Dame Sally Davies told the Dawn Sturgess Inquiry she had worried about the disposal of the nerve agent.

At least 20 children are among the dead in attacks north of Beirut and in northern Gaza, officials rescuers and medics say.

What was known as Armistice Day became Remembrance Sunday following the end of World War Two.

President Trump officially announced that he has selected Judge Amy Coney Barrett as his nominee to fill the vacancy of late Justice Ruth Bader Ginsburg to the Supreme Court, setting up a bitter Senate confirmation battle with just five weeks left until Election Day. “I stand before you today to fulfill one of my highest […]

The post Trump Officially Nominates Amy Coney Barrett To Fill Supreme Court Vacancy appeared first on Hispolitica.

Monday Night Club's Mark Chapman is joined by Rory Smith to discuss Ruben Amorim's arrival at Manchester United and how difficult his first game will be.

Billions of dollars were funneled to school districts across the U.S. to help them make up for learning loss from the pandemic. But new research shows that even with that extra money, school districts are still struggling to close the gaps in reading, writing and math. Stephanie Sy discussed the findings with Karyn Lewis of the Center for School and Student Progress and a lead researcher at NWEA.

A federal judge in Manhattan has agreed to hear Sean "Diddy" Combs argue again to be let out of jail pending his May 5 trial date on sex-trafficking.

When my job announced we were returning to the office, I was able to quit and rely on my emergency fund while job searching. I still wish I had saved more.

Sean Combs is trying to sell the private jet, which prosecutors have said makes him a flight risk.

Elon Musk and Vivek Ramaswamy will lead the Department of Government Efficiency, also known as DOGE, under Donald Trump's administration, Trump said.

Szuhi Attila of ITE.HU placed third in our recent Avangate Network Affiliate Wars Contest despite being relatively new to the world of affiliate marketing. We interviewed him about his affiliate marketing techniques and overall approach to creating online content.

It’s time to hang your winter jacket in the closet and change your wardrobe to warmer clothes, because “Spring Is Coming” to the Avangate Affiliate Network. Our spring contest will make your sales bloom and may even fulfill your Amazon wishlist. (Feel free to think “beyond the wall” with creative promotions!)

It was business as usual at the Lebombo border post between SA and Mozambique on Saturday morning, with vehicles moving freely between both countries after a shutdown earlier this week.

Informational text — resources whose purpose is to inform — is essential to daily life and fundamental to literacy. Unfortunately, young children typically have limited exposure to informational text. Two 9-week randomized controlled trials with 263 first-grade children from low-income communities examined whether free educational videos and digital games from the PBS KIDS show “Molly of Denali” supported children’s ability to use informational text to answer real-world questions. Study 1 found significant positive intervention impacts on child outcomes; Study 2 replicated these findings.

A formal disciplinary process, or lack thereof, around the suspensions of two high-ranking officials at the National Student Financial Aid Scheme (NSFAS) has pitted Higher Education and Training Minister Nobuhle Pamela Nkabane against NSFAS administrator Freeman Nomvalo.

There is a reason Joe Rogan became the world's largest podcaster. He doesn't take his audience -- or his guests -- for granted. He wants MEANINGFUL conversations.

The post Joe Rogan Officially Backs A Candidate… Could Be The Biggest Endorsement Yet appeared first on Clash Daily.

A Chicago-area Democrat hurled an insult at police Sunday after being charged with drunken driving, according to local news reports. Samantha Steele represents the Second District on the Cook County […]

The post Democratic Politician Crashes Her Car While Allegedly Drunk, Hurls Vile Insults at Responding Officer: Police Report appeared first on The Western Journal.

Pro-Trump businessmen Elon Musk (the richest man in the world) and Vivek Ramaswamy have officially joined the incoming Trump administration. President-elect Donald Trump announced in a statement published Tuesday that […]

The post Breaking: Musk, Ramaswamy Officially Join Trump Administration - Their Job Is to Destroy Bureaucracy appeared first on The Western Journal.

Springbok coach Rassie Erasmus wants a tour whitewash and, with the Scotland win, he's a third of the way there. He didn't say it would be pretty, as Sunday's success at Murrayfield showed.

