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Google Keywords Disrupting Website Analysis

As you may know or not know, Google is not providing keywords data when users are logged in to their accounts. This has been an on-going topic throughout the SEO world for sometime now. Link Worx Seo wrote about this topic on 10/23/2011 and 11/03/2011 and the effects it is having on SEO analysis. As […]




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Are Search Engine Optimization Services Beneficial?

SEO services are very indispensable in internet marketing. They are a great boon to web promotion. Provision of quality SEO services require the brilliant minds, availability of intricate technology and more astute marketers all ready to enable you get popular with your online business. There are numerous visitors who utilize search engines to get various […]




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What are Some of the Benefits of Video Marketing and Optimization?

Video Marketing Video marketing is a widespread choice for businesses now a day’s. With increasing market tactics and gaining popularity, video marketing is an aspect of not just SEO, but a solid way to get your message across to your subscribers. Creating a video marketing plan is a great way to find new customers and […]




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Xbox Game Pass Ultimate: 3 Month Subscription (Digital Delivery - Stackable) $26.99

GCMGames via Eneba has Xbox Game Pass Ultimate: 3 Month Subscription (Digital Delivery - Stackable) on sale for around $26.99 when you follow the instructions below:

Deal Instructions:

  • Go to product page
  • Click on Buy Now.
  • Click on "Got discount code?" under "Total Price" and apply discount code XGPUUS
  • Proceed to checkout.
  • Total price after service/payment fees should be around $26.99

Note: Codes are stackable, you can stack up to three years.





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'I Wrote The Law': Warren Says Trump Already Committing 'Illegal Corruption'

Massachusetts Sen. Liz Warren called out Donald Trump for 'corruption' even though he hasn't been sworn into office yet. Who would have thought Trump would violate a law that Warren wrote before getting the keys to the White House -- besides all of us?

Trump has not submitted a legally required ethics agreement stating he will avoid conflicts of interest, which must be signed before the presidential transaction occurs. According to the Presidential Transition Act, the signed agreement was due by Oct. 1.

Warren took to Xitter, and she was not pleased, but it doesn't do any good unless something is done about it.

Xitter had some thoughts:

read more




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Installation-ception

Client: “I have a CD here that I want to install.”

Me: “What’s on the CD?”

The client starts reading out all the files on the CD.

Me: “That isn’t helping.”

Client: “Okay, could you come over and help me install the CD?”

Me: “Can we do this over Team Viewer?”

Client: “Sure, could you come over and install Team Viewer for me?”




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5 unique and sustainable fencing options for your garden

Gardening is one of the most ecologically conscious projects that most people can practice. With concepts such as net-zero gardening taking shape, gardeners go to unimaginable lengths to avoid harming the environment. The one aspect most gardeners never consider is that a garden fence can have negative environmental effects and must be installed with consciousness. Creating a sustainable garden only to install an unsustainable fence negates the entire purpose of your project. Interestingly, installing a sustainable fence is easy and often more affordable than traditional options. [...]




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The best climate-adaptive watering systems for your garden

If you've grown a garden for a while, you may have noticed that the last few years have been brutal due to climate change-related patterns. One month it's drought and the next it's flooding. What is the best watering system for your home garden and can it help you navigate the climate ups and downs? Here are some great options with the pros and cons so you can decide the right garden irrigation system for your micro climate.[...]




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Winos 4.0 Malware Infects Gamers Through Malicious Game Optimization Apps

Cybersecurity researchers are warning that a command-and-control (C&C) framework called Winos is being distributed within gaming-related applications like installation tools, speed boosters, and optimization utilities. "Winos 4.0 is an advanced malicious framework that offers comprehensive functionality, a stable architecture, and efficient control over numerous online endpoints to execute




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Diamonds On A Budget: Affordable Alternatives And Lab-Grown Options

In a world captivated by the glimmer of diamonds, these gems epitomize luxury, romance, and opulence. However, in recent times, traditional diamonds have not only become increasingly costly but also subject to scrutiny due to ethical concerns surrounding their mining. For lovebirds desiring the sparkle without the extravagant price tag, or for ethical buyers, the ... Read more

The post Diamonds On A Budget: Affordable Alternatives And Lab-Grown Options appeared first on Star Two.




