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Discordant Protein and mRNA Expression in Lung Adenocarcinomas

Guoan Chen
Apr 1, 2002; 1:304-313
Research




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Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein

Yasushi Ishihama
Sep 1, 2005; 4:1265-1272
Research




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The Dangers of Tribalism in South Sudan

19 December 2013

Hannah Bryce
Former Assistant Head, International Security

20131219SudanClashesTruck.jpg

South Sudanese soldiers patrol the streets of Juba 2 January 2014. Thousands of people are feared to have been killed, pitting army units loyal to President Salva Kiir against ethnic militia forces and mutinous army commanders nominally headed by former vice president Riek Machar. Photo by Samir Bol/AFP/Getty Images.

The violence in South Sudan this week suggests there could be worse times to come for the country. It will exacerbate the deep-rooted inter- and intra-tribal tensions that have defined the political landscape in South Sudan since it gained independence in 2011. It could also create a refugee dilemma for the country’s neighbours.

The dynamics of the leadership struggle between President Salva Kiir, a Dinka, and former vice president Riek Macher, a Nuer, colours politics throughout the country, illustrating the prevalence of political tribalism at the highest office. Following Kiir’s dismissal of Machar and the entire cabinet in July, neither this week’s attempted coup nor its heavy suppression will have come as a surprise to many in South Sudan.

The perception of Dinka domination pervading the Sudan People Liberation Movement (SPLM) and the Sudan People Liberation Army (SPLA) by other ethnic groups is not new. But it has become increasingly marked in a country with a fragile economy, limited opportunities for employment and deep-rooted patrimonialism throughout all tiers of government.

While there is a long-standing rivalry for power between the Dinka and Nuer, South Sudan’s two largest tribal groups, others, such as the Equatorians, perceive both groups as monopolizing power. Addressing this perceived inequity within the government will be integral to move beyond political tribalism towards an inclusive system of government that guarantees minority representation. Without this change, discontent and frustrations within the disenfranchised rural communities that make up the majority of the population are liable to rise to the surface, as this week’s events demonstrate.

While government policies since independence have been careful to use the language of inclusivity, the reality is very different. Jonglei, the largest of South Sudan’s ten states and home of the Nuer, has seen severe fighting between the Dinka, Nuer and Murle, for example. In December 2011 tribal attacks and counterattacks between Nuer and Murle caused at least 1,000 deaths. 

These tensions have been further aggravated by the failure of the central government to provide even basic levels of local governance, made worse by systemic corruption and patrimonialism. The extent of corruption, and the government’s lack of control over it, was demonstrated in 2012 when President Kiir issued a somewhat plaintive call to his government officials to return stolen cash.

Government reforms and legislation have stripped traditional authorities of their former functions and roles within local society, without reintegrating them into new roles within the government apparatus or providing viable alternatives. This has resulted in inconsistent and disparate systems of local governance throughout South Sudan, contributing to existing perceptions of inequity. This is often assumed to be based on tribal factors, regardless of whether this is in fact the case.

With tensions appearing to be unabated in the capital, Juba, and with the dry season approaching, which will facilitate a more mobile population, there is significant potential for security to deteriorate further. And it may not recover for a long time. Disgruntled and marginalized, the tribal populations that have felt excluded from the political process, or in the case of the Nuer, undermined in that process, may use the current political turbulence to bring matters to a head and challenge the authority of South Sudan’s leading figures.

A lasting conflict in South Sudan would likely lead to further displacement of people, which would place an increased strain on host communities in neighbouring countries. Ethiopia, Kenya and Uganda already have a long history of accepting refugees from the Sudanese civil war. With the current flows of displaced populations from conflicts in Somalia, the Central African Republic and Democratic Republic of the Congo however, an additional influx of South Sudanese refugees would have the potential to overburden and destabilize the region further.

