Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function

Is this Twitter event a disaster?

Ponencias, comunicaciones y pósters presentados en el 17th AGILE Conference on Geographic Information Science "Connecting a Digital Europe through Location and Place", celebrado en la Universitat Jaume I del 3 al 6 de junio de 2014.Social media services such as Twitter have become an important channel for reporting real-world events. For example, they can describe the current situation during a disaster. The decisions in crises management are based on detailed on-site information such as what is happening, where and when an event is happening, and who is involved. Thus, in real applications, monitoring the events over social media will enable to analyse the current overall situation. In this paper, the authors introduce a prototype for real-time Twitter-based natural disaster detection and monitoring. The detection approach is multilingual and calculates a statistical based probability for a potential disaster event. For an automatic geo-referencing of the disaster, the approach applies spatial gridding. On this basis the grid cells are subject to a spatial-thematic clustering which uses a method similar to region growing. The application’s output is an automatically generated email alert, containing specific information on the disaster

Earthquake modelling at the country level using aggregated spatio-temporal point processes

The goal of this paper is to derive a hazard map for earthquake occurrences in Pakistan from a catalogue that contains spatial coordinates of shallow earthquakes of magnitude 4.5 or larger aggregated over calendar years. We test relative temporal stationarity by the KPSS statistic and use the inhomogeneous J-function to test for inter-point interactions. We then formulate a cluster model, and de-convolve in order to calculate the hazard map, and verify that no particular year has an undue influence on the map. Within the borders of the single country, the KPSS test did not show any deviation from homogeneity in the spatial intensities. The inhomogeneous J-function indicated clustering that could not be attributed to inhomogeneity, and the analysis of aftershocks showed some evidence of two major shocks instead of one during the 2005 Kashmir earthquake disaster. Thus, the spatial point pattern analysis carried out for these data was insightful in various aspects and the hazard map that was obtained may lead to improved measures to protect the population against the disastrous effects of earthquakes

Esterase Cleavable 2D Assemblies of Magnetic Iron Oxide Nanocubes: Exploiting Enzymatic Polymer Disassembling to Improve Magnetic Hyperthermia Heat Losses

Here, we report a nanoplatform based on iron oxide nanocubes (IONCs) coated with a bioresorbable polymer that, upon exposure to lytic enzymes can be disassembled increasing the heat performances in comparison with the initial clusters. We have developed bi-dimensional (2D) clusters by exploiting benchmark iron oxide nanocubes as heat mediators for magnetic hyperthermia and a polyhydroxyalkanoate (PHA) copolymer, a biodegradable polymer produced by bacteria that can be digested by intracellular esterase enzymes. The comparison of magnetic heat performance of the 2D assemblies with 3D centro-symmetrical assemblies or single iron oxide nanocubes emphasize the benefit of the 2D assembly. On one hand, the heat losses of 2D assemblies dispersed in water are better than the 3D assemblies, but worse than for single nanocubes. On the other hand, when the bi-dimensional magnetic beads (2D-MNBs) are incubated with the esterase enzyme at a physiological temperature, their magnetic heat performances began to progressively increase. After 2 hours of incubation, specific absorption rate values of the 2D assembly double the ones of individually coated nanocubes. Such an increase can be mainly correlated to the splitting of the 2D-MNBs into smaller size clusters with a chain- like configuration containing few nanocubes. Moreover, 2D-MNBs exhibited non-variable-heat performances even after intentionally inducing their aggregation. Magnetophoresis measurements indicate a comparable response of 3D and 2D clusters to external magnets (0.3T) that is by far faster than that of single nanocubes. This feature is crucial for a physical accumulation of magnetic materials in the presence of magnetic field gradients. This system is the first example of a nanoplatform that, upon exposure to lytic enzymes, such as those present in a tumor environment, can be disassembled from the initial 2D-MNB organization to chain-like assemblies with clear improvement of the heat magnetic losses resulting in better heat dissipation performances. The potential application of 2D nano-assemblies based on the cleavable PHAs for preserving their magnetic losses inside cells will benefit hyperthermia therapies mediated by magnetic nanoparticles under alternating magnetic fields

Proceedings of Abstracts Engineering and Computer Science Research Conference 2019

© 2019 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Note: Keynote: Fluorescence visualisation to evaluate effectiveness of personal protective equipment for infection control is © 2019 Crown copyright and so is licensed under the Open Government Licence v3.0. Under this licence users are permitted to copy, publish, distribute and transmit the Information; adapt the Information; exploit the Information commercially and non-commercially for example, by combining it with other Information, or by including it in your own product or application. Where you do any of the above you must acknowledge the source of the Information in your product or application by including or linking to any attribution statement specified by the Information Provider(s) and, where possible, provide a link to this licence: http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/This book is the record of abstracts submitted and accepted for presentation at the Inaugural Engineering and Computer Science Research Conference held 17th April 2019 at the University of Hertfordshire, Hatfield, UK. This conference is a local event aiming at bringing together the research students, staff and eminent external guests to celebrate Engineering and Computer Science Research at the University of Hertfordshire. The ECS Research Conference aims to showcase the broad landscape of research taking place in the School of Engineering and Computer Science. The 2019 conference was articulated around three topical cross-disciplinary themes: Make and Preserve the Future; Connect the People and Cities; and Protect and Care

