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In Vivo Identification of Human Small Ubiquitin-like Modifier Polymerization Sites by High Accuracy Mass Spectrometry and an in Vitro to in Vivo Strategy

Ivan Matic
Jan 1, 2008; 7:132-144
Research




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Comparative Proteomic Analysis of Eleven Common Cell Lines Reveals Ubiquitous but Varying Expression of Most Proteins

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time




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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




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A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research




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A Tandem Affinity Tag for Two-step Purification under Fully Denaturing Conditions: Application in Ubiquitin Profiling and Protein Complex Identification Combined with in vivoCross-Linking

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research




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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




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Absolute Quantification of Proteins by LCMSE: A Virtue of Parallel ms Acquisition

Jeffrey C. Silva
Jan 1, 2006; 5:144-156
Research




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Building a Fantasy Army — Environment & Society

This article is by Toni Šušnjar.

Warfare and military are an integral part of much of ancient and medieval fantasy. This is no surprise: warfare was a key element in development of society and of history, and much of mythology is also about it. As such, it is difficult for fantasy writers and readers alike to avoid war and military matters in general. And if you are going to do something, try to do it well. Army does not spring from the ground like the spartoi of Jason.

Environment and Geography

Environmental conditions include terrain, climate and resources. All three influence how an army will fight and which weapons it will use.

Terrain can be highly varied, but I will divide it into three categories: mountainous, rolling hills and flat. Mountains and forests – and especially forested mountains – are conductive to infantry warfare. Depending on other conditions (such as society, climate etc.), this can mean either light infantry with focus on ambushes, raiding and guerilla warfare; or heavy infantry, with focus on direct confrontation. Both of these were, at different points, in evidence in Spain and Greece.

Continue reading Building a Fantasy Army — Environment & Society at Mythic Scribes.




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Building a Fantasy Army — Strategy & Organization

This article is by Toni Šušnjar.

Strategy and Enemies

The structure of an army will depend on the strategy, as strategy will determine the army’s role and tasks. A state which carries out expansion through outright territorial conquest will have large numbers of heavy infantry, combat engineers and artillery, and possibly some heavy cavalry as well (e.g. Roman Empire, 10th century Byzantine Empire). If conquest is done by slowly destroying an opponent’s economic and social structures through constant raiding (such as chevauchee or razzia / ghazw), then majority of the army will be light cavalry, with some heavy cavalry support (e.g. Seljuk and Ottoman Empires), and light infantry will be used if terrain is unsuitable for cavalry. If a state is defending against cavalry raids, then light cavalry will be dominant (e.g. 15th century Hungary), whereas heavy cavalry will predominate if enemy raiders are primarily infantry. If enemy armies are too powerful to face in the field, light and heavy cavalry will be used to harass the invading army and cut off its supplies and foraging. In terrain unsuitable for cavalry operations, heavy infantry will be used instead.

Raiding — as a strategy — is generally preferred against a peer opponent, especially if a state cannot have a developed logistical support system.

Continue reading Building a Fantasy Army — Strategy & Organization at Mythic Scribes.




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Building a Fantasy Army — Recruitment & Logistics

This article is by Toni Šušnjar.

Recruitment and Numbers

The most basic style of recruitment is that of a local militia – rural or urban – where a portion or all of the free men take up arms. Militiamen are usually not highly trained, but they make up for lack of training with motivation: fleeing not only carries social stigma, but is also harshly punished. As such, militias were more effective than what would be expected of “civilians in arms”. Militias almost always depended on relatively cheap and easy to use weapons, though urban militias might have access to more expensive weapons – such as hoplite panoply or crossbows. Tribal militias typically used weapons that were also used for hunting and sport. Peasant levy however was only ever used in a support and harassment role, and often had weapons modified from agricultural implements. Only urban militias could have heavy equipment. A common disadvantage of militia armies is the inability to deploy over long distances and time-frames due to soldiers having a day job; thus, focus on long-term warfare (be it conquest or defence) typically brings about the professionalization of the army. This also means that militias are best used in cases with high political fragmentation – such as city-states.

Continue reading Building a Fantasy Army — Recruitment & Logistics at Mythic Scribes.




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Building a Fantasy Army — Weapons & Tactics

This article is by Toni Šušnjar.

In Antiquity and early the Middle Ages, the main weapon was the spear. Only a few exceptions appeared: Roman legions, which used javelins instead, and Macedonian pike phalanx with its sarissa. In the later Middle Ages, the main weapon could be a pike or a polearm (such as polehammer, poleaxe, halberd etc.), before the pike made its return in early modernity. Ranged weapons were not used to cause casualties, but rather to inconvenience the enemies and break up their formation.

Weapons and tactics will adapt to each other, as well as to the terrain and the enemies faced – but adaptations will be done within the boundaries of the society. A society without a significant tradition of horse archery will not counter horse archers with their own, but rather with foot archers. Horse archery was important for nomadic societies, because they could not afford the casualties which resulted from the shock and attrition tactics of the settled societies.

Weapons and armour likewise have a relationship, but since armour is the more difficult to produce of the two, it is developments in armour which typically drive the adaptation of weapons, rather than the other way around.

Continue reading Building a Fantasy Army — Weapons & Tactics at Mythic Scribes.




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Questions for Worldbuilding the Concept of Wisdom

Wisdom to my mind is a bit of a paradox. It is subjective and context-dependent, but inherently universal. I say this, because for something to be wise it ought to be applicable across time and space, yet whether the claims are appraised as being “wise” hinges on the perception of a past, present or future audience. It is beyond the self, yet dependent upon the self. So that then begs the fantasy writing question: What if the self is not human? If culture already morphs the form and substance of wisdom, what effect might a different state of being have on it?