The QT interval is a recording of cardiac electrical activity. Previous genome-wide association studies identified genetic variants that modify the QT interval upstream of LITAF (lipopolysaccharide-induced tumor necrosis factor-α factor), a protein encoding a regulator of endosomal trafficking. However, it was not clear how LITAF might impact cardiac excitation. We investigated the effect of LITAF on the voltage-gated sodium channel Nav1.5, which is critical for cardiac depolarization. We show that overexpressed LITAF resulted in a significant increase in the density of Nav1.5-generated voltage-gated sodium current INa and Nav1.5 surface protein levels in rabbit cardiomyocytes and in HEK cells stably expressing Nav1.5. Proximity ligation assays showed co-localization of endogenous LITAF and Nav1.5 in cardiomyocytes, whereas co-immunoprecipitations confirmed they are in the same complex when overexpressed in HEK cells. In vitro data suggest that LITAF interacts with the ubiquitin ligase NEDD4-2, a regulator of Nav1.5. LITAF overexpression down-regulated NEDD4-2 in cardiomyocytes and HEK cells. In HEK cells, LITAF increased ubiquitination and proteasomal degradation of co-expressed NEDD4-2 and significantly blunted the negative effect of NEDD4-2 on INa. We conclude that LITAF controls cardiac excitability by promoting degradation of NEDD4-2, which is essential for removal of surface Nav1.5. LITAF-knockout zebrafish showed increased variation in and a nonsignificant 15% prolongation of action potential duration. Computer simulations using a rabbit-cardiomyocyte model demonstrated that changes in Ca2+ and Na+ homeostasis are responsible for the surprisingly modest action potential duration shortening. These computational data thus corroborate findings from several genome-wide association studies that associated LITAF with QT interval variation.

In conversation with Martin Griffiths: How can a divided world address conflict? 1 October 2024 — 10:00AM TO 11:00AM Anonymous (not verified) 16 September 2024 Chatham House and Online

The former United Nations Under-Secretary-General describes how a weakening multilateralism system and dysfunctional political diplomacy can be revitalized by a humanitarian approach.

Numerous iron-sulfur (Fe-S) proteins with diverse functions are present in the matrix and respiratory chain complexes of mitochondria. Although [4Fe-4S] clusters are the most common type of Fe-S cluster in mitochondria, the molecular mechanism of [4Fe-4S] cluster assembly and insertion into target proteins by the mitochondrial iron-sulfur cluster (ISC) maturation system is not well-understood. Here we report a detailed characterization of two late-acting Fe-S cluster-carrier proteins from Arabidopsis thaliana, NFU4 and NFU5. Yeast two-hybrid and bimolecular fluorescence complementation studies demonstrated interaction of both the NFU4 and NFU5 proteins with the ISCA class of Fe-S carrier proteins. Recombinant NFU4 and NFU5 were purified as apo-proteins after expression in Escherichia coli. In vitro Fe-S cluster reconstitution led to the insertion of one [4Fe-4S]2+ cluster per homodimer as determined by UV-visible absorption/CD, resonance Raman and EPR spectroscopy, and analytical studies. Cluster transfer reactions, monitored by UV-visible absorption and CD spectroscopy, showed that a [4Fe-4S]2+ cluster-bound ISCA1a/2 heterodimer is effective in transferring [4Fe-4S]2+ clusters to both NFU4 and NFU5 with negligible back reaction. In addition, [4Fe-4S]2+ cluster-bound ISCA1a/2, NFU4, and NFU5 were all found to be effective [4Fe-4S]2+ cluster donors for maturation of the mitochondrial apo-aconitase 2 as assessed by enzyme activity measurements. The results demonstrate rapid, unidirectional, and quantitative [4Fe-4S]2+ cluster transfer from ISCA1a/2 to NFU4 or NFU5 that further delineates their respective positions in the plant ISC machinery and their contributions to the maturation of client [4Fe-4S] cluster-containing proteins.

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.