To comment on this article, please contact Chatham House Feedback




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Jordan: Regime Survival and Politics Beyond the State




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Undercurrents: Episode 19 - Green Building Projects in Jordan, and Qatar's Football World Cup




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Voices of Jordan: The Kingdom in the Centre of the Middle East




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




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Tracking isotopically labeled oxidants using boronate-based redox probes [Methods and Resources]

Reactive oxygen and nitrogen species have been implicated in many biological processes and diseases, including immune responses, cardiovascular dysfunction, neurodegeneration, and cancer. These chemical species are short-lived in biological settings, and detecting them in these conditions and diseases requires the use of molecular probes that form stable, easily detectable, products. The chemical mechanisms and limitations of many of the currently used probes are not well-understood, hampering their effective applications. Boronates have emerged as a class of probes for the detection of nucleophilic two-electron oxidants. Here, we report the results of an oxygen-18–labeling MS study to identify the origin of oxygen atoms in the oxidation products of phenylboronate targeted to mitochondria. We demonstrate that boronate oxidation by hydrogen peroxide, peroxymonocarbonate, hypochlorite, or peroxynitrite involves the incorporation of oxygen atoms from these oxidants. We therefore conclude that boronates can be used as probes to track isotopically labeled oxidants. This suggests that the detection of specific products formed from these redox probes could enable precise identification of oxidants formed in biological systems. We discuss the implications of these results for understanding the mechanism of conversion of the boronate-based redox probes to oxidant-specific products.




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Blaming China Is a Dangerous Distraction

15 April 2020

Jim O'Neill

Chair, Chatham House
Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake.

2020-04-15-China-coronavirus-health

Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images.

As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.

China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.

For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account.

Unhelpful and dangerous

At a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.

Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.

Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.

Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.

Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.

In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.

I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.

If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.

In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.

When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.

And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.

So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.

And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.

If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.

This article was originally published in Project Syndicate




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Summary Outcomes of the Fifth Meeting of the BCH Informal Advisory Committee (BCH IAC). The BCH IAC provides guidance regarding the technical issues associated with the ongoing development of the BCH.




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CBD News: Déclaration de M. Ahmed Djoghlaf, Secretaire executif de la Convention sur la diversite biologique, à la série de conférences: Intégrer la biodiversité dans les stratégies d'entreprise, Montréal, Qu




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CBD News: Statement by Ahmed Djoghlaf, Executive Secretary, at the Expert Workshop on Scientific and Technical Guidance on the Use of Biogeographic Classification Systems and Identification of Marine Areas in Need of Protection beyond National Jurisdictio




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CBD News: Statement by Mr. Ahmed Djoghlaf, Executive Secretary of the Convention on Biological Diversity, on the occasion of the Fifteenth Meeting of the Conference of the Parties to the Convention on International Trade in Endangered Species of Wild Faun




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CBD Communiqué: Sudan Becomes the 11th Country to Sign the Nagoya Protocol on Access and Benefit Sharing of Genetic Resources.




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CBD News: In conjunction with the 61st meeting of the Standing Committee of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), the Government of Switzerland, in partnership with the Japanese presidency of the tent




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CBD Press Release: Jordan becomes first country in the Arab region to ratify the Nagoya Protocol on genetic resources




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CBD Press Release: Managing biodiversity data from local government: Guidance for local authorities on publishing through the GBIF network, helping preserve knowledge about biodiversity




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CBD News: Statement by Mr. Braulio F. de Souza Dias, CBD Executive Secretary, to the National Workshop on Indicators and NBSAP for Iraq, Amman, Jordan, 1-4 July 2013




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CBD News: Montreal, 7 March 2014 - South Sudan deposited its instrument of accession to the Convention on Biological Diversity (CBD) on 17 February 2014, thus becoming the 194th Party to the global treaty on biodiversity and sustainable development. With




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CBD News: Déclaration de M. Braulio ferreira de Souza Dias, Secrétaire exécutif de la CDB, à l'occasion de l'atelier sur les synergies entre redd + et la conservation et restauration des écosystèmes dans les strat




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CBD News: Statement by Mr. Braulio F. de Souza Dias, CBD Executive Secretary, at the opening of the Expert Workshop to Provide Consolidated Practical Guidance and a Toolkit for Marine Spatial Planning, Montreal, Canada, 9 - 11 September 2014




