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velocityconf: If you don't understand your ppl, you don't understand #Ops http://t.co/DQTBLJlWza New #velocityconf interview w/ @katemats

velocityconf: If you don't understand your ppl, you don't understand #Ops http://t.co/DQTBLJlWza New #velocityconf interview w/ @katemats




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velocityconf: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/Z0EetiQshZ

velocityconf: RT @oreillyanimals Vote Instant Wild's Digital Eyes & Ears for Wildlife Protection to win Google Global Impact Award http://t.co/Z0EetiQshZ




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Understanding through history

War is back in daily headlines. It’s devastating to think about the impact on children here and where the actual fighting is taking place.





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Upgraded: Stopovers in Istanbul, with free tours courtesy of Turkish Airlines

Sure, some airlines let you work in a free stopover. But Turkish Airlines goes one step further and offers up a free city tour on a stopover as short as six hours. Maybe getting into a shuttle bus and tooling around Istanbul after seven hours on an Airbus isn’t your cup of tea, but if […]

The post Upgraded: Stopovers in Istanbul, with free tours courtesy of Turkish Airlines first appeared on UPGRADE: TRAVEL BETTER.





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News24 Business | Microsoft beefs-up its AI assistant with voice, vision

Microsoft on Tuesday doubled down on deploying artificial intelligence to consumers, releasing an updated version of its Copilot chatbot that can hold voice conversations and interpret images.




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IVT MediaPlatform 4.1 Sets New Standard for Enterprise Video Communications

IVT released its latest upgrades to its MediaPlatform software.

Click to view the announcement.




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Independent Consultant Chooses WebCaster

Jan Ozer is a streaming media consultant and frequent contributor to industry magazines and websites on streaming related topics and the author of Video Compression for Flash, Apple Devices and HTML5.  This year he reviewed both the MediaPlatform WebCaster platform and the Polycom Accordent Capture Station and Media management System for Streaming Media magazine.

Here is a link to the Accordent review, which appeared in the August, 2011 edition of Streaming media magazine: Accordent Capture Station and Media Management System: Review

Here is a link to the WebCaster review, which appeared in the June, 2011 edition of Streaming media magazine:  MediaPlatform WebCaster Review: A Strong Option for Webcasts

We think it is important to note that an independent consultant with recent and intimate knowledge of the two leading webcasting platforms is running his next webcast on the WebCaster platform.  You can register to watch his webcast, titled Introduction to Live Event Streaming, which will be broadcast live on Tuesday, October 4, 2:00 - 3:00 PM EST.


Here is Ozer’s description of the event: “This seminar will introduce attendees to live event streaming. It will start by discussing the technologies underlying live event streaming, like codecs and formats, and how most live event platforms can reach both a desktop player (usually Flash) and Apple and Android devices.”









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‘Blatant Weaponization’: FEMA Facing Investigations For Targeting Suffering Trump Supporters

The following article, ‘Blatant Weaponization’: FEMA Facing Investigations For Targeting Suffering Trump Supporters, was first published on Conservative Firing Line.

Republicans are calling for investigations, or are already launching their own, into charges that the federal government deliberately and willfully discriminated against supporters of President-elect Donald Trump following a hurricane disaster in Florida. It was the Daily Wire that initially documented how Marn’I Washington, a Federal Emergency Management Agency supervisor, instructed employees under her authority …

Continue reading ‘Blatant Weaponization’: FEMA Facing Investigations For Targeting Suffering Trump Supporters ...




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Sport | Sri Lanka hires McKenzie as consultant coach ahead of Proteas Test tour

Sri Lanka's cricket board named former South African batsman Neil McKenzie as a consultant coach ahead of their Test tour of South Africa.




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China’s high-stakes incursion in the heights of Bhutan

China’s high-stakes incursion in the heights of Bhutan The World Today mhiggins.drupal 28 September 2022

Why is Beijing establishing settlements over the Bhutanese border? To undermine India’s strategic security, say John Pollock and Damien Symon.

