Threat actors with ties to the Democratic People's Republic of Korea (DPRK aka North Korea) have been found embedding malware within Flutter applications, marking the first time this tactic has been adopted by the adversary to infect Apple macOS devices. Jamf Threat Labs, which made the discovery based on artifacts uploaded to the VirusTotal platform earlier this month, said the Flutter-built

In the waning days of his campaign, former President Donald Trump has further embraced some of Robert F. Kennedy Jr.’s incorrect or controversial views on health, including vaccines and fluoride.

The post Trump Embraces RFK Jr.’s Views on Vaccines, Fluoride appeared first on FactCheck.org.

velocityconf: RT @courtneynash: Bill Scott's #fluentconf keynote theme also rings true re #velocityconf: tech change is really about people/culture change

Morgan Stanley analysts say Tesla will surge if it can expand to be an AI giant, which may be more likely if Elon Musk exerts influence in a second Trump term.

Too much fluoride can make your teeth brown, but getting a little bit is a dentist's dream. Here's the complete history of fluoridated water.

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.

TikTok will have more US users than Snapchat and Pinterest in 2022   January 24, 2022 (New York, NY) – YouTube is the “OG” of influencer marketing platforms, and it’s […]

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.

China’s renewed influence in the Gulf Interview LJefferson 14 April 2023

By disseminating narratives of its own supremacy, China deepened relations with the Gulf during the COVID-19 pandemic.

China has used the COVID-19 pandemic as an opportunity to rebrand its international role as a ‘responsible’ and ‘great’ power by voicing narratives of its own supremacy to regions like the Gulf.

In this interview, Julia Gurol-Haller draws on her International Affairs article to trace how the UAE, Saudi Arabia, Qatar and Iran have responded to China’s narratives, with key implications for Sino-US competition and regional autonomy for the Gulf. This illustrates how words and narratives help bolster authoritarian power.

What have the China-Gulf relations looked like in context of the COVID-19 pandemic?

Bilateral relations between China and the Gulf countries have grown in importance over the past decade, particularly since 2013 with the Belt and Road Initiative. The Gulf plays a crucial role in China’s Belt and Road Initiative and its westward expansion, owing to its favourable geographic position and proximity to the Red Sea. 

In the beginning, transregional relations were mainly economic partnerships since China has a growing appetite for oil and gas and the Gulf monarchies fulfil these needs. China is one of the most important markets for Saudi Arabia, the UAE, and Qatar to export these goods.

Over time, we’ve seen the Sino-Gulf relations expand beyond just economic ties and towards policy fields like security and cultural relations. While these processes were already in place, they were boosted during the COVID-19 pandemic, not only in material terms but also in respect of Chinese attempts to advance its soft power, leverage, and influence in the Gulf region.

When COVID-19 began to ravage the globe, China took that window of opportunity to rebrand its international role. Through efforts such as mask diplomacy, vaccine diplomacy and the strategic diffusion of narratives, China tried to project its image as a ‘global saviour’ and a responsible and great power.

The Gulf monarchies and Iran were among the main target audiences for this public diplomacy campaign. So, the COVID-19 pandemic has been a catalysing factor for deepening relations between China and the Gulf region.

What exactly are narratives and why are they important in China’s approach to the Gulf states during the COVID-19 pandemic?

Through diplomatic statements, news outlets and social media, China has engaged in, what I call, a ‘narrative power-play’. To understand what that is, we need to understand the political importance of narratives.

Narratives are deliberately constructed by (political) actors to influence a certain target audience. In authoritarian contexts, narratives are a useful resource for political actors to bind audiences to their rule and to appeal to people’s emotions by strategically projecting certain images. 

Ultimately, this creates linkages via attraction or persuasion that enhance the actors’ legitimacy and consolidate their power. So, in the narrative power-play, authoritarian leaders function as ‘storytellers-in-chief’, shaping reality in their favour.

What kinds of narratives has China disseminated to the Gulf region in backdrop of the COVID-19 pandemic?

There are two sets of narratives that China disseminated to the Gulf: narratives of supremacy and narratives of a new world order.

China disseminates narratives of systemic supremacy which include praising the overall efficiency of its governance structures. For instance, the Chinese political system is presented as highly efficient and centralized. It has high amounts of ‘state capacity’ for mobilization and the ability to ‘quickly adapt’ to changing situations.