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CBD News: The guidance addresses a major pathway for introduction and spread of invasive alien species, as a significant percentage of global invasive introductions result from pets, aquarium and terrarium species that escape from confined conditions and




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CBD News: CBD Expert Workshop to Prepare Practical Guidance on Preventing and Mitigating the Significant Adverse Impacts of Marine Debris on Marine and Coastal Biodiversity and Habitats, Baltimore, United States of America, 2 to 4 December 2014




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CBD News: The Food and Agriculture Organization of the United Nations (FAO) and the Secretariat of the Convention on Biological Diversity (CBD) have launched a technical guidance document which aims to promote mainstreaming of biodiversity and ecosystem s




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CBD News: It is a great pleasure and honour to address the seventeenth meeting of the Conference of the Parties to the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES).




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CBD News: The Food and Agriculture Organization of the United Nations (FAO), the Secretariat of the Pacific Regional Environment Programme (SPREP) and the Convention on Biological Diversity (CBD), today released a technical document that provides guidance




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CBD News: Today we celebrate World Wildlife Day. CITES (the Convention on International Trade in Endangered Species of Wild Fauna and Flora) has chosen the theme of "Big cats: predators under threat."




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CBD News: Over the next two weeks, the Convention on Biological Diversity's (CBD) bodies on science and implementation will meet to provide further guidance on accelerated efforts to achieve the Aichi Biodiversity Targets by the end of the year 2020,




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CBD News: The world has two years to secure a deal for nature to halt a 'silent killer' as dangerous as climate change, says biodiversity chief




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CBD News: Two major pieces of research reveal the clear and present danger biodiversity loss and climate change pose to the health, security and well-being of humanity.




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CBD News: The Secretariats of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) and the Convention on Biological Diversity, the United Nations Development Programme, the United Nations Environment Programme and Ja





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Inhibiting thrombin protects against dangerous infant digestive disease

(University of South Florida (USF Health)) A new preclinical study by researchers at the University of South Florida Health (USF Health) Morsani College of Medicine and Johns Hopkins University School of Medicine offers promise of a specific treatment for NEC, a rare inflammatory bowel disease that is a leading cause of death in premature infants. The team found that inhibiting the inflammatory and blood-clotting molecule thrombin with targeted nanotherapy can protect against NEC-like injury in newborn mice.




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Life-Saving Lullabies warn against the dangers of COVID-19 to African women

(University of Huddersfield) A team of researchers received funding of almost £130,000 to work with a group of women in Zambia and create songs that warn against the dangers of the coronavirus -- and now New York wants to hear them.




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Daniiboo releases ‘Drop It N Pop It’

Known for her creative dance moves and twerking style, dancer-turned-artiste Daniiboo dropped a new twerking song, titled ' Drop It N Pop It', in an attempt to put a smile on her fans' faces in a time of unprecedented uncertainty. The song is...




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Dancers' Paradise: Devon Unruly working hard to expand dance group

He's celebrating 10 years of dancing both competitively and in the street, and the co-founder of Unruly Skankaz, Devon Brown, says he is looking to expand the brand. The once three-member male dance group has grown to five, he told THE WEEKEND...




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The Destabilizing Danger of Cyberattacks on Missile Systems

2 July 2019

Dr Patricia Lewis

Research Director, Conflict, Science & Transformation; Director, International Security Programme

Dr Beyza Unal

Senior Research Fellow, International Security Programme
‘Left-of-launch’ attacks that aim to disable enemy missile systems may increase the chance of them being used, not least because the systems are so vulnerable.

2019-07-02-NKMissile.jpg

This undated photo released by North Korea's news agency in March 2017 shows the launch of four ballistic missiles during a military drill at an undisclosed location in North Korea. Photo: STR/AFP/Getty Images.

After President Trump decided to halt a missile attack on Iran in response to the downing of a US drone, it was revealed that the US had conducted cyberattacks on Iranian weapons systems to prevent Iran launching missiles against US assets in the region.

