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rHDL modelling and the anchoring mechanism of LCAT activation

Tommaso Laurenzi
Dec 2, 2020; 0:jlr.RA120000843v1-jlr.RA120000843
Research Articles




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Problem Notes for SAS®9 - 33449: An error might occur when you use SAS 9 BULKLOAD= and BULKEXTRACT= options to load data to or extract data from the HP Neoview database on the HP Itanium platform

An error might occur when you use the SAS 9 BULKLOAD= and BULKEXTRACT= options load data to or extract data from HP Neoview on the HP Itanium platform. The problem occurs because Hewlett-Packard changed the name of one of




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WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles]

This manuscript has been withdrawn by the Author.




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Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome [Research Articles]

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.




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rHDL modelling and the anchoring mechanism of LCAT activation [Research Articles]

Lecithin:cholesterol-acyl-transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodelling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT func- tionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences. Although several hypotheses were formulated, the exact molecular recognition mechanism between LCAT and HDLs is still unknown. We employed a combination of structural bioinformatics procedures to deepen the insights into the HDL-LCAT interplay that promotes LCAT activation and cholesterol esterification. We have generated a data-driven model of reconstituted HDL (rHDL) and studied the dynamics of an assembled rHDL::LCAT supramolecular complex, pinpointing the conformational changes originating from the interaction between LCAT and apolipoprotein A-I (apoA-I) that are necessary for LCAT activation. Specifically, we propose a mechanism in which the anchoring of LCAT lid to apoA-I helices allows the formation of a hydrophobic hood that expands LCAT active site and shields it from the solvent, allowing the enzyme to process large hydrophobic substrates.




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Time for a detente in the war on the mechanism of cellular fatty acid uptake [Letters to the Editor]




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Post-translational regulation of the maȷor drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides [Protein Structure and Folding]

The organic anion transporters (OATs) and organic anion–transporting polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and, thereby, drug exposure in the target organs or cells. Various mechanisms (e.g. genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently, evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.




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Conserved biophysical features of the CaV2 presynaptic Ca2+ channel homologue from the early-diverging animal Trichoplax adhaerens [Membrane Biology]

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.




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Solvent accessibility changes in a Na+-dependent C4-dicarboxylate transporter suggest differential substrate effects in a multistep mechanism [Membrane Biology]

The divalent anion sodium symporter (DASS) family (SLC13) plays critical roles in metabolic homeostasis, influencing many processes, including fatty acid synthesis, insulin resistance, and adiposity. DASS transporters catalyze the Na+-driven concentrative uptake of Krebs cycle intermediates and sulfate into cells; disrupting their function can protect against age-related metabolic diseases and can extend lifespan. An inward-facing crystal structure and an outward-facing model of a bacterial DASS family member, VcINDY from Vibrio cholerae, predict an elevator-like transport mechanism involving a large rigid body movement of the substrate-binding site. How substrate binding influences the conformational state of VcINDY is currently unknown. Here, we probe the interaction between substrate binding and protein conformation by monitoring substrate-induced solvent accessibility changes of broadly distributed positions in VcINDY using a site-specific alkylation strategy. Our findings reveal that accessibility to all positions tested is modulated by the presence of substrates, with the majority becoming less accessible in the presence of saturating concentrations of both Na+ and succinate. We also observe separable effects of Na+ and succinate binding at several positions suggesting distinct effects of the two substrates. Furthermore, accessibility changes to a solely succinate-sensitive position suggests that substrate binding is a low-affinity, ordered process. Mapping these accessibility changes onto the structures of VcINDY suggests that Na+ binding drives the transporter into an as-yet-unidentified conformational state, involving rearrangement of the substrate-binding site–associated re-entrant hairpin loops. These findings provide insight into the mechanism of VcINDY, which is currently the only structurally characterized representative of the entire DASS family.