A confrontation is fomenting on the roof of the world in a country that rarely warrants international attention.

In the tiny Kingdom of Bhutan, China is building villages in isolated, mountainous regions, upping the pressure on the capital Thimphu to yield contested areas to Beijing. In doing so, China risks a collision with South Asia’s largest state and Bhutan’s principal security guarantor, India.


Sitting on top of fragile geopolitical fault lines in the Himalayas, China’s Central Military Commission has seemingly authorized a series of incursions into the Bhutanese regions of Doklam, Jakarlung, and Pasamlung. Beijing has also announced fresh claims in the east towards Sakteng. Taken together, these amount to 12 per cent of Bhutan’s total territory according to Nathan Ruser, an analyst at the Australian Strategic Policy Institute.

India is wary of Beijing’s increased assertiveness in the Himalayas following a large-scale incursion by the Chinese People’s Liberation Army (PLA) into Ladakh two years ago when dozens of Indian and Chinese soldiers were killed in a stand-off.

The appearance of Chinese roads, villages and a host of other infrastructure projects within largely uninhabited areas of Bhutan close to Tibet, have, for sections of India’s national security establishment, confirmed their worst fears – Beijing is altering the status quo across the Himalayas in a bid to undermine India’s strategic security through territorial alterations.

As a country of only 780,000 people, Bhutan is greatly influenced by New Delhi when it comes to its foreign affairs. In exchange, India guarantees the defence of the kingdom and trains the Royal Bhutanese Army. The appearance of Chinese villages on its territory risks Bhutan becoming a victim of the wider regional tensions.

The trauma of China-Bhutan border relations

Bhutan is no stranger to the territorial aspirations of its northern neighbour. Thousands of refugees fled into the country after China annexed Tibet, damaging longstanding cultural and religious links between the Tibetan and Bhutanese people – a trauma still being felt today.

Now, Beijing is laying claim to three areas within Bhutan, including Doklam in the west. This plateau is close to the Siliguri Corridor which connects to the ‘Seven Sister’ states in northeast India. Indeed, such is India’s concern over any Chinese presence near Doklam that in 2017 local Indian commanders sent troops into Bhutan to prevent PLA engineers building a road near the Doka La pass, resulting in a 72-day stand-off on Bhutanese soil between India and China, an experience Thimphu is unwilling to repeat.

Once again, China is looking to force the border issue unilaterally, altering the status quo and building villages and outposts on Bhutanese soil. On the available evidence, it has been doing so for at least three years.

The presence of Chinese villages in uninhabited areas of Bhutan serves a strategic purpose. They appear to be intended to pressure Bhutan into accepting an earlier version of a border deal that concedes Doklam to the Chinese.

Bhutan’s increasing concern is that China now views the Sino-Bhutanese border dispute as a way of unravelling India’s strategic position by stealth. Here we see a growing pattern of behaviour across the Himalayas. China is testing the boundaries in isolated and contested areas of India to attain local advantages that ensure New Delhi’s gaze remains fixed on the Himalayas.

The costly choice facing Bhutan

Bhutan for its part has very deliberately opted to remain silent, despite clear violations of its border deal with Beijing. Thimphu has made no public comment on any of the Chinese incursions.

The choice now facing Bhutan is a costly one. To concede Doklam would devastate relations with India, its closest partner. But to ignore China’s ambitions would be to risk further violations of its sovereign territory.

Bhutan may yet agree in principle to a land swap but then delay its implementation in the hope China limits any further advances. Thus Bhutan, India and China stand at a crossroads, with an impending confrontation that has not yet arrived and one that through Thimphu’s delicate diplomacy, Bhutan hopes never does.

China’s incursions into Bhutan

Key to map: 1 - Pangda; 2 - Dramana and Shakhatoe; 3 - Menchuma Valley. Areas of incursion are circled; the red shaded areas are disputed. The star is the capital Thimphu, and the international airport lies to the west.