MESOSCALE ASSEMBLIES OF INORGANIC NANOPARTICLES FOR THERANOSTIC APPLICATIONS

During the three years of my Ph.D, Ph.D cycle XXXII (2016-2019), at the Fondazione Istituto Italiano di Tecnologia, under the supervision of Dr.Teresa Pellegrino and the co-supervision of Prof.Orietta Monticelli (University of Genova), my focus was mainly on developing colloidally stable nanoclusters assembled at well-defined geometries produced from benchmark iron oxide nanocubes. These nanoclusters were designed, exploited and characterized for their potential use in theranostic applications comprising their exploitation in Magnetic Hyperthermia, Magnetic Resonance Imaging (MRI) and Magnetic Nanoparticles Imaging. As the first aim, my focus was on building a two-dimensional nanoplatform based on highly efficient iron oxide nanocubes enwrapped with a bacteria extracted, biodegradable and biocompatible polyhydroxyalkanoate copolymer. Moreover, these magnetic polymeric clusters exhibit the unique feature to disassemble upon exposure to an intracellular rich lytic enzyme solution thus providing a gradual change in the cluster configuration accompanied by a gradual increase of magnetic heat performances in comparison to the initial 2D-clusters and to the individual iron oxide nanocubes used as building blocks for the cluster preparation. Indeed, comparing magnetic heat properties of the 2D assemblies with three dimensional centro-symmetrical assemblies (3D-MNBs) or single iron oxide nanocubes from same batch of cubes, emphasize how the initial 2D-assembly of iron oxide nanocubes s (2D-MNBs) dispersed in water are more advanced than the 3D-assemblies, but worse with respect to individual nanocubes. In addition, the heat abilities of these 2D clusters progressively increased when incubated in presence of esterase enzyme under physiological temperature, after 3 hours of incubation the specific absorption rate values, a measure of the heat-ability of the nanoparticles under a radio frequency were almost double than that of single cubes. Such an increase corresponds to disassembling of 2D-MNBs into short chain-like clusters of few nanocubes. Remarkably, our 2D-MNBs did not exhibit any variations in heat performance even after inducing an intentional aggregation. This is not the case for individual nanocubes. Magnetophoresis measurements suggest a faster response of 3D and 2D clusters to external magnets (0.3T) than that of individual nanocubes. This feature is desirable for the physical accumulation of magnetic materials under external magnetic field gradients. To the best of our knowledge, this is the first example of a nanoplatform, which combined enzymatic cleavable properties to a clear enhancement of the magnetic heat losses. In addition to this cluster study, I have also contributed to characterize other chain-like assemblies, named Dimer/Trimer obtained by assembling low interacting core-shell of wustite/magnetite iron oxide nanocubes into an amphiphilic copolymer, poly(styrene-co-maleic anhydride) cumene-terminated. Interestingly, by modulating the amount of polymer to nanoparticle surface ratio, the geometry of the same clusters could be modulated from a single structure to Dimer/Trimer to centrosymmetric structures. The short chains of nanocubes exhibit even in this case an enhanced specific absorption rate value with respect to single cubes and centrosymmetric clusters. Overall these studies reveal the significance of particle arrangement as a means to improve magnetic heating performances of the same building blocks, the nanocubes in our case. According to our second aim, the above nanoclusters (developed for magnetic hyperthermia mentioned) were investigated as magnetic tracers, to unveil their diagnostic features for, recently emerging magnetic nanoparticles imaging (MPI) and for Magnetic resonance imaging (MRI). The multimodal imaging models with combined MPI and MRI properties could assist in real-time mapping of tissues that expected to improve the diagnostic accuracy. We found that the 2D-MNBs based on high interacting Iron oxide nanocubes exhibit poor MPI signal than that of standard Resovist. However, this signal of 2D-MNBs underwent a progressive increase upon incubation with esterase enzyme under physiological temperature (almost doubled) starting from their initial state, which attributes to the splitting of 2D beads into a small chain-like configuration. These results show a similar trend to the enzymatic triggered increase in heat performance, as mentioned above. Moreover, the 2D-MNBs possess a remarkable transverse relaxation rate (r2), indicating an efficient negative contrast of 2D-MNBs as agents for MRI. This value reduced by half upon exposure to lytic enzyme providing a significant T2-signal change upon to a stimulus triggered change (the enzymatic degradation). On the other side, among the nanoclusters based on core-shell iron oxide nanocubes; single structure, Dimer/Trimer to centrosymmetric structures, Dimer/Trimer exhibit a very remarkable MPI signal in comparison to the nanocube assemblies and to the individual nanoparticles and with respect to Resovist the most accepted FDA approved standard. Complementing the signal dominance in short chains of 2D-MNBs, the increase of MPI signal in Dimer/Trimer can also corresponds to their short uniaxial configuration. In addition, they have given a very significant transverse relaxation rate (r2) than many other superparamagnetic iron oxide nanoparticles. This kind of nanovectors with multifunctional theranostic features of MRI, MPI and magnetic hyperthermia are beneficial to improve thermo-therapy treatment of cancerous tissues while offering at the same time a potential readable and changing signal for image mapping. Finally, as reported in chapter 3, we aim to develop an assembled nanoplatform made of magnetic iron oxide nanocube-based clusters and gadolinium-based nanoparticles that make the assembly responsive to the tumor microenvironment. This will enable to track tumor accumulation and disassembly of the nanoplatform for efficient thermotherapy based on T1 gadolinium-changing signal. For this purpose, we synthesize multicomponent nanostructures starting from iron oxide nanocubes embedded in a polymeric bead (MNBs) with a surface negative charge and decorated with Sodium gadolinium fluoride nanoparticles (NaGdF4 NPs), placed in between enzyme-degradable polymer spacers. Our hybrid structure achieved desired heating abilities under an alternative magnetic field of biological relevance. In addition to prominent T2 properties coming from MNBs, we demonstrated disassembling and detaching of polymer and NaGdF4 NPs from the surface of the MNBs upon exposure to enzymes that in turn improved water accessibility to NaGdF4 NP surface with a corresponding increase of T1 signal. In this way, we tracked the morphological changes of the systems at different time points of incubation in the presence of an enzyme, by MRI changing signal. This data was also confirmed by observing structural changes using TEM imaging. The integration of diagnostic tools to benchmark therapeutic probes could be a smart approach that enables to track the nanoparticle accumulation through artifact-free diagnosis and improve the heat efficiency of the magnetic hyperthermia treatment at the tumor