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Molecular Profiling of Innate Immune Response Mechanisms in Ventilator-associated Pneumonia [Research]

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection, leading to high morbidity and mortality. Currently, bronchoalveolar lavage (BAL) is used in hospitals for VAP diagnosis and guiding treatment options. Although BAL collection procedures are invasive, alternatives such as endotracheal aspirates (ETA) may be of diagnostic value, however, their use has not been thoroughly explored. Longitudinal ETA and BAL were collected from 16 intubated patients up to 15 days, of which 11 developed VAP. We conducted a comprehensive LC–MS/MS based proteome and metabolome characterization of longitudinal ETA and BAL to detect host and pathogen responses to VAP infection. We discovered a diverse ETA proteome of the upper airways reflective of a rich and dynamic host-microbe interface. Prior to VAP diagnosis by microbial cultures from BAL, patient ETA presented characteristic signatures of reactive oxygen species and neutrophil degranulation, indicative of neutrophil mediated pathogen processing as a key host response to the VAP infection. Along with an increase in amino acids, this is suggestive of extracellular membrane degradation resulting from proteolytic activity of neutrophil proteases. The metaproteome approach successfully allowed simultaneous detection of pathogen peptides in patients' ETA, which may have potential use in diagnosis. Our findings suggest that ETA may facilitate early mechanistic insights into host-pathogen interactions associated with VAP infection and therefore provide its diagnosis and treatment.




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Sialylation of Asparagine 612 Inhibits Aconitase Activity during Mouse Sperm Capacitation; a Possible Mechanism for the Switch from Oxidative Phosphorylation to Glycolysis [Research]

After ejaculation, mammalian spermatozoa must undergo a process known as capacitation in order to successfully fertilize the oocyte. Several post-translational modifications occur during capacitation, including sialylation, which despite being limited to a few proteins, seems to be essential for proper sperm-oocyte interaction. Regardless of its importance, to date, no single study has ever identified nor quantified which glycoproteins bearing terminal sialic acid (Sia) are altered during capacitation. Here we characterize sialylation during mouse sperm capacitation. Using tandem MS coupled with liquid chromatography (LC–MS/MS), we found 142 nonreductant peptides, with 9 of them showing potential modifications on their sialylated oligosaccharides during capacitation. As such, N-linked sialoglycopeptides from C4b-binding protein, endothelial lipase (EL), serine proteases 39 and 52, testis-expressed protein 101 and zonadhesin were reduced following capacitation. In contrast, mitochondrial aconitate hydratase (aconitase; ACO2), a TCA cycle enzyme, was the only protein to show an increase in Sia content during capacitation. Interestingly, although the loss of Sia within EL (N62) was accompanied by a reduction in its phospholipase A1 activity, a decrease in the activity of ACO2 (i.e. stereospecific isomerization of citrate to isocitrate) occurred when sialylation increased (N612). The latter was confirmed by N612D recombinant protein tagged with both His and GFP. The replacement of Sia for the negatively charged Aspartic acid in the N612D mutant caused complete loss of aconitase activity compared with the WT. Computer modeling show that N612 sits atop the catalytic site of ACO2. The introduction of Sia causes a large conformational change in the alpha helix, essentially, distorting the active site, leading to complete loss of function. These findings suggest that the switch from oxidative phosphorylation, over to glycolysis that occurs during capacitation may come about through sialylation of ACO2.




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Identification of Microorganisms by Liquid Chromatography-Mass Spectrometry (LC-MS1) and in Silico Peptide Mass Libraries [Technological Innovation and Resources]

Over the past decade, modern methods of MS (MS) have emerged that allow reliable, fast and cost-effective identification of pathogenic microorganisms. Although MALDI-TOF MS has already revolutionized the way microorganisms are identified, recent years have witnessed also substantial progress in the development of liquid chromatography (LC)-MS based proteomics for microbiological applications. For example, LC-tandem MS (LC-MS2) has been proposed for microbial characterization by means of multiple discriminative peptides that enable identification at the species, or sometimes at the strain level. However, such investigations can be laborious and time-consuming, especially if the experimental LC-MS2 data are tested against sequence databases covering a broad panel of different microbiological taxa. In this proof of concept study, we present an alternative bottom-up proteomics method for microbial identification. The proposed approach involves efficient extraction of proteins from cultivated microbial cells, digestion by trypsin and LC–MS measurements. Peptide masses are then extracted from MS1 data and systematically tested against an in silico library of all possible peptide mass data compiled in-house. The library has been computed from the UniProt Knowledgebase covering Swiss-Prot and TrEMBL databases and comprises more than 12,000 strain-specific in silico profiles, each containing tens of thousands of peptide mass entries. Identification analysis involves computation of score values derived from correlation coefficients between experimental and strain-specific in silico peptide mass profiles and compilation of score ranking lists. The taxonomic positions of the microbial samples are then determined by using the best-matching database entries. The suggested method is computationally efficient – less than 2 mins per sample - and has been successfully tested by a test set of 39 LC-MS1 peak lists obtained from 19 different microbial pathogens. The proposed method is rapid, simple and automatable and we foresee wide application potential for future microbiological applications.




