A return to in-person public engagement at STFC

Since 2020, UKRI/STFC’s Scientific Computing Department (SCD) have developed several remote-first public engagement activities, drawing on its long and rich history of delivering face to face public engagement and outreach, as part of the wider STFC programme. With COVID19 restrictions lifted in the UK, STFC has been able to resume in-person public engagement, both on site and in public places. However, this has not meant a complete return to exclusively in-person engagement, but rather, recognising the clear benefits of remote engagement to meeting our strategic public engagement aims, STFC has produced a blended programme for 2022/23, with a mixture of in-person, remote and hybrid events. This paper presents how the remote activities have evolved since their initial creation, how the remote activities have become part of a blended programme and how the in-person activities in place since before the pandemic have been improved as a result of developing the remote activities

Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines

BackgroundImatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.MethodsWe conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.ResultsCytotoxicity within cell lines was highly heritable following imatinib treatment (h2&thinsp;=&thinsp;0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly &gt;10).ConclusionsInduction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.<br /

Explicit modelling of resources for multi-agent microservices using the cartago framework

The 19th International Conference on Autonomous Agents and Multiagent Systems (AAMS 2020), Auckland, New Zealand, 9-13 May 2020This paper describes the first agent programming language agnostic implementation of the Multi-Agent MicroServices (MAMS) model - an approach to integrating agents within microservices-based architectures where agents expose aspects of their state as virtual resources, realised as CArtAgO artifacts, that are externally accessible through REpresentational State Transfer (REST).Science Foundation Irelan

MAMS: Multi-Agent MicroServices

The 2019 World Wide Web Conference (WWW'19), San Francisco, United States of America, 13-17 May 2019This paper explores the intersection between microservices and Multi-Agent Systems (MAS), introducing the notion of a new approach to building MAS known as Multi-Agent MicroServices (MAMS). Our approach is illustrated through a worked example of a Vickrey Auction implemented as a microservice.Science Foundation IrelandOrigin Enterprises Pl

Two-Dimensional Molecular Electronics Circuits

Addressing an array of bistable [2]rotaxanes through a two‐dimensional crossbar arrangement provides the device element of a current‐driven molecular electronic circuit. The development of the [2]rotaxane switches through an iterative, evolutionary process is described. The arrangement reported here allows both memory and logic functions to use the same elements

Foreign Aid as a Signal to Investors: Predicting FDI in Post-conflict Countries

Does development aid attract foreign direct investment (FDI) in post-conflict countries? This article contributes to the growing literature on effects of aid and on determinants of FDI by explaining how development aid in low-information environments is a signal that can attract investment. Before investing abroad, firms seek data on potential host countries. In post-conflict countries, reliable information is poor, in part because governments face unusual incentives to misrepresent information. In these conditions, firms look to signals. One is development aid, because donors tend to give more to countries they trust to properly handle the funds. Our results show that aid seems to draw FDI—however, this is conditional on whether the aid can be considered geostrategically motivated. We also show that this effect decreases as time elapses after the conflict. This suggests that aid’s signaling effect is specific to low-information environments, and helps rule out alternative causal mechanisms linking aid and FDI

Friedrich Hayek and his visits to Chile

F. A. Hayek took two trips to Chile, the first in 1977, the second in 1981. The visits were controversial. On the first trip he met with General Augusto Pinochet, who had led a coup that overthrew Salvador Allende in 1973. During his 1981 visit, Hayek gave interviews that were published in the Chilean newspaper El Mercurio and in which he discussed authoritarian regimes and the problem of unlimited democracy. After each trip, he complained that the western press had painted an unfair picture of the economic situation under the Pinochet regime. Drawing on archival material, interviews, and past research, we provide a full account of this controversial episode in Hayek’s life

Regulation of skeletal muscle oxidative capacity and insulin signaling by the Mitochondrial Rhomboid Protease PARL

Type 2 diabetes mellitus (T2DM) and aging are characterized by insulin resistance and impaired mitochondrial energetics. In lower organisms, remodeling by the protease pcp1 (PARL ortholog) maintains the function and lifecycle of mitochondria. We examined whether variation in PARL protein content is associated with mitochondrial abnormalities and insulin resistance. PARL mRNA and mitochondrial mass were both reduced in elderly subjects and in subjects with T2DM. Muscle knockdown of PARL in mice resulted in malformed mitochondrial cristae, lower mitochondrial content, decreased PGC1&alpha; protein levels, and impaired insulin signaling. Suppression of PARL protein in healthy myotubes lowered mitochondrial mass and insulin-stimulated glycogen synthesis and increased reactive oxygen species production. We propose that lower PARL expression may contribute to the mitochondrial abnormalities seen in aging and T2DM.<br /

Genetic variation in selenoprotein S influences inflammatory response

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1b and TNF-a. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatorycytokines. One promoter variant, 105G-A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-a. To investigate further the significance of the observed associations, we genotyped 105G-A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significantassociation with both TNF-a (P = 0.0049) and IL-1b (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.<br /