This ‘left-of-launch’ strategy – the pre-emptive action to prevent an adversary launch missiles – has been part of the US missile defence strategy for some time now. President George W Bush asked the US military and intelligence community to infiltrate the supply chain of North Korean missiles. It was claimed that the US hacked the North Korean ballistic missile programme, causing a failed ballistic missile test, in 2012.

It was not clear then – or now – whether these ‘left-of-launch’ cyberattacks aimed at North Korea were successful as described or whether they were primarily a bluff. But that is somewhat irrelevant; the belief in the possibility and the understanding of the potential impact of such cyber capabilities undermines North Korean or Iranian confidence in their abilities to launch their missiles. In times of conflict, loss of confidence in weapons systems may lead to escalation.

In other words, the adversary may be left with no option but to take the chance to use these missiles or to lose them in a conflict setting. ‘Left of launch’ is a dangerous game. If it is based on a bluff, it could be called upon and lead to deterrence failure. If it is based on real action, then it could create an asymmetrical power struggle. If the attacker establishes false confidence in the power of a cyber weapon, then it might lead to false signalling and messaging.

This is the new normal. The cat-and-mouse game has to be taken seriously, not least because missile systems are so vulnerable.

There are several ways an offensive cyber operation against missile systems might work. These include exploiting missile designs, altering software or hardware, or creating clandestine pathways to the missile command and control systems.

They can also be attacked in space, targeting space assets and their link to strategic systems.

Most missile systems rely, at least in part, on digital information that comes from or via space-based or space-dependent assets such as: communication satellites; satellites that provide position, navigation and timing (PNT) information (for example GPS or Galileo); weather satellites to help predict flight paths, accurate targeting and launch conditions; and remote imagery satellites to assist with information and intelligence for the planning and targeting.

Missile launches themselves depend on 1) the command and control systems of the missiles, 2) the way in which information is transmitted to the missile launch facilities and 3) the way in which information is transmitted to the missiles themselves in flight. All these aspects rely on space technology.

In addition, the ground stations that transmit and receive data to and from satellites are also vulnerable to cyberattack – either through their known and unknown internet connectivity or through malicious use of flash drives that contain a deliberate cyber infection.

Non-space-based communications systems that use cable and ground-to-air-to-ground masts are likewise under threat from cyberattacks that find their way in via internet connectivity, proximity interference or memory sticks. Human error in introducing connectivity via phones, laptops and external drives, and in clicking on malicious links in sophisticated phishing lures, is common in facilitating inadvertent connectivity and malware infection.

All of these can create a military capacity able to interfere with missile launches. Malware might have been sitting on the missile command and control system for months or even years, remaining inactivated until a chosen time or by a trigger that sets in motion a disruption either to the launch or to the flight path of the missile. The country that launches the missile that either fails to launch or fails to reach the target may never know if this was the result of a design flaw, a common malfunction or a deliberate cyberattack.

States with these capabilities must exercise caution: cyber offence manoeuvres may prevent the launch of missile attacks against US assets in the Middle East or in the Pacific regions, but they may also interfere with US missile launches in the future. Even, as has recently been revealed, US cyber weapons targeting an adversary may blow back and inadvertently infect US systems. Nobody is invulnerable.




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Sudan Stakeholder Dialogues: Options for Economic Stabilization, Recovery and Inclusive Growth

3 October 2019

The Chatham House Africa Programme designed the Sudan Stakeholder Dialogues series to help identify the factors that have led to the current economic crisis, the immediate steps that need to be taken to avert collapse and stabilize the economy, and the longer-term structural reforms required to set Sudan on the path to recovery. The project is funded by Humanity United.

Ahmed Soliman

Research Fellow, Horn of Africa, Africa Programme

2019-10-03-Sudan.jpg

An employee removes bread from the oven at a bakery in the Sudanese capital, Khartoum, on 24 May 2019. Photo: Getty Images.

Three private roundtable meetings were convened in the first quarter of 2019, with the aim of generating informed and constructive new thinking on policy options and reforms that could help Sudan build a more economically prosperous, stable and inclusive nation. The roundtables were held under the Chatham House Rule.

