Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1.

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles

If you have configured more than one SAS Application Server, then SAS Visual Data Builder might unexpectedly use the wrong application server when you preview or schedule queries. This problem occurs even though you h

The SAS 9.4M4 (TS1M4) Hot Fix D7G004 for ODS Templates installs national language support (NLS) content regardless of whether the languages were installed during the initial deployment. Having sparse

Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD). More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for lutein and zeaxanthin supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with lutein and zeaxanthin might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.

The analysis of T cell lipid raft proteome is challenging due to the highly dynamic nature of rafts and the hydrophobic character of raft-resident proteins. We explored an innovative strategy for bottom-up lipid raftomics based on suspension-trapping (S-Trap) sample preparation. Mouse T cells were prepared from splenocytes by negative immunoselection, and rafts were isolated by a detergent-free method and OptiPrep gradient ultracentrifugation. Microdomains enriched in flotillin-1, LAT, and cholesterol were subjected to proteomic analysis through an optimized protocol based on S-Trap and high pH fractionation, followed by nano-LC-MS/MS. Using this method, we identified 2,680 proteins in the raft-rich fraction and established a database of 894 T cell raft proteins. We then performed a differential analysis on the raft-rich fraction from nonstimulated versus anti-CD3/CD28 T cell receptor (TCR)-stimulated T cells. Our results revealed 42 proteins present in one condition and absent in the other. For the first time, we performed a proteomic analysis on rafts from ex vivo T cells obtained from individual mice, before and after TCR activation. This work demonstrates that the proposed method utilizing an S-Trap-based approach for sample preparation increases the specificity and sensitivity of lipid raftomics.

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.

The assembly of the postsynaptic transmitter sensing machinery at inhibitory nerve cell synapses requires the intimate interplay between cell adhesion proteins, scaffold and adaptor proteins, and γ-aminobutyric acid (GABA) or glycine receptors. We developed an in vitro membrane system to reconstitute this process, to identify the essential protein components, and to define their mechanism of action, with a specific focus on the mechanism by which the cytosolic C terminus of the synaptic cell adhesion protein Neuroligin-2 alters the conformation of the adaptor protein Collybistin-2 and thereby controls Collybistin-2-interactions with phosphoinositides (PtdInsPs) in the plasma membrane. Supported hybrid membranes doped with different PtdInsPs and 1,2-dioleoyl-sn-glycero-3-{[N-(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl} nickel salt (DGS-NTA(Ni)) to allow for the specific adsorption of the His6-tagged intracellular domain of Neuroligin-2 (His-cytNL2) were prepared on hydrophobically functionalized silicon dioxide substrates via vesicle spreading. Two different collybistin variants, the WT protein (CB2SH3) and a mutant that adopts an intrinsically 'open' and activated conformation (CB2SH3/W24A-E262A), were bound to supported membranes in the absence or presence of His-cytNL2. The corresponding binding data, obtained by reflectometric interference spectroscopy, show that the interaction of the C terminus of Neuroligin-2 with Collybistin-2 induces a conformational change in Collybistin-2 that promotes its interaction with distinct membrane PtdInsPs.

Kir2.1, a strong inward rectifier potassium channel encoded by the KCNJ2 gene, is a key regulator of the resting membrane potential of the cardiomyocyte and plays an important role in controlling ventricular excitation and action potential duration in the human heart. Mutations in KCNJ2 result in inheritable cardiac diseases in humans, e.g. the type-1 Andersen-Tawil syndrome (ATS1). Understanding the molecular mechanisms that govern the regulation of inward rectifier potassium currents by Kir2.1 in both normal and disease contexts should help uncover novel targets for therapeutic intervention in ATS1 and other Kir2.1-associated channelopathies. The information available to date on protein-protein interactions involving Kir2.1 channels remains limited. Additional efforts are necessary to provide a comprehensive map of the Kir2.1 interactome. Here we describe the generation of a comprehensive map of the Kir2.1 interactome using the proximity-labeling approach BioID. Most of the 218 high-confidence Kir2.1 channel interactions we identified are novel and encompass various molecular mechanisms of Kir2.1 function, ranging from intracellular trafficking to cross-talk with the insulin-like growth factor receptor signaling pathway, as well as lysosomal degradation. Our map also explores the variations in the interactome profiles of Kir2.1^WT versus Kir2.1^314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. Finally, using patch-clamp analysis, we validate the functional relevance of PKP4, one of our top BioID interactors, to the modulation of Kir2.1-controlled inward rectifier potassium currents. Our results validate the power of our BioID approach in identifying functionally relevant Kir2.1 interactors and underline the value of our Kir2.1 interactome as a repository for numerous novel biological hypotheses on Kir2.1 and Kir2.1-associated diseases.