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Why Tonga’s volcanic eruption was so destructive

Explore these NOVA resources to better understand the volcanology behind Tonga’s massive undersea eruption in January.




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Adapting national parks for wheelchair hiking

The trails through our public lands weren’t designed for wheelchairs, but new wheelchairs are designed for those trails. National Park Service accessibility specialist Quinn Brett wants parks to catch up with wheelchair technology, increasing access to American wilderness.




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Bali flights cancelled after volcanic eruption near holiday spot creates dangerous ash cloud

Over a dozen flights cancelled or delayed between Bali and Australia




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Growth of AI Adoption Slows Among US Workers, Study Says

The percentage of workers in the U.S. who say they are using AI at work has remained largely flat over the last three months, according to a new study commissioned by Slack. From a report: If AI's rapid adoption curve slows or flattens, a lot of very rosy assumptions about the technology -- and very high market valuations tied to them -- could change. Slack said its most recent survey found 33% of U.S. workers say they are using AI at work, an increase of just a single percentage point. That represents a significant flattening of the rapid growth noted in prior surveys. Global adoption of AI use at work, meanwhile, rose from 32% to 36%. Between the lines: Slack also found that globally, nearly half of workers (48%) said they were uncomfortable telling their managers they use AI at work. Among the top reasons cited were a fear of being seen as lazy, cheating or incompetent.

Read more of this story at Slashdot.




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Red Hat is Acquiring AI Optimization Startup Neural Magic

Red Hat, the IBM-owned open source software firm, is acquiring Neural Magic, a startup that optimizes AI models to run faster on commodity processors and GPUs. From a report: The terms of the deal weren't disclosed. MIT research scientist Alex Matveev and professor Nir Shavit founded Somerville, Massachusetts-based Neural Magic in 2018, inspired by their work in high-performance execution engines for AI. Neural Magic's software aims to process AI workloads on processors and GPUs at speeds equivalent to specialized AI chips (e.g. TPUs). By running models on off-the-shelf processors, which usually have more available memory, the company's software can realize these performance gains. Big tech companies like AMD and a host of other startups, including NeuReality, Deci, CoCoPie, OctoML and DeepCube, offer some sort of AI optimization software. But Neural Magic is one of the few with a free platform and a collection of open source tools to complement it. Neural Magic had so far managed to raise $50 million in venture capital from backers like Andreessen Horowitz, New Enterprise Associations, Amdocs, Comcast Ventures, Pillar VC and Ridgeline Ventures.

Read more of this story at Slashdot.




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Corruption review finds 'red flags' in more than 130 Covid contracts

An anti-corruption charity finds significant concerns in £15.3bn worth of contracts awarded during the pandemic.




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£30,000 limit on disabled adaptions grants reviewed

A court challenge means the government will look again at the cap on the Disabled Facilities Grant.




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Optimism and uncertainty at summit as Middle East awaits Trump’s return

As heads of Arab and Islamic states meet in Riyadh, Trump's victory raises questions for the region.





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27 SaaS & Subscription Influencers and Experts to Follow into 2019

If you’re an entrepreneur nurturing your own company to a full-blown success, you are always looking for insights and ideas to take your business to the next level, right? But you’re probably super busy as well, and don’t always have the time to figure out where you should be looking for those insights.




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Factoring In PayPal Fees When Sending Money Using the Goods and Services Option

With more and more online marketplaces popping up, many individuals prefer to pay for items, whether they be new or second hand using the PayPal Goods and Services option. The PayPal ‘Goods and Services’ option gives buyers further peace of mind with the PayPal guarantee. If the seller does not provide what they have described, […]

The post Factoring In PayPal Fees When Sending Money Using the Goods and Services Option appeared first on Tips and Tricks HQ.




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Subscription Button Graphics for eCommerce Websites

If you run an eCommerce website, you may prefer to use a graphic as the call-to-action button for your subscription-style products or services. Below you can find a number of different subscription buttons suitable for use on a website’s landing page or the product page. Want some Buy Now button or Add to Cart button […]

The post Subscription Button Graphics for eCommerce Websites appeared first on Tips and Tricks HQ.





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Egyptian Government Television Episode About Farahat’s Book

Cairo, Egypt Oct. 28, 2022 On Egyptian TV show, “Headlines,” Dr. Hossam Farouk dedicated an episode to discussing national and international coverage of the Secret Apparatus: The Muslim Brotherhood’s Industry of Death. It was a great honor having the book featured on this great show.