That would be terribly dull to prescribe, but I can help get some readers’ creativity going. Below I have listed relevant questions with examples you might consider when building your setting, so you may merrily thread into your fantastic realms to shape oddities rich and strange.

I would advise readers of this article to try and let go of their own presumptions on what is wise for the sake of worldbuilding. There are few cultures in our modern, human world whose philosophers deem obtuse narcissists dressed in mink robes as being wise, but why wouldn’t a race of bobcat-folk?

Continue reading Questions for Worldbuilding the Concept of Wisdom at Mythic Scribes.




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After Truss, the UK can still rebuild its global reputation

After Truss, the UK can still rebuild its global reputation Expert comment NCapeling 20 October 2022

Following a chaotic few weeks as UK prime minister, Liz Truss has stepped down. And that is the best outcome for her party and for the country.

Liz Truss could not command support for her calamitous – and misnamed – mini-budget. And once her new Chancellor Jeremy Hunt had overturned its provisions, she had no mission or credibility left.

The budget pushed interest rates higher and they did not fall much on the scrapping of it, leaving her open to the charge she pushed up mortgage and interest costs for every person and business in the country. Her apology for ‘mistakes made’ was not going to reverse that, so her MPs were right to tell her to go.

Her departure does mark a victory for at least some of the UK’s institutions, even if it might not seem that way to observers around the world.

There is no question the UK’s standing in the world has been severely battered by this episode and by the revolving door of prime ministers

The position of the UK parliament has been reaffirmed, and so has that of the Office for Budget Responsibility (OBR) – it will be a long time before a government tries to dispense with the comments of the independent watchdog of national finances.

This also reinforces the principle that governments must explain how they will pay for their programmes. The Bank of England remains unencumbered – despite Truss’s apparent intentions of giving it a pro-growth addition to its mandate – to pursue its aim of tackling inflation.

New leader needs legitimacy quickly

The Conservative party has a chance – perhaps – to produce another prime minister without being forced into a general election, as that is the constitutional principle in the UK’s parliamentary system.

But the clamour that the new leader, as the third prime minister in one year, lacks legitimacy may prove impossible to resist for long.

In attempting to select a leader with a chance of uniting the party, the Conservatives are right to be considering options for restricting this leadership election to MPs should there be only one candidate with enough support.

But no such candidate may emerge and the pressure within the Commons – and the country – for an early election will not let up.

There is no question the UK’s standing in the world has been severely battered by this episode and by the revolving door of prime ministers. For the UK to regain respect – and an image of reliability – it needs to move fast and find someone capable of putting policies into action.

Those policies need to be based on economic stability but must also include a resolution of the relationship with Europe as much of the current upheaval represents the bitter aftermath of Brexit.

The UK must show its reputation for being a country which holds respect for law and good government high in its values. The country is more capable of change – and willing to impose it on itself – than many in other countries often imagine

Concluding a deal with Brussels over the Northern Ireland protocol – avoiding ripping up the treaty the UK signed – and continuing to smooth the considerable friction that the exit from the EU has brought for exporters is essential work for the next prime minister.

Pursuing a deal for scientists to take part in the European Union (EU) Horizon research should be a priority. UK universities and researchers are already reluctantly preparing for a future where that does not come, with signs of the feared drain of talent already clear.

UK’s international reputation now at risk

Beyond that, there is much about UK policy which needs clarifying if the country is to regain its international standing. Just weeks from the start of COP27 and less than one year since the Glasgow climate change summit it hosted, the UK position on climate change commitments appears in flux.

The UK government pledge to help Ukraine is clear and has won it gratitude there and respect within Europe, but its intentions for defence spending are less clear.




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Building Resistance to Violent Extremism




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Undercurrents: Episode 11 - New Approaches to Peacebuilding, and Gender-Inclusive Growth at the G20




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




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Undercurrents: Episode 24 - Christmas Quiz




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Screening Room: Inside Europe - We Quit




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




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Brexit in a Historical Context: Pursuing a Global Vision at the Expense of Domestic Harmony?




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Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells

W Gamble
Nov 1, 1978; 19:1068-1070
Articles




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

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




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Rebuilding trust is central to the UN’s future

Rebuilding trust is central to the UN’s future Expert comment NCapeling 25 March 2021

António Guterres is under scrutiny as he prepares to report on the future of the United Nations, with a renewed focus on trust, resilience and prevention.

The United Nations Secretary-General’s inbox is full as his organization celebrates its 75th anniversary. Trust must be rebuilt amid increased geo-political rivalry, North-South divisions, and sceptical citizens left behind by globalization. The international community has manifestly underinvested in institutional resilience and prevention. Better partnerships are needed with the private sector, and innovative forms of cross-regional cooperation fostered.

There are positive signs UN member states want things to change. They unanimously agreed a Political Declaration last September strongly reaffirming multilateralism, and they gave António Guterres one year to present a roadmap on how to respond, ‘building back better’ in the face of climate change and COVID-19.

Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart

A key challenge is to steer mandates and resources towards prevention. The World Bank-WHO Global Preparedness Monitoring Board, which eerily predicted the pandemic in its inaugural report in September 2019, reminds us successful prevention rests not on warning alone, but on aligned incentives for early action.