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A Novel Mechanism for NF-{kappa}B-activation via I{kappa}B-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation [Research]

Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-B activation. However, the precise mechanism that links protein aggregation to NF-B-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IBα-loss with consequent NF-B activation. Four known mechanisms of IBα-loss i.e. the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IBα-loss was due to its sequestration along with IBβ into insoluble aggregates, thereby releasing NF-B. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-B subunit p65, which stably interacts with IBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IBα-nuclear import. The concurrent aggregation of IBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IBα and its consequent binding and termination of NF-B activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a bona fide protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.




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The Mechanism of NEDD8 Activation of CUL5 Ubiquitin E3 Ligases [Research]

Cullin RING E3 Ligases (CRLs) ubiquitylate hundreds of important cellular substrates. Here we have assembled and purified the Ankyrin repeat and SOCS Box protein 9 CUL5 RBX2 Ligase (ASB9-CRL) in vitro and show how it ubiquitylates one of its substrates, CKB. CRLs occasionally collaborate with RING between RING E3 ligases (RBRLs) and indeed, mass spectrometry analysis showed that CKB is specifically ubiquitylated by the ASB9-CRL-ARIH2-UBE2L3 complex. Addition of other E2s such as UBE2R1 or UBE2D2 contribute to polyubiquitylation but do not alter the sites of CKB ubiquitylation. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis revealed that CUL5 neddylation allosterically exposes its ARIH2 binding site, promoting high affinity binding, and it also sequesters the NEDD8 E2 (UBE2F) binding site on RBX2. Once bound, ARIH2 helices near the Ariadne domain active site are exposed, presumably relieving its autoinhibition. These results allow us to propose a model of how neddylation activates ASB-CRLs to ubiquitylate their substrates.




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Global lysine acetylation and 2-hydroxyisobutyrylation reveal the metabolism conversion mechanism in Giardia lamblia [Research]

Giardia lamblia (G. lamblia) disease is a zoonosis with a-infection rate affecting the general population of the world. Despite the constant possibility of damage due to their own metabolism, G. lamblia have survived and evolved to adapt to various environments. However, research on energy-metabolism conversion in G. lamblia is limited. This study aimed to reveal the dynamic metabolism-conversion mechanism in G. lamblia under sugar starvation by detecting global lysine acetylation and 2-hydroxyisobutyrylation sites combined with quantitative proteome analyses. A total of 2999 acetylation sites on 956 proteins and 8877 2-hydroxyisobutyryl sites on 1546 proteins were quantified under sugar starvation. Integrated Kac and Khib data revealed that modified proteins were associated with arginine biosynthesis, glycolysis/gluconeogenesis, and alanine, aspartate, and glutamate metabolism. These findings suggested that lysine acetylation and 2-hydroxyisobutyrylation were ubiquitous and provided deep insight into the metabolism-conversion mechanism in G. lamblia under sugar starvation. Overall, these results can help understand the biology of G. lamblia infections and reveal the evolution rule from prokaryote to eukaryote.




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The Costs of Fuelling Humanitarian Aid

The Costs of Fuelling Humanitarian Aid Research paper sysadmin 7 December 2018

As humanitarian crises become more protracted and aid budgets face unprecedented scrutiny, agencies could save millions by switching from diesel and oil fuels to cleaner energy sources.

A convoy of trucks carrying humanitarian assistance provided by the World Food Program (WFP) to Southern Sudanese refugees. Photo by ASHRAF SHAZLY/AFP/Getty Images.

Download the accompanying toolkit

Most refugee and internal displacement camps are in remote locations, so humanitarian agencies consume large amounts of fuel on the transport of staff, equipment, and goods such as food and water.

Operations tend to rely on on-site electricity generation to power reception centres, clinics, schools, food storage, water-pumping and street lighting. Despite the essential role of energy in humanitarian action, and the UN’s stated commitment to carbon neutrality by 2020, there is no concerted effort to move away from fossil fuel to date.

