on inadequate information and a biased analysis for invading Iraq has had a negative impact on US and UK credibility in the international security policy environment and domestically with ramifications that persist to this day.  

Impacts on soft power and trust

The invasion had an impact on US and UK soft power due to negative perceptions of the decision to go to war and the competence of the UK and US: public opinion polling by the Pew Center showed that perceptions of the US declined significantly as a result of the invasion of Iraq, especially in the Middle East and Central Asia.

This is undoubtedly a challenge for the US, but arguably an even bigger challenge for the UK, which due to its size and power relies much more on diplomacy and coalition-building in order to achieve its goals within various international treaty frameworks.   

The accuracy of the US/UK intelligence on Russia’s invasion, coupled with their sharing it openly, may well have restored faith in their capabilities and analysis.

Over nearly two decades, the US and the UK no longer seemed to enjoy the same foundation of trust, even with close allies, as they did previously. This changed in February 2022.

Towards the end of 2021, both the US and the UK were sounding the alarm about an impending Russian invasion of Ukraine based on information and analysis from their intelligence services. Despite the amassing of Russian troops, tanks and artillery on the border clearly visible from the air and by satellite imagery, several allies remained unconvinced until the invasion happened.  

This was in part due to their own assessments which indicated that Russia would stop short of an invasion, and in part because allies were unwilling to take US and UK statements on faith, without being able to assess the information themselves.

US officials found this frustrating as it meant that NATO and the EU were slower off the mark with support for Ukraine than they might otherwise have been. However, the accuracy of the US/UK intelligence on Russia’s invasion, coupled with their sharing it openly, may well have restored faith in their capabilities and analysis.  

A more open approach to intelligence  

Over the last few years, there seems to have been a change in accepted practice regarding sharing and using intelligence. The UK Ministry of Defence has taken a much more open approach to intelligence in the war in Ukraine, sharing the most recent defence information publicly in order to counter Russian disinformation.  

This is a positive step to ensure that intelligence can be discussed and assessed critically. Being more open about secret intelligence may also be linked to the increasing capabilities of open-source intelligence (OSINT). Non-governmental and international organizations and the media all now have access to data from, for example, imaging satellites and can independently verify information coming from governments. 

Perceived double standards 

A reduction of trust in US and UK intelligence was not the only impact of the invasion of Iraq. Russia and China have repeatedly called out the US and UK for acting without a second UN Security Council mandate. Putin uses the decision to invade Iraq, as well as the NATO humanitarian intervention in Kosovo, to justify Russia’s actions in Crimea. He invokes parallel language to spread disinformation about a ‘responsibility to protect life’ of the (‘ethnically Russian’) Crimean population. Russia has also repeatedly used the WMD trope to create false narratives around Ukrainian biosecurity laboratories to justify Russian military actions against Ukraine.  

Putin uses the decision to invade Iraq, as well as the NATO humanitarian intervention in Kosovo, to justify Russia’s actions in Crimea.

Deciding to invade Iraq under what turned out to be a false pretext has weakened the application of the international rule of law and has led to a perceived double standard whereby powerful states can use UN processes in their favour, or completely disregard them if they do not deliver their goals.

As the Chilcot Inquiry found, there was very little preparation for the post-invasion period either in the US or the UK. Confirmation bias led not only to trusting shaky intelligence but also to believing in a best-case scenario and a ‘relatively benign security environment’ once the invasion had prevailed. Mismanaging the country’s occupation afterwards also led to the perception that the UK and US are less competent than projected. 

Problems for the international order  

The Iraq War has left many smaller and medium-sized states outside Europe and North America with the impression that powerful states are not committed to an equitable international system and instead will bend the rules to suit them while nonetheless holding other states to account. This dynamic poses a serious problem for the international system. 

It opens the door to ‘whataboutism’ in Russia’s false justifications for invading Ukraine and undermines faith in international law, destabilizing the international order in the longer term. Beyond the immediate challenges of dealing with the war in Ukraine, reforming and strengthening the international order to make it more equitable will be one of the most significant challenges the US and UK will face over the next decade. 