Geopolitical tensions persist

China has invested significantly in the multilateral system over the last decade, both in formal organizations such as the UN and the African Union, and in fostering a set of China-centred ‘mini-lateral’ fora such as the SCO, BRICS and BRI. It has also deepened its ties with Russia in the UN Security Council. Western countries both begrudgingly admire and deeply distrust China’s nimbleness in advancing its interests and values in this way but are divided on how to respond.

The Biden administration has recommitted itself to multilateral processes but US bilateral relations are likely to remain the main foreign policy driver. The UK has sought to convert the G7 into an enlarged summit-level meeting for democracies but Europe is divided over the wisdom of formalizing a group which may increase divisions with China, and some major democracies – India for example – have divergent approaches on issues such as trade protection.

An increase in cross-regional informal caucusing within the UN system to advance norms and progress around specific common objectives is likely. Guterres can encourage smaller powers to become ‘bridge builders’ sitting in the middle of a ‘Venn diagram’ of such new member state constellations at the UN.

Guterres can also build on the recent Abraham Accords to encourage cross-regional cultural, political and security relationships on the back of trade and investment, and map practical opportunities for strategic cooperation between China and the West in health and food security, climate and biodiversity, and global macroeconomic management, while fostering new normative frameworks to manage strategic competition in artificial intelligence (AI), big data, cyber resilience, gene-editing, and automation.

North-South mistrust

Realizing the Sustainable Development Goals (SDGs) and climate objectives rests in part in mobilizing the expertise and resources of sub-state actors such as business and city and regional authorities. However, developing countries remain wary of granting the UN Secretary-General a greater role in fostering partnerships with the private sector and mobilizing private finance, out of fear this may overshadow the global North’s promises to provide aid and create fairer trade and debt conditions.

In addition, African governments are expressing growing frustration at their continued lack of ‘agency’ in UN decision-making, the reneging of promises on climate financing by the global North, and the slow rollout of the COVAX facility to developing countries.

Progress may lie in two areas. First, developing country leadership of initiatives – such as the Friends Group on SDG financing established by the Jamaican and Canadian ambassadors to the UN – can help build trust and allay concerns, which is vital to incentivise transformative investment by sovereign wealth, pension, and insurance funds in pro-poor low carbon infrastructure in developing countries.

The second area is curating multi-stakeholder initiatives outside the UN framework and then linking them back to the organization once they have proven to be beneficial to both developed and developing countries. Successful initiatives such as the Vaccine Alliance can be a model of how to do this while not detracting from state obligations.

Scepticism among citizens

Trust in governance also needs rebuilding at the level of the individual citizen. Mobilized by populist movements and ‘fake news’ online, individuals left behind by the uneven economic benefits of globalization view governments and international organizations as unaccountable and lacking their interests at heart.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives

Guterres has called for a new ‘social contract’ between governments and their citizens, and for ‘Multilateralism 2.0’ to demonstrate a practical ‘hard interest’ as well as a ‘values’ case for why international cooperation inclusively benefits individuals as well as states. And technological innovation can also help citizens hold governments to account. As the first Secretary-General with a science and engineering background, Guterres has championed how technology enhances UN delivery of its objectives.

The pairing of artificial intelligence (AI) with satellites and drones for geospatial insight has been pioneered by both the United Nations Environment Programme (UNEP) and the Food and Agriculture Organization (FAO) to help communities preserve ecosystems and agricultural productivity. The resultant data, accessible on smart phones and computers, enables civil society to measure governments’ promises against real-time progress, through monitoring greenhouse gas emissions from power stations.

Alongside trust and accountability, fostering inclusiveness is likely to be central to Guterres’ report as he navigates how the UN can legitimize multi-stakeholder partnerships, enhance transparency, and bring coherence to diverse ‘mini-lateral’ initiatives.

These themes are explored further in the forthcoming synthesis paper ‘Reflections on building more inclusive global governance: Ten insights into emerging practice




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Building trust in trade deals – is human rights monitoring the answer?

Building trust in trade deals – is human rights monitoring the answer? 27 May 2021 — 4:00PM TO 5:15PM Anonymous (not verified) 14 May 2021 Online

Exploring the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running.

Please click on the below link to confirm your participation and receive your individual joining details from Zoom for this event. You will receive a confirmation email from Zoom, which contains the option to add the event to your calendar if you so wish.

The recent signing of the EU-China Investment Agreement has reignited arguments about trade and human rights. While many trade agreements envisage human rights monitoring in some shape or form, the monitoring systems that have emerged so far are not especially coherent, systematic or impactful. 

Are the human rights commitments in trade agreements more than just window-dressing?  If so, what kind of monitoring is needed to ensure they are lived up to? 

At this panel event, which marks the launch of a new Chatham House research paper, participants explore the arguments in favour of more robust human rights monitoring systems and why effective monitoring mechanisms have proved so difficult to get up and running in this context. 

  • What factors are presently holding governments back, and where is innovation and investment most needed?
  • What are the political, economic and structural conditions for fair and effective human rights monitoring of trade agreements? 
  • Is human rights monitoring best done unilaterally – or should more effort be put into developing joint approaches? 
  • What role might human rights monitoring have to play in governments’ strategies to ‘build back better’ from the COVID-19 pandemic?






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Building better polymerases: Engineering the replication of expanded genetic alphabets [Molecular Biophysics]

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.




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Novel fluorescent GPCR biosensor detects retinal equilibrium binding to opsin and active G protein and arrestin signaling conformations [Molecular Biophysics]

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.