Summary points

  • Agencies are paying too much for the energy they consume. They are overwhelmingly dependent on oil fuel for electricity generation, even though renewable energy solutions are reducing costs for those deploying them in similar conditions. Well-below-optimum standards of efficiency in buildings, generator use and fleet management are also the norm.
  • Agencies typically have few incentives to do things better. There is rarely motivation to conserve fuel, nor performance indicators for energy or fuel use. In addition, energy spending and use lacks transparency.
  • Few agencies collect and report on energy use. Where numbers are available, they are usually partial and unverified. Energy costs are rarely transparent in budgets; and donors do not know how much is being spent.
  • We estimate that around 5 per cent of humanitarian agencies’ expenditure goes on diesel, petrol and associated costs such as fixing generators. That would mean that the sector spent some $1.2 billion on polluting fuel in 2017.
  • Based on current best-practice, the sector could save at least 10 per cent of fuel costs on ground transport, 37 per cent through behaviour change and more efficient technologies, and 60 per cent on generation – all using currently available, affordable and proven practice and technology changes.
  • At current prices, this could mean operational savings of over $517 million a year for the humanitarian sector, roughly equal to 5 per cent of UNHCR’s funding gap for 2017.
  • In Kenya, annual spending on diesel and petrol for the seven agencies surveyed was $6.7 million in 2017. Replacing gensets with solar systems could create significant savings due the costs of diesel, the likelihood of protracted camp situations, and the opportunities that off-grid solar would offer for extending electricity access to refugees and local populations in Garissa and Turkana counties.
  • In Jordan, solar energy now powers the majority of camp facilities and many households. However, the use of grid electricity by humanitarian agencies’ large head offices in Amman remains high and expensive. Improving the energy efficiency of buildings is a priority for savings.
  • In Burkina Faso’s Goudoubo camp, NGO offices are desperately short of power – they have no computers or air-conditioning. Investment in renewable forms of energy for this and other camp services such as street lighting and water pumping would enable better service provision, and could drive increased rural energy access among host populations across this area of the Sahel.

Toolkit

An accompanying toolkit, Powering Ahead: Improving How We Use and Account for Energy in Humanitarian Operations, provides practical guidance for humanitarian agencies that want to make energy cost savings and reduce their carbon and emissions footprint.




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Innovative Financing for Humanitarian Energy Interventions

Innovative Financing for Humanitarian Energy Interventions Research paper sysadmin 28 February 2019

This paper explores the increase in resources and funding needed to improve the access of displaced people to modern and sustainable energy services.

SOLARKIOSK stall in Talek, Kenya on 17 May 2017. Photo: Getty Images

Summary

  • In settings that host displaced and refugee communities, energy can act as an enabler for improved healthcare, education and access to clean water. More efficient sources of energy can also save money that can be reinvested in life-saving interventions. A range of challenges exist that inhibit the uptake and effective management of cleaner energy solutions in displacement settings. These are magnified by a lack of available and appropriate funding.
  • The current funding gap is significant. In many cases, involving the private sector (both enterprises and investors) is viewed as a way to accelerate delivery of sustainable energy solutions, leverage additional capital, efficiency and expertise, and adopt more sustainable and market-based approaches.
  • Displacement settings are an extreme example of complex and unpredictable operating environments. Traditional approaches to the financing of energy access will not be supported by the risk/return characteristics of this market opportunity, so alternative structures are needed.
  • Such structures can include mechanisms such as grants, guarantees, ‘results-based financing’ and ‘impact bonds’. These blended financial instruments should aim to leverage first losses – whereby, in the case of default, the first loss is taken by the ‘impact-first’ investors, or guarantors, thereby fully or partially protecting ‘finance-first’ investors.
  • Given the specific constraints of displacement settings, any financing mechanisms at present are likely to fall between the categories of providing ‘more efficient aid’ and ‘more efficient aid through markets’. They are likely to constitute a transitional step from grant-making towards the use of commercial investment vehicles.
  • While a number of financial mechanisms could be applied to attract private-sector engagement, most remain theoretical, with few being implemented extensively or at scale. Where such financial mechanisms have already been used, access to relevant data is poor, especially in circumstances where the desired outcomes were not achieved.
  • The Moving Energy Initiative (MEI) completed feasibility work into the concept of an energy humanitarian fund and found that, while a need for this type of facility has emerged, it sits in a difficult position between energy access, climate and humanitarian funding sources. Key donors are needed to drive forward innovative financing vehicles and further testing of these mechanisms, in order to generate market data and evidence for further iterations and additional investments.