A trust deficit  

Domestically, for already disappointed citizens, the deceit over intelligence it is yet another piece of evidence which suggests that their government is not trustworthy and may not have their best interests at heart. This has profound implications for US and UK democracies, making it harder for governments to counter citizens’ susceptibilities to disinformation campaigns. 




ted

Relative and Absolute Quantification of Postsynaptic Density Proteome Isolated from Rat Forebrain and Cerebellum

Dongmei Cheng
Jun 1, 2006; 5:1158-1170
Datasets




ted

Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach

Steven A. Carr
Mar 1, 2014; 13:907-917
Technological Innovation and Resources




ted

Quantitative, Multiplexed Assays for Low Abundance Proteins in Plasma by Targeted Mass Spectrometry and Stable Isotope Dilution

Hasmik Keshishian
Dec 1, 2007; 6:2212-2229
Research




ted

Large Scale Screening for Novel Rab Effectors Reveals Unexpected Broad Rab Binding Specificity

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research




ted

Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources




ted

Extending the Limits of Quantitative Proteome Profiling with Data-Independent Acquisition and Application to Acetaminophen-Treated Three-Dimensional Liver Microtissues

Roland Bruderer
May 1, 2015; 14:1400-1410
Research




ted

Integrated Genomic and Proteomic Analyses of Gene Expression in Mammalian Cells

Qiang Tian
Oct 1, 2004; 3:960-969
Research




ted

Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
Research




ted

Highly Selective Enrichment of Phosphorylated Peptides from Peptide Mixtures Using Titanium Dioxide Microcolumns

Martin R. Larsen
Jul 1, 2005; 4:873-886
Technology




ted

Phosphate-binding Tag, a New Tool to Visualize Phosphorylated Proteins

Eiji Kinoshita
Apr 1, 2006; 5:749-757
Technology




ted

Enhanced enzyme kinetics of reverse transcriptase variants cloned from animals infected with SIVmac239 lacking viral protein X [Microbiology]

HIV Type 1 (HIV-1) and simian immunodeficiency virus (SIV) display differential replication kinetics in macrophages. This is because high expression levels of the active host deoxynucleotide triphosphohydrolase sterile α motif domain and histidine-aspartate domain–containing protein 1 (SAMHD1) deplete intracellular dNTPs, which restrict HIV-1 reverse transcription, and result in a restrictive infection in this myeloid cell type. Some SIVs overcome SAMHD1 restriction using viral protein X (Vpx), a viral accessory protein that induces proteasomal degradation of SAMHD1, increasing cellular dNTP concentrations and enabling efficient proviral DNA synthesis. We previously reported that SAMHD1-noncounteracting lentiviruses may have evolved to harbor RT proteins that efficiently polymerize DNA, even at low dNTP concentrations, to circumvent SAMHD1 restriction. Here we investigated whether RTs from SIVmac239 virus lacking a Vpx protein evolve during in vivo infection to more efficiently synthesize DNA at the low dNTP concentrations found in macrophages. Sequence analysis of RTs cloned from Vpx (+) and Vpx (−) SIVmac239–infected animals revealed that Vpx (−) RTs contained more extensive mutations than Vpx (+) RTs. Although the amino acid substitutions were dispersed indiscriminately across the protein, steady-state and pre-steady-state analysis demonstrated that selected SIVmac239 Vpx (−) RTs are characterized by higher catalytic efficiency and incorporation efficiency values than RTs cloned from SIVmac239 Vpx (+) infections. Overall, this study supports the possibility that the loss of Vpx may generate in vivo SIVmac239 RT variants that can counteract the limited availability of dNTP substrate in macrophages.




ted

Helen Clark elected president of Chatham House

Helen Clark elected president of Chatham House News release jon.wallace 23 July 2021

The former New Zealand prime minister and Head of UN Development Programme has been elected president of Chatham House.

Former New Zealand prime minister and Head of the United Nations Development Programme, Helen Clark, has been elected president of Chatham House.

Ms Clark will replace former United Kingdom Prime Minister, Sir John Major, who is retiring from the role. She will join Baroness Eliza Manningham-Buller and Lord Darling as one of the institute’s three serving presidents.

Helen Clark was prime minister of New Zealand from 1999-2008. She then became the 8th and first female administrator of the UN Development Programme, completing two terms from 2009-2017.  