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Shared requirements for key residues in the antibiotic resistance enzymes ErmC and ErmE suggest a common mode of RNA recognition [Enzymology]

Erythromycin-resistance methyltransferases are SAM dependent Rossmann fold methyltransferases that convert A2058 of 23S rRNA to m6 2A2058. This modification sterically blocks binding of several classes of antibiotics to 23S rRNA, resulting in a multidrug-resistant phenotype in bacteria expressing the enzyme. ErmC is an erythromycin resistance methyltransferase found in many Gram-positive pathogens, whereas ErmE is found in the soil bacterium that biosynthesizes erythromycin. Whether ErmC and ErmE, which possess only 24% sequence identity, use similar structural elements for rRNA substrate recognition and positioning is not known. To investigate this question, we used structural data from related proteins to guide site-saturation mutagenesis of key residues and characterized selected variants by antibiotic susceptibility testing, single turnover kinetics, and RNA affinity–binding assays. We demonstrate that residues in α4, α5, and the α5-α6 linker are essential for methyltransferase function, including an aromatic residue on α4 that likely forms stacking interactions with the substrate adenosine and basic residues in α5 and the α5-α6 linker that likely mediate conformational rearrangements in the protein and cognate rRNA upon interaction. The functional studies led us to a new structural model for the ErmC or ErmE-rRNA complex.




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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.




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Prioritizing equity and justice in climate action

Prioritizing equity and justice in climate action 30 June 2021 — 11:00AM TO 12:00PM Anonymous (not verified) 10 June 2021 Online

London Climate Action Week event: Why understanding equity and justice is essential to the ability to meaningfully inform climate politics.

Citizen-led climate activism is demonstrating the need to think about climate change ‘not just as a problem for science to solve’ but also as a problem of equity, human rights and justice.

The disproportionate impacts of climate change on the poor and the marginalized across the world means that understanding equity and justice is essential for the ability to meaningfully inform climate politics.

Excluding these issues risks ignoring, or intentionally omitting, the consequences of policies, tools and frameworks on those who are most likely to face the severe costs of any climate action or inaction.

In a pivotal year for climate decision-making, this event explores the necessity of equity and justice in climate action and how the world can move the political conversation to one that is more inclusive.

The speakers explore how communities themselves articulate the justice dimensions of climate change and how fairness can create a greener future for current and future generations.

This event is being hosted as a part of Strengthening Climate Diplomacy, a series of events from Chatham House during London Climate Action Week 2021.




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Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities

Artificial Intelligence Apps Risk Entrenching India’s Socio-economic Inequities Expert comment sysadmin 14 March 2018

Artificial intelligence applications will not be a panacea for addressing India’s grand challenges. Data bias and unequal access to technology gains will entrench existing socio-economic fissures.

Participants at an AI event in Bangalore. Photo: Getty Images.

Artificial intelligence (AI) is high on the Indian government’s agenda. Some days ago, Prime Minister Narendra Modi inaugurated the Wadhwani Institute for Artificial Intelligence, reportedly India’s first research institute focused on AI solutions for social good. In the same week, Niti Aayog CEO Amitabh Kant argued that AI could potentially add $957 billion to the economy and outlined ways in which AI could be a ‘game changer’.

During his budget speech, Finance Minister Arun Jaitley announced that Niti Aayog would spearhead a national programme on AI; with the near doubling of the Digital India budget, the IT ministry also announced the setting up of four committees for AI-related research. An industrial policy for AI is also in the pipeline, expected to provide incentives to businesses for creating a globally competitive Indian AI industry.

Narratives on the emerging digital economy often suffer from technological determinism — assuming that the march of technological transformation has an inner logic, independent of social choice and capable of automatically delivering positive social change. However, technological trajectories can and must be steered by social choice and aligned with societal objectives. Modi’s address hit all the right notes, as he argued that the ‘road ahead for AI depends on and will be driven by human intentions’. Emphasising the need to direct AI technologies towards solutions for the poor, he called upon students and teachers to identify ‘the grand challenges facing India’ – to ‘Make AI in India and for India’.

To do so, will undoubtedly require substantial investments in R&D, digital infrastructure and education and re-skilling. But, two other critical issues must be simultaneously addressed: data bias and access to technology gains.

While computers have been mimicking human intelligence for some decades now, a massive increase in computational power and the quantity of available data are enabling a process of ‘machine learning.’ Instead of coding software with specific instructions to accomplish a set task, machine learning involves training an algorithm on large quantities of data to enable it to self-learn; refining and improving its results through multiple iterations of the same task. The quality of data sets used to train machines is thus a critical concern in building AI applications.

Much recent research shows that applications based on machine learning reflect existing social biases and prejudice. Such bias can occur if the data set the algorithm is trained on is unrepresentative of the reality it seeks to represent. If for example, a system is trained on photos of people that are predominantly white, it will have a harder time recognizing non-white people. This is what led a recent Google application to tag black people as gorillas.

Alternatively, bias can also occur if the data set itself reflects existing discriminatory or exclusionary practices. A recent study by ProPublica found for example that software that was being used to assess the risk of recidivism in criminals in the United States was twice as likely to mistakenly flag black defendants as being at higher risk of committing future crimes.

The impact of such data bias can be seriously damaging in India, particularly at a time of growing social fragmentation. It can contribute to the entrenchment of social bias and discriminatory practices, while rendering both invisible and pervasive the processes through which discrimination occurs. Women are 34 per cent less likely to own a mobile phone than men – manifested in only 14 per cent of women in rural India owning a mobile phone, while only 30 per cent of India’s internet users are women.