The project sought to offer a neutral space for discussion to policymakers and influencers from a broad range of backgrounds: Sudanese government officials, opposition figures, economists, experts on Sudan’s political economy and governance, civil society figures, representatives of international financial institutions, and other international policymakers.

This paper draws together the key themes and findings from each of the three roundtables, ranging from broad structural economic issues to sector-specific priority interventions. It presents options and recommendations for Sudanese leaders, including the transitional government, in support of building a more economically prosperous, peaceful and inclusive nation.




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Prospects for Peace and Stability in South Sudan

Research Event

11 November 2019 - 5:00pm to 6:15pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Alan Boswell, Senior Analyst for South Sudan, International Crisis Group
Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee Council
Naomi Pendle, Research Fellow, Firoz Lalji Centre for Africa, London School of Economics
Golda Abbé, Founding Member, Ghidam (Via Skype)
Chair: Teohna Williams, CEO, Business Plan for Peace

South Sudan’s prolonged peace process is approaching a critical juncture. There is uncertainty about whether the country’s political leaders will meet the 12 November 2019 deadline to form a transitional government of national unity – a process already delayed after a revitalized power-sharing deal was signed in September 2018. A political impasse has been caused by a lack of progress on outstanding issues such as deciding on the number of states and reunifying the security forces. The latter issue is seen as critical to preventing the reoccurrence of large-scale violence which would exacerbate already considerable humanitarian needs. Continued mediation by regional and international partners remains important to finding a way forward and preventing a return to widespread conflict.

At this event, a panel of speakers will examine the status of the peace deal, the issue of federalism and subdivision, measures needed to prevent the humanitarian crisis from worsening and opportunities to foster greater security and unity in the country.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Realizing South Sudan's Peace Deal

Invitation Only Research Event

24 February 2020 - 5:00pm to 6:15pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee Council
Matthew F. Pritchard, Research and Policy Specialist, McGill University
Joshua Craze, Writer and Researcher
Teohna Williams, CEO, Business Plan for Peace

South Sudan’s new power sharing government must be formed by 22 February 2020, as specified in the Revitalized Agreement on the Resolution of the Conflict in the Republic of South Sudan (R-ARCSS). There have been two extensions to this process already, reflecting the continued distrust among leaders and the complexity of the conflict.

The lack of progress in several contentious areas has delayed the formation of the Revitalized Transitional Government of National Unity (R-TGoNU) for nine months, but the recent decision taken by President Salva Kiir Mayardit to re-establish 10 states has been welcomed by opposition groups, regional mediators and international partners.

It is seen as the breakthrough needed for an agreement to be reached, despite some outstanding concerns. Further meaningful compromises and difficult decisions will be needed to implement a lasting peace agreement.

At this event, a panel of speakers will examine the status of the peace deal following the February deadline and the steps needed to progress the key issues underlying implementation.

Event attributes

Chatham House Rule

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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Combining Precursor and Fragment Information for Improved Detection of Differential Abundance in Data Independent Acquisition [Technological Innovation and Resources]

In bottom-up, label-free discovery proteomics, biological samples are acquired in a data-dependent (DDA) or data-independent (DIA) manner, with peptide signals recorded in an intact (MS1) and fragmented (MS2) form. While DDA has only the MS1 space for quantification, DIA contains both MS1 and MS2 at high quantitative quality. DIA profiles of complex biological matrices such as tissues or cells can contain quantitative interferences, and the interferences at the MS1 and the MS2 signals are often independent. When comparing biological conditions, the interferences can compromise the detection of differential peptide or protein abundance and lead to false positive or false negative conclusions.

We hypothesized that the combined use of MS1 and MS2 quantitative signals could improve our ability to detect differentially abundant proteins. Therefore, we developed a statistical procedure incorporating both MS1 and MS2 quantitative information of DIA. We benchmarked the performance of the MS1-MS2-combined method to the individual use of MS1 or MS2 in DIA using four previously published controlled mixtures, as well as in two previously unpublished controlled mixtures. In the majority of the comparisons, the combined method outperformed the individual use of MS1 or MS2. This was particularly true for comparisons with low fold changes, few replicates, and situations where MS1 and MS2 were of similar quality. When applied to a previously unpublished investigation of lung cancer, the MS1-MS2-combined method increased the coverage of known activated pathways.

