This article provides a large-scale dataset for South African energy system modeling intended to aid long-term energy planning. The dataset, which is accessible on Zenodo, contains comprehensive data on installed capacity, resource potentials, historical and projected electricity production and consumption, capacity factors, and capital, fixed, and variable costs. The data was rigorously collected from national institutions, international organizations, and scholarly journals and organized into an easy-to-use Excel workbook.
View Article and Find Full Text PDFPower sector and energy systems models are widely used to explore the impacts of demographic, socio-economic or policy changes on the cost and emissions of electricity generation. Technology cost and performance data are essential inputs to such models. Despite the ubiquity and importance of these parameters, there is no standardised database which collates the variety of values from across the literature, so modellers must collect them independently each time they populate or update model inputs, leading to duplicated efforts and inconsistencies which can profoundly influence model results.
View Article and Find Full Text PDFMacrophages often abound within tumors, express colony-stimulating factor 1 receptor (CSF1R), and are linked to adverse patient survival. Drugs blocking CSF1R signaling have been used to suppress tumor-promoting macrophage responses; however, their mechanisms of action remain incompletely understood. Here, we assessed the lung tumor immune microenvironment in mice treated with BLZ945, a prototypical small-molecule CSF1R inhibitor, using single-cell RNA sequencing and mechanistic validation approaches.
View Article and Find Full Text PDFThere is a need for novel analytical techniques to study the composition of single extracellular vesicles (EV). Such techniques are required to improve the understanding of heterogeneous EV populations, to allow identification of unique subpopulations, and to enable earlier and more sensitive disease detection. Because of the small size of EV and their low protein content, ultrahigh sensitivity technologies are required.
View Article and Find Full Text PDFDisulfide rebridging methods have recently emerged as a route to hinge region-specific antibody modification, and there exist numerous examples of successful rebridging chemistry applied to clinically relevant human IgG1 antibodies. Here, dibromopyridazinedione disulfide rebridging is adapted to fast trans-cyclooctene/tetrazine (TCO/Tz) bioorthogonal ligations and extended beyond therapeutic human IgG1 antibodies for the first time to include mouse and rat monoclonal antibodies integral to multiplexed analytical diagnostics. In spite of a common architecture, only a subset of antibody host species and IgG isotype subclasses can be rebridged, highlighting the intricate relationship between hinge region sequence, structure, biological activity, and the conjugation chemistry of IgG antibodies.
View Article and Find Full Text PDFMutation-derived neoantigens are important targets for T cell-mediated reactivity toward tumors and, due to their unique tumor expression, an attractive target for immunotherapy. Neoepitope-specific T cells have been detected across a number of solid cancers with high mutational burden tumors, but neoepitopes have been mostly selected from single nucleotide variations (SNVs), and little focus has been given to neoepitopes derived from in-frame and frameshift indels, which might be equally important and potentially highly immunogenic. Clear cell renal cell carcinomas (ccRCCs) are medium-range mutational burden tumors with a high pan-cancer proportion of frameshift mutations.
View Article and Find Full Text PDFEmerging point-of-care diagnostic tests capable of analyzing whole mammalian cells often rely on the attachment of harvested cells to glass surfaces for subsequent molecular characterization. We set out to develop and optimize a kit for the diagnosis of lymphoma in low- and middle-income countries where access to advanced healthcare testing is often absent or prone to error. Here, we optimized a process for the lyophilization of neutravidin-coated glass and cocktails of antibodies relevant to lymphoma diagnosis to establish long-term stability of reagents required for point-of-care cell capture technology.
View Article and Find Full Text PDFNarcolepsy Type 1 (NT1) is a neurological sleep disorder, characterized by the loss of hypocretin/orexin signaling in the brain. Genetic, epidemiological and experimental data support the hypothesis that NT1 is a T-cell-mediated autoimmune disease targeting the hypocretin producing neurons. While autoreactive CD4 T cells have been detected in patients, CD8 T cells have only been examined to a minor extent.
View Article and Find Full Text PDFThe promiscuous nature of T-cell receptors (TCRs) allows T cells to recognize a large variety of pathogens, but makes it challenging to understand and control T-cell recognition. Existing technologies provide limited information about the key requirements for T-cell recognition and the ability of TCRs to cross-recognize structurally related elements. Here we present a 'one-pot' strategy for determining the interactions that govern TCR recognition of peptide-major histocompatibility complex (pMHC).