Women’s participation in the labour force, currently at around 27 per cent, is also declining, and is one of the lowest in South Asia. Data sets used for machine learning are thus likely to have a marked gender bias. The same observations are likely to hold true for other marginalized groups as well.

Accorded to a 2014 report, Muslims, Dalits and tribals make up 53 per cent of all prisoners in India; National Crime Records Bureau data from 2016 shows in some states, the percentage of Muslims in the incarcerated population was almost three times the percentage of Muslims in the overall population. If AI applications for law and order are built on this data, it is not unlikely that it will be prejudiced against these groups.

(It is worth pointing out that the recently set-up national AI task force is comprised of mostly Hindu men – only two women are on the task force, and no Muslims or Christians. A recent article in the New York Times talked about AI’s ‘white guy problem’; will India suffer from a ‘Hindu male bias’?)

Yet, improving the quality, or diversity, of data sets may not be able to solve the problem. The processes of machine learning and reasoning involve a quagmire of mathematical functions, variables and permutations, the logic of which are not readily traceable or predictable. The dazzle of AI-enabled efficiency gains must not blind us to the fact that while AI systems are being integrated into key socio-economic systems, their accuracy and logic of reasoning have not been fully understood or studied.

The other big challenge stems from the distribution of AI-led technology gains. Even if estimates of AI contribution to GDP are correct, the adoption of these technologies is likely to be in niches within the organized sector. These industries are likely to be capital- rather than labour-intensive, and thus unlikely to contribute to large-scale job creation.

At the same time, AI applications can most readily replace low- to medium-skilled jobs within the organized sector. This is already being witnessed in the outsourcing sector – where basic call and chat tasks are now automated. Re-skilling will be important, but it is unlikely that those who lose their jobs will also be those who are being re-skilled – the long arch of technological change and societal adaptation is longer than that of people’s lives. The contractualization of work, already on the rise, is likely to further increase as large industries prefer to have a flexible workforce to adapt to technological change. A shift from formal employment to contractual work can imply a loss of access to formal social protection mechanisms, increasing the precariousness of work for workers.

The adoption of AI technologies is also unlikely in the short- to medium-term in the unorganized sector, which engages more than 80 per cent of India’s labor force. The cost of developing and deploying AI applications, particularly in relation to the cost of labour, will inhibit adoption. Moreover, most enterprises within the unorganized sector still have limited access to basic, older technologies – two-thirds of the workforce are employed in enterprises without electricity. Eco-system upgrades will be important but incremental. Given the high costs of developing AI-based applications, most start-ups are unlikely to be working towards creating bottom-of-the-pyramid solutions.

Access to AI-led technology gains is thus likely to be heavily differentiated – a few high-growth industries can be expected, but these will not necessarily result in the welfare of labour. Studies show that labour share of national income, especially routine labour, has been declining steadily across developing countries.

We should be clear that new technological applications themselves are not going to transform or disrupt this trend – rather, without adequate policy steering, these trends will be exacerbated.

Policy debates about AI applications in India need to take these two issues seriously. AI applications will not be a panacea for addressing ‘India’s grand challenges’. Data bias and unequal access to technology gains will entrench existing socio-economic fissures, even making them technologically binding.

In addition to developing AI applications and creating a skilled workforce, the government needs to prioritize research that examines the complex social, ethical and governance challenges associated with the spread of AI-driven technologies. Blind technological optimism might entrench rather than alleviate the grand Indian challenge of inequity and growth.

This article was originally published in the Indian Express.





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46 Receive AMS-Simons Research Enhancement Grants for PUI Faculty

Forty-six mathematical scientists have been named recipients of AMS-Simons Research Enhancement Grants for Primarily Undergraduate Institution (PUI) Faculty. Each awardee will receive $3,000 per year for three years. 

The grants foster and support research collaboration by full-time mid-career mathematicians at US institutions that do not offer a mathematics doctoral degree.

This year’s grant recipients hail from 42 institutions across 21 US states. The grants will support their research in several different areas, from number theory to applied mathematics.

This is the grant program’s second cohort, said Sarah Bryant, associate vice president of programs. “Over the first two years, we’ve worked with faculty from 75 different institutions, including 19 minority-serving institutions, which shows just how much this program is expanding and making an impact,” Bryant said. She noted that “in the first year, the grants supported 87 trips, helped produce 70 publications and preprints, and gave awardees the resources needed to collaborate and advance their work.”

The grant allows for any activities that will further the awardee’s research program. Expenses include but are not limited to conference participation, institute visits, collaboration travel (awardee or collaborator), computer equipment or software, family-care expenses, and teaching assistants.

Administration of the award by the grantee’s institution is required; annual discretionary funds for a grantee’s department and administrative funds for a grantee's institution will be available at the end of each grant year.

The grants are made possible through funding from the Simons Foundation and the American Mathematical Society (AMS), as well as Eve, Kirsten, Lenore, and Ada of the Menger family.

Applications for the next cohort are anticipated to open on MathPrograms.org on January 9, 2025. Visit the AMS website to view an informational PowerPoint or sign up to receive email updates about the program. Faculty who applied for but did not receive the 2023 or 2024 awards are encouraged to reapply if they are still eligible for the grant. 




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US Navy destroyers unscathed after fighting off a complex attack of cruise and ballistic missiles and exploding drones




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This powerful, quiet, exhaust-free generator is almost 55% off ahead of Black Friday




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Enhancing the role of women in peacebuilding and politics in Ethiopia

Enhancing the role of women in peacebuilding and politics in Ethiopia 29 June 2022 — 1:00PM TO 2:30PM Anonymous (not verified) 16 June 2022 Online

Panellists discuss the priorities for promoting the agency of women in politics and peacebuilding in Ethiopia and approaches for combatting gender-based discrimination and violence.