Earthquake-induced deformation structures in lake deposits: A Late Pleistocene to Holocene paleoseismic record for Central Switzerland

Zusammenfassung.: In den bis zu 15,000 Jahre alten Sedimenten von vier Seen in der Zentralschweiz wurden Spuren von drei starken historischen und mindestens sieben prähistorischen Erdbeben gefunden. Der Schweizer Erdbebenkatalog der letzten 1000 Jahre verzeichnet in der Zentralschweiz drei grössere Erdbeben mit Magnituden zwischen Mw=5.7 und Mw = 6.2 (1964 AD Alpnach, 1774 AD Altdorf, 1601 AD Unterwalden) sowie ein katastrophales Mw = 6.9 Ereignis in Basel im Jahre 1356 AD. Zur Bestimmung der Wiederkehrraten dieser starken Erdbeben wurden mit Hilfe von hochauflösender Seismik und Sedimentkernanalysen paläoseismische Untersuchungen in vier verschiedenen Seen in der Zentralschweiz durchgeführt (Lungerer See, Baldegger See, Seelisberg Seeli und Vierwaldstätter See). In Abhängigkeit von der Geometrie des Seebeckens, des Sedimenttyps und der lokalen Bodenerschütterung treten während eines Erdbebens grosse subaquatische Rutschungen oder kleine in-situ Deformationsstrukturen auf. Die Spuren der historischen Erdbeben zeigen, dass Seesedimente nur ab einer Magnitude von Mw>5.7 und bei einer lokalen Bodenerschütterung der Intensität ≥ VII deformiert werden. Mindestens sechs prähistorische Erdbeben in der Zentralschweiz (Epizentrum und Magnitude ähnlich wie beim Mw=6.2 Unterwalden Erdbeben), sowie ein starkes prähistorisches Erdbeben in der Baselregion (Magnitude ähnlich wie beim Mw = 6.9 Basel Erdbeben) konnten anhand der Art und regionalen Verteilung der Deformationsstrukturen bestimmt werden. Darüber hinaus gibt es Hinweise auf ein weiteres Ereignis in der Nähe von Basel und vier weitere Ereignisse in der Zentralschweiz. Im Vergleich zum Mittleren Holozän scheint die Erdbebenhäufigkeit in der Zentralschweiz erhöht während des Spätpleistozäns/Frühholozäns und während der letzten 4000 Jahre. Dies kann einerseits auf isostatische Ausgleichsbewegungen nach dem Abschmelzen des Eises vor 15,000 Jahren, sowie auf eine periodische Aktivierung einer alpinen seismogenen Zone in jüngerer Zeit zurückgeführt werde