1. Pangda

Aerial image of Pangda, a village of some 124 people established by China which sits 2km over the border with Bhutan. Image: Maxar (March 2022).

The most high-profile incursion is in the disputed areas in Doklam. Running adjacent to the previous Doka La stand-off site, a series of Chinese projects are visible, following the Amo Chu River that runs from the Chumbi Valley in Tibet into Bhutan.

The most well-known of these xiaokang – meaning peaceful and prosperous – border projects is Pangda, a village of 124 people that sits roughly two kilometres within Bhutan from the border. First spotted by open-source intelligence analysts in October-November 2020, Chinese state media says that 27 households were moved from the Shangdui village to Pangda in September of that year and that the village is located in Yadong County, Tibet. Pangda, however, lies on territory internationally recognized as belonging to Bhutan.

Since Pangda was first identified, two more villages and an additional excavation site have been noted through satellite photographs taken in March this year, steadily following the river further into Bhutanese territory. In recent reporting by journalist Vishnu Som, a connecting road is also visible that runs 9km into Bhutan.

Given the geopolitical sensitivities of the area vis-a-vis India, speculation points to Chinese attempts to increase pressure on the Jampheri ridge overlooking the 2017 stand-off site, which according to journalist Tenzing Lamsang, is currently occupied by a small Royal Bhutanese Army detachment. As ever in the Himalayas, small tactical alterations have strategic implications. Chinese control of the Jampheri ridge would command views towards Sikkim, increase the scope of China’s surveillance operations near the border and place India’s Eastern Theatre Command at a terrain disadvantage were it to intervene as it did at Doka La.

 

2. Dramana and Shakhatoe

Aerial image showing one of several villages recently built by China in the Dramana and Shakhatoe region of Bhutan. The Chinese military is said to be patrolling this area aggressively. Image: Maxar (2022). 

Further north of Doklam, at Dramana and Shakhatoe, more villages have been identified, with recent photographs taken in November 2021 showing a collection of structures nestled between snow-capped mountains. Varying in size, the largest village identified by journalist Devjyot Ghoshal comprises more than 84 buildings with construction having been started in December 2020 and seemingly completed by December 2021.

Little is known about the nature of these villages or their occupants other than their size and location. However, the Chinese PLA has patrolled these areas aggressively, warning away Bhutanese herders and challenging counter patrols by the Royal Bhutanese Army.

A permanent PLA presence in the area would be a significant change to the status quo. Informed speculation suggests that these may house either civilian contractors brought in from Tibet to oversee construction projects in the area, Tibetan or Chinese citizens brought across the border, or they could even be barracks for the PLA to help facilitate increased patrols in these contested areas.

3. Menchuma Valley

Aerial image of one of several Chinese-built settlements in and around Menchuma Valley in Bhutan; the area is home to holy sites important to both Bhutanese and Tibetan culture. Image: PlanetLabs (2022). 

Amid the sustained activity in the west of Bhutan, we are seeing similar levels of activity mirrored in the northern contested areas in Jakarlung, Pasumlung and the Menchuma Valley, a well-known entry point into Tibet for Bhutanese pilgrims.

In May 2021, a team of researchers led by Robert Barnett from the London School of Oriental and African Studies discovered three additional villages in these contested areas, alongside a series of infrastructure projects, sitting between 3km and 5km south of the Chinese border in Bhutan. Barnett identified what appears to be police and military posts near these villages, as well as a communications tower.

While the building efforts at Doklam are seen as having a geopolitical intent towards India, these villages and their locations are seemingly aimed to maximize China’s leverage over Bhutan. They are considered sacred in Tibetan Buddhist teachings as the birthplace of ancient Himalayan cultural heroes, with strong links to the Bhutanese royal family. Today they are the home to holy sites and temples, such as the Singye Dzong.

