32151 research outputs found
Sort by
Experimental analysis to quantify inactivation of microorganisms by Far-UVC irradiation in indoor environments
Funding: The research in this study was supported by NHS Scotland Assure grant reference 21–0001.Far-UVC irradiation at a 222 nm wavelength is a promising technology for inactivating microorganisms in indoor environments to mitigate transmission of infection. Here we report experimental measurements in a room-scale chamber to evaluate the performance of filtered Krypton-Chloride (KrCl) lamps in reducing the steady-state concentration of Staphylococcus aureus and Pseudomonas aeruginosa under different ventilation rates in indoor environments. The results showed a mean 95.5 % lowering of S. aureus load and 94.9 % of P. aeruginosa load at 3 air changes per hour (ACH) using one Far-UVC lamp and 97.8 % and >97.5 % using five lamps. At 1.5 ACH, the mean microbial reduction for S. aureus was >94.6 % and >99.5 % and at 9 ACH, it was 66.3 % and 91.9 % for 1 lamp and 5 lamps, respectively. Initial results at a shorter distance between the microbial source and collection sampling show a reduced but still substantial effect of the Far-UVC. The findings indicate that within these experimental conditions, Far-UVC can be effective at room-scale inactivation of a range of pathogens in a range of ventilation scenarios and also show promise at short-range inactivation. This research paves the way for future work to explore efficacy in real-world scenarios and to quantify usability and acceptability.Peer reviewe
Distinct mitochondrial remodeling during mesoderm differentiation in a human-based stem cell model
Funding: This work was supported by grants from The Research Council of Norway (NFR, Project No. 229652), Bergen Stem Cell Consortium (BSCC), Haukeland University Hospital, University of Bergen, and the Rakel og Otto-Kristian Bruun’s Legat. This work was also supported by the Research Council of Norway through its Centre of 248 Excellence Scheme (Project No. 262613).Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental role in maintaining pluripotency and stem cell fate. It has been suggested that the metabolic “switch” from glycolysis to OXPHOS is germ layer-specific as glycolysis remains active during early ectoderm commitment but is downregulated during the transition to mesoderm and endoderm lineages. How mitochondria adapt during these metabolic changes and whether mitochondria remodeling is tissue specific remain unclear. Here, we address the question of mitochondrial adaptation by examining the differentiation of human pluripotent stem cells to cardiac progenitors and further to differentiated mesodermal derivatives, including functional cardiomyocytes. In contrast to recent findings in neuronal differentiation, we found that mitochondrial content decreases continuously during mesoderm differentiation, despite increased mitochondrial activity and higher levels of ATP-linked respiration. Thus, our work highlights similarities in mitochondrial remodeling during the transition from pluripotent to multipotent state in ectodermal and mesodermal lineages, while at the same time demonstrating cell-lineage-specific adaptations upon further differentiation. Our results improve the understanding of how mitochondrial remodeling and the metabolism interact during mesoderm differentiation and show that it is erroneous to assume that increased OXPHOS activity during differentiation requires a simultaneous expansion of mitochondrial content.Peer reviewe
The horses of the Commune : the assignatio equorum between institutional administration and hippiatric knowledge in late 13th century Perugia
This dissertation aims to investigate, through an interdisciplinary approach that combines written documents, literary works, and visual evidence, the role of horses in the society of Communal Italy, specifically focusing on Perugia in the second half of the 13th century. The research draws from a wide range of registers produced by the Commune of Perugia's chancery, with the core primary sources being the so-called «assignatio» registers, census lists of horses used for communal tasks and necessities. These documents offer fresh insights into the daily functioning of an understudied administrative system, called Impositio Equorum, which is only partially described in the city's Statutes and for which little evidence survives today.
The aim of this study is to understand and re-frame animals that have existed historically, instead of “culturally mediated” ones, which have dominated historiography to date, and are rather symbols and man-made products within human culture. In the complex socio-political landscape of a 13th century Commune, the horse emerges as a multi-dimensional figure, serving various roles: military mount, means of transport and communication, labour resource, economic asset, and a powerful symbol of status and representation.
This research clarifies and enriches our understanding of the horse's significance in late medieval society. It not only reinterprets familiar aspects with greater clarity but also opens new and unexpected avenues of inquiry, such as that of the hippiatric-veterinary dimension. In this regard, the multifaceted figures of the marescalchi (equine veterinarians), particularly within the unique institutional framework provided by the Commune of Perugia, shed light on a profession of considerable cultural importance, yet one that remains largely understudied today.