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Angels' hope: Ohtani returns as DH in May

Brad Ausmus held his first media session of the spring on the day pitchers and catchers officially reported on Tuesday, giving updates on rehabbing players such as Shohei Ohtani, Albert Pujols and Zack Cozart.




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Limited to DH, Ohtani's at-bats still must-watch

Shohei Ohtani remains a must-watch player for Angels fans in 2019, and his recovery from Tommy John surgery will be worth monitoring throughout the season as he prepares to pitch again in '20.




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Ohtani upbeat about Tommy John rehab

Shohei Ohtani, who is aiming for a return in May as a designated hitter but won't pitch in 2019, isn't able to participate in the on-field workouts with his teammates, but has progressed to swinging the bat and working out indoors.




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Where are Trout, Ohtani on Top 100 Right Now?

The 2019 MLB season feels so close now. Spring Training has begun. Players are taking the field. So it's time to rank the best of the best.




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The next Ohtani? Walsh to get two-way shot

After Ohtani's nearly unprecedented two-way success during his American League Rookie of the Year campaign last year, more clubs are looking into the possibility of having players who can both pitch and play a position. Walsh fits that bill, as he has been a power-hitting first baseman and outfielder in the Minors, but he's made 10 pitching appearances over the past three seasons as well. The Angels are experimenting with him doing both this spring and this upcoming season.




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Ohtani focused on next step of hitting off tee

Shohei Ohtani is continuing to make progress in his rehab from Tommy John surgery. On Sunday, he said he is hopeful he'll be able to start hitting off a tee in the next week.




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War on Ukraine: Exploring the humanitarian response to the conflict

War on Ukraine: Exploring the humanitarian response to the conflict 12 April 2022 — 12:00PM TO 1:00PM Anonymous (not verified) 6 April 2022 Online

This event explores the implications of the humanitarian realities from Russia’s invasion of Ukraine, the largest ground campaign in Europe since World War Two.

Reports from humanitarian organizations working in Ukraine are dire and reveal that a humanitarian disaster on an epic scale is unfolding.

The United Nations (UN) and other organizations estimate 12 million of Ukraine’s population are in need of assistance, 4.1 million have been displaced to neighbouring countries, and 6.4 million have become internally displaced.

Gillian Triggs, the assistant secretary-general and assistant high commissioner for protection at the UNHCR, joins other experts to discuss the humanitarian situation in Ukraine.

The panel considers:

  • What are the greatest needs in Ukraine now?
  • How can aid agencies meet those needs?
  • What are the short and long-term implications of the crisis for Ukraine and Europe?
  • How do international organizations work with local NGOs to provide food, medical aid and shelter?

This event is part of a regular series of events offering insight and analysis from experts and policymakers on how the war is affecting Ukraine, the region and the world.

This event is part of Chatham House’s ongoing work on the future of conflict.

Read the transcript




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In conversation with Edi Rama, prime minister of Albania

In conversation with Edi Rama, prime minister of Albania 23 March 2023 — 5:30PM TO 6:30PM Anonymous (not verified) 13 March 2023 Chatham House and Online

From migration to Russia and China, how is Albania responding to the geopolitical challenges of today?

In late 2022, the UK government made a pointed remark that many of the illegal migrants attempting to get into the country were from Albania. In response, Albania prime minister Edi Rama replied that targeting Albanians as the cause of Britain’s crime and border problems ‘makes for easy rhetoric but ignores hard fact’. 

This nuanced response demonstrated the challenges and complexities that Albania faces, the same as many other countries. As well as being embroiled in the major challenge of international migration, Albania has suffered from a serious cyber-attack in July 2022 from Iran. Government networks were compromised for a month with Tirana removing the Iranian embassy in the capital.

Then there is the ongoing threat from Russia and China. Nestled in the already volatile Balkans, Albania has been at the heart of international affairs in recent months.

Prime Minister Rama speaks at Chatham House to discuss:

  • How is Albania responding to Russian aggression and what is its stance on Ukraine?
  • Where does Tirana believe China poses the most serious threat?
  • How can countries in Europe best respond to illegal migration and better control the flow of people?
  • How is the region of the Western Balkans effected by the war in Ukraine and how can it contribute to the security challenges posed by the war?

As with all member events, questions from the audience drive the conversation.




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U.S. Navy, Lebanese military begin partnership to improve construction, humanitarian capabilities

The USNS Choctaw County has arrived in Beirut, Lebanon, to participate in a first-of-its-kind mission intended to strengthen military ties between the countries, the U.S. Navy said Tuesday.




