A conceptual framework for studying collective reactions to events in location-based social media

Events are a core concept of spatial information, but location-based social media (LBSM) provide information on reactions to events. Individuals have varied degrees of agency in initiating, reacting to or modifying the course of events, and reactions include observations of occurrence, expressions containing sentiment or emotions, or a call to action. Key characteristics of reactions include referent events and information about who reacted, when, where and how. Collective reactions are composed of multiple individual reactions sharing common referents. They can be characterized according to the following dimensions: spatial, temporal, social, thematic and interlinkage. We present a conceptual framework, which allows characterization and comparison of collective reactions. For a thematically well-defined class of event such as storms, we can explore differences and similarities in collective attribution of meaning across space and time. Other events may have very complex spatio-temporal signatures (e.g. political processes such as Brexit or elections), which can be decomposed into series of individual events (e.g. a temporal window around the result of a vote). The purpose of our framework is to explore ways in which collective reactions to events in LBSM can be described and underpin the development of methods for analysing and understanding collective reactions to events

Therapeutic Potential of a Novel Vitamin D3 Oxime Analogue, VD1-6, with CYP24A1 Enzyme Inhibitory Activity and Negligible Vitamin D Receptor Binding

Abstract: The regulation of vitamin D3 actions in humans occurs mainly through the Cytochrome P450 24-hydroxylase (CYP24A1) enzyme activity. CYP24A1 hydroxylates both 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is the first step of vitamin D catabolism. An abnormal status of the upregulation of CYP24A1 occurs in many diseases, including chronic kidney disease (CKD). CYP24A1 upregulation in CKD and diminished activation of vitamin D3 contribute to secondary hyperparathyroidism (SHPT), progressive bone deterioration, and soft tissue and cardiovascular calcification. Previous studies have indicated that CYP24A1 inhibition may be an effective strategy to increase endogenous vitamin D activity and decrease SHPT. This study has designed and synthesized a novel C-24 O-methyloxime analogue of vitamin D3 (VD1-6) to have specific CYP24A1 inhibitory properties. VD1-6 did not bind to the vitamin D receptor (VDR) in concentrations up to 10-7 M, assessed by a VDR binding assay. The absence of VDR binding by VD1-6 was confirmed in human embryonic kidney HEK293T cultures through the lack of CYP24A1 induction. However, in silico docking experiments demonstrated that VD1-6 was predicted to have superior binding to CYP24A1, when compared to that of 1,25(OH)2D3. The inhibition of CYP24A1 by VD1-6 was also evident by the synergistic potentiation of 1,25(OH)2D3-mediated transcription and reduced 1,25(OH)2D3 catabolism over 24 h. A further indication of CYP24A1 inhibition by VD1-6 was the reduced accumulation of the 24,25(OH)D3, the first metabolite of 25(OH)D catabolism by CYP24A1. Our findings suggest the potent CYP24A1 inhibitory properties of VD1-6 and its potential for testing as an alternative therapeutic candidate for treating SHPT.Ali K. Alshabrawy, Yingjie Cui, Cyan Sylvester, Dongqing Yang, Emilio S. Petito, Kate R. Barratt, Rebecca K. Sawyer, Jessica K. Heatlie, Ruhi Polara, Matthew J. Sykes, Gerald J. Atkins, Shane M. Hickey, Michael D. Wiese, Andrea M. Stringer, Zhaopeng Liu, and Paul H. Anderso

Author Correction: A chickpea genetic variation map based on the sequencing of 3,366 genomes

In Extended Data Fig. 1 of this Article, the labels ‘Market class’ and ‘Biological status’ were inadvertently swapped. In the corresponding figure legend, “Track 1: Biological status; Track 2: Market class;” should have been “Track 1: Market class; Track 2: Biological status;”. The original Article has been corrected online

Financialisation of the South African economy: impact on the economic growth path and employment

We propose here a number of approaches to implement constraint propagation for arithmetic constraints on integer intervals. To this end we introduce integer interval arithmetic. Each approach is explained using appropriate proof rules that reduce the variable domains. We compare these approaches using a set of benchmarks.Comment: 24 pages. To appear in "Recent Advances in Constraints, 2003" K.R. Apt, F. Fages, F. Rossi, P. Szeredi and J. Vancza, eds, LNAI 3010, Springer-Verlag, 200

A chickpea genetic variation map based on the sequencing of 3,366 genomes

Zero hunger and good health could be realized by 2030 through effective conservation, characterization and utilization of germplasm resources1. So far, few chickpea (Cicer arietinum) germplasm accessions have been characterized at the genome sequence level2. Here we present a detailed map of variation in 3,171 cultivated and 195 wild accessions to provide publicly available resources for chickpea genomics research and breeding. We constructed a chickpea pan-genome to describe genomic diversity across cultivated chickpea and its wild progenitor accessions. A divergence tree using genes present in around 80% of individuals in one species allowed us to estimate the divergence of Cicer over the last 21 million years. Our analysis found chromosomal segments and genes that show signatures of selection during domestication, migration and improvement. The chromosomal locations of deleterious mutations responsible for limited genetic diversity and decreased fitness were identified in elite germplasm. We identified superior haplotypes for improvement-related traits in landraces that can be introgressed into elite breeding lines through haplotype-based breeding, and found targets for purging deleterious alleles through genomics-assisted breeding and/or gene editing. Finally, we propose three crop breeding strategies based on genomic prediction to enhance crop productivity for 16 traits while avoiding the erosion of genetic diversity through optimal contribution selection (OCS)-based pre-breeding. The predicted performance for 100-seed weight, an important yield-related trait, increased by up to 23% and 12% with OCS- and haplotype-based genomic approaches, respectively