Ultimately, this study confirms the socio-cultural significance of horses, their indirect yet pivotal role in stimulating scientific and cultural production, and their profound agency in human events – an influence that it is finally time for History to recognize
The Viking paradigm in early medieval history
In this short note I query not so much the use of the word ‘vikings’ or the fraught question of whether it should be capitalised, but rather whether ‘the Vikings’ is a useful concept that helps us understand history, or whether it creates an inaccurate essentialist category for which there is no historical evidence. The piece argues for more nuance and specificity when dealing with Scandinavia and the Scandinavian diaspora in our period, and argues that the variety of phenomena across times and space warrants more serious consideration. The time has come to ditch this twentieth-century concept and to return to the sources.Peer reviewe
The tidal deformation and atmosphere of WASP-12b from its phase curve
Funding: LCa and CHe acknowledge support from the European Union H2020-MSCA-ITN-2019 under Grant Agreement no. 860470 (CHAMELEON). ACCa and TWi acknowledge support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant number ST/R003203/1. PM acknowledges support from STFC research grant number ST/M001040/1. NAW acknowledges UKSA grant ST/R004838/1.Context. Ultra-hot Jupiters present a unique opportunity to understand the physics and chemistry of planets, their atmospheres, and interiors at extreme conditions. WASP-12 b stands out as an archetype of this class of exoplanets, with a close-in orbit around its star that results in intense stellar irradiation and tidal effects. Aims. The goals are to measure the planet’s tidal deformation, atmospheric properties, and also to refine its orbital decay rate. Methods. We performed comprehensive analyses of the transits, occultations, and phase curves of WASP-12b by combining new CHEOPS observations with previous TESS and Spitzer data. The planet was modeled as a triaxial ellipsoid parameterized by the second-order fluid Love number of the planet, h2, which quantifies its radial deformation and provides insight into the interior structure. Results. We measured the tidal deformation of WASP-12b and estimated a Love number of h2 = 1.55−0.49+0.45 (at 3.2σ) from its phase curve. We measured occultation depths of 333 ± 24 ppm and 493 ± 29 ppm in the CHEOPS and TESS bands, respectively, while the nightside fluxes are consistent with zero, and also marginal eastward phase offsets. Our modeling of the dayside emission spectrum indicates that CHEOPS and TESS probe similar pressure levels in the atmosphere at a temperature of ~2900 K. We also estimated low geometric albedos of Ag = 0.086 ± 0.017 and Ag = 0.01 ± 0.023 in the CHEOPS and TESS passbands, respectively, suggesting the absence of reflective clouds in the high-temperature dayside of the planet. The CHEOPS occultations do not show strong evidence for variability in the dayside atmosphere of the planet at the median occultation depth precision of 120 ppm attained. Finally, combining the new CHEOPS timings with previous measurements refines the precision of the orbital decay rate by 12% to a value of −30.23 ± 0.82 ms yr−1, resulting in a modified stellar tidal quality factor of Q′★ = 1.70 ± 0.14 × 105. Conclusions. WASP-12 b becomes the second exoplanet, after WASP-103b, for which the Love number has been measured from the effect of tidal deformation in the light curve. However, constraining the core mass fraction of the planet requires measuring h2 with a higher precision. This can be achieved with high signal-to-noise observations with JWST since the phase curve amplitude, and consequently the induced tidal deformation effect, is higher in the infrared.Peer reviewe
The 1831 CE mystery eruption identified as Zavaritskii caldera, Simushir Island (Kurils)
Funding: W. Hutchison is funded by a UKRI Future Leaders Fellowship (MR/S033505/1). A. Burke is funded by a Philip Leverhulme prize in Earth Sciences (PLP-2021-167) from the Leverhulme Trust. P. Abbott and M. Sigl received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 820047). S. Davies acknowledges support from a Royal Society Leverhulme Trust Senior Fellowship. The St Andrews EPMA was supported by the EPSRC Light Element Analysis Facility Grant EP/T019298/1 and the EPSRC Strategic Equipment Resource Grant EP/R023751/1.Polar ice cores and historical records evidence a large-magnitude volcanic eruption in 1831 CE. This event was estimated to have injected ~13 Tg of sulfur (S) into the stratosphere which produced various atmospheric optical phenomena and led to Northern Hemisphere climate cooling of ~1 °C. The source of this volcanic event remains enigmatic, though one hypothesis has linked it to a modest phreatomagmatic eruption of Ferdinandea in the Strait of Sicily, which may have emitted additional S through magma–crust interactions with evaporite rocks. Here, we undertake a high-resolution multiproxy geochemical analysis of ice-core archives spanning the 1831 CE volcanic event. S isotopes confirm a major Northern Hemisphere stratospheric eruption but, importantly, rule out significant contributions from external evaporite S. In multiple ice cores, we identify cryptotephra layers of low K andesite-dacite glass shards occurring in summer 1831 CE and immediately prior to the stratospheric S fallout. This tephra matches the chemistry of the youngest Plinian eruption of Zavaritskii, a remote nested caldera on Simushir Island (Kurils). Radiocarbon ages confirm a recent (<300 y) eruption of Zavaritskii, and erupted volume estimates are consistent with a magnitude 5 to 6 event. The reconstructed radiative forcing of Zavaritskii (−2 ± 1 W m−2) is comparable to the 1991 CE Pinatubo eruption and can readily account for the climate cooling in 1831–1833 CE. These data provide compelling evidence that Zavaritskii was the source of the 1831 CE mystery eruption and solve a confounding case of multiple closely spaced observed and unobserved volcanic eruptions.Peer reviewe