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

Accumulation of the microtubule-associated protein tau is associated with Alzheimer's disease (AD). In AD brain, tau is abnormally phosphorylated at many sites, and phosphorylation at Ser-262 and Ser-356 plays critical roles in tau accumulation and toxicity. Microtubule affinity–regulating kinase 4 (MARK4) phosphorylates tau at those sites, and a double de novo mutation in the linker region of MARK4, ΔG316E317D, is associated with an elevated risk of AD. However, it remains unclear how this mutation affects phosphorylation, aggregation, and accumulation of tau and tau-induced neurodegeneration. Here, we report that MARK4ΔG316E317D increases the abundance of highly phosphorylated, insoluble tau species and exacerbates neurodegeneration via Ser-262/356–dependent and –independent mechanisms. Using transgenic Drosophila expressing human MARK4 (MARK4wt) or a mutant version of MARK4 (MARK4ΔG316E317D), we found that coexpression of MARK4wt and MARK4ΔG316E317D increased total tau levels and enhanced tau-induced neurodegeneration and that MARK4ΔG316E317D had more potent effects than MARK4wt. Interestingly, the in vitro kinase activities of MARK4wt and MARK4ΔG316E317D were similar. When tau phosphorylation at Ser-262 and Ser-356 was blocked by alanine substitutions, MARK4wt did not promote tau accumulation or exacerbate neurodegeneration, whereas coexpression of MARK4ΔG316E317D did. Both MARK4wt and MARK4ΔG316E317D increased the levels of oligomeric forms of tau; however, only MARK4ΔG316E317D further increased the detergent insolubility of tau in vivo. Together, these findings suggest that MARK4ΔG316E317D increases tau levels and exacerbates tau toxicity via a novel gain-of-function mechanism and that modification in this region of MARK4 may affect disease pathogenesis.

Renata Dwan Joins as Deputy Director and Senior Executive Officer News Release sysadmin 19 August 2020

Renata Dwan has been appointed deputy director and senior executive officer of Chatham House.

Combatting Human Trafficking: The Situation in East Asia 16 September 2019 — 10:30AM TO 5:30PM Anonymous (not verified) 30 August 2019 Taipei, Taiwan

In 2017, there were an estimated 40.3 million victims of modern slavery worldwide. The prevalence for individuals to fall victim to forced labour practices is highest in the Asia-Pacific region where four out of every 1,000 people have been found to be victims of forced labour and labour trafficking. Many of these victims end up in the more developed economies of East Asia as destination countries of labour trafficking. Such cases are, however, often under-reported and under-detected, largely owing to a lack of a coherent response to trafficking across the sub-region.

At this roundtable, organized in partnership with the Taiwan Foundation for Democracy, the Taiwan-Asia Exchange Foundation and the University of Portsmouth, participants will discuss emerging anti-trafficking practices from a regional perspective including legal and policy frameworks and the role of business and recruitment agencies.

Attendance at this event is by invitation only.

Clostridium difficile is an anaerobic and spore-forming bacterium responsible for 15–25% of postantibiotic diarrhea and 95% of pseudomembranous colitis. Peptidoglycan is a crucial element of the bacterial cell wall that is exposed to the host, making it an important target for the innate immune system. The C. difficile peptidoglycan is largely N-deacetylated on its glucosamine (93% of muropeptides) through the activity of enzymes known as N-deacetylases, and this N-deacetylation modulates host–pathogen interactions, such as resistance to the bacteriolytic activity of lysozyme, virulence, and host innate immune responses. C. difficile genome analysis showed that 12 genes potentially encode N-deacetylases; however, which of these N-deacetylases are involved in peptidoglycan N-deacetylation remains unknown. Here, we report the enzymes responsible for peptidoglycan N-deacetylation and their respective regulation. Through peptidoglycan analysis of several mutants, we found that the N-deacetylases PdaV and PgdA act in synergy. Together they are responsible for the high level of peptidoglycan N-deacetylation in C. difficile and the consequent resistance to lysozyme. We also characterized a third enzyme, PgdB, as a glucosamine N-deacetylase. However, its impact on N-deacetylation and lysozyme resistance is limited, and its physiological role remains to be dissected. Finally, given the influence of peptidoglycan N-deacetylation on host defense against pathogens, we investigated the virulence and colonization ability of the mutants. Unlike what has been shown in other pathogenic bacteria, a lack of N-deacetylation in C. difficile is not linked to a decrease in virulence.