Trypsin is the protease of choice in bottom-up proteomics. However, its application can be limited by the amino acid composition of target proteins and the pH of the digestion solution. In this study we characterize ProAlanase, a protease from the fungus Aspergillus niger that cleaves primarily on the C-terminal side of proline and alanine residues. ProAlanase achieves high proteolytic activity and specificity when digestion is carried out at acidic pH (1.5) for relatively short (2 h) time periods. To elucidate the potential of ProAlanase in proteomics applications, we conducted a series of investigations comprising comparative multi-enzymatic profiling of a human cell line proteome, histone PTM analysis, ancient bone protein identification, phosphosite mapping and de novo sequencing of a proline-rich protein and disulfide bond mapping in mAb. The results demonstrate that ProAlanase is highly suitable for proteomics analysis of the arginine- and lysine-rich histones, enabling high sequence coverage of multiple histone family members. It also facilitates an efficient digestion of bone collagen thanks to the cleavage at the C terminus of hydroxyproline which is highly prevalent in collagen. This allows to identify complementary proteins in ProAlanase- and trypsin-digested ancient bone samples, as well as to increase sequence coverage of noncollagenous proteins. Moreover, digestion with ProAlanase improves protein sequence coverage and phosphosite localization for the proline-rich protein Notch3 intracellular domain (N3ICD). Furthermore, we achieve a nearly complete coverage of N3ICD protein by de novo sequencing using the combination of ProAlanase and tryptic peptides. Finally, we demonstrate that ProAlanase is efficient in disulfide bond mapping, showing high coverage of disulfide-containing regions in a nonreduced mAb.

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.

Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures in the hyper-acute phase of ischemic stroke is still a primary interest for translational research on stroke diagnosis, prognosis, and treatment. Data integration from high-throughput -omics techniques has become crucial to unraveling key interactions among different molecular elements in complex biological contexts, such as ischemic stroke. Thus, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics data sets obtained from mouse brains at 2 h after cerebral ischemia. By modeling net-like correlation structures, we identified an integrated network of genes and proteins that are differentially expressed at a very early stage after stroke. We validated 10 of these deregulated elements in acute stroke, and changes in their expression pattern over time after cerebral ischemia were described. Of these, CLDN20, GADD45G, RGS2, BAG5, and CTNND2 were next evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples, which were obtained from stroke patients and patients presenting stroke-mimicking conditions. Our findings indicate that CTNND2 levels in blood might potentially be useful for distinguishing ischemic strokes from stroke-mimicking conditions in the hyper-acute phase of the disease. Furthermore, circulating GADD45G content within the first 6 h after stroke could also play a key role in predicting poor outcomes in stroke patients. For the first time, we have used an integrative biostatistical approach to elucidate key molecules in the initial stages of stroke pathophysiology and highlight new notable molecules that might be further considered as blood biomarkers of ischemic stroke.

Growing implications of glycosylation in physiological occurrences and human disease have prompted intensive focus on revealing glycomic perturbations through absolute and relative quantification. Empowered by seminal methodologies and increasing capacity for detection, identification, and characterization, the past decade has provided a significant increase in the number of suitable strategies for glycan and glycopeptide quantification. Mass spectrometry-based strategies for glycomic quantitation have grown to include metabolic incorporation of stable isotopes, deposition of mass difference and mass defect isotopic labels, and isobaric chemical labeling, providing researchers with ample tools for accurate and robust quantitation. Beyond this, workflows have been designed to harness instrument capability for label-free quantification and numerous software packages have been developed to facilitate reliable spectrum scoring. In this review, we present and highlight the most recent advances in chemical labeling and associated techniques for glycan and glycopeptide quantification.