Narratives of performative supremacy refer to the tangible performance of the Chinese Communist Party or China as a whole, such as economic performance, performance in governance, provision of public goods or pandemic response. The performance narratives also highlight the ‘incredible logistical efficacy’, the highly professionalized medical sector and the innovative scientific sector. 

Narratives of normative supremacy are often informed by nationalist notions such as the reclaiming of China’s rightful position in the world and negative feelings towards Western imperial powers who are depicted as having inflicted great pains on China during the ‘century of humiliation’. Overall, these narratives serve to depict China as a responsible, caring and loyal world power that helps other states. The whole idea of mask diplomacy was also carved into that notion of China’s normative supremacy.

Together, China has used these narratives to construct the idea of a new world order in which China is believed to play a much bigger role. The world order narratives are closely linked to stories about the failure of the Western system and show the intertwinement of practices of othering and self-glorification that can also be observed in Chinese official media narratives in other contexts such as diplomatic stand-offs with the United States.

What do these narratives tell us about how China understands the world order?

The narratives China disseminated to the Gulf region show that in the Chinese understanding of politics, the world order is in flux and undergoing major power reconfigurations. For China, this implies a window of opportunity to position itself as a responsible and great power and move from the side-lines to the centre stage of international politics.

This is a trend that has been long in the making in Chinese foreign policy. For instance, the launch of the Chinese Global Security Initiative or the recent brokering of the Iran-Saudi rapprochement agreement show clearly that China is becoming much more than an economic powerhouse and is adopting a more proactive foreign policy.

During the recent state visit of Xi Jinping to Moscow, he said at one point that China stands ready to ‘safeguard (…) the international order underpinned by international law ’. These examples are quite telling regarding the role China ascribes itself on the international stage.

How have the Gulf countries responded to China’s power narratives during the COVID-19 pandemic?

Saudi Arabia, the UAE, Qatar and Iran all picked up the narrative of China’s superior performance during the global crisis. That was a unified response, but they did that to different degrees and by highlighting different aspects.

The strongest reproduction of Chinese narratives can be found in the Emirati media. They buy into the story of the COVID-19 pandemic as evoking a global power shift, which includes a decline of US hegemony and a corresponding rise of China. The explicit wording of Chinese narratives such as ‘community of shared future of humankind’ has been picked up word-for-word by some Emirati media outlets.

Iranian newspapers have also reproduced Chinese narratives. However, the difference is that they also praise China’s unconditional solidarity during the COVID-19 pandemic, which is believed to be superior and more ‘responsible’ than the ostensible individualism of the West. This tells us a lot about Iran’s relationship with the West and how China is believed to be a lifeline or anchor for stability.

Saudi Arabia has been more cautious in reproducing the Chinese narratives. While it does not contest China’s role in containing the COVID-19 pandemic, Saudi Arabia has adopted a more inward-looking perspective, stressing its own role as a responsible regional player during the pandemic.

This might be explained by the kingdom’s own regional leadership claims and the attempt to use the crisis as an opportunity to strengthen this role. The most pressing questions seem to be whether the post-COVID world will be a multipolar order, and what Saudi Arabia’s own position within it might be. 

Ileana M. Cristea
Dec 1, 2005; 4:1933-1941
Research

Ilka Wittig
Jul 1, 2007; 6:1215-1225
Research

Ulrich Rothbauer
Feb 1, 2008; 7:282-289
Research

George H. Rothblat
May 1, 1999; 40:781-796
Reviews

William R. Morrison
Oct 1, 1964; 5:600-608
Articles

Influence of soft law grows in international governance Expert comment NCapeling 17 June 2021

Soft law is increasingly being used by policymakers to enable greater cooperation and inclusivity, and its role is here to stay in creating effective regimes.

As the UK government’s recent Integrated Review points out, international law-making in a fragmented international order is becoming increasingly difficult.

Geopolitical tensions, and the length of time required to agree multilateral treaties – typically decades – make it challenging to reach binding agreements in complex and fast-evolving policy areas such as climate change and technology governance.

As a result, the regulation of international behaviour through soft law – meaning non-binding instruments such as principles, codes of conduct or declarations – is starting to assume greater significance. And states increasingly find soft law-making attractive because there are relatively fewer decision costs involved.

Soft law also lays the ground for the possibility of transforming into hard law if, over time, its principles become widely accepted and it is evident states are treating them as legal obligations. And the emergence of a hybrid of both soft and hard law components in treaties has started to develop in recent years, such as the Paris Agreement on Climate Change.