For China to intrude on this area, and in some cases even deny entry to parts of it, is suppression of Bhutanese history, culture and traditions. By design or by default, Beijing is managing Tibetan religion and culture beyond the borders of the Tibetan Administrative Region.

 

 

 




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Analysis of {beta}-lactone formation by clinically observed carbapenemases informs on a novel antibiotic resistance mechanism [Enzymology]

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.




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Fluorescence assay for simultaneous quantification of CFTR ion-channel function and plasma membrane proximity [Methods and Resources]

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays a key role in controlling transepithelial fluid movement. Excessive activation results in intestinal fluid loss during secretory diarrheas, whereas CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well CFTR channels work (permeation/gating) and on how many are present at the membrane. Recently, treatments with two drug classes targeting CFTR—one boosting ion-channel function (potentiators) and the other increasing plasma membrane density (correctors)—have provided significant health benefits to CF patients. Here, we present an image-based fluorescence assay that can rapidly and simultaneously estimate both CFTR ion-channel function and the protein's proximity to the membrane. We monitor F508del-CFTR, the most common CF-causing variant, and confirm rescue by low temperature, CFTR-targeting drugs and second-site revertant mutation R1070W. In addition, we characterize a panel of 62 CF-causing mutations. Our measurements correlate well with published data (electrophysiology and biochemistry), further confirming validity of the assay. Finally, we profile effects of acute treatment with approved potentiator drug VX-770 on the rare-mutation panel. Mapping the potentiation profile on CFTR structures raises mechanistic hypotheses on drug action, suggesting that VX-770 might allow an open-channel conformation with an alternative arrangement of domain interfaces. The assay is a valuable tool for investigation of CFTR molecular mechanisms, allowing accurate inferences on gating/permeation. In addition, by providing a two-dimensional characterization of the CFTR protein, it could better inform development of single-drug and precision therapies addressing the root cause of CF disease.




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

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




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

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




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A "Proteomic Ruler" for Protein Copy Number and Concentration Estimation without Spike-in Standards

Jacek R. Wiśniewski
Dec 1, 2014; 13:3497-3506
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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The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra

Ignat V. Shilov
Sep 1, 2007; 6:1638-1655
Technology




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

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




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A drug-resistant {beta}-lactamase variant changes the conformation of its active-site proton shuttle to alter substrate specificity and inhibitor potency [Microbiology]

Lys234 is one of the residues present in class A β-lactamases that is under selective pressure due to antibiotic use. Located adjacent to proton shuttle residue Ser130, it is suggested to play a role in proton transfer during catalysis of the antibiotics. The mechanism underpinning how substitutions in this position modulate inhibitor efficiency and substrate specificity leading to drug resistance is unclear. The K234R substitution identified in several inhibitor-resistant β-lactamase variants is associated with decreased potency of the inhibitor clavulanic acid, which is used in combination with amoxicillin to overcome β-lactamase–mediated antibiotic resistance. Here we show that for CTX-M-14 β-lactamase, whereas Lys234 is required for hydrolysis of cephalosporins such as cefotaxime, either lysine or arginine is sufficient for hydrolysis of ampicillin. Further, by determining the acylation and deacylation rates for cefotaxime hydrolysis, we show that both rates are fast, and neither is rate-limiting. The K234R substitution causes a 1500-fold decrease in the cefotaxime acylation rate but a 5-fold increase in kcat for ampicillin, suggesting that the K234R enzyme is a good penicillinase but a poor cephalosporinase due to slow acylation. Structural results suggest that the slow acylation by the K234R enzyme is due to a conformational change in Ser130, and this change also leads to decreased inhibition potency of clavulanic acid. Because other inhibitor resistance mutations also act through changes at Ser130 and such changes drastically reduce cephalosporin but not penicillin hydrolysis, we suggest that clavulanic acid paired with an oxyimino-cephalosporin rather than penicillin would impede the evolution of resistance.