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Why More Organizations Are Running HPC Workloads in the Cloud

Hyperion Research shows how organizations running high performance computing (HPC) workloads are looking to the cloud to accelerate performance. Projected to reach $11.5 billion by 2026, the cloud market for […]

The post Why More Organizations Are Running HPC Workloads in the Cloud appeared first on HPCwire.




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Granite Rapids HPC Benchmarks: I’m Thinking Intel Is Back (Updated)

Waiting is the hardest part. In the fall of 2023, HPCwire wrote about the new diverging Xeon processor strategy from Intel. Instead of a on-size-fits all approach; Intel has opted […]

The post Granite Rapids HPC Benchmarks: I’m Thinking Intel Is Back (Updated) appeared first on HPCwire.




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Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024

It’s a wrap! The Texas Advanced Computing Center (TACC) at UT Austin welcomed more than 100 participants for the 7th annual TACC Symposium for Texas Researchers (TACCSTER). The event exists […]

The post Research Insights, HPC Expertise, Meaningful Collaborations Abound at TACCSTER 2024 appeared first on HPCwire.




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How to live a meaningful life | Brian S. Lowery

What makes for a meaningful life? Social psychologist Brian S. Lowery explores three ideas tied to the experience of meaning and shows why simply pursuing personal achievements isn't the best way to find it.




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How to come together in a meaningful way | Priya Parker

Looking to infuse more connection into your time with friends and family? Facilitator Priya Parker urges us to approach gathering with intention and creativity. Diving into the evolving significance of coming together both in-person and virtually, she demystifies the role of a host, outlines mistakes we should avoid and shares the potential of thoughtfully designed get-togethers to bring lasting change to communities, workplaces and personal relationships. (This conversation was hosted by TED's Cloe Shasha Brooks. Visit ted.com/membership to support TED today and join more exclusive events like this one.)




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How a worm could save humanity from bad AI | Ramin Hasani

What if AI could think and adapt like a real brain? TED Fellow and AI scientist Ramin Hasani shares how liquid neural networks — a new, more flexible AI technology inspired by physics and living brains — could transform how we solve complex problems.




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Networking doesn't have to feel gross | Daniel Hallak

Networking doesn’t always have to feel like a self-serving transaction, says executive coach Daniel Hallak. Highlighting the importance of focusing on giving rather than taking when it comes to making connections, he outlines a mindset shift to help you build better relationships — in a way that doesn't feel gross.




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Why friendship can be just as meaningful as romantic love | Rhaina Cohen

We tend to consider romantic partners and family ties to be our most important relationships, but deep friendships can be just as meaningful. In a perspective-shifting talk, author Rhaina Cohen introduces us to the people unsettling norms by choosing a friend as a life partner — and shows why we're all better off recognizing there's more than one kind of significant other.





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Pennsylvania

Distinguished educators are assigned by the state to help low-scoring districts in Pennsylvania. Part of Education Week's special annual report, Leading for Learning.




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Trial Set for 2020 in Long-Running Pennsylvania School Funding Lawsuit

The lawsuit, filed in 2014, alleges that the state was severely underfunding schools, forcing school districts to lean heavily on property taxes, which especially disadvantages students in property-poor areas.





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A Big Charter School Struggle Has Been Galvanized by a Democratic Governor

Pennsylvania Gov. Tom Wolf, a Democrat, has become increasingly critical of charter schools this year, and his new proposals for charters would change how they operate and how they are funded.




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Educational Opportunities and Performance in Pennsylvania

This Quality Counts 2019 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.




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Educational Opportunities and Performance in Pennsylvania

This Quality Counts 2020 Highlights Report captures all the data you need to assess your state's performance on key educational outcomes.




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Teachers union: More Pennsylvania schools should go virtual




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Pennsylvania school disciplined for marching band's costumes




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$11B budget package passes Pennsylvania Legislature




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Pennsylvania expands virus app to school-age phone users




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Teachers union: More Pennsylvania schools should go virtual




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Pennsylvania school disciplined for marching band's costumes




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$11B budget package passes Pennsylvania Legislature




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Pennsylvania expands virus app to school-age phone users




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Student Perspective: The True Meaning of Aloha

"Aloha" isn't just a greeting; in a way it is their way of life, and when you distort that sacred word, you distort their way of life.