Regulation of gene expression is essential for the functioning of all eukaryotic organisms. Understanding gene expression regulation requires determining which proteins interact with regulatory elements in chromatin. Mass spectrometry-based analysis of chromatin has emerged as a powerful tool to identify proteins associated with gene regulation, as it allows studying protein function and protein complex formation in their in vivo chromatin-bound context. Total chromatin isolated from cells can be directly analysed using mass spectrometry or further fractionated into transcriptionally active and inactive chromatin prior to MS-based analysis. Newly formed chromatin that is assembled during DNA replication can also be specifically isolated and analysed. Furthermore, capturing specific chromatin domains facilitates the identification of previously unknown transcription factors interacting with these domains. Finally, in recent years, advances have been made towards identifying proteins that interact with a single genomic locus of interest. In this review, we highlight the power of chromatin proteomics approaches and how these provide complementary alternatives compared to conventional affinity purification methods. Furthermore, we discuss the biochemical challenges that should be addressed to consolidate and expand the role of chromatin proteomics as a key technology in the context of gene expression regulation and epigenetics research in health and disease.

Antibodies play essential roles in both diagnostics and therapeutics. Epitope mapping is essential to understand how an antibody works and to protect intellectual property. Given the millions of antibodies for which epitope information is lacking, there is a need for high-throughput epitope mapping. To address this, we developed a strategy, Antibody binding epitope Mapping (AbMap), by combining a phage displayed peptide library with next generation sequencing. Using AbMap, profiles of the peptides bound by 202 antibodies were determined in a single test, and linear epitopes were identified for >50% of the antibodies. Using spike protein (S1 and S2)-enriched antibodies from the convalescent serum of one COVID-19 patient as the input, both linear and conformational epitopes of spike protein specific antibodies were identified. We defined peptide-binding profile of an antibody as the Binding Capacity (BiC). Conceptually, the BiC could serve as a systematic and functional descriptor of any antibody. Requiring at least one order of magnitude less time and money to map linear epitopes than traditional technologies, AbMap allows for high-throughput epitope mapping and creates many possibilities.

Histone post-translational modifications (PTMs) are one of the main mechanisms of epigenetic regulation. Dysregulation of histone PTMs leads to many human diseases, such as cancer. Due to its high-throughput, accuracy, and flexibility, mass spectrometry (MS) has emerged as a powerful tool in the epigenetic histone modification field, allowing the comprehensive and unbiased analysis of histone PTMs and chromatin-associated factors. Coupled with various techniques from molecular biology, biochemistry, chemical biology and biophysics, MS has been employed to characterize distinct aspects of histone PTMs in the epigenetic regulation of chromatin functions. In this review we will describe advancements in the field of MS that have facilitated the analysis of histone PTMs and chromatin biology.  

In all cells, proteins are continuously synthesized and degraded in order to maintain protein homeostasis and modify gene expression levels in response to stimuli. Collectively, the processes of protein synthesis and degradation are referred to as protein turnover. At steady state, protein turnover is constant to maintain protein homeostasis, but in dynamic responses, proteins change their rates of synthesis and degradation in order to adjust their proteomes to internal or external stimuli. Thus, probing the kinetics and dynamics of protein turnover lends insight into how cells regulate essential processes such as growth, differentiation, and stress response. Here we outline historical and current approaches to measuring the kinetics of protein turnover on a proteome-wide scale in both steady-state and dynamic systems, with an emphasis on metabolic tracing using stable-isotope-labeled amino acids. We highlight important considerations for designing proteome turnover experiments, key biological findings regarding the conserved principles of proteome turnover regulation, and future perspectives for both technological and biological investigation.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/ HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. Additionally, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1) – LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14 and KAI2 protein network by tandem affinity purification using Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were co-purified among which general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination in suboptimal conditions and seedling development. Additionally, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic strigolactone analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14 and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL- related phenotypes and, hence, provide another link with the light pathway.

Recent advances in MS-based proteomics have vastly increased the quality and scope of biological information that can be derived from human samples. These advances have rendered current workflows increasingly applicable in biomedical and clinical contexts. As proteomics is poised to take an important role in the clinic, associated ethical responsibilities increase in tandem with the impact on the health, privacy, and well-being of individuals. Here we conducted and report a systematic literature review of ethical issues in clinical proteomics. We add our perspectives from a background of bioethics, the results of our accompanying paper extracting individual-sensitive results from patient samples, and the literature addressing similar issues in genomics. The spectrum of potential issues ranges from patient re-identification to incidental findings of clinical significance. The latter can be divided into actionable and unactionable findings. Some of these have the potential to be employed in discriminatory or privacy-infringing ways. However, incidental findings may also have great positive potential. A plasma proteome profile, for instance, could inform on the general health or disease status of an individual regardless of the narrow diagnostic question that prompted it. We suggest that early discussion of ethical issues in clinical proteomics is important to ensure that eventual regulations reflect the considered judgment of the community as well as to anticipate opportunities and problems that may arise as the technology matures further.