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The aftermath: Navigating a Taliban-led Afghanistan

The aftermath: Navigating a Taliban-led Afghanistan Expert comment NCapeling 20 August 2021

In the coming weeks, governments and international organizations must work through an approach to the Taliban takeover of Afghanistan. It will not be simple.

A failure to acknowledge that the legitimate, elected representatives of Afghanistan are no longer in control of territory or institutions, and to refuse to deal with those that are, will only make for further misery for a population which has already endured decades of violence and poverty.

But to recognize the Taliban risks condemning tens of thousands of Afghan women, children, and men to brutal repression and, for some, potential death, as well as mocking the human rights and rule of law which the US and its allies sought to promote in Afghanistan, and globally, as cornerstones of values-based foreign policies.

The dilemma western governments find themselves in is one they have studiously sought to avoid despite mounting evidence that, without a negotiated deal, a Taliban takeover was only a matter of time. As late as 6 August, the UN Security Council refused to countenance appeals by the UN mission and Afghan civil society activists to press the Taliban and the government to negotiate a ceasefire.

The US reiterated its refrain that it ‘will not accept a military takeover of Afghanistan’ and the UK stressed the Taliban’s only route to power was through meaningful engagement in a peace process. Meanwhile, not until 11 August did Germany and the Netherlands stop deporting Afghan migrants despite the pleas of Afghan authorities and refugee organizations that the country was on the brink of crisis.

Delaying the inevitable

Belief that a military takeover was still some months away may have led diplomats to view dealing with the Taliban as a distant task. The unilateral nature of the US deal with the Taliban and the resistance of the Ghani government to any suggestion of power-sharing arrangements compounded a lack of international coordination and planning on what the conditions for engagement might be.

Formal recognition of a Taliban-led government is simply not an option, even for those maintaining a diplomatic presence in Kabul such as China, Iran, Pakistan, and Russia

It cannot be delayed further. The scale of the humanitarian crisis in Afghanistan is daunting, with more than half a million displaced by fighting in 2021 alone, almost 17 million facing crisis levels of food insecurity, and nearly half of all children under five malnourished as a consequence of drought and the COVID-19 pandemic.

With one of the highest global refugee populations and an estimated up 20-30,000 Afghans fleeing the country weekly – even before the government collapsed – Afghanistan evokes still raw memories of the 2015 Syria migrant crisis for Europe. Pakistan and Turkey, home to some of the largest Afghan refugee communities, have already closed their borders to more.

The ongoing chaos at Kabul airport highlights the challenges ahead. But there is a small window – before the UN Security Council is scheduled to review the mandate of the UN mission in Afghanistan by 17 September – for the US and its allies to craft an approach to dealing with the Taliban.

Formal recognition of a Taliban-led government is simply not an option, even for those maintaining a diplomatic presence in Kabul such as China, Iran, Pakistan, and Russia. Technically the Afghan republic has not yet dissolved with vice-president Amrullah Saleh, reportedly in hiding in the Panjshir valley, claiming he is the country’s ‘caretaker’ president.

Conditions for international acceptance

Afghanistan’s ‘enduring partners’ must now focus on building a consensus around five conditions for international acceptance of a Taliban-administered Afghanistan and prevent the Taliban again reaping the benefits of international divisions. The G7 began to articulate some of these conditions but they need to be set out and negotiated with Afghanistan’s neighbours before being formally articulated by the UN Security Council.

  1. Adherence to Afghanistan’s human rights obligations. This must specify the rights of women and girls to education and work, the protection of ethnic and religious minorities, and safe passage for all Afghans and internationals leaving the country.
  2. Amnesty for all individuals who worked for the Afghan government or international embassies, forces, or aid organizations since 2001.
  3. No harbouring of terrorist groups. This has been the central condition for the US deal with the Taliban, and the overriding concern for both China and Russia.
  4. Non-lethal public order. The provision of public order to enable supply routes to open, evacuations to continue, and aid to be delivered, is essential and one that Russia has made as a condition for its future relations.
  5. Negotiation of inclusive political arrangements with Afghanistan’s political and ethnic factions.