α1-antitrypsin (AAT) regulates the activity of multiple proteases in the lungs and liver. A mutant of AAT (E342K) called ATZ forms polymers that are present at only low levels in the serum and induce intracellular protein inclusions, causing lung emphysema and liver cirrhosis. An understanding of factors that can reduce the intracellular accumulation of ATZ is of great interest. We now show that calreticulin (CRT), an endoplasmic reticulum (ER) glycoprotein chaperone, promotes the secretory trafficking of ATZ, enhancing the media:cell ratio. This effect is more pronounced for ATZ than with AAT and is only partially dependent on the glycan-binding site of CRT, which is generally relevant to substrate recruitment and folding by CRT. The CRT-related chaperone calnexin does not enhance ATZ secretory trafficking, despite the higher cellular abundance of calnexin-ATZ complexes. CRT deficiency alters the distributions of ATZ-ER chaperone complexes, increasing ATZ-BiP binding and inclusion body formation and reducing ATZ interactions with components required for ER-Golgi trafficking, coincident with reduced levels of the protein transport protein Sec31A in CRT-deficient cells. These findings indicate a novel role for CRT in promoting the secretory trafficking of a protein that forms polymers and large intracellular inclusions. Inefficient secretory trafficking of ATZ in the absence of CRT is coincident with enhanced accumulation of ER-derived ATZ inclusion bodies. Further understanding of the factors that control the secretory trafficking of ATZ and their regulation by CRT could lead to new therapies for lung and liver diseases linked to AAT deficiency.

The actin cytoskeleton is of profound importance to cell shape, division, and intracellular force generation. Profilins bind to globular (G-)actin and regulate actin filament formation. Although profilins are well-established actin regulators, the distinct roles of the dominant profilin, profilin 1 (PFN1), versus the less abundant profilin 2 (PFN2) remain enigmatic. In this study, we use interaction proteomics to discover that PFN2 is an interaction partner of the actin N-terminal acetyltransferase NAA80, and further confirm this by analytical ultracentrifugation. Enzyme assays with NAA80 and different profilins demonstrate that PFN2 binding specifically increases the intrinsic catalytic activity of NAA80. NAA80 binds PFN2 through a proline-rich loop, deletion of which abrogates PFN2 binding. Small-angle X-ray scattering shows that NAA80, actin, and PFN2 form a ternary complex and that NAA80 has partly disordered regions in the N-terminus and the proline-rich loop, the latter of which is partly ordered upon PFN2 binding. Furthermore, binding of PFN2 to NAA80 via the proline-rich loop promotes binding between the globular domains of actin and NAA80, and thus acetylation of actin. However, the majority of cellular NAA80 is stably bound to PFN2 and not to actin, and we propose that this complex acetylates G-actin before it is incorporated into filaments. In conclusion, we reveal a functionally specific role of PFN2 as a stable interactor and regulator of the actin N-terminal acetyltransferase NAA80, and establish the modus operandi for NAA80-mediated actin N-terminal acetylation, a modification with a major impact on cytoskeletal dynamics.

COP27: Navigating a difficult road to Sharm El-Sheikh Expert comment NCapeling 6 July 2022

Against a backdrop of rising urgency, COP27 in Egypt will bring all aspects of climate action into the spotlight – but especially the role of the host country.

As COP26 drew to a close in Glasgow, Egyptian officials announced their priorities for COP27, emphasizing climate finance and climate adaptation – a new approach given previous COPs mainly focused on mitigation, reducing emissions to limit climate damage.

This was followed by the COP27 presidency outlining its vision at MENA Climate Week 2022 to achieve ‘substantive and equal progress’ on all aspects of the negotiations, and Egypt emphasizing its intention to focus on implementing existing carbon reduction targets rather than pushing for further carbon cuts.

Egypt argues it is hosting COP27 on behalf of African nations and that, while it is promoting the interests of the developing world, it will be an impartial arbiter. However it is also useful to consider its priorities from the Egyptian government’s perspective.

Agenda drivers

Egypt has long prioritized climate finance and adaptation because it remains in need of technical and financial support to adapt, especially in agriculture and tourism.

It plans to expand its access to climate funding and investment, an area in which Egypt has been relatively successful as it currently receives 27 per cent of all multilateral climate finance in the MENA region and has issued the region’s first sovereign green bonds.