Tackling Illegal Wildlife Trade in Africa: Economic Incentives and Approaches Research paper sysadmin 5 October 2018

Combating illegal wildlife trade and further pursuing conservation-development models could help generate considerable economic benefits for African countries, while ensuring the long-term preservation of Africa’s wealth of natural capital.

Summary

• The illegal wildlife trade (IWT) significantly impacts African economies by destroying and corroding natural, human and social capital stocks. This hinders the achievement of the Sustainable Development Goals (SDGs) and has an impact on national budgets. Illicit financial flows from IWT deny revenue to governments where legal wildlife product trade exists and perpetuate cash externalization. IWT diverts national budgets away from social or development programmes, increases insecurity and threatens vulnerable populations.
• In expanding wildlife economies and pursuing conservation-driven development models, governments can protect their citizens, derive revenue from wildlife products, and establish world class tourism offerings. The illegal exploitation of wildlife is often due to a failure to enforce rights over those resources, where rights are unclearly defined or not fully exercised. Southern African countries have defined these rights in various ways, contributing to regional differences in conservation practices and the socio-economic benefits derived from wildlife resources. Combating IWT is an important step towards allowing legitimate business and communities to develop livelihoods that incentivize stewardship and connect people to conservation.
• The Southern African Development Community (SADC) has several framework policies for the establishment of transfrontier conservation areas (TFCAs). These promote local stewardship across multiple land-use areas to conserve biodiversity and increase the welfare and socioeconomic development of rural communities. Private-sector partnerships also increase skills transfer, improve access to investment finance, and expand economic opportunities, including through the promotion of local procurement. The economic benefits of TFCAs extend beyond tourism.
• The economic value of African ecosystems is often under-recognized because they remain unquantified, partly due to the lack of available data on the broader economic costs of IWT. Improved monitoring and evaluation with key performance indicators would help governments and citizens to appreciate the economic value of combating IWT.

Cooking in Displacement Settings: Engaging the Private Sector in Non-wood-based Fuel Supply Research paper sysadmin 22 January 2019

In displacement settings, providing cooking solutions that reduce negative impacts on the environment and health remains a challenge for local governments, humanitarian agencies, businesses and refugees.

Summary

• Providing adequate cooking fuel and clean-burning, fuel-efficient stoves in displacement settings has long been a major challenge for local authorities, humanitarian agencies, non-governmental organizations, local communities and refugees themselves. Refugees generally have limited access to modern cooking solutions. Most either depend on insufficient humanitarian agency handouts of ‘in-kind’ firewood or have to travel long distances to collect firewood.
• There is significant potential for private-sector engagement in this context – which, though largely overlooked to date, could result in win-win scenarios for all stakeholders. Refugee camps and other displacement settings present opportunities for private-sector cooking fuel companies to expand their customer bases, with the added advantage for vendors of offering concentrated demand and scope for economies of scale.
• For the Kakuma refugee camp complex in Kenya, the Moving Energy Initiative (MEI) decided to engage with the private sector directly. The MEI requested expressions of interest from local private-sector companies for expanding sales and distribution of fuels in the complex through the concession. The winning company – National Oil Corporation of Kenya – is to receive a prize of $50,000 for its proposed concession to supply liquefied petroleum gas both to refugees in the Kakuma complex and to the surrounding host community.
• The MEI also conducted interviews with various stakeholders in other contexts and countries who are engaged in efforts to develop market-based approaches to providing clean, fuel-efficient cooking solutions to refugees.
• Based on the interviews and the concession process, the MEI recommends greater donor investment and longer-term guaranteed funding for cooking interventions. This is needed to allow sufficient time to build sustainable markets and secure the requisite engagement and investments from the private sector.
• Larger, longer-term investments by the private sector – supported through partnerships with donors and humanitarian agencies – in infrastructure and demand creation (both in and outside the refugee community) can reduce the price of alternative solutions and support a gradual transition away from subsidies.

Adopting a Market-based Approach to Boost Energy Access in Displaced Contexts Research paper sysadmin 25 March 2019

This paper evaluates the market-based approaches adopted in the MEI projects in Kenya and Burkina Faso. It articulates how such commercial strategies can be applied to the delivery of energy in displacement settings and compares this to real world examples.