She is actively engaged in important international issues that are central to the institute’s priorities. She is currently chairing the Independent Panel for Pandemic Preparedness and Response with former president of Liberia, Ellen Johnson Sirleaf, which was convened by the World Health Organization last year and has just completed its main report. Her expertise extends to sustainable development, tackling climate change and developments in the Asia-Pacific.

Chatham House Director Robin Niblett welcomed the appointment:

‘We are excited to have found someone with the high-level political experience and who shares the strong reputation for integrity that Sir John enjoys. Helen Clark is highly regarded around the world for her past and current endeavours. Her election also underscores the institute’s global outlook and priorities, which she is so well qualified to help guide.’

Ms Clark was elected at the Annual General Meeting of Chatham House on 20 July which also marked the last official engagement for Lord O’Neill, who has now handed over to Sir Nigel Sheinwald as Chair of the institute.

Chatham House is delighted that Sir John Major will remain affiliated with the institute as president emeritus, and that Lord O’Neill will become a member of the institute’s panel of senior advisers.

 




ted

Independent Thinking: UK Integrated Review, Georgia protests

Independent Thinking: UK Integrated Review, Georgia protests Audio NCapeling 16 March 2023

Episode 19 of our weekly podcast examines the AUKUS deal, UK defence priorities, and the state of Georgia’s democracy following anti-government protests.

The UK and Australia will soon be building nuclear submarines together, but is the UK’s tilt to the Indo-Pacific sustainable? Two years on from the last Integrated Review, has the UK finally clarified its foreign policy priorities on Russia, China, and on defence? And is the money there to do it all?

Also on the show, the panel discusses Georgia following recent anti-government protests in Tbilisi. Following the Rose revolution in 2003, Georgia seemed to be on a path towards closer ties with NATO and the European Union (EU). But the country’s government has recently moved closer to Russia and Vladimir Putin. What is the state of Georgia’s democracy and where is the country heading?

Joining Bronwen Maddox from Chatham House is Creon Butler, director of our Global Economy and Finance programme, Professor Andrew Dorman, editor of the International Affairs journal, and Alice Billon-Galland, research fellow in our Europe Programme.

They are joined by Natia Seskuria, associate fellow with the Royal United Services Institute (RUSI) and Arthur Snell, former diplomat and host of the podcast Doomsday Watch.

About Independent Thinking

A weekly podcast hosted by Chatham House director Bronwen Maddox, in conversation with leading policymakers, journalists, and Chatham House experts providing insight on the latest international issues.




ted

Microtubule affinity-regulating kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and exacerbates neurodegeneration [Neurobiology]

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.




ted

The UK must focus on how the Chagos decision is implemented to gain its benefits and minimize risks

The UK must focus on how the Chagos decision is implemented to gain its benefits and minimize risks Expert comment jon.wallace

The UK decision was welcomed by India and the US, and shows a capacity for fresh thinking. But the transfer of sovereignty must be handled carefully.

The UK announced on 3 October that it would cede sovereignty over the Chagos Archipelago to Mauritius.

There are potential strategic and reputation-related upsides for the UK from the decision – but these can only be realized if the deal is implemented in ways that meet the UK’s stated goals.

First, the UK aims to safeguard the utility and security of the joint US–UK base on Diego Garcia. It also intends for the decision to benefit the Chagossians, who were displaced by the British decision in 1965 to separate the Archipelago from Mauritius as part of a deal to grant Mauritian independence.

The decision has already proved deeply controversial in the UK, provoking sustained criticism from former Conservative government ministers and commentary that has branded it naive, dangerous, and a blow to British prestige.

Part of the reason for the welter of criticism may be the apparent suddenness of the announcement. The impression that this was a hasty decision is likely because it came just three months after the Labour government came to office. But this belies the far longer gestation period around the decision.

World opinion

In fact, the previous Conservative UK government decided to begin negotiations over sovereignty of Chagos – following Mauritius bringing the matter to the International Court of Justice. In 2019, the court issued a non-binding opinion in favour of Mauritius.