With public debt currently 94 per cent of GDP, Egyptian officials have also called for debt relief for Egypt and other developing countries.

Egypt’s Climate Change Strategy reflects this approach, aiming to enhance Egypt’s rank on the Climate Change Performance Index in order to ‘attract more investments and acquire more climate funding’.

Limiting the mitigation scope and the focus on finance also echoes Egypt’s own reluctance to make carbon reduction commitments. The Egyptian nationally determined contribution (NDC) – its 2030 pledge under the Paris Agreement – does not include any quantifiable emission reduction targets.

Egypt is one of only a few countries which failed to submit an updated NDC in 2021 and its upcoming update will not include an economy-wide carbon reduction target.

Egypt has also never published a long-term strategy and has no decarbonization plans despite independent estimates it should cut rising emissions by one-quarter by 2030, and by two-thirds by 2050 to be aligned with the Paris Agreement. This partly explains why observers rate Egypt’s climate action as highly insufficient.

Furthermore, Egypt’s championing of ‘moving from pledges to implementation’ without having quantifiable carbon reduction pledges of its own effectively exempts it from both pledging and implementation.

As a developing country, Egypt’s negotiating position is supported by UNFCCC provisions which recognize differentiated responsibilities and respective capabilities of nations.

Its proposal to focus COP27 on the implementation of climate action and finance pledges is important in consolidating progress. But not pushing for more emission reductions at this critical moment risks derailing global decarbonization momentum and undermining global climate action.

According to optimistic estimates, if current climate pledges were implemented the world would still remain on track for 2°C of warming by the end of the century, with far worse impacts than if warming was curbed at 1.5°C.

Under a 2°C scenario, 37 per cent of the global population could regularly be exposed to extreme heat waves compared to 14 per cent in a 1.5°C warmer world, with developing countries expected to be worst-affected.

A 2°C trajectory also runs the risk of tipping points such as the melting of ice sheets in Antarctica and Greenland, triggering runaway climate change. Time to change the warming trajectory is running out as the latest IPCC assessment warns the window of opportunity is now ‘brief and rapidly closing’, and the UN Secretary General recently called for faster carbon cuts by the end of 2022 to avoid a ‘climate catastrophe’.

A different energy transition

Egypt opted not to join any of the voluntary sectoral coalitions at COP26 on reducing methane, clean energy transition, transition to zero-emissions vehicles, or moving beyond oil and gas.

This position is explained by its growing role as an exporter and advocate for fossil gas in the energy transition. Egypt is the second-largest producer of natural gas in Africa and is emerging as a fossil gas hub for the eastern Mediterranean, which is shaping its domestic energy policy.

Its 59GW electricity generation capacity is almost double the peak demand and is dominated by gas-powered electricity generation, which currently represents 42 per cent of all Africa’s gas generation.

Egypt’s climate policy is also shaped by fossil gas, and its national Climate Change Strategy encourages the expansion of gas use by promoting a transition to compressed natural gas for vehicles, the expansion of its domestic natural gas network – despite having universal access to electricity – and shifting to a gas-fuelled shipping sector.

Egypt also voiced support for other African countries to extract and deploy fossil gas and oil resources, making it one of the protagonists of the ‘great fossil gas pushback’. These advocates defend the right of developing countries to deploy fossil gas as a ‘transition fuel’ and champion its necessity to solve energy poverty.

But their position is not shared by all African and developing countries, and is rejected by some civil society groups, who argue it risks locking in greenhouse gases and local emissions for decades as well as delaying future development of low carbon energy systems.

Egypt’s huge spare generation capacity has contributed to a slowdown in renewable energy projects over the past two years. With renewables representing just 6GW, Egypt is expected to miss its renewable energy target for 2022, set at 20 per cent of generating capacity.

Engaging Egypt better

But these positions are more malleable than they seem, and Egypt is open to dialogue – not just on refining the COP27 agenda but also on reviewing its own climate priorities and leveraging its energy sector for a more ambitious transition.