Belief that a military takeover was still some months away may have led diplomats to view dealing with the Taliban as a distant task

The UN mission in Afghanistan, including its human rights component, and the Al-Qaida Sanctions Committee’s Analytical Support and Sanctions Monitoring Team should be mandated with reporting monthly on the progress toward these five conditions. Their assessments should form the basis for any reconsideration of the Taliban’s status as a terrorist organization. And a negotiated political settlement must be a precondition to the release of the government’s foreign reserves, estimated to be $9.5 billion.

Before this, the humanitarian and development aid on which Afghanistan is almost completely reliant must be recalibrated to flow through international agencies. Models such as Hamas-run Gaza, Assad’s Syria, or Aristide’s Haiti, show that while far from effective, it is possible to provide urgent assistance outside government channels.

This is one of the reasons why the Taliban has sought to retain a strong UN presence across Afghanistan and why the UN must be given a more significant political mandate and resources. The World Bank-administered Afghan Reconstruction Trust Fund should remain the principal channel for international funds.

It is difficult in the short-term to see the US leading this collective effort, given its defensive and domestic-focused position. It could be a moment for the UK and EU to demonstrate their multilateral commitments and forge a coordinated conditions-based approach to a Taliban-administered Afghanistan at the UN.

Going beyond handwringing or gesture politics will be difficult and messy and, ultimately, Afghanistan’s future must be decided by Afghans. Until that day, however, this will save lives.




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Independent Thinking: Western tanks head for Ukraine

Independent Thinking: Western tanks head for Ukraine Audio NCapeling 26 January 2023

Episode 12 of our weekly podcast analyses the deployment of international battle tanks to Ukraine and the contentious diplomacy putting pressure on Germany.

The panel examines what kind of capabilities will new weapons give to Ukraine amid fears of a new Russian offensive looming in the spring, and the intense pressure Olaf Scholz’s German government has been under since the invasion of Ukraine started.

How has Germany’s standing changed over the past 12 months, and what are the challenges facing the country in its relations with Russia as a long and cold winter sets in?   

Joining Bronwen Maddox this week from Chatham House are Orysia Lutsevych, head of the Ukraine Forum, and Marion Messmer, senior research fellow in the International Security programme, along with Jeremy Cliffe, writer-at-large for The New Statesman magazine, and Ed Arnold, research fellow for European security at the Royal United Services Institute (RUSI).

About Independent Thinking

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




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What is COP29 and why is it important?

What is COP29 and why is it important? Explainer jon.wallace

The COP29 summit will see negotiators try to agree how to finance the climate action the world urgently needs.

COP29, the 29th UN annual conference on climate change, takes place in Baku, Azerbaijan from 11–22 November 2024.

Every COP conference is an important opportunity for international collaboration on climate change. COP29 will have a particular focus on how to make finance available to developing countries for climate action.

COP29 is already contentious, because Azerbaijan’s economy is highly dependent on fossil fuels, the main cause of climate change. That means that Azerbaijan’s government, which will preside over the summit, has a strong incentive to avoid rapid multilateral progress towards phasing out fossil fuels. 

It’s urgent that progress is made at COP29. Climate action lags far behind both what has been promised by countries, and what scientists agree is needed. The impacts of climate change are also rapidly escalating, while backlash against government policies to reduce fossil fuel use is being seen in many places around the world. 

What is a ‘COP’?

The ‘Conference of the Parties’ or ‘COP’ is an annual event that brings together the governments which have signed up to environmental action under the United Nations (UN)

Governments or ‘parties’ attend the climate change COP if they are part of the United Nations Framework Convention on Climate Change, or the international environmental treaties the Kyoto Protocol (1997) or the landmark and legally binding Paris Agreement (2015).