The same year the UN General Assembly voted 116 in favour to 6 against, and with 56 abstentions, for a resolution ‘welcoming a 25 February 2019 International Court of Justice advisory opinion on the legal consequences of separating the Chagos Archipelago from Mauritius in 1965, demanding that the UK unconditionally withdraw its colonial administration from the area within six months’ to ‘enable Mauritius to complete the decolonization of its territory.’

But returning the islands will not necessarily boost the UK’s international standing. Issues relating to the Archipelago are complex, and it will take work to convince interested international parties that the UK is acting fairly against a colonized and displaced population.

Mauritius has no pre-colonial history of controlling the Chagos islands, which are located some 1,500 miles away from Mauritius across a vast sprawl of the Indian Ocean. It is true that the Chagos Islands were a colonial remnant, but to ensure that UK is seen by global audiences to be acting fairly, the handover of sovereignty must be carefully handled. Perhaps the greatest reputational risk will come from failing to adequately account for the rights of Chagossians.  

The more pertinent historical injustice has been to them. And reporting by the BBC has shown that at least some Chagossians were dismayed by not having been consulted in negotiations between the UK and Mauritius.

This deal was reached in close consultation with US officials and puts the (Diego Garcia) base on legally safe ground for the first time in decades. 

The UK government announcement on the deal did state that that ‘the welfare of Chagossians’ will be paramount and that ‘the UK will capitalize a new trust fund, as well as separately provide other support, for the benefit of Chagossians’. But for the Chagossians, there will be a clamour to see this realized in full.

Strategic interests

On the strategic question, the utility of the joint US–UK military base on Diego Garcia has been guaranteed in a 99-year lease. As the UK negotiator Jonathan Powell has explained, this deal was reached in close consultation with US officials and puts the base on legally safe ground for the first time in decades. 

Indeed, Powell has explained that Joe Biden was keen to reach agreement ahead of the US elections so that US military access to Diego Garcia was safeguarded against any possible contrary decision by a possible returning Trump presidency.

There are understandable concerns that, as a result of the decision, China may develop commercial ports in the region and seek to compete with India for economic and strategic relationships. But this is a long-term matter of concern to monitor, regardless of the UK’s decision on Chagos.

Chinese naval influence in the Indian Ocean is currently limited, compared to its assertiveness in the South China Sea, where it is building artificial islands, or in the South Pacific where it is pursuing policing assistance deals like that secured with the Solomon Islands.

And the strategic situations in the Pacific and Indian Oceans are not at all alike. Indeed, the Chagos Islands are far closer to India and its economic influence than they are to any other major economic power. 

The fact that India has welcomed the UK’s decision over Chagos sovereignty is noteworthy, given the UK’s separate attempts to modernize and expand its bilateral relations with New Delhi.

In the long run, it is likely that India will play a leading role in Indian Ocean security, and the UK will want to be well-placed to explore how to play a role as an effectively partner.

There are legitimate questions to be raised over setting a precedent that could undermine RAF Akrotiri and Dhekelia in Cyprus.

The more pertinent immediate concern is the implications for other overseas UK territorial responsibilities. There are legitimate questions to be raised over setting a precedent that could undermine RAF Akrotiri and Dhekelia in Cyprus, which remained sovereign UK bases after Cyprus’s independence in 1960.




ted

As the ruling party claims victory in Georgia’s disputed election, Western condemnation is no longer enough

As the ruling party claims victory in Georgia’s disputed election, Western condemnation is no longer enough Expert comment LToremark

As tens of thousands take to the streets to protest the election results, Georgia faces a familiar crisis – with a few key differences.

As the people of Georgia went to the polls on 26 October, many were hoping not only for a democratic change of government but also for an end to one-party dominance and a return to the path of European integration. The previously weak and divided opposition had grouped itself into four major electoral centres, promising a coalition government and framing these elections as a choice between Europe and Russia. 

Ahead of the election, President Salome Zourabishvili had put forward the Georgian Charter, a blueprint for a stable and democratic transition to a new style of governance and for initiating reforms to fulfil conditions for EU accession. It was signed by all pro-European and pro-Western opposition parties. 

A new electoral system had created a not unreasonable expectation that these elections, if held freely, would result in a coalition government.