• Development of long-term energy solutions in displacement settings tends to be perceived as investment that falls outside the remit of emergency responses. In addition, when emergency energy supply measures are implemented they often result in expensive, unreliable and unhealthy energy provision for those in protracted or recurrent crises.
• There is widespread agreement among humanitarian and development experts that an effective refugee response should include long-term development solutions as well as emergency relief.
• The energy access imperative is more pronounced when considering the need for effective energy distribution in practically all camp activities and basic necessities: pumping and treatment of clean water; heating and cooling for food storage and cooking; energy for livelihood activities; and provision of light for schooling, hospitals and the prevention of violence against women and children.
• Minor shifts in household energy use to basic solar lighting options and non-wood fuels would save $303 million annually on refugee fuel costs.
• Within refugee contexts in Kenya and Burkina Faso, the MEI sought to examine opportunities to use market interventions, rather than in-kind distributions, to improve clean energy access over the long-term and test the delivery of market-based approaches.

Online Disinformation and Political Discourse: Applying a Human Rights Framework Research paper sysadmin 5 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law.

This paper examines how human rights frameworks should guide digital technology.

Summary

• Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
• Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
• International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
• The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
• The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
• Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
• The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
• The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.

Subsidies and Sustainable Agriculture: Mapping the Policy Landscape Research paper sysadmin 10 December 2019

Agricultural subsidies shape production and consumption patterns, with potentially significant effects on poverty, nutrition and other sustainability concerns. This paper maps the different types of support provided by governments to the agricultural sector, and highlights some of the complex political economy dynamics that underpin the relevant policies.

Summary

• Agricultural subsidies, a mainstay of government policy, have a large part in shaping production and consumption patterns, with potentially significant effects as regards poverty, food security, nutrition, and other sustainability concerns such as climate change, land use practices and biodiversity.
• There are multiple types of direct and indirect support provided by governments to various actors in the agricultural sector; and in terms of political economy, there are complex dynamics underpinning the policies that sustain these subsidies.
• Overall, subsidies targeting producers have the most significant effect on production, and the greater trade-distorting effect. These subsidies promote domestic production and discourage imports, leading to overproduction that is largely disposed of on the international market, with the help of export subsidies. This can tend to intensify negative environmental agricultural practices, such as cultivating marginal land, unsustainable types of intensification, or incentivizing excessive pesticide and fertilizer use.
• On the other hand, producer subsidies that are not tied to output of a specific commodity (i.e. delinked) have far fewer distorting impacts and could help to deliver sustainable outcomes. For example, this type of subsidies can require crop diversification or be linked to conservation of permanent grassland.
• Subsidies that enable transfers to consumers, for example through food stamp programmes, also serve to delink production from consumption, can foster healthier diets, can play an important role in delivering food accessibility and security among low-income groups, and can represent one of the less trade-distorting subsidies.
• If subsidies are to be reformed to help promote healthier diets and encourage more sustainable production, it is essential to understand not only the type and amount of support that key countries provide, but also the domestic dynamics that can shape such policies.
• While price support, input subsidies or investment aids remain the central pillars of programmes in large developing countries such as Brazil, China or India, other economies – notably including the EU and Japan – focus on direct payments, support for general services and set-aside schemes, as well as significant border protection. The US, for its part, has tended to focus on subsidized insurance schemes and food programmes for poorer consumers.
• If subsidies are to deliver policy objectives, their design and implementation should delink production from consumption. For example, consumer subsidies designed to deliver nutrition and food security, or payments for environmental services to enable more environmentally friendly production systems, could prove to be the most effective, least trade-distorting means of achieving more sustainable and equitable agricultural production.
• The political economy of food means that the removal of subsidies is often highly sensitive, and tends to be met with significant resistance. However, reform that delinks support from production through a gradual transition process could ultimately prove successful in delivering effective subsidy schemes.
• Effective subsidy schemes must by design be truly result- and performance-based, supported by robust and objective indicators. At the same time, engaging multiple actors along key commodity value chains – including leading importing and exporting countries, traders and transporters – could lead to the development of international, commodity-specific arrangements that are able to deliver effective nutrition and sustainability goals.

COP26: What happened, what does this mean, and what happens next? Chatham House briefing NCapeling 15 November 2021

Analysing a crucial opportunity for enhancing ambitions on climate finance, adaptation, and ‘loss and damage’, and the implementation of the Paris Agreement.

Key findings

Raising the ambition of national emission reduction targets (nationally determined contributions – NDCs) was a critical task for COP26. On this front, governments fell short: although over 120 parties have submitted new or updated NDCs, the new targets only narrow the gap to 1.5°C by 15–17 per cent, and are, if fully implemented (and this is far from certain), projected to result in warming of 2.4°C by the end of the century.