Since recent technological developments continue to increase the quality of MS1 signals (e.g. using the BoxCar scan mode for Orbitrap instruments), the combination of the MS1 and MS2 information has a high potential for future statistical analysis of DIA data.




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Guidance Document: Validation of a High-Performance Liquid Chromatography-Tandem Mass Spectrometry Immunopeptidomics Assay for the Identification of HLA Class I Ligands Suitable for Pharmaceutical Therapies [Commentary]

For more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions. To support clinical trials based on HLA-presented tumor-associated antigens, in this study the sensitive LC-MS/MS HLA class I antigen identification pipeline was fully validated for our technical equipment according to the current US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines.

The immunopeptidomes of JY cells with or without spiked-in, isotope labeled peptides, of peripheral blood mononuclear cells of healthy volunteers as well as a chronic lymphocytic leukemia and a bladder cancer sample were reliably identified using a data-dependent acquisition method. As the LC-MS/MS pipeline is used for identification purposes, the validation parameters include accuracy, precision, specificity, limit of detection and robustness.




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Victorian Premier Daniel Andrews announces 175 new tech jobs for Melbourne

State government commits to five-year funding round as software company launches community centre and new jobs.




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Tax time in danger from ATO's tech wreck

IT projects thrown overboard as ATO orders all hands to keep tax time afloat.




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Blaming China Is a Dangerous Distraction

15 April 2020

Jim O'Neill

Chair, Chatham House
Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake.

2020-04-15-China-coronavirus-health

Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images.

As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.

China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.

For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account.

Unhelpful and dangerous

At a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.

Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.

Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.

Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.

Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.

In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.

I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.

If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.

In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.

When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.

And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.

So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.

And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.

If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.

This article was originally published in Project Syndicate




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Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells

Kotaro Hama
Apr 1, 2020; 61:523-536
Patient-Oriented and Epidemiological Research




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Blaming China Is a Dangerous Distraction

15 April 2020

Jim O'Neill

Chair, Chatham House
Chinese officials' initial effort to cover up the coronavirus outbreak was appallingly misguided. But anyone still focusing on China's failings instead of working toward a solution is essentially making the same mistake.

2020-04-15-China-coronavirus-health

Medical staff on their rounds at a quarantine zone in Wuhan, China. Photo by STR/AFP via Getty Images.

As the COVID-19 crisis roars on, so have debates about China’s role in it. Based on what is known, it is clear that some Chinese officials made a major error in late December and early January, when they tried to prevent disclosures of the coronavirus outbreak in Wuhan, even silencing healthcare workers who tried to sound the alarm.

China’s leaders will have to live with these mistakes, even if they succeed in resolving the crisis and adopting adequate measures to prevent a future outbreak. What is less clear is why other countries think it is in their interest to keep referring to China’s initial errors, rather than working toward solutions.

For many governments, naming and shaming China appears to be a ploy to divert attention from their own lack of preparedness. Equally concerning is the growing criticism of the World Health Organization (WHO), not least by Donald Trump who has attacked the organization - and threatens to withdraw US funding - for supposedly failing to hold the Chinese government to account.

Unhelpful and dangerous

At a time when the top global priority should be to organize a comprehensive coordinated response to the dual health and economic crises unleashed by the coronavirus, this blame game is not just unhelpful but dangerous.

Globally and at the country level, we all desperately need to do everything possible to accelerate the development of a safe and effective vaccine, while in the meantime stepping up collective efforts to deploy the diagnostic and therapeutic tools necessary to keep the health crisis under control.

Given there is no other global health organization with the capacity to confront the pandemic, the WHO will remain at the center of the response, whether certain political leaders like it or not.

Having dealt with the WHO to a modest degree during my time as chairman of the UK’s independent Review on Antimicrobial Resistance (AMR), I can say that it is similar to most large, bureaucratic international organizations.