The official election results gave the ruling Georgian Dream party a 54 per cent majority in contrast with exit polls that gave the opposition a 10 per cent lead. President Zourabishvili and the opposition parties refuse to recognize the results, beginning a long process of contestation with allegations of fraud and street protests. As the disappointment sets in and the streets once again replace the ballot box as a conduit for democratic change, there is a sense of déja vu.

Georgia has seen this before. A party sweeps to power on the tide of popular protest, initiates reforms to meet public expectations but, by the end of its second term, it takes an authoritarian turn. As it overstays its welcome, it starts manipulating elections to cling to power. People once again take to the streets and a new party wins by a landslide only to repeat the same cycle. But with each turn, the grip the ruling elites have on power gets stronger and the methods they use become more sophisticated. State security becomes equated with regime stability, leaving no space for normal democratic contestation or expressions of dissent. 

Although what is happening in Georgia fits this familiar pattern, there are some consequential differences. 

First, these were the first fully proportional elections. Previously, a mixed system of representation meant that the incumbency always had an advantage by dominating majoritarian districts. A new electoral system had created a not unreasonable expectation that these elections, if held freely, would result in a coalition government. The hope was this could help break the vicious cycle of Georgian politics, sustained by an extreme form of majoritarianism and a winner-takes-all political culture.

The Georgian Dream party was contesting its fourth consecutive term against a backdrop of falling popularity and growing societal mobilization in opposition to its authoritarian inclinations. Despite all this, it secured – some would insist manufactured – an absolute majority in elections that international observers say were marred by serious irregularities and fell short of democratic standards. 

The second important difference is that these elections were not only about saving Georgia’s democracy but also about rescuing its European perspective. Since Georgia was granted EU candidate status in December 2023, its parliament has adopted Russian-style laws on foreign agents and combating LGBTIQ+ ‘propaganda’. 

It has also adopted a strongly Eurosceptic political discourse, pushing back on international criticism and accusing EU and US officials of interference in domestic affairs and disregard for Georgia’s sovereignty. In response, the EU has suspended accession talks with Georgia indefinitely while the US has imposed targeted sanctions on high-ranking Georgian officials and judges. 

Georgia’s democratic backsliding at home and its pivot away from the West are both simultaneous and interrelated. It was widely hoped these elections would be a course correction and return Georgia to the path of European and Euro-Atlantic integration. The election results, if they stick, will prevent this from happening. A Georgian Dream government will not work to fulfil conditions for EU accession, viewed as a challenge to its hold on power. 

The third and final difference is that these elections took place in the context of heightened geopolitical confrontation. The Georgian Dream ‘victory’ is a win for anti-liberal, conservative forces around the world championed, among others, by Hungary’s Viktor Orbán. He was the first to congratulate Georgian Dream for its declared success and even visited Tbilisi in a show of solidarity and ideological alignment. 

The election result is also a win for Russia. It strengthens Moscow’s influence in the South Caucasus, which has waned as a result of the war in Ukraine and the fall of Nagorny-Karabakh. Russian officials and propagandist were quick to congratulate Georgian Dream, wishing them success in standing up to Western pressures and offering help in case things got tough. 

From Moscow’s perspective, Georgia’s elections are part of a global hybrid war. They represent a local battle in the ongoing geopolitical contest between Russia and the West, between the rules-based global order and competitive multipolarity. 

As Georgia repeats a familiar pattern, what do the election results mean for its future? While clear predictions are difficult at this stage, it is worth bearing in mind that as the democratic resilience of the Georgian society has strengthened over time, so too has the state capacity to supress and control. 




ted

Following its snap election, Japanese politics has entered uncharted waters

Following its snap election, Japanese politics has entered uncharted waters Expert comment LToremark

Prime Minister Ishiba’s election gamble has failed. Japan now faces another period of political uncertainty, which could affect its international standing.

In Japan’s snap election on 27 October, the ruling coalition of the Liberal Democratic Party (LDP) and New Komeito lost the overwhelming majority it had held since the 2012 general election. The ruling coalition now has 215 seats, leaving it 18 seats short of a majority. 