Opening access to global governance

A major attraction of soft law-making is that it provides for non-traditional, non-state actors to take part in the process of global governance. Non-governmental organizations (NGOs), social movements, corporate sector, and individuals are more easily drawn into soft law-making compared to treaties, to which only states can be party.

This holds out the promise for greater inclusiveness in global rulemaking and governance, but soft law processes also pose many challenges. Soft law provides an avenue for states to avoid legal obligations on important subjects and developing rules in such an informal manner can lead to fragmentation and a lack of coherence in the international system.

As noted in dialogues held under Chatham House’s Inclusive Governance Initiative, some areas of international interaction require hard law, such as economic competition, certain international security issues, and aspects of the global commons. In these areas, soft law is just not appropriate or enough.

Soft law measures such as codes of conduct may be useful in rapidly developing areas such as technology, as they are more flexible and adaptable than hard law. And they may be particularly effective if used in conjunction with binding regulation, and subject to monitoring and enforcement by a regulator, as in recent proposals by the European Union (EU) for a Digital Services Act.

The Chatham House Inclusive Governance Initiative report highlights that the proliferation of soft law does not necessarily have to compete with the existing system of hard law, so long as soft law solutions do not conflict with, or undermine, hard law such as existing treaty provisions.

Case study: Business and human rights

The UN Guiding Principles on Business and Human Rights (UNGPs) are an interesting example of both the promise of soft law-making, and its challenges. Officially adopted by the UN General Assembly in 2011, the UNGPs set out the global standard of what is expected of companies as regards human rights due diligence (HRDD) to prevent and address business-related human rights harms.

The sections on HRDD in the UNGPs have been constructed as a non-binding ‘social’ standard of conduct, though with the expectation that this would eventually be reinforced through a “smart mix” of both soft law and hard law initiatives. Arguments in favour of the predominantly soft law approach at the time – subsequently borne out in practice – were that this would encourage a higher level of participation, by states and businesses in particular, and better foster creativity and innovation in a still-developing field.

The UNGPs recognize and reinforce the importance of meaningful and inclusive stakeholder engagement for both the credibility and legitimacy of processes, and for the quality of substantive outcomes. The Ruggie process which led to the UNGPs, drew extensively from a wide range of stakeholder engagement processes covering many different jurisdictions and all UN regional groupings. The importance of deep and inclusive stakeholder engagement is also recognized in the mandate of the UN Working Group on Business and Human Rights.

The annual UN Forum on Business and Human Rights is one of the largest and most vibrant multi-stakeholder events in the UN calendar. Now in its tenth year, the forum provides an opportunity for an annual review by stakeholders – government, business and civil society – of past achievements in implementing the UNGPs and knowledge sharing on ways to address more persistent, underlying challenges.

Its relatively informal approach to agenda setting has, year on year, enabled an increasingly diverse array of stakeholder-organized sessions, supporting a ‘bottom up’ approach which raises awareness of under-reported issues and undervalued solutions.

In addition, while the UNGPs provide the substantive framework for discussion, flexible governance arrangements allow for rapid reorientation to respond to present and emerging crises, such as COVID-19 pandemic and climate change.

However, the sluggish responses of many companies, coupled with revulsion at reports of serious abuses in the value chains of many well-known brands, have prompted some governments to seek ways of translating some aspects of HRDD methodologies into binding legal standards. France passed a Corporate Duty of Vigilance Law in 2017 and Germany adopted a new law on supply chain due diligence in June 2021 which is to enter into effect on 1 January 2023. The European Commission is also working up proposals for an EU-wide regime to be unveiled in mid-2021.

Soft law versus hard law

At the international level, there are signs of divergence between those states which see value in persevering with the soft law route towards better regulation and corporate standards, and those which want to move as rapidly as possible to a hard law framework for business and human rights, enshrined in treaty, to improve domestic-level regulation and access to effective remedies.

Those supporting the hard law route – largely less industrialized states – received a boost in 2016 when the UN Human Rights Council mandated an Intergovernmental Working Group to explore options for a new treaty on business and human rights.

This initiative, known as the ‘treaty process’, has completed six rounds of negotiations. Despite the necessarily greater formality, these treaty negotiation sessions continue to emphasize the importance of stakeholder consultation. NGOs with ECOSOC status are invited to contribute views on the framing and content of draft treaty provisions immediately following the interventions by states, intergovernmental organizations and national human rights institutions, in that order.