If warming is to be limited to 1.5°C above pre-industrial levels, additional emissions reductions before 2030, over and above current NDC pledges, will need to equate to reducing emissions by the equivalent of two years of current annual emissions. To keep warming to 2°C, the equivalent reductions would be needed of one year’s total emissions.

The Glasgow Climate Pact – the main political outcome of COP26 – requests governments to revisit and strengthen their NDCs before the end of 2022 to bring these in line with the Paris Agreement’s temperature goal. To keep 1.5°C within reach, it will be absolutely essential that governments return to the table with significantly enhanced offers ahead of COP27, which will take place at Sharm El-Sheikh, Egypt, in 2022.

Another key feature of the Glasgow Climate Pact is the reference to ‘accelerating efforts towards the phasedown of unabated coal power and phase-out of inefficient fossil fuel subsidies’. Although the language was watered down over the course of the negotiations, COP26 marks the first time ever reducing fossil fuels is mentioned in a COP decision.

Discussions around climate finance, adaptation, and loss and damage were centre stage in Glasgow, and were critical points of contention. Although the Glasgow Climate Pact urges developed countries to ‘fully’ deliver on the $100 billion annual climate finance pledge through to 2025, it remains unclear when this sum will actually be raised in full – and if a total of $500 billion will be mobilized between 2020 and 2025 to make up for initial shortfalls.

And while the Pact urges developed countries to double their adaptation finance by 2025, and establishes a dialogue on loss and damage finance, much more will need to be done to address the needs of climate-vulnerable developing countries. 

COP26 saw a flurry of plurilateral deals on key issues such as phasing out various forms of fossil fuels and ending deforestation. These initiatives have the potential to accelerate decarbonization, but monitoring their implementation and holding governments and other institutions to account will be critical. Future COPs provide a platform for doing this, and governments should seek to incorporate the pledges made outside the formal remits of the UNFCCC process in their NDCs.

While some progress was made at COP26, the next 12 months will be crucial in determining if the formal agreements reached in Glasgow provide grounds for optimism that 1.5°C remains firmly in sight, and are sufficient to build trust between countries and between citizens and governments.

Read the full analysis

Political Opposition and Policy Alternatives in Zambia 31 October 2017 — 10:30AM TO 11:30AM Anonymous (not verified) 19 October 2017 Chatham House, London

In Zambia’s 2016 national election, the Patriotic Front (PF) was re-elected by a narrow margin. The PF’s Edgar Lungu secured 50.35 per cent of the vote according to the Electoral Commission of Zambia, narrowly avoiding a second round, while his main rival, Hakainde Hichilema, won 47.67 per cent. The UPND, led by Mr Hichilema, alleges electoral fraud and has challenged the result in the courts and through direct protests. Mr Hichilema was imprisoned for 100 days.

At this meeting, Hakainde Hichilema will discuss his UPND priorities, how to strengthen opposition parties and their role in Zambia’s democratic future.

Read transcript

Angola Forum 2021: Policy options to support economic recovery in Angola 7 October 2021 — 2:00PM TO 5:00PM Anonymous (not verified) 22 September 2021 Online

Speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The government of Angola has made some progress on a range of policies targeting macroeconomic stability and structural reform. However, the country has been suffering from a recurring economic recession for six consecutive years, with the last positive annual GDP growth rate posted in 2015 at 0.9 per cent.

The national budget remains dependent on oil revenue, leaving the country highly exposed to volatile oil prices particularly during the COVID-19 pandemic. While revenues collapsed, increased spending was needed to respond to the health crisis and estimates of Angola’s debt spike range from 130 to 150 per cent of its GDP by the close of 2020.

At this virtual Angola Forum, speakers discuss policy options to support economic recovery in Angola as the country transitions away from a state-led oil economy to a private-sector-led growth model.

The Forum launches the English translation of the Angola Economic Report 2019-20 by the Centro de Estudos de Investigação (CEIC) of the Catholic University of Angola in partnership with the Konrad-Adenauer-Stiftung (KAS), and the findings of Afrobarometer’s first ever survey in Angola, Ovilongwa – Estudos de Opinião Pública, which interviewed 2,400 adult Angolans and sampled individual perceptions on democracy and economic reform in Angola.

This event will be held in English and Portuguese with simultaneous interpretation.

The Forum will also be broadcast live on the Africa Programme Facebook page.