The largest opposition party is the Constitutional Democratic Party of Japan (CDP), which gained 50 seats to 148. The second largest opposition party is the Japan Innovation Party (Ishin), which lost six seats to 38, and the third largest opposition party is the National Democratic Party (NDP), which gained 21 seats to 28.

But the opposition is divided and there is no real appetite to form a coalition government. This will likely result in a hung parliament, which will further destabilize Japan’s government.

The election results reveal three key things  about the state of Japanese politics and what comes next.

First, that Prime Minister Ishiba’s snap election gamble has failed. The aim was for Ishiba, a non-mainstream member of the LDP, to strengthen the party base and stabilize his administration. But with the ruling coalition losing its majority, the party base has been further weakened and the Ishiba administration is now more likely to be short-lived. LDP voters as well as the public in general  had hoped that Ishiba, as the ‘opposition within the party’, would change the LDP’s structure and government policies, eliminate the uncertainty surrounding party funding and increase transparency on how MPs use public funds to finance political activities.

However, when Ishiba became LDP leader and prime minister, he abandoned his previously more critical stance and prioritized carrying on the policies of the mainstream LDP, leaving his supporters feeling betrayed.

Second, while the ruling coalition has been punished, the people of Japan still did not vote for a change of government. The opposition is divided and, despite its gains in this election, the CDP is not fully committed to take the lead and consolidate the opposition to form a coalition. The CDP also suffers from internal division. The left wing of the party would prefer a coalition with the Communist Party, while the right wing of the party does not want to form a coalition with the LDP or the Communist Party, preferring a partner such as the NDP.

The NDP is in a position to control the fate of Ishiba administration. 

Third, the NDP has become the key to future Japanese politics. By becoming the minority ruling party, the NDP is in a position to control the fate of Ishiba administration. While the CDP has no intention of cooperating with the LDP, the NDP is more willing to do so in order to implement its own policies. As the budget cannot be passed without the NDP’s cooperation, the ruling coalition will have no choice but to accept the NDP’s policy of substantial tax cuts through the expansion of tax credits. It will also likely have to accept an option for married couples to decide their family names, which requires a change of civil codes and is something it has been reluctant to do so far. 

If the NDP’s demands are rejected, a no-confidence motion will likely be submitted and passed, leaving the Ishiba cabinet with no choice but to resign or dissolve the House of Representatives (the lower house of Japan’s parliament).

But the NDP has chosen to not form a coalition with the ruling party and enter government. Why? From the NDP’s point of view, forming a coalition with the LDP, would mean getting involved in the LDP’s internal turmoil – something it wishes to avoid. In addition, elections to the House of Councillors (upper house of parliament) will be held in the summer of 2025. The NDP may have judged that it will have a better chance of implementing its policies by cooperating with the government on a case-by-case basis, rather than forming a coalition with a party that is losing public support and risk following suit.

The minority ruling system that has emerged after the election is extremely rare in Japan’s political history and is likely to make its politics even more unstable in the years ahead. The Ishiba administration will probably be able to survive until the budget is passed in March next year by cooperating with the NDP, but beyond that its prospects are unclear.

As the House of Councillors elections get closer, some in the LDP may say that they cannot fight the election with Ishiba as prime minister. If so, they may choose the option of a same-day election for the lower and the upper house. The cost of an election campaign is significant, and the LDP’s financial strength gives it an advantage in the case of a same-day election. There is also a strong possibility that the public will choose the LDP to regain stability in government. However, this election has shown that public distrust of the LDP is high, and if Ishiba continues to be pushed around by the NDP, his party’s chances of winning would be reduced.

Japanese politics has entered uncharted waters, where the patterns and customs of the past do not apply. There are now doubts both at home and abroad as to whether Ishiba, who has a weak party base, will be able to stay on and steer the government. Over the past decade, the Abe and Kishida administrations have provided Japan with political stability, which has in turn enhanced its international presence. An unstable political system, with frequent changes of government, will likely lead to a decline in Japan’s international influence.

Although Trump might be open to Ishiba’s demand for parity with the US, he could become irritated with Ishiba’s weak domestic position.