Serosurvey for Japanese encephalitis virus antibodies following an outbreak in an immunologically naïve population, Victoria, 2022 : a cross-sectional study
Objectives: To investigate the distribution and prevalence of Japanese encephalitis virus (JEV) antibody (as evidence of past infection) in northern Victoria following the 2022 Japanese encephalitis outbreak, seeking to identify groups of people at particular risk of infection; to investigate the distribution and prevalence of antibodies to two related flaviviruses, Murray Valley encephalitis virus (MVEV) and West Nile virus Kunjin subtype (KUNV). Study design: Cross-sectional serosurvey (part of a national JEV serosurveillance program). Setting: Three northern Victorian local public health units (Ovens Murray, Goulburn Valley, Loddon Mallee), 8 August - 1 December 2022. Participants: People opportunistically recruited at pathology collection centres and by targeted recruitment through community outreach and advertisements. People vaccinated against or who had been diagnosed with Japanese encephalitis were ineligible for participation, as were those born in countries where JEV is endemic. Main outcome measures: Seroprevalence of JEV IgG antibody, overall and by selected factors of interest (occupations, water body exposure, recreational activities and locations, exposure to animals, protective measures). Results: 813 participants were recruited (median age, 59 years [interquartile range, 42-69 years]; 496 female [61%]); 27 were JEV IgG-seropositive (3.3%; 95% confidence interval [CI], 2.2-4.8%) (median age, 73 years [interquartile range, 63-78 years]; 13 female [48%]); none were IgM-seropositive. JEV IgG-seropositive participants were identified at all recruitment locations, including those without identified cases of Japanese encephalitis. The only risk factors associated with JEV IgG-seropositivity were age (per year: prevalence odds ratio [POR], 1.07; 95% CI, 1.03-1.10) and exposure to feral pigs (POR, 21; 95% CI, 1.7-190). The seroprevalence of antibody to MVEV was 3.0% (95% CI, 1.9-4.5%; 23 of 760 participants), and of KUNV antibody 3.3% (95% CI, 2.1-4.8%; 25 of 761). Conclusions: People living in northern Victoria are vulnerable to future JEV infection, but few risk factors are consistently associated with infection. Additional prevention strategies, including expanding vaccine eligibility, may be required to protect people in this region from Japanese encephalitis.Peer reviewe
Prevalence of cefixime-resistant Neisseria gonorrhoeae in Melbourne, Australia, 2021-2022
Funding: This work was supported by an National Health and Medical Research Council Emerging Leadership Investigator Grant (GNT1172873 to E. P. F. C. and GNT1174555 to D. A. W.); and an National Health and Medical Research Council Leadership Investigator.While ceftriaxone remains the first-line treatment for gonorrhea, the US Centers for Disease Control and Prevention recommended cefixime as a second-line treatment in 2021. We tested 1176 Neisseria gonorrhoeae isolates among clients attending the Melbourne Sexual Health Centre in 2021 and 2022. The prevalence of cefixime resistance was 6.3% (74/1176), azithromycin resistance was 4.9% (58/1176), and ceftriaxone resistance was 0% (0/1176). Cefixime resistance was highest among women (16.4%, 10/61), followed by men who have sex with women (6.4%, 7/109) and men who have sex with men (5.8%, 57/982). The prevalence of cefixime-resistant N gonorrhoeae exceeds the threshold of the 5% resistance level recommended by the World Health Organization; thus, cefixime treatment would have limited benefits in Australia.Peer reviewe
Specimens of settler colonialism : collecting and displaying natural history at the University of St Andrews, 1838-1917
This thesis investigates the history of the natural science collection of the University of St Andrews to examine the relationship between natural history and empire during the nineteenth and early twentieth centuries. Focusing on the foundation of the collection, during the years of the Literary and Philosophical Society of St Andrews (1838-1917), this thesis analyses the acquisition and movement of human and non-human remains from colonial Australia and Aotearoa New Zealand to the imperial rhetoric of display and education in Scotland. Natural science collections can provide insights into how the natural world was interwoven with imperial ideologies and the settler-colonial processes of violence, displacement, dispossession, and assimilation that irreparably harmed Indigenous communities. In recovering the histories of extant and non-extant objects, this examination highlights the contributions and experiences of naturalists, settlers, and Indigenous peoples in the history of science. By centring Indigenous agency, survival, and autonomy within moments of cross-cultural exchange, this thesis argues that collections have the potential to reconstruct invisible Indigenous histories that continue to be absent from museum displays.
Employing a critical lens to the methodological approach of ‘object biographies’, this study illustrates the advantages and limitations of recovering Indigenous and colonial histories through objects and archival sources. Divided into two, the first part of this thesis examines the practices of naturalists in nineteenth-century colonial Australia, charting their reliance upon systems of power, colonial infrastructures, and the labour and knowledge of Aboriginal Australian peoples. The second part of this thesis explores the ‘afterlives’ of objects, both human and non-human remains, once they entered the museums at St Andrews, examining their changing roles in displays, scientific theories, and university education. This thesis provokes future discussions about the imperial and colonial legacies within university collections and offers new approaches for museum professionals and historians to examine natural science collections."This PhD project has been supported through the United College Scholarship awarded by the Museums of University of St Andrews and the School of History from 1 September