World leaders, ministers, and negotiators convene at the COP to negotiate and rubber stamp plans to jointly address climate change and its impacts. 

Civil society, businesses, international organizations and the media normally ‘observe’ proceedings to bring transparency, accountability and wider perspectives to the process.

‘Mission 1.5°C’ 

COP28, the 2023 climate conference held in Dubai, was the first of three consecutive COP summits intended to ‘reset’ global climate action – what the UN calls the ‘Roadmap to Mission 1.5°C’ – the ambition to keep global temperatures from rising more than 1.5°C above pre-industrial levels. 

To support continuity and progress across the three COPs, the UAE (COP28), Azerbaijan (COP29) and Brazil (COP30) have formed a COP presidential ‘Troika’ or group of three.

COP29 will be the third consecutive COP held in an authoritarian state, and the second consecutive COP hosted by a petro-state. 

In 2023 the first ‘global stocktake’ of international action to address climate change indicated that the world was far off track for targets set by the Paris Agreement. The ‘UAE Consensus’ agreement, which formed the main output of COP28, set out how parties should respond. 

COP29, the second of the three COPs, is intended to get the finance in place to enable this response. COP30, to be held in Brazil in 2025, will then try to agree how a new round of nationally determined climate plans or ‘contributions’ to global climate efforts (NDCs) should be put into action.

COP29 will be the third consecutive COP held in an authoritarian state, and the second consecutive COP hosted by a petro-state. Taken together, the ‘Troika’ hosts make up the world’s 4th largest oil producer, after the United States, Russia and Saudi Arabia. 

This presents both an opportunity and a risk: the countries are well placed to understand and tackle the core issue of fossil fuel extraction and use. But they also have strong incentives to stall, distract and deflect the negotiations away from phasing out fossil fuels.

Key issues at COP29

Finance – money on the table, and a New Collective Quantified Goal

COP29 has a remit to secure funding for a ‘course correction’ on global climate action. Countries’ revised climate plans (NDCs) are due in February 2025. For developing countries to deliver new ambitious NDCs, however, COP29 must first make clear what finance will be available to help them.

The previous climate finance goal of $100 billion per year…was symbolic (being a fraction of the sum actually needed) and contentious.

Climate finance is one of the thorniest issues in the negotiations. The previous climate finance goal, of $100 billion per year from developed to developing countries between 2020-25, was symbolic (being a fraction of the sum actually needed) and contentious (developed countries did not meet the target until 2022, and then only with accusations of double-counting). 

A New Collective Quantified Goal (NCQGs), to be agreed at COP29, will need to reflect developing countries’ needs and priorities. Estimates vary, but it is accepted that the scale will be trillions, not billions. To bridge this enormous gap, private finance will need to be mobilized and broader reforms made to global financial architecture. Issues such as subsidies, fossil fuel profits and ‘solidarity levies’ will also need to be on the table. 

Little progress has been made in the run-up to COP29. Parties disagree on who should pay, how much should be paid, what forms the funding should take (loans or grants) and how the funds should be accessed. 

Also up for debate is how funds should be directed – towards mitigating the impacts of climate change (preventing climate change becoming worse), adapting to its effects, or supporting countries to manage loss and damage (climate impacts that have already happened or cannot be avoided).  

In discussions of the NCQG to date, developed countries have consistently called for higher income developing countries, such as China and India, to contribute. 

Such countries have pushed back forcefully against this. For a new goal to be agreed, such divisions will need to be resolved.

Enhanced transparency?

COPs act as showcases for international agreement, but many processes rumble on behind the scenes. COP29 will be an important moment for transparency under the Paris Agreement, as the Parties’ first Biennial Enhanced Transparency Reports (BTRs) are due in December 2024. 

BTRs are an important tool in the Paris Agreement, requiring countries to provide a snapshot of their progress in cutting emissions, setting climate policies, and providing resources for national and international climate action. 