Like the International Monetary Fund (IMF), the World Bank, and the United Nations, it is not especially dynamic or inclined to think outside the box. But rather than sniping at these organizations from the sidelines, we should be working to improve them.

In the current crisis, we all should be doing everything we can to help both the WHO and the IMF to play an effective, leading role in the global response. As I have argued before, the IMF should expand the scope of its annual Article IV assessments to include national public-health systems, given that these are critical determinants in a country’s ability to prevent or at least manage a crisis like the one we are now experiencing.

I have even raised this idea with IMF officials themselves, only to be told that such reporting falls outside their remit because they lack the relevant expertise. That answer was not good enough then, and it definitely isn’t good enough now.

If the IMF lacks the expertise to assess public health systems, it should acquire it. As the COVID-19 crisis makes abundantly clear, there is no useful distinction to be made between health and finance. The two policy domains are deeply interconnected, and should be treated as such.

In thinking about an international response to today’s health and economic emergency, the obvious analogy is the 2008 global financial crisis which started with an unsustainable US housing bubble, fed by foreign savings owing to the lack of domestic savings in the United States.

When the bubble finally burst, many other countries sustained more harm than the US did, just as the COVID-19 pandemic has hit some countries much harder than it hit China.

And yet not many countries around the world sought to single out the US for presiding over a massively destructive housing bubble, even though the scars from that previous crisis are still visible. On the contrary, many welcomed the US economy’s return to sustained growth in recent years, because a strong US economy benefits the rest of the world.

So, rather than applying a double standard and fixating on China’s undoubtedly large errors, we would do better to consider what China can teach us. Specifically, we should be focused on better understanding the technologies and diagnostic techniques that China used to keep its - apparent - death toll so low compared to other countries, and to restart parts of its economy within weeks of the height of the outbreak.

And for our own sakes, we also should be considering what policies China could adopt to put itself back on a path toward 6% annual growth, because the Chinese economy inevitably will play a significant role in the global recovery.

If China’s post-pandemic growth model makes good on its leaders’ efforts in recent years to boost domestic consumption and imports from the rest of the world, we will all be better off.

This article was originally published in Project Syndicate




dan

Russia and Georgia: A Dangerous Game

1 October 2008 , Number 3

Dilemmas and dangers abound for the west as it tries to come to terms with the ‘new’ Russia. There is a mood of defiance and injury, which can only be answered with firmness and prudence.

James Sherr

Head, Russia and Eurasia Programme, Chatham House




dan

Hexacosenoyl-CoA is the most abundant very long-chain acyl-CoA in ATP binding cassette transporter D1-deficient cells [Patient-Oriented and Epidemiological Research]

X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by deleterious mutations in the ABCD1 gene. The ABCD1 protein transports very long-chain FAs (VLCFAs) from the cytosol into the peroxisome where the VLCFAs are degraded through β-oxidation. ABCD1 dysfunction leads to VLCFA accumulation in individuals with X-ALD. FAs are activated by esterification to CoA before metabolic utilization. However, the intracellular pools and metabolic profiles of individual acyl-CoA esters have not been fully analyzed. In this study, we profiled the acyl-CoA species in fibroblasts from X-ALD patients and in ABCD1-deficient HeLa cells. We found that hexacosenoyl (26:1)-CoA, but not hexacosanoyl (26:0)-CoA, was the most abundantly concentrated among the VLCFA-CoA species in these cells. We also show that 26:1-CoA is mainly synthesized from oleoyl-CoA, and the metabolic turnover rate of 26:1-CoA was almost identical to that of oleoyl-CoA in both WT and ABCD1-deficient HeLa cells. The findings of our study provide precise quantitative and metabolic information of each acyl-CoA species in living cells. Our results suggest that VLCFA is endogenously synthesized as VLCFA-CoA through a FA elongation pathway and is then efficiently converted to other metabolites, such as phospholipids, in the absence of ABCD1.




dan

Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 with Clostridia and Insulin Sensitivity in Humans

Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22 producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales. This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22 and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.