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China is attempting a precarious balancing act

China is attempting a precarious balancing act Expert comment NCapeling 9 March 2023

In its efforts to maintain ties with both Russia and Europe, China is having to wade through conflicting interests and rapidly changing sentiments.

Precisely how far China will go in supporting Russia has been one of the most important questions of the war in Ukraine.

On 20 February, US secretary of state Antony Blinken warned China may soon provide arms (‘lethal support’) to Moscow. But then, on 24 February – the anniversary of Russia’s invasion – China released a position paper calling for a political settlement to end the conflict, tellingly omitting any mention of its ‘no-limits partnership’ with Russia.

China’s goal was to present itself as a neutral mediator. In fact, Beijing’s ties with Russia remain unchanged, even if this relationship has grown more exasperating for Chinese diplomats over the past year.

Their job is to continue striking a delicate balance, a task that is becoming increasingly difficult as Russian president Vladimir Putin doubles down on nuclear brinkmanship and reckless rhetoric.

Staying out of the Ukraine war

With Putin extolling the law of the jungle in its most brutal form, China must be careful not to involve itself too much in the conflict. After all, Russia is clearly losing, and China has high hopes of repairing ties with major European economies.

With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders

But Putin is of course keen to signal that China has his back. That is why he recently rolled out the red carpet for China’s top diplomat Wang Yi and then alluded to an (unconfirmed) upcoming visit by Chinese president Xi Jinping.

Such diplomatic developments allow him to present China’s ambivalent position as, in fact, an endorsement of the invasion. While the costs of aligning with Russia could easily outweigh the benefits for China, one must remember that China’s reasons for maintaining good relations with the Kremlin go beyond the war in Ukraine.

For starters, the two countries share a 2,672-mile (4,300-kilometer) border – roughly equivalent to the width of Europe – and the frontier’s exact location was not even finally settled until the beginning of this century, after generations of negotiations that included some 2,000 meetings.

Yet to this day, the spectre of the Sino-Soviet split in the 1950s and 1960s looms large on both sides and it is not likely to be exorcised anytime soon. With China focused on moves by the US and its allies in East Asia and the Indo-Pacific, it simply cannot afford sabre-rattling or unrest on its other borders.

Moreover, unlike the collective West, China’s foreign policy has always been shaped by interests rather than by values. Even with respect to Russia, the two countries’ bond is based mainly on shared resentment of US hegemony. By deepening their bilateral cooperation in recent years, they have been able to achieve a level of great-power status with which to counterbalance America.

Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy

But Putin’s misadventure in Ukraine has forced Xi and China’s newly minted Politburo to manage a new set of economic, financial, and political risks.

Russia’s war has left the West more firmly united than it has been in years. As China’s relations with the US have reached new lows, Chinese leaders want to avoid also alienating the European Union (EU), which is one of the country’s biggest trading partners.

This is why Xi and Chinese diplomats have been so careful not to accept the Kremlin’s talking points in full. Being isolated from the ‘collective West’ is not an attractive option for China, given its hopes of achieving a robust economic rebound after years of the zero-COVID policy.

Balancing Europe with the Global South

In seeking to keep diplomatic and trade channels open, China’s main tactic has been to reassure European countries that it will use its own ties with Russia to restrain Putin from deploying nuclear weapons.

At the same time, China is making a renewed push to strengthen its ties with the Global South where many countries do not see the war in Ukraine in the same stark moral terms as the West does.

The emphasis on energy and food security in China’s recent position paper may have struck a chord with developing countries that have been reeling from the war’s negative knock-on effects on their economies.




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Structure, mechanism, and regulation of mitochondrial DNA transcription initiation [Enzymology]

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.




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High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity [Molecular Bases of Disease]

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.




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The Indo-Pacific: Geostrategic Perspectives until 2024 – Japanese perceptions

The Indo-Pacific: Geostrategic Perspectives until 2024 – Japanese perceptions 24 February 2020 — 9:00AM TO 1:00PM Anonymous (not verified) 22 March 2021 Chatham House

The roundtable brought together stakeholders within Japan’s strategic and policymaking communities to explore Japanese perceptions of evolving strategic shifts in the Indo-Pacific until 2024. The roundtable took place in Tokyo and was organized in partnership with the Indo-Pacific Studies Group.