The war in northern Ethiopia and conflicts elsewhere have disproportionately affected women and girls – including through the infliction of physical and sexual violence, the heightened impacts of displacement and disruptions to education, and the co-option of women’s experiences in narratives by aggressors of conflict.

Hard-won political gains in women’s rights have been undermined and deep-rooted gender inequalities exacerbated. Despite this, women remain central actors in politics, as well as in conflict resolution and mediation efforts. However, more needs to be done to promote the security and inclusion of women in finding sustainable solutions for Ethiopia’s long-term recovery and to institutionalize reforms for gender equity and development.

At this public event, panellists will discuss the priorities for improving women’s participation and equality in public decision-making in Ethiopia and how to strengthen the implementation of legislation on women’s rights. They will also discuss what societal shifts and approaches are needed to combat gender-based discrimination and violence and to promote the agency of women in peacebuilding.

This webinar is part of a series of events and outputs on Ethiopia’s political transition.

This event will also be broadcast live on the Chatham House Africa Programme’s Facebook page.




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Eight ways to build better African cities

Eight ways to build better African cities The World Today mhiggins.drupal 2 August 2022

Young professionals from across the continent tell Emmanuel Adegboye how city life could be improved: from high-speed rail to people-centred urban planning.


Ahmed Elsawy, 33, Director of Talent
Cairo, Egypt
We must amend employment law in Egypt to support individual contractors to match with the global demand for short-term and project-based assignments within the tech and service industries. While we have a new, decent education system, I think we should care more about foreign languages to have a higher rank when it comes to the global competition of skilled workers.

Iman Abubaker, 31, Urban Mobility Project Manager, WRI Africa
Addis Ababa, Ethiopia
Rapid urbanization and increased motorization have exacerbated the city’s urban challenges. Addis Ababa would benefit from safer street design and people-centred city planning. Urban amenities should be located within walking and cycling distances. For longer trips, the city needs to invest in improving the accessibility, safety, integration and multimodality of its public transport system. I would love to see more pockets of green spaces and parks all around the city. 

Bree, 31, Project Manager
Nairobi, Kenya
I have a love-hate relationship with Nairobi. I spent four years smack in the middle of the city while attending the University of Nairobi. Being in the middle of all the hustle and bustle made the transition to a sleepy-ish coastal town easy. I would happily trade matatus [shared taxis] for tuktuks any day. I do miss the conveniences that come with a big city like a 24-hour grocery store and delivery services on those lazy days.

Mfon Bassey, 30, Co-Founder, TalentX Africa
Lagos, Nigeria
The government should improve the road networks and public transport systems, because the common challenge most Lagosians face is commuting from point A to B without traffic. There are so many private cars on the road because the public transport system isn’t optimally efficient yet. Once you take away the commute time most workers spend just to get work done, we’ll surely have happier Lagosians.

Olga Kiconco, 32, Innovation Strategist
Kampala, Uganda
As one of Africa’s fastest-growing cities with a projected 112 per cent population growth by 2035, there are a number of critical changes that need to be made in preparation for this. Our leaders should embrace coherent policies that will catalyze socio-economic transformation. We need to hold them accountable for better infrastructure and delivery of public services, while taking personal responsibility to protect our environment against the prevalent threat of climate change.

Etienne Amougou, 30, Curator/Arts Project Manager
Yaounde, Cameroon
What would make Yaounde better would be a good ecosystem that provides more opportunities for young people. If it was possible, I would like to see the creation of more cultural spaces, like parks, zoos, cinemas and sport areas. Also, we could use a more effective approach to waste management – sometimes we have trash everywhere in the ’hood.

Valentino Fernandez, 23, Writer
Johannesburg, South Africa
 We need better transportation to bridge the inequality gap and allow the youth to access spaces to be inspired and create change. Apartheid spatial planning is still affecting us. People of colour were relegated to the outskirts of the city, and very little has changed. It’s virtually impossible to move out of your childhood home, which means you’re looking at a two-hour commute every morning and two more hours to get home. I would like a reliable, affordable, high-speed rail system.

Jean-Louis Mbaka, 34, Co-Founder and Director, Education at Kinshasa Digital
Kinshasa, DRC
Our youth must receive a sufficient education that is in line with the strategic requirements of their future workplaces. By 2030, more than 130 million jobs in Africa will require digital skills, according to the International Finance Corporation. To close the gap between the conventional educational system and the labour market, our organisation is providing training for digital jobs. Initiatives like ours must be supported if the current and next generations are to have the means for their economic and social advancement. Scaling up investments in vital facilities like the internet is also necessary.




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Africa in 2023: Continuing political and economic volatility

Africa in 2023: Continuing political and economic volatility Expert comment NCapeling 6 January 2023

Despite few African trade and financial links with Russia and Ukraine, the war in Ukraine will cause civil strife in Africa due to food and energy inflation.

Africa’s economy was recovering from the COVID-19 pandemic in 2022 when a range of internal and external shocks struck such as adverse weather conditions, a devastating locust invasion, and the Russian invasion of Ukraine – all of which worsened already rapidly-rising rates of inflation and borrowing costs.

Although the direct trade and financial linkages of Africa with Russia and Ukraine are small, the war has damaged the continent’s economies through higher commodity prices, higher food, fuel, and headline inflation.