The key question is whether this dynamism and inclusivity can be preserved as the transition is made from soft law to more binding approaches. Translating soft law standards into binding regimes inevitably means making hard choices, and different stakeholder groups have different views as to where legal lines should be drawn, how key concepts should be defined, and where the balance between legal certainty and flexibility should be struck.

The negotiations needed to strike an effective balance between competing objectives and needs can be challenging and time-consuming, as experiences with the treaty process have shown. But stakeholder demand for inclusive processes to help shape the law remains strong. Stakeholder groups clearly want a say in how the new EU-wide regime for ‘mandatory human rights due diligence’ will work in practice. A recent online ‘stakeholder survey’ garnered more than 400,000 responses.

Ultimately, the most effective domestic regimes are likely to be a mix of hard law standards supported by more flexible standards and guidance. Civil society organizations and trade unions will continue to have a multi-faceted role to play. Not only are they vital sources of expertise on human rights challenges connected to business activities, at home and abroad, they can also act as private enforcers of standards and advocates for affected people and communities.

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.

Stromal interaction molecule 1 (STIM1) plays a pivotal role in store-operated Ca2+ entry (SOCE), an essential mechanism in cellular calcium signaling and in maintaining cellular calcium balance. Because O-GlcNAcylation plays pivotal roles in various cellular function, we examined the effect of fluctuation in STIM1 O-GlcNAcylation on SOCE activity. We found that both increase and decrease in STIM1 O-GlcNAcylation impaired SOCE activity. To determine the molecular basis, we established STIM1-knockout HEK293 (STIM1-KO-HEK) cells using the CRISPR/Cas9 system and transfected STIM1 WT (STIM1-KO-WT-HEK), S621A (STIM1-KO-S621A-HEK), or T626A (STIM1-KO-T626A-HEK) cells. Using these cells, we examined the possible O-GlcNAcylation sites of STIM1 to determine whether the sites were O-GlcNAcylated. Co-immunoprecipitation analysis revealed that Ser621 and Thr626 were O-GlcNAcylated and that Thr626 was O-GlcNAcylated in the steady state but Ser621 was not. The SOCE activity in STIM1-KO-S621A-HEK and STIM1-KO-T626A-HEK cells was lower than that in STIM1-KO-WT-HEK cells because of reduced phosphorylation at Ser621. Treatment with the O-GlcNAcase inhibitor Thiamet G or O-GlcNAc transferase (OGT) transfection, which increases O-GlcNAcylation, reduced SOCE activity, whereas treatment with the OGT inhibitor ST045849 or siOGT transfection, which decreases O-GlcNAcylation, also reduced SOCE activity. Decrease in SOCE activity due to increase and decrease in O-GlcNAcylation was attributable to reduced phosphorylation at Ser621. These data suggest that both decrease in O-GlcNAcylation at Thr626 and increase in O-GlcNAcylation at Ser621 in STIM1 lead to impairment of SOCE activity through decrease in Ser621 phosphorylation. Targeting STIM1 O-GlcNAcylation could provide a promising treatment option for the related diseases, such as neurodegenerative diseases.

Visual Abstract

Oktawia Nilsson
Nov 17, 2020; 0:jlr.RA120000920v1-jlr.RA120000920
Research Articles

Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/ HDL-cholesterol. To explain this paradox, we show that the HDL particle profile of patients carrying either L75P or L174S ApoA-I amyloidogenic variants a higher relative abundance of the 8.4 nm vs 9.6 nm particles, and that serum from patients, as well as reconstituted 8.4 and 9.6 nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4 nm rHDL have altered secondary structure composition and display a more flexible binding to lipids compared to their native counterpart. The reduced HDL-cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles and better cholesterol efflux due to altered, region-specific protein structure dynamics.