The report below contains a summary of the discussions and an essay by Hiroki Sekine, Visiting Fellow, Asia-Pacific Programme, Chatham House.

Read a summary and essay




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

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




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

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




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Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation

Michal Bassani-Sternberg
Mar 1, 2015; 14:658-673
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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Exponentially Modified Protein Abundance Index (emPAI) for Estimation of Absolute Protein Amount in Proteomics by the Number of Sequenced Peptides per Protein

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




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Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ

Jürgen Cox
Sep 1, 2014; 13:2513-2526
Technological Innovation and Resources




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Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes [Microbiology]

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether–containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC–MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.




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Resetting Africa-Europe relations: From self-deception to economic transformation

Resetting Africa-Europe relations: From self-deception to economic transformation 28 October 2024 — 12:30PM TO 1:30PM Anonymous (not verified) Chatham House and Online

Experts assess the status of ties between Africa and Europe in a rapidly changing world, launching a new book that explores how misconceptions in the relationship can harm Africa’s economic agenda.

The relationship between Africa and Europe has long been shaped by colonial legacies, power imbalance and shifting geopolitical interests.

Almost three years on from the last EU-AU summit in Brussels in February 2022, questions remain over the delivery of headline commitments under the continent-to-continent partnership – ranging from the EU’s Global Gateway infrastructure strategy to wider climate financing promises.

As Africa seeks to strengthen its standing on the global stage, marked by the African Union’s upcoming debut at the G20 summit in November, a critical reassessment of these dynamics is needed to examine whether the continent’s relationship with Europe can overcome stigmatized narratives in search of genuine economic benefit.

At this event, which launches a new book by Professor Carlos Lopes: The Self-Deception Trap: Exploring the Economic Dimensions of Charity Dependency within Africa-Europe Relations, speakers assess the prospects for a transformative shift towards a more equitable and mutually beneficial Africa-Europe partnership.




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Iraq’s Future: Elections, Corruption and the Struggle for a State




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Undercurrents: Episode 15 - Brexit Update, and Corruption in the World of the Global Super-Rich




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Brexit: In Search of A Solution - The Common Market 2.0 Option




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Disrupting the Humanitarian Enterprise




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Artificial Intelligence and the Public: Prospects, Perceptions and Implications




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The 2019 Arab Youth Survey: Pragmatism, Frustration and Optimism




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Challenges and Opportunities in the Fight Against Corruption




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Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles




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Humanitarian exceptions: A turning point in UN sanctions

Humanitarian exceptions: A turning point in UN sanctions Expert comment LJefferson 20 December 2022

The UN Security Council has adopted a cross-cutting exception for humanitarian action in UN sanctions. What does it cover? What must happen next?

The UN Security Council has removed an obstacle to humanitarian work. On 9 December 2022, it adopted a resolution establishing a cross-cutting exception to existing – and future – UN financial sanctions for funds or assets necessary for humanitarian assistance and activities to meet basic human needs. In a coup for multilateralism, the council has been able to act, even when the Russian invasion of Ukraine has caused paralysis in other areas.

Whilst sanctions are not intended to have adverse humanitarian consequences for civilian populations, aid agencies have argued for years that they do just this.

Resolution 2664 – introduced by Ireland and the US, co-sponsored by 53 states, and adopted by 14 votes in favour, with India abstaining – is the culmination of a decade of engagement between humanitarian organizations and states to find ways of avoiding the adverse impact of sanctions on the most vulnerable: people relying on humanitarian action for survival.

A reminder of the problem

Whilst sanctions are not intended to have adverse humanitarian consequences for civilian populations, aid agencies have argued for years that they do just this. UN financial sanctions prohibit making funds or other assets available directly or indirectly to designated persons or entities. Without adequate safeguards, incidental payments made during humanitarian operations, or relief consignments that are diverted and end up in the hands of such persons or entities can violate this prohibition.

Exceptions in Afghanistan and Haiti sanctions pave the way

Humanitarian actors have been decrying and documenting the impact of sanctions on their operations for years. Ensuring that sanctions did not hinder the COVID-19 response was a turning point in states’ willingness to address the issue.

The return to power of the Taliban in Afghanistan called for a more radical approach.