View Article and Find Full Text PDFThe interplay between micromorphology and electronic properties is an important theme in organic electronic materials. Here, we show that a spirofluorene-functionalized boron-dipyrromethene (BODIPY) with an alkyl norbornyl tail self-assembles into nanoparticles with qualitatively different properties as compared to the polymerized species. Further, the nanoparticles exhibit a host of unique emissive properties, including photobrightening, a blue satellite peak, and spectral diffusion.
View Article and Find Full Text PDFMicrobial biofilms are omnipresent in nature and relevant to a broad spectrum of industries ranging from bioremediation and food production to biomedical applications. To date little is understood about how multi-species biofilm communities develop and function on a molecular level, due to the complexity of these biological systems. Here we apply a meta-proteomics approach to investigate the mechanisms influencing biofilm formation in a model consortium of four bacterial soil isolates; Stenotrophomonas rhizophila, Xanthomonas retroflexus, Microbacterium oxydans and Paenibacillus amylolyticus.
View Article and Find Full Text PDFIntra-tumour genetic heterogeneity (ITH) fosters drug resistance and is a critical hurdle to clinical treatment. ITH can be well-measured using multi-region sampling but this is costly and challenging to implement. There is therefore a need for tools to estimate ITH in individual samples, using standard genomic data such as SNP-arrays, that could be implemented routinely.
View Article and Find Full Text PDFThe action of molecular catalysts comprises multiple microscopic kinetic steps whose nature is of central importance in determining catalyst activity and selectivity. Single-molecule microscopy enables the direct examination of these steps, including elucidation of molecule-to-molecule variability. Such molecular diversity is particularly important for the behavior of molecular catalysts supported at surfaces.
View Article and Find Full Text PDFBackground: A substantial proportion of cancer cases present with a metastatic tumor and require further testing to determine the primary site; many of these are never fully diagnosed and remain cancer of unknown primary origin (CUP). It has been previously demonstrated that the somatic point mutations detected in a tumor can be used to identify its site of origin with limited accuracy. We hypothesized that higher accuracy could be achieved by a classification algorithm based on the following feature sets: 1) the number of nonsynonymous point mutations in a set of 232 specific cancer-associated genes, 2) frequencies of the 96 classes of single-nucleotide substitution determined by the flanking bases, and 3) copy number profiles, if available.
View Article and Find Full Text PDFBackground: Ovarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment with PARP inhibitors and platinum-based cytotoxic agents and show an accumulation of genomic scars in the form of gross DNA copy number aberrations. Cancers without BRCA1 or BRCA2 loss but with accumulation of similar genomic scars also show increased sensitivity to platinum-based chemotherapy. Therefore, reliable biomarkers to identify DNA repair-deficient cancers prior to treatment may be useful for directing patients to platinum chemotherapy and possibly PARP inhibitors.
View Article and Find Full Text PDFBackground: Exome or whole-genome deep sequencing of tumor DNA along with paired normal DNA can potentially provide a detailed picture of the somatic mutations that characterize the tumor. However, analysis of such sequence data can be complicated by the presence of normal cells in the tumor specimen, by intratumor heterogeneity, and by the sheer size of the raw data. In particular, determination of copy number variations from exome sequencing data alone has proven difficult; thus, single nucleotide polymorphism (SNP) arrays have often been used for this task.
View Article and Find Full Text PDFMembers of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1) family expressed on the surface of malaria-infected erythrocytes mediate binding of the parasite to different receptors on the vascular lining. This process drives pathologies, and severe childhood malaria has been associated with the expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into subtypes based on upstream sequences and the presence of semi-conserved PfEMP1 domain compositions named domain cassettes (DCs).
View Article and Find Full Text PDFThe clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P.
View Article and Find Full Text PDFBackground: Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion antigen family are major contributors to the pathogenesis of P. falciparum malaria infections. The PfEMP1-encoding var genes are among the most diverse sequences in nature, but three genes, var1, var2csa and var3 are found conserved in most parasite genomes.
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