The backbone of all sphingolipids (SLs) is a sphingoid long-chain base (LCB) to which a fatty acid is N-acylated. Considerable variability exists in the chain length and degree of saturation of both of these hydrophobic chains, and recent work has implicated ceramides with different LCBs and N-acyl chains in distinct biological processes; moreover, they may play different roles in disease states and possibly even act as prognostic markers. We now demonstrate that the half-life, or turnover rate, of ceramides containing diverse N-acyl chains is different. By means of a pulse-labeling protocol using stable-isotope, deuterated free fatty acids, and following their incorporation into ceramide and downstream SLs, we show that very-long-chain (VLC) ceramides containing C24:0 or C24:1 fatty acids turn over much more rapidly than long-chain (LC) ceramides containing C16:0 or C18:0 fatty acids due to the more rapid metabolism of the former into VLC sphingomyelin and VLC hexosylceramide. In contrast, d16:1 and d18:1 ceramides show similar rates of turnover, indicating that the length of the sphingoid LCB does not influence the flux of ceramides through the biosynthetic pathway. Together, these data demonstrate that the N-acyl chain length of SLs may not only affect membrane biophysical properties but also influence the rate of metabolism of SLs so as to regulate their levels and perhaps their biological functions.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

How Influential Is China in Zimbabwe? Expert comment sysadmin 20 November 2017

A trip to Beijing by Zimbabwe’s military chief was a ‘normal military exchange’, China’s foreign ministry said after the army seized power in Harare. Alex Vines examines the extent of China’s influence in Zimbabwe.

The news that General Constantino Chiwenga had visited China only a few days before the military takeover in Zimbabwe was a coincidence that did not go unnoticed. There was also speculation after China said it was closely watching developments, but stopped short of condemning President Robert Mugabe’s apparent removal from power.

China is Zimbabwe’s fourth-largest trading partner and its largest source of investment - with stakes worth many billions of pounds in everything from agriculture to construction. Zimbabwe is the dependent partner - with China providing the largest market for its exports and much needed support to its fragile economy.

China’s relations with Zimbabwe are deep, starting during the Rhodesian Bush War. Robert Mugabe failed in 1979 to get Soviet backing, so turned to China, which provided his guerrilla fighters with weapons and training. Both countries formally established diplomatic relations at Zimbabwean independence in 1980 and Mugabe visited Beijing as prime minister the following year. He has been a regular visitor since.

For years, Zimbabwe’s officials have tried to play off China against the West, advocating the country’s ‘Look East’ strategy, particularly following the introduction of EU sanctions in 2002. Indeed, a decade ago, Mugabe told a packed rally at the Chinese-built national sports stadium in Harare: ‘We have turned east, where the sun rises, and given our back to the west, where the sun sets.’

China’s military engagement also deepened during Zimbabwe’s ‘Look East’ era. Significant purchases were made, including Hongdu JL-8 jet aircraft, JF-17 Thunder fighter aircraft, vehicles, radar and weapons. However, following a controversy about a shipment of arms in 2008, Beijing decided to list Zimbabwe for ‘limited level’ military trading.

Despite Zimbabwe’s efforts, the ‘Look East’ strategy did not bring the investment flood hoped for and a decade later, in August 2015, Mugabe openly asked for Western re-engagement in his ‘state of the nation’ address.

Now, the reality is that increasingly Chinese and Western interests - particularly those of the UK - have become aligned. Not far from each other in the outer suburbs of Harare, two of the biggest embassies in Zimbabwe are the British and the Chinese. As other embassies scaled down or closed, Beijing’s expanded. Whereas British diplomats were well connected with business, civil society and opposition figures, the Chinese invested in ‘technical support’ of the party of government Zanu-PF, including state security and the presidency. When it came to Zanu-PF politics and factionalism, Chinese diplomats were well connected and insightful and, like their Western colleagues, concerned about stability, a better investment climate and adherence to the rule of law.

President Xi Jinping visited Zimbabwe in 2015 and President Mugabe visited Beijing in January 2017. In public, the Chinese leader said his country is willing to encourage capable companies to invest in Zimbabwe. But in private, the message was that there would be no more loans until Zimbabwe stabilized its economy.

In 2016 trade between the two countries amounted to $1.1 billion, with China the biggest buyer of Zimbabwean tobacco and also importing cotton and various minerals. In return Zimbabwe imported electronics, clothing and other finished products. Chinese state construction firms have also been active, building infrastructure including Zimbabwe’s $100 million National Defence College. And last year China agreed to finance a new 650-seat parliament in Harare.

But Chinese diplomats and many businesses are waiting for better days in Zimbabwe. Some companies have found the investment climate challenging - being burned on diamonds, for example - and have looked for alternative markets. A couple of weeks ago I was in China, attending a meeting on China-Africa relations and Zimbabwe was not mentioned once. Unlike Ethiopia, Sudan, or Angola that are strategic partners, or big markets like Nigeria, Kenya and South Africa, Zimbabwe is far from being Beijing’s new priority.