Improving the assessment of seismic hazard in the North Sea

The following PhD thesis provides a comprehensive reassessment of probabilistic seismic hazard assessment (PSHA) in the North Sea. PSHA provides probabilistic representations of the expected ground-shaking at sites of interest, which can be used to assess the seismic risk for structures located at (or proximal to) said sites. In the North Sea, the seismic risk for offshore infrastructure including (1) oil and gas platforms and (2) wind turbine facilities must be considered. The seismic risk of this offshore infrastructure is important to consider because certain levels of seismic damage can result in negative impacts upon (1) the environmental health of the North Sea, (2) the personal health of employees on or near the considered infrastructure and (3) the economic health of governments and corporations which are reliant upon this infrastructure. The most recent publicly available North Sea PSHA was undertaken by Bungum et al. (2000). Two decades have passed since this study, since which substantial developments in PSHA have been made, and additional North Sea ground-motion data has been collected. Furthermore, the 2001 Ekofisk earthquake was the first hydrocarbon production induced earthquake in the North Sea to have been deemed of engineering significance for platforms in the region, but was not considered within the Bungum et al. (2000) study. In this investigation, North Sea PSHA is reassessed in several ways. Firstly, a pre-existing ground-motion prediction equation (GMPE) which performs well in the North Sea is identified as a base model for a North Sea GMPE using an additional 20 years of ground motion records available since the Bungum et al. (2000) study. This base model GMPE is then improved incrementally through the constrainment of North Sea path and site effects using novel techniques. Following the development of this North Sea GMPE, the seismogenic source model of Bungum et al. (2000) is updated using an additional two decades of North Sea earthquake observations. The impact of the North Sea GMPE and the updated source model are evaluated using (1) macroseismic earthquake observations and (2) assessment of the seismic risk of offshore infrastructure in the region. The updated PSHA formulation developed within this investigation results in moderate but significant differences in the seismic risk for offshore infrastructure in the North Sea. These seismic risk estimates are potentially more appropriate than those computed using the Bungum et al. (2000) PSHA formulation due to the additional ground-motion data and the PSHA advancements available since the Bungum et al. (2000) PSHA study. Ultimately, the improved seismic hazard estimates potentially help to better assess the structural health of offshore North Sea infrastructure, and subsequently minimise the likelihood of levels of seismic damage which could be detrimental to the North Sea environment or the personnel and/or economies operating within the region.The following PhD thesis provides a comprehensive reassessment of probabilistic seismic hazard assessment (PSHA) in the North Sea. PSHA provides probabilistic representations of the expected ground-shaking at sites of interest, which can be used to assess the seismic risk for structures located at (or proximal to) said sites. In the North Sea, the seismic risk for offshore infrastructure including (1) oil and gas platforms and (2) wind turbine facilities must be considered. The seismic risk of this offshore infrastructure is important to consider because certain levels of seismic damage can result in negative impacts upon (1) the environmental health of the North Sea, (2) the personal health of employees on or near the considered infrastructure and (3) the economic health of governments and corporations which are reliant upon this infrastructure. The most recent publicly available North Sea PSHA was undertaken by Bungum et al. (2000). Two decades have passed since this study, since which substantial developments in PSHA have been made, and additional North Sea ground-motion data has been collected. Furthermore, the 2001 Ekofisk earthquake was the first hydrocarbon production induced earthquake in the North Sea to have been deemed of engineering significance for platforms in the region, but was not considered within the Bungum et al. (2000) study. In this investigation, North Sea PSHA is reassessed in several ways. Firstly, a pre-existing ground-motion prediction equation (GMPE) which performs well in the North Sea is identified as a base model for a North Sea GMPE using an additional 20 years of ground motion records available since the Bungum et al. (2000) study. This base model GMPE is then improved incrementally through the constrainment of North Sea path and site effects using novel techniques. Following the development of this North Sea GMPE, the seismogenic source model of Bungum et al. (2000) is updated using an additional two decades of North Sea earthquake observations. The impact of the North Sea GMPE and the updated source model are evaluated using (1) macroseismic earthquake observations and (2) assessment of the seismic risk of offshore infrastructure in the region. The updated PSHA formulation developed within this investigation results in moderate but significant differences in the seismic risk for offshore infrastructure in the North Sea. These seismic risk estimates are potentially more appropriate than those computed using the Bungum et al. (2000) PSHA formulation due to the additional ground-motion data and the PSHA advancements available since the Bungum et al. (2000) PSHA study. Ultimately, the improved seismic hazard estimates potentially help to better assess the structural health of offshore North Sea infrastructure, and subsequently minimise the likelihood of levels of seismic damage which could be detrimental to the North Sea environment or the personnel and/or economies operating within the region