Turkey's Foreign Policy: The Perspective of the Main Opposition Party 5 November 2020 — 12:00PM TO 1:00PM Anonymous (not verified) 14 October 2020 Online

The Republican People’s Party (CHP), the main Turkish opposition party, is becoming a serious contender for a leading role in the country’s politics.

This is an online only event.

CHP’s mayoral candidates defeated the Justice and Development Party (AKP) incumbents in the 2019 local elections in Ankara and Istanbul, which held both cities for a quarter of a century. Its ascendency in Turkish politics is improving prospects for a CHP-led government after the next general election in 2023.

In this webinar, the speaker will share CHP’s stance on the country’s foreign policy towards key regional allies in Europe, as well as its take on relations with Russia, the US and Turkey’s position and role in the Middle East. Finally, the speaker will share how CHP’s external policy might differ from the ruling AKP. 

McKesson Medical-Surgical Inc. entered into an agreement with the Labor Department on Monday resolving employment discrimination issues involving nearly 900 Black, Hispanic, and White applicants at a distribution center

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.

2025 Luis J. Alvarez and Admiral Grace M. Hopper Postdoc Fellowship in Computing Sciences - 102564 Division: AC-Computing Luis J. Alvarez Postdoctoral Fellowship and Admiral Grace M. Hopper Postdoctoral Fellowship in Computing Sciences The Computing Sciences Area (https://cs.lbl.gov/) at Lawrence Berkeley National Laboratory (https://www.lbl.gov) is now accepting applications for two distinguished postdoctoral fellowships in Computing Sciences: • Luis W. Alvarez Postdoctoral Fellowship, and • Admiral Grace M. Hopper Postdoctoral Fellowship. Researchers in computer science, mathematics, data science, or any computational science discipline who have received their Ph.D. no earlier than January 1, 2022 but no later than September 30, 2025 are encouraged to apply. Only one (1) application is needed and it will be considered for both postdoctoral fellowships. The successful candidates will participate in research activities in computer science, mathematics, data science, or any computational science discipline of interest to the Computing Sciences Area and Berkeley Lab. Alvarez Fellows apply advances in computer science, mathematics, computational science, data science, machine learning or AI to computational modeling, simulations, and advanced data analytics for scientific discovery in materials science, biology, astronomy, environmental science, energy, particle physics, genomics, and other scientific domains. Hopper Fellows concentrate on the development and optimization of scientific and engineering applications leveraging high-speed network capability provided by the Energy Sciences Network or run on next-generation high performance computing and data systems hosted by the National Energy Research Scientific Computing Center at Berkeley Lab. Since its founding in 2002, Berkeley Lab’s Luis W. Alvarez Postdoctoral Fellowship (go.lbl.gov/alvarez) has cultivated exceptional early career scientists who have gone on to make outstanding contributions to computer science, mathematics, data science, and computational sciences. The Admiral Grace Hopper Postdoctoral Fellowship (go.lbl.gov/hopper) was first awarded in 2015 with the goal of enabling early career scientists to make outstanding contributions in computer science and high performance computing (HPC) research. About Computing Sciences at Berkeley Lab: Whether running extreme-scale simulations on a supercomputer or applying machine-learning or data analysis to massive datasets, scientists today rely on advances in and integration across applied mathematics, computer science, and computational science, as well as large-scale computing and networking facilities, to increase our understanding of ourselves, our planet, and our universe. Berkeley Labs Computing Sciences Area researches, develops, and deploys new tools and technologies to meet these needs and to advance research in our core capabilities of applied mathematics, computer science, data science, and computational science. In addition to fundamental advances in our core capabilities, we impact such areas as astrophysics and cosmology, accelerator physics, chemical science and materials science, combustion, fusion energy, nuclear physics, biology, climate change, and HPC systems and network technology. Research areas in Computing Sciences include but are not limited to: • Developing scientific applications and software technologies for extreme-scale and energy-efficient • Developing mathematical modeling for complex scientific problems • Designing algorithms to improve the performance of scientific applications • Researching digital and post-digital computer architectures for science • Developing and advancing extreme-scale scientific data management, analysis, and visualization • Developing and advancing next-generation machine learning, AI, and data science approaches for science • Advancing quantum computing and networking technologies, software, algorithms and applications • Evaluating or developing new and promising HPC systems and networking technologies • Researching methods to control and manage next-generation networks • Managing scientific data and workflows in distributed environments Qualifications: • Requires a Ph.D. in computer science, mathematics, computational science, or related discipline. • Candidates must have no more than 3 years of Postdoctoral Researcher or similar experience. • Expertise with advanced algorithms, software techniques, HPC systems and/or networking in a related research field. • Demonstrated creativity and the ability to perform independent research. • Demonstrated excellence in a related research field. • Ability to develop new cross-disciplinary partnerships that use advanced computational and/or mathematical techniques to produce unique lab capabilities. • Excellent communication skills with the ability to facilitate communications and collaborations with internal and external stakeholders. Additional Desired Qualifications: • Knowledge of advanced computing and high-performance computing. Application Process: 1. As part of your application process, you must upload and submit the following materials with your online application. 1. Cover letter 2. CV, with publication list included 3. Research Statement (no more than five (5) pages in length when printed using standard letter-size (8.5 inch x 11 inch) paper with 1-inch margins (top, bottom, left, and right) and a font size not smaller than 11 point; figures and references cited, if included, must fit within the five-page limit) 4. Contact information (name, affiliation, and email address) of at least three (3) individuals who will be able to provide letters of reference. 2. Application deadline: October 31, 2024. * It is highly advisable that you have all the required application materials and information ready and available prior to completing and submitting your application. Your application will not be considered complete if any of the above information is missing. Tentative Application Timeline: The Computing Sciences Fellowship Selection Committee is made up of a diverse representation of scientists and engineers across Berkeley Lab’s Computing Sciences Area who will conduct a thorough review of all applications received. • Application deadline: October 31, 2024 • Review and Selection: October 2024 - December 2024 • Decisions made: January/February 2025 Want to learn more about working at Berkeley Lab? Please visit: careers.lbl.gov How To Apply Apply directly online at http://50.73.55.13/counter.php?id=290341 and follow the on-line instructions to complete the application process. Berkeley Lab is committed to inclusion, diversity, equity and accessibility and strives to continue building community with these shared values and commitments. Berkeley Lab is an Equal Opportunity and Affirmative Action Employer. We heartily welcome applications from women, minorities, veterans, and all who would contribute to the Labs mission of leading scientific discovery, inclusion, and professionalism. In support of our diverse global community, all qualified applicants will be considered for employment without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability, age, or protected veteran status. Equal Opportunity and IDEA Information Links: Know your rights, click here (http://www.dol.gov/ofccp/regs/compliance/posters/ofccpost.htm) for the supplement: Equal Employment Opportunity is the Law and the Pay Transparency Nondiscrimination Provision (https://www.dol.gov/sites/dolgov/files/ofccp/pdf/pay-transp_%20English_formattedESQA508c.pdf) under 41 CFR 60-1.4.