The main impact is on the increasing likelihood of civil strife because of food and energy-fuelled inflation amid an environment of heightened political instability.

Key African economies such as South Africa and Nigeria were already stuck with low growth and many African governments have seen their debt burdens increase – some such as Ethiopia and Ghana now have dollar debt trading at distressed levels – and more countries will follow in 2023.

On average the public sector debt-to-GDP ratio of African countries stood at above 60 per cent in 2022. The era of Chinese state-backed big loans and mega-projects which started 20 years ago in Angola after the end of its civil war may be coming to an end but Chinese private sector investments on the continent will continue through its Belt and Road Initiative and dual circulation model of development.

Great and middle powers building influence

Geopolitical competition in Africa has intensified in 2022, particularly among great powers such as China, Russia, the US, and the EU but also by middle powers such as Turkey, Japan, and the Gulf states.

The sixth AU-EU summit held in Brussels in February 2022 agreed on the principles for a new partnership, although the Russian invasion of Ukraine which followed disrupted these ambitions. Japan’s pledge of $30 billion in aid for Africa at TICAD 8 in August 2022 was clearly made due to the $40 billion pledged at the China–Africa summit in November 2021.

The geopolitical and geoeconomic ramifications of the war in Ukraine has directly impacted the African continent by contributing to food and cooking oil inflation and humanitarian aid delivery

The US also launched a new strategy to strengthen its partnership and held a second US-Africa Leaders’ summit in Washington in December, the first since 2014. Russia’s ambition has been curtailed by its invasion of Ukraine, postponing its second summit with African states to 2023.

The imposition of international sanctions complicated its trade and investments, and military support such as that provided by Russian paramilitary group Wagner focused on Mali, Libya and the Central African Republic (CAR) has been curtailed.

The strategic importance of Africa has resulted in all the UN P5 members calling on the G20 to make the African Union (AU) its 21st member in 2023 under India’s presidency.

International competition to secure Africa’s critical and strategic minerals and energy products intensified in 2022 and, in the energy sector, European countries are seeking to diversify away from Russian oil and gas with alternative supplies, such as those from Africa.

Western mining companies and commodity traders are also increasingly seeking alternative supplies from Africa. Decarbonization is becoming a driver of resource nationalism and geopolitical competition in certain African mining markets, home to large deposits of critical ‘transition minerals’ such as copper, cobalt, graphite, lithium, or nickel.

COP27 was hosted in Egypt in November and gave African leaders an opportunity to shape climate discussions by pushing priority areas such as loss and damage, stranded assets, access to climate finance, adaptation, and desertification. Climate adaptation in Africa is a key condition to preserving economic growth and maintaining social cohesion.

The Horn of Africa, particularly Somalia, is suffering from one of the worst droughts in memory. The geopolitical and geoeconomic ramifications of the war in Ukraine has directly impacted the African continent by contributing to food and cooking oil inflation and humanitarian aid delivery.

Thoughout 2022 the AU was undergoing intensive reform and it struggled to respond to the growing number of security crises across the continent. Hotspots in 2023 will be in the western Sahel and Lake Chad Basin, eastern DRC, and northern Mozambique, all of them crossing state borders.

In Mozambique, a 2019 peace deal assisted by the United Nations (UN) will see the last ex-guerrillas from Renamo demobilized in 2023 to reintegrate into civilian life – some having been recruited in 1978.

Jihadist activity may spread further into coastal states which has resulted in international partners such as France and the UK redesigning their security assistance strategies for the region

In eastern Congo, M23 – one of around 120 armed groups – resumed its conflict against the central government. After lying dormant for several years, it took up arms again in 2021 and has been leading an offensive in eastern DRC against the Congolese army.

According to the UN, Rwanda has been supporting M23, and Kenya’s parliament approved in November the deployment of about 900 soldiers to the DRC as part of a joint military force from the East African Community (EAC) bloc – DRC joined the EAC in March.

In the Horn of Africa, Ethiopia saw an uneasy ceasefire agreed between the federal government and the Tigray People’s Liberation Front (TPLF).

Islamist militant groups in Africa further expanded their territorial reach in 2022, particularly in the western Sahel where al-Qaeda and Islamic State affiliates are competing for influence and continued to make inroads.

The drawdown and exit of western forces from Mali, both the French Operation Barkane and international contributions for the UN’s MINUSMA mission there, adds new dimensions to regional security challenges.

Mali’s decision in May to withdraw from the G5 Sahel has also eroded the regional security architecture. Jihadist activity may spread further into coastal states which has resulted in international partners such as France and the UK redesigning their security assistance strategies for the region.

Coups on the increase again

Since 2020, there have been successful military coups in Burkina Faso (twice), Chad, Guinea, Mali (twice), and Sudan, and failed ones in the CAR, Djibouti, Guinea-Bissau, Madagascar, Niger, and possibly Gambia and São Tomé and Príncipe.

Three national elections illustrate the state of African democracy in 2022. In Angola’s August elections, the ruling MPLA lost its absolute majority with the opposition UNITA winning the majority in Luanda for the first time.




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Building carbon markets that work for Africa

Building carbon markets that work for Africa 31 January 2023 — 2:00PM TO 3:30PM Anonymous (not verified) 19 January 2023 Online

At this webinar, held in partnership with UNDP, speakers share experiences on carbon market advancement in Africa, highlighting challenges and obstacles.

Carbon finance offers a major opening towards meeting the goals of the Paris Agreement but progress across regions has been uneven, with the African continent accounting for just 15 per cent of voluntary carbon credits issued globally in 2021.