Movement at Security Council level was gradual, starting off with demands in the renewals of certain country-specific sanctions that measures taken by member states to give effect to them comply with international law. The return to power of the Taliban called for a more radical approach.

In December 2021, the Council adopted a broad exception to the Afghanistan financial sanctions, covering the provision, payment and processing of funds and assets necessary for humanitarian action and for activities to meet basic human needs. A similar exception was adopted – almost unnoticed – in October 2022 in the newly-established Haiti sanctions.

These developments, coupled with the determination of elected Council member Ireland to find solutions, paved the way for the adoption of SCR 2664.

The scope of the humanitarian exception

SCR 2664 introduces a clear and broad exception that addresses the key challenges financial sanctions pose to humanitarian action. The exception expressly refers to the different ways in which funds or assets are allowed to reach designated persons or entities: by the provision of goods or payment of funds by humanitarian actors themselves; by the processing of funds by financial institutions; and by the provision of goods and services by other commercial actors whose services are necessary for humanitarian action such as insurers and freight companies.

SCR 2664 introduces a clear and broad exception that addresses the key challenges financial sanctions pose to humanitarian action.

The exception is broad in terms of the excluded activities: the provision of funds and assets necessary for humanitarian assistance and activities to meet basic human needs. The UN Somalia sanctions – the first, and for a decade the only, regime to include an express exception – exclude funds necessary for ‘humanitarian assistance’.

SCR 2615 on Afghanistan added the expression ‘activities to meet basic human needs’.  These go beyond humanitarian assistance, and have been interpreted as including activities necessary to sustain essential social services such as health and education, preserve essential community systems, and promote livelihoods and social cohesion.  These are essentially development programmes.  ‘Activities that support basic needs’ should be understood in a similar manner in SCR 2664.

SCR 2664 is not, however, a ‘blanket’ exception.  It only applies to financial sanctions.  These are not the only type of restriction in UN sanctions that can hinder humanitarian action. For example, organizations that send commodities into the Democratic People’s Republic of Korea must still go through the notoriously slow procedure of authorization by the sanctions committee.  Similarly, authorizations are still required for import of demining materials that fall within the scope of arms embargoes.

Opportunities for further engagement and additional safeguards

Recognizing that additional challenges remain, SCR 2664 requests the UN Secretary-General to draft a report on unintended adverse humanitarian consequences of all types of restrictions in UN sanctions. He is asked to include recommendations for minimizing and such unintended consequences, including by the adoption of additional cross-cutting exceptions.

Humanitarian organizations have played a pivotal role in advancing the agenda. SCR 2664 is the result of their relentless engagement with the Security Council. It is not the end of the road. Other restrictions raise problems, and the Council has left the door open to finding ways of addressing them.

Humanitarian organizations have played a pivotal role in advancing the agenda. SCR 2664 is the result of their relentless engagement with the Security Council.

Humanitarian actors should seize this opportunity to provide information, identifying the problematic types of restrictions and their consequences on their operations as specifically as possible.

What happens next?

It is UN member states that implement UN sanctions. For SCR 2664 to be truly effective, it is imperative that states give effect to it in domestic law and practice. In doing so, they must not narrow the scope of the exception.

Recent experience in Afghanistan has shown that even in situations when significant safeguards exist, key actors may be unaware of them or unclear as to their precise scope. Financial institutions in particular are fast to de-risk when sanctions are imposed, and remain wary of conducting transactions that they perceive as high-risk even though exceptions permit this.

For SCR 2664 to be truly effective, it is imperative that states give effect to it in domestic law and practice. In doing so, they must not narrow the scope of the exception.

OFAC – the Office of Foreign Assets Control in the US Treasury – has issued extensive guidance on the Afghanistan sanctions in the form of frequently asked questions.  These have played an extremely important role in ensuring full advantage is taken of the exceptions.

States should follow this example, and adopt guidance to raise awareness of the exception in SCR 2664 and to clarify its scope.

A valuable precedent for autonomous sanctions

SCR 2664 only applies to sanctions adopted by the UN Security Council. It does not extend to autonomous sanctions adopted by states or relevant international organizations such as the EU.




pti

Hepatocyte nuclear factor 1{beta} suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1 [Molecular Bases of Disease]

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.





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FRET and optical trapping reveal mechanisms of actin activation of the power stroke and phosphate release in myosin V [Enzymology]

Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.