There is also a risk that US–Japan relations  could become unstable. Although the NDP does not have a strong agenda to change the course of this relationship, Ishiba may struggle to keep the promise made by his predecessors to increase defence spending. Ishiba’s nationalist posture could also create a confrontational relationship with the United States, while his weak leadership means he may not seek to invest in strengthening the US–Japan alliance. 

Donald Trump’s win in the US presidential election could pose a further risk. Although Trump might be open to Ishiba’s demand for parity with the US, he could become irritated with Ishiba’s weak domestic position. Ishiba may not be able to make decisions – or a deal with Trump – unless the NDP agrees to it.




ted

Undercurrents: Episode 7 - Libya's War Economy, and Is the United Nations Still Relevant?




ted

Empire in Retreat? The Future of the United States




ted

The United States in Afghanistan and Pakistan




ted

Unelected Power: Finding Legitimacy in Central Banking and the Regulatory State




ted

Protecting the Environment in Areas Affected by Armed Conflict




ted

Getting to a New Deal: Guidance for the United States, Europe and Iran




ted

Kazakhstan: Tested by Transition




ted

Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol

James M. Ntambi
Sep 1, 1999; 40:1549-1558
Reviews




ted

Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes

EJ Blanchette-Mackie
Jun 1, 1995; 36:1211-1226
Articles




ted

Apolipoprotein-mediated removal of cellular cholesterol and phospholipids

JF Oram
Dec 1, 1996; 37:2473-2491
Reviews




ted

Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein

DL Brasaemle
Nov 1, 1997; 38:2249-2263
Articles




ted

Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression

K Schoonjans
May 1, 1996; 37:907-925
Reviews




ted

Creon Butler appointed to lead Global Economy and Finance Programme

Creon Butler appointed to lead Global Economy and Finance Programme News Release sysadmin 22 October 2019

Creon Butler has been appointed to lead the Global Economy and Finance programme at Chatham House, joining the institute at the beginning of December. He will also form part of the institute’s senior leadership team.




ted

Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel

Elizabeth Wilmshurst CMG appointed Honorary Queen’s Counsel News release jon.wallace 14 January 2022

Founder of the International Law Programme at Chatham House recognized for her major contribution to the law of England and Wales.

Elizabeth Wilmshurst CMG, distinguished fellow of Chatham House’s International Law Programme, has been awarded the title of Honorary Queen’s Counsel (QC Honoris Causa), recognizing her major contribution to the law of England and Wales, outside practice in the courts. The Lord Chancellor will preside over an appointment ceremony at Westminster Hall on 21 March 2022.

Elizabeth founded the International Law Programme at Chatham House and is an academic expert member of Doughty Street Chambers. She was a legal adviser in the United Kingdom diplomatic service between 1974 and 2003. Between 1994 and 1997 she was the Legal Adviser to the United Kingdom mission to the United Nations in New York. She also took part in the negotiations for the establishment of the International Criminal Court.

Throughout her career, Elizabeth has worked to strengthen the role of international law in reducing global tensions, addressing cross-border challenges and promoting individual liberty, including through influential publications at the Institute such as The Chatham House Principles of International Law on the Use of Force in Self-Defence

Robin Niblett CMG, Director and Chief Executive of Chatham House said:

‘We are delighted by this award which recognizes Elizabeth’s outstanding contribution to the field of international law, both in government and – on a continuing basis – through the International Law Programme at Chatham House.’




ted

How are war crimes prosecuted?

How are war crimes prosecuted? Explainer Video NCapeling 26 April 2022

Explaining what war crimes are and how, in the circumstances of Ukraine, could war crimes be prosecuted.

The Geneva Conventions and Protocol 1 describe what they call ‘grave breaches’ of international humanitarian law, and both Ukraine and Russia are parties to these treaties.

Grave breaches include directly attacking civilians and launching an indiscriminate attack affecting the civilian population or civilian property.

Many states and the International Criminal Court (ICC) also have the possibility to prosecute a wider set of war crimes although, in the past, states have not prosecuted many such crimes committed outside their own territory.

Neither Russia nor Ukraine is a party to the ICC Statute, but Ukraine did declared it accepted the Court’s jurisdiction for crimes on its territory, and and investigations have now started.