Harnessing the potential of carbon markets may offer one route towards closing the significant shortfall in climate financing for Africa, as well as accelerating transition in cooking and energy solutions and limiting deforestation.

Article 6 of the Paris Agreement requires significant adjustment of regulatory and policy frameworks at national level in order to align with emerging global imperatives within carbon markets. Various stakeholders, including the private sector, need to take these realities into considerations as they seek to meet commitments towards a more sustainable future.

Governments and the private sector alike need to address the obstacles that have held back Africa’s participation in carbon markets, and should explore all options including both the compliance and voluntary markets, and market-based alternatives such as emissions trading schemes and carbon taxes.

At this webinar, held in partnership with UNDP, speakers share experiences on carbon market advancement in Africa, highlighting challenges and obstacles. Speakers also explore in-country experiences and make proposals on how Africa might benefit from a functional global carbon market.




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Guidance and best practices for nuclear cardiology laboratories during the coronavirus disease 2019 (COVID-19) pandemic: An Information Statement from ASNC and SNMMI




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Pattern of Failure in Patients with Biochemical Recurrence After PSMA Radioguided Surgery

Visual Abstract




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Theranostics for Meningioma on the Rise: New EANM/EANO/RANO/SNMMI Guidelines Pave the Way to Improved Patient Outcomes Using Radiolabeled Somatostatin Receptor Ligands




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SNMMI Procedure Standard/EANM Practice Guideline for Brain [18F]FDG PET Imaging, Version 2.0

PREAMBLE

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.

The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.

Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.

These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.

The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.

The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.

Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.




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Modeling PET Data Acquired During Nonsteady Conditions: What If Brain Conditions Change During the Scan?

Researchers use dynamic PET imaging with target-selective tracer molecules to probe molecular processes. Kinetic models have been developed to describe these processes. The models are typically fitted to the measured PET data with the assumption that the brain is in a steady-state condition for the duration of the scan. The end results are quantitative parameters that characterize the molecular processes. The most common kinetic modeling endpoints are estimates of volume of distribution or the binding potential of a tracer. If the steady state is violated during the scanning period, the standard kinetic models may not apply. To address this issue, time-variant kinetic models have been developed for the characterization of dynamic PET data acquired while significant changes (e.g., short-lived neurotransmitter changes) are occurring in brain processes. These models are intended to extract a transient signal from data. This work in the PET field dates back at least to the 1990s. As interest has grown in imaging nonsteady events, development and refinement of time-variant models has accelerated. These new models, which we classify as belonging to the first, second, or third generation according to their innovation, have used the latest progress in mathematics, image processing, artificial intelligence, and statistics to improve the sensitivity and performance of the earliest practical time-variant models to detect and describe nonsteady phenomena. This review provides a detailed overview of the history of time-variant models in PET. It puts key advancements in the field into historical and scientific context. The sum total of the methods is an ongoing attempt to better understand the nature and implications of neurotransmitter fluctuations and other brief neurochemical phenomena.




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The role of Data-Independent Acquisition for Glycoproteomics

Zilu Ye
Dec 28, 2020; 0:R120.002204v1-mcp.R120.002204
Review




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Identification of Microorganisms by Liquid Chromatography-Mass Spectrometry (LC-MS1) and in Silico Peptide Mass Libraries

Peter Lasch
Dec 1, 2020; 19:2125-2138
Technological Innovation and Resources




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The Mechanism of NEDD8 Activation of CUL5 Ubiquitin E3 Ligases

Ryan J Lumpkin
Dec 2, 2020; 0:RA120.002414v1-mcp.RA120.002414
Research




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Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling [Signal Transduction]

The glucagon receptor (GCGR) activated by the peptide hormone glucagon is a seven-transmembrane G protein–coupled receptor (GPCR) that regulates blood glucose levels. Ubiquitination influences trafficking and signaling of many GPCRs, but its characterization for the GCGR is lacking. Using endocytic colocalization and ubiquitination assays, we have identified a correlation between the ubiquitination profile and recycling of the GCGR. Our experiments revealed that GCGRs are constitutively ubiquitinated at the cell surface. Glucagon stimulation not only promoted GCGR endocytic trafficking through Rab5a early endosomes and Rab4a recycling endosomes, but also induced rapid deubiquitination of GCGRs. Inhibiting GCGR internalization or disrupting endocytic trafficking prevented agonist-induced deubiquitination of the GCGR. Furthermore, a Rab4a dominant negative (DN) that blocks trafficking at recycling endosomes enabled GCGR deubiquitination, whereas a Rab5a DN that blocks trafficking at early endosomes eliminated agonist-induced GCGR deubiquitination. By down-regulating candidate deubiquitinases that are either linked with GPCR trafficking or localized on endosomes, we identified signal-transducing adaptor molecule–binding protein (STAMBP) and ubiquitin-specific protease 33 (USP33) as cognate deubiquitinases for the GCGR. Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist-activated GCGRs at early endosomes. A mutant GCGR with all five intracellular lysines altered to arginines remains deubiquitinated and shows augmented trafficking to Rab4a recycling endosomes compared with the WT, thus affirming the role of deubiquitination in GCGR recycling. We conclude that the GCGRs are rapidly deubiquitinated after agonist-activation to facilitate Rab4a-dependent recycling and that USP33 and STAMBP activities are critical for the endocytic recycling of the GCGR.




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Stimulation of ABCB4/MDR3 ATPase activity requires an intact phosphatidylcholine lipid

Martin Prescher
Dec 1, 2020; 61:1605-1616
Research Articles