So, Beijing’s interest is in a better investment climate in Zimbabwe. A clear transitional arrangement resulting in elections for a legitimate government in Harare is as much in Beijing’s interest as London’s.

The ‘Look East’ and the ‘Re-engagement with the West’ strategies have not brought about the confidence and investment that Zimbabwe needs. What Zimbabwe requires is stable and accountable government - then investors from Asia, America and Europe will seriously consider that Zimbabwe has an investment future. This was the message that Mugabe received in Beijing in January. And the one which Zimbabwe’s military chief also was given last week.

This article was originally published by BBC News.

Inclusion, agency and influence: The role of women in Zimbabwe’s economy 8 July 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 2 July 2021 Online

Speakers discuss the changing role of women in Zimbabwe’s economic structures and the priorities for promoting greater economic inclusion, agency and influence of women.

Zimbabwe’s National Development Strategy of 2021-2025 highlights the importance of gender sensitivity in policymaking and of women’s economic participation in attaining the government’s Vision 2030.

However, women have been among the worst affected groups by the devastating effects that COVID-19 has had on Zimbabwe’s already floundering economy, which has exacerbated the challenges they face in economic life, such as access to credit, financial services and social security.

Leveraging existing structures such as women’s groups, micro-finance facilities, education and training, and national gender mechanisms, as well as supporting wider financial and digital inclusion in Zimbabwe, is central for the country’s sustained economic recovery.

This event also focuses on the differing impacts of COVID-19 on women’s economic activities across various sectors, as well as along rural-urban and formal-informal economy lines.

Read a meeting summary

This webinar is part of a series of events in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic recovery and reform.

This event will also be broadcast live on the Africa Programme Facebook page.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

Tumor hypoxia, an integral biomarker to guide radiotherapy, can be imaged with ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) hypoxia PET. One major obstacle to its broader application is the lack of standardized interpretation criteria. We sought to develop and validate practical interpretation criteria and a dedicated training protocol for nuclear medicine physicians to interpret ¹⁸F-FMISO hypoxia PET. Methods: We randomly selected 123 patients with human papillomavirus–positive oropharyngeal cancer enrolled in a phase II trial who underwent 123 ¹⁸F-FDG PET/CT and 134 ¹⁸F-FMISO PET/CT scans. Four independent nuclear medicine physicians with no ¹⁸F-FMISO experience read the scans. Interpretation by a fifth nuclear medicine physician with over 2 decades of ¹⁸F-FMISO experience was the reference standard. Performance was evaluated after initial instruction and subsequent dedicated training. Scans were considered positive for hypoxia by visual assessment if ¹⁸F-FMISO uptake was greater than floor-of-mouth uptake. Additionally, SUV_max was determined to evaluate whether quantitative assessment using tumor-to-background ratios could be helpful to define hypoxia positivity. Results: Visual assessment produced a mean sensitivity and specificity of 77.3% and 80.9%, with fair interreader agreement ( = 0.34), after initial instruction. After dedicated training, mean sensitivity and specificity improved to 97.6% and 86.9%, with almost perfect agreement ( = 0.86). Quantitative assessment with an estimated best SUV_max ratio threshold of more than 1.2 to define hypoxia positivity produced a mean sensitivity and specificity of 56.8% and 95.9%, respectively, with substantial interreader agreement ( = 0.66), after initial instruction. After dedicated training, mean sensitivity improved to 89.6% whereas mean specificity remained high at 95.3%, with near-perfect interreader agreement ( = 0.86). Conclusion: Nuclear medicine physicians without ¹⁸F-FMISO hypoxia PET reading experience demonstrate much improved interreader agreement with dedicated training using specific interpretation criteria.

In this era, expansion in digital infrastructure capacity is inevitable. Parallel to this, climate change consciousness is also rising, making sustainability a mandatory part of the organization’s functioning. As computing […]

The post Why IT Must Have an Influential Role in Strategic Decisions About Sustainability appeared first on HPCwire.

Four agricultural workers in Washington state have tested positive for bird flu, the first human cases of H5N1 virus to be reported in the state. Washington is the sixth state to report a human infection of avian flu.