BTRs are meant to build the evidence base for strong NDCs, build trust and promote ambitious climate action. They are also meant to help developing countries showcase achievements and attract climate finance. 

Azerbaijan…ranks highly on indexes of corruption and has repeatedly restricted space for NGOs and wider civil society actors.

The COP29 presidency has launched the Baku Global Climate Transparency Platform to encourage participation, and support countries in finalising their BTRs. The Platform is meant to provide space for collaboration between government, NGO and private sector stakeholders. 

This is one of the areas in which COP29 host, Azerbaijan, runs into criticism. The country ranks highly on indexes of corruption, and has repeatedly restricted space for NGOs and wider civil society actors through a series of escalating government crackdowns, including imprisonment of environmental activists, in the run-up to the conference.




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In conversation with Julien Harneis, UN Assistant Secretary-General

In conversation with Julien Harneis, UN Assistant Secretary-General 18 November 2024 — 2:30PM TO 3:30PM Anonymous (not verified) Chatham House and Online

In this discussion, Julien Harneis will give critical insights into the UN’s humanitarian response in Yemen and the importance of maintaining independent humanitarian assistance.

According to the United Nations, Yemen has faced the world’s worst humanitarian crisis in the last decade, with over 20 million people in need of assistance. Years of ongoing conflict have devastated infrastructure, displaced millions, and caused widespread food insecurity and health emergencies. Access to essential services remains a daily struggle, and the escalating economic collapse has left vulnerable communities facing critical shortages in food, water, and medical supplies.

However, humanitarian actors are continually facing challenges in delivering aid to Yemen due to security threats and supply chain barriers, highlighting the urgent need for coordinated and sustainable international assistance.

UN Assistant Secretary-General and Humanitarian Coordinator for Yemen, Julien Harneis, will provide an account of the humanitarian mission and evolving strategies in Yemen, the impact of regional conflicts in the delivery of aid and discuss other key questions including:

  • What are the priorities and goals of the UN’s current aid plan for Yemen, and how is it designed to reach those most in need?
  • How are recent developments in the Red Sea affecting food security, trade routes, and humanitarian access in Yemen?
  • What strategies are in place to ensure the delivery of humanitarian aid remains independent and neutral?

This is a ‘register interest’ event. Confirmations to successful applicants for in-person attendance will be sent on Thursday at 16.00 GMT. Virtual attendees will be granted access to the event.

The institute occupies a position of respect and trust, and is committed to fostering inclusive dialogue at all events. Event attendees are expected to uphold this by adhering to our code of conduct.

 

 




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Building Resistance to Violent Extremism




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The United States in Afghanistan and Pakistan




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Talking to North Korea: Ending the Nuclear Standoff?




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Martin Wight Memorial Lecture: The Future of Think-Tanks




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Frosty Neighbours? Unpacking Narratives of Afghanistan-Pakistan Relations




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Undercurrents: Episode 23 - Robin Niblett on the Future of Think-Tanks




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Afghanistan in 2018: A Survey of the Afghan People




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Jihad and Terrorism in Pakistan: The Case of Lashkar-e-Taiba




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Understanding South Africa's Political Landscape




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Kazakhstan: Tested by Transition




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Undercurrents: Episode 45 - Politics in Kazakhstan, and Youth Engagement in Politics




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Understanding Decolonization in the 21st Century




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Undercurrents: Episode 46 - Understanding Decolonization, and China’s Response to Coronavirus




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Undercurrents: Episode 47 - Pakistan's Blasphemy Laws




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Undercurrents: Episode 55 - Benjamin Netanyahu's Trial, and the Identity Politics of Eurovision




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Undercurrents: Episode 61 - LGBTQ+ Rights, and China's Post-COVID Global Standing





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Regional politics of Kazakhstan in Central Asia

Source

Central Asia Analytical Network

Release date

03 December 2019

Expert

Annette Bohr

In the news type

Op-ed

Hide date on homepage





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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.