But there are several problems to be overcome to achieve successful prosecutions, such as the collection and preservation of evidence, proof of the intent of the suspects in the heat of war, how to be arrest suspects, and the issue of immunity.




ted

Cyberspace governance at the United Nations

Cyberspace governance at the United Nations 18 January 2023 — 3:00PM TO 4:00PM Anonymous (not verified) 30 November 2022 Online

How can member states achieve lasting, adaptable, and meaningful success in cyberspace governance at the United Nations?

Now in its second iteration, the Open-ended Working Group on Information and Communications Technologies (OEWG) has been a space for United Nations member states to discuss the use, regulation and governance of cyberspace since 2019.

The progress of this forum in shaping cyberspace and its governance is evidenced by two consensus reports including a framework for responsible state behaviour in cyberspace and, more recently, plans for a Programme of Action. 
 
However, the true impact of these UN processes in limiting the threats of ICTs to international peace and security is contingent upon operationalizing the consensus at the international level and reflecting it in national policies and practices.

Pervasive challenges continue to hamper operationalization efforts, including differences in national capacities and capabilities, and divergences in national perspectives regarding the application of international law to cyberspace.

So, how can member states overcome these challenges and set this vital forum up for lasting, adaptable and meaningful success? What role does ‘multi-stakeholderism’ play in realizing responsible state behaviour in cyberspace?

With a dual focus on cyber capacity building and international law, this event considers how these two elements interact and intersect, how discussions on them could progress in the UN space and outside it and how the two contribute to a safer and more secure cyberspace for all. 
 
This event is organized jointly by the International Security and International Law Programmes at Chatham House to launch Phase 2 of the project ‘Cyberspace4All: Towards an inclusive approach to cyber governance’ which is funded by the Ministry of Foreign Affairs of the Netherlands.





ted

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states

What's next for environmental peacebuilding? Lessons learned and opportunities from conflict-affected states 17 February 2021 — 3:00PM TO 4:00PM Anonymous (not verified) 8 February 2021 Online

 This event explores lessons and opportunities from conflict-affected states.

In the field of peacebuilding, scholars and policymakers increasingly recognize the importance of environmental restoration, afforestation and infrastructural renewal for creating the sustainable livelihoods necessary for successful peacebuilding efforts.

Featuring academics writing for International Affairs on environmental peacebuilding in Colombia, Yemen and the Sahel, this webinar discusses the policy implications of the turn to environmental peacebuilding.

This event is part of the Chatham House’s Environment and Society Discussion Series in which the Energy Environment and Resources Programme brings together leading academics and policymakers to discuss key issues in environmental policy.

In particular, this event focuses on the role of environmental peacebuilding in creating sustainable livelihoods. From the impact the destruction of infrastructure can have on poverty as a driver of conflict, to the role environmental peacebuilding can play in bringing communities together by creating sustainable shared spaces of employment, the importance of the environmental livelihood creation is difficult to overstate.

Panellists focus on how policymakers can best encourage inclusive and sustainable livelihood creation and on addressing the key challenges such approaches face in the context of environmental peacebuilding efforts.




ted

Identifying the source term in the potential equation with weighted sparsity regularization

Ole Løseth Elvetun and Bjørn Fredrik Nielsen
Math. Comp. 93 (), 2811-2836.
Abstract, references and article information




ted

High-order splitting finite element methods for the subdiffusion equation with limited smoothing property

Buyang Li, Zongze Yang and Zhi Zhou
Math. Comp. 93 (), 2557-2586.
Abstract, references and article information







ted

Tekno - The Irish Collection - Ref. 258 - Scania Articulated Truck - Glynns, Galway - Miniature Diecast Metal Scale Model Heavy Goods Vehicle

firehouse.ie posted a photo:




ted

Tekno - The Irish Collection - Ref. 258 - Scania Articulated Truck - Glynns, Galway - Miniature Diecast Metal Scale Model Heavy Goods Vehicle

firehouse.ie posted a photo:




ted

Strong laws of large numbers for weighted sums of ????-dimensional arrays of random variables and applications to marked point processes

Ta Cong Son, Tran Manh Cuong, Le Quang Dung and Le Van Dung
Theor. Probability and Math. Statist. 111 (), 153-165.
Abstract, references and article information