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.

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.

Premier League reference David Coote is suspended indefinitely after videos surfaced that appeared to show him criticizing former Liverpool coach Jurgen Klopp, officials announced Monday.

What can be achieved using applications such as AI/ML, Deep Learning, and Big Data Analytics has been revolutionized by Magnum IO GPUDirect Storage’s capabilities. Agencies have invested in these solutions […]

The post Accelerating GPU Based Applications with NVIDIA Validated Magnum IO GPUDirect Storage and Pavilion appeared first on HPCwire.

LONDON, Nov. 1, 2024 — Quantum Motion, a UK-based quantum computing scale-up founded by Professor John Morton, University College London (UCL), and Professor Simon Benjamin, University of Oxford, has worked […]

The post Quantum Motion and Goldman Sachs Identify Quantum Applications in Financial Services Project appeared first on HPCwire.

U.S. Defense Secretary Lloyd Austin said Ukraine continues to have U.S. support against Russian aggression and is free to decide its own foreign policy during a visit to Kyiv Tuesday. 

Making the Most of Today’s Cloud-First Approach to Running HPC and AI Workloads With Penguin Scyld Cloud Central™ Bursting to cloud has long been used to complement on-premises HPC capacity […]

The post Penguin Computing Scyld Cloud Central™: A New Cloud-First Approach to HPC and AI Workloads appeared first on HPCwire.

Nov. 8, 2024 — Across the United States, research shows that computer science (CS) courses teach a range of transferable skills that help students as they enter the workforce. But in […]

The post UT Austin-UTEP Partnership Supports Growth of Texas CS Education appeared first on HPCwire.

HPE’s cooling expert, Jason Zeiler, explains why liquid cooling is ideally suited to cool next-generation accelerators for greater efficiency, sustainability, and density in future AI data centers In this article […]

The post Liquid Cooling: A Cool Approach for AI appeared first on HPCwire.