Visual Abstract

Johannes Griss
Dec 1, 2020; 19:2115-2124
Technological Innovation and Resources

The subcellular localization of Arf family proteins is generally thought to be determined by their corresponding guanine nucleotide exchange factors. By promoting GTP binding, guanine nucleotide exchange factors induce conformational changes of Arf proteins exposing their N-terminal amphipathic helices, which then insert into the membranes to stabilize the membrane association process. Here, we found that the N-terminal amphipathic motifs of the Golgi-localized Arf family protein, Arfrp1, and the endosome- and plasma membrane–localized Arf family protein, Arl14, play critical roles in spatial determination. Exchanging the amphipathic helix motifs between these two Arf proteins causes the switch of their localizations. Moreover, the amphipathic helices of Arfrp1 and Arl14 are sufficient for cytosolic proteins to be localized into a specific cellular compartment. The spatial determination mediated by the Arfrp1 helix requires its binding partner Sys1. In addition, the residues that are required for the acetylation of the Arfrp1 helix and the myristoylation of the Arl14 helix are important for the specific subcellular localization. Interestingly, Arfrp1 and Arl14 are recruited to their specific cellular compartments independent of GTP binding. Our results demonstrate that the amphipathic motifs of Arfrp1 and Arl14 are sufficient for determining specific subcellular localizations in a GTP-independent manner, suggesting that the membrane association and activation of some Arf proteins are uncoupled.

For data that is being loaded from a SAS Stored Process Server, an insertion process might fail to a MySQL database with a warning, as well as an error message that says "During insert: Incorrect datetime value…"

Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.

Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.

We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity. We compared B cell rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumor associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.

Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro.

Political Reform in Angola: Challenges and Priorities for Elected Officials 31 October 2018 — 4:00PM TO 5:00PM Anonymous (not verified) 26 October 2018 Chatham House, London

Angola’s reformulated National Assembly has passed a series of legislative reforms since elections in August 2017, in which the ruling MPLA won a majority of 150 seats to the 51 held by the UNITA leading opposition party.

Many of the changes have targeted the revitalization of an underperforming economy and improved governance: in June 2018 parliament approved a new private investment law aimed at diversifying Angola’s fiscal base beyond oil revenues while new legislation in May mandated the return of illicitly exported capital of over $100,000.

As the appetite for measurable progress across all sectors of society remains high, and with newly constituted municipal elections scheduled for 2020, inclusive and accountable political debate will remain critical to Angola’s future.

At the event, a cross-party delegation discuss the role of the National Assembly in affecting political change and the importance of maintaining open dialogue among opposing voices to address the challenges facing Angola.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

President-elect Donald Trump announced Tuesday that Elon Musk and Vivek Ramaswamy will lead his administration's new Department of Government Efficiency, or DOGE, to end "government waste" and "slash excess regulations."

French President Emmanuel Macron was joined in Paris on Monday by British Prime Minister Keir Starmer for Armistice Day commemorations after a meeting at which both leaders reaffirmed "unwavering" support for Ukraine.

As U.S. and Slovenian troops wrapped up a joint exercise, military officials from both countries met to discuss their response to potential threats, the Air Force said Wednesday.

Data centers are experiencing increasing power consumption, space constraints and cooling demands due to the unprecedented computing power required by today’s chips and servers. HVAC cooling systems consume approximately 40% […]

The post How Direct Liquid Cooling Improves Data Center Energy Efficiency appeared first on HPCwire.

The surge in digital transformation across industries has led to exponential data growth, driving a heightened demand for computing power. However, this growth also intensifies concerns about energy consumption and […]

The post Renewable Power Unlock New Efficiencies for High-Performance Computing appeared first on HPCwire.

MANCHESTER, England, Nov. 12, 2024 — PEAK:AIO today announced it has achieved 400% growth in U.S. sales over the past year. This expansion, driven by its high-performance, energy-efficient solutions, solidifies PEAK:AIO’s […]

The post PEAK:AIO Showcases Expansive Growth and Energy-Efficient Solutions Ahead of SC24 appeared first on HPCwire.

TOKYO, March 7, 2024 — Fujitsu Limited and Carnegie Mellon University today announced the development of a new technology to visualize traffic situations, including people and vehicles, as part of […]

The post Fujitsu and Carnegie Mellon University Develop AI-powered Social Digital Twin Tech with Traffic Data from Pittsburgh appeared first on HPCwire.