The nation's depleted supply of IV solutions is recovering after a North Carolina facility recently resumed production after Hurricane Helene temporarily put it out of business.

WALLISELLEN, Switzerland, Nov. 15, 2023 — Hewlett Packard Enterprise (HPE) today announced that Sauber Motorsport AG is partnering with HPE to advance aerodynamics of its Formula One race cars. The […]

The post HPE Unveils Advanced Computational Fluid Dynamics Solutions for Sauber Motorsport appeared first on HPCwire.

Many people overthink persuasion, when it is the most natural approaches that work best.

Roger Dooley's Brainfluence has been translated into eleven languages, but the new Spanish reading is the first audio audio translation.

The post Spanish Audiobook for Brainfluence appeared first on Neuromarketing.

Many states have recently enacted laws or rules designed to ensure that teachers are well versed in evidence-based reading instruction. Here are some highlights.

Several school districts have been forced to close due to a large number of teachers calling out sick in protest of a pension-reform bill.

With coronavirus cases surging, labor groups are continuing to flex their political muscle, most often pushing for a conservative approach to getting teachers and kids back in buildings.

Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

Hannah Grotzinger
May 29, 2024; 44:e1856232024-e1856232024
BehavioralSystemsCognitive

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

FAO Director-General José Graziano da Silva has been selected as one of the world's most influential Latin Americans for his work against hunger and malnutrition in the world. In its [...]

By late September 1918, in a bid to contain the spread of the flu, the U.S. had made the decision to cancel the draft. It was too little, too late—in October alone, over 200,000 Americans were killed by the disease.

Kleptoparasitism, in which a bird harasses another to steal its food, might introduce avian flu to the continent, currently the only one without the severe H5N1 strain

Thousands of years ago, our ancestors used symbols to track the sale of textile and agricultural products. New research suggests that these markings informed the development of writing

Quebec provincial police have confirmed that the body found in a Montreal nature park on Oct. 30 was that of kidnapping victim and cryptocurrency influencer Kevin Mirshahi.

Mosquito-borne disease is a major global public health issue. One path toward the development of evidence-based strategies to limit mosquito biting is the study of the mosquito nervous system—in particular, the sensory systems that drive biting behavior. The central nervous system of insects consists of the brain and the ventral nerve cord. Here, we describe a protocol for dissecting, immunofluorescent labeling, and imaging both of these structures in the mosquito. This protocol was optimized for Aedes aegypti and works well on Anopheles gambiae tissue. It has not been tested in other mosquito species, but we anticipate that it would work on a range of mosquitoes, and, if not, our protocol will provide a starting point from which to optimize. Notably, a limited number of antibodies cross-react with Ae. aegypti proteins. This protocol is intended for use with validated antibodies and can also be used to test new antibodies as they are generated. It has been successfully used to visualize protein tags, such as green fluorescent protein, that have been introduced into the mosquito to amplify or detect their presence.

In insects, oocyte resorption (oosorption) or follicular atresia is one of the key physiological processes and evolutionary strategies used to optimize reproductive fitness. Mosquitoes are ideal model organisms for studying egg maturation in arthropods, as their follicle development is initiated only following the ingestion of a blood meal, followed by a carefully orchestrated series of hormonally regulated events leading to egg maturation. A cohort of approximately 100 follicles per mosquito ovary begin developing synchronously. However, a significant fraction of follicles ultimately undergo apoptosis and oosorption, especially when available resources from the blood meal are limited. Therefore, simple, rapid, and reliable techniques to accurately evaluate follicular atresia are necessary to understand mechanisms underlying follicle development in insects. This protocol describes how to detect apoptotic follicle cells within the Aedes aegypti mosquito ovaries using a commercially available fluorescent-labeled inhibitor of caspases (FLICA). Caspases are key players in animal apoptosis. In this assay, the FLICA reagent enters the intracellular compartment of follicles in dissected mosquito ovaries and covalently binds to active caspases. The bound reagent remains within the cell and its fluorescent signal can be observed by confocal microscopy. Although this method was specifically developed for visualizing apoptotic ovarian follicles during Ae. aegypti mosquito egg development, it should be applicable to other mosquito tissues that undergo caspase-mediated program cell death in a time-dependent manner.

On Day 3 of TeenStreet there were separate meetings for girls and boys in the Main Hall. The theme of the day was 'influence', and the key verse of the day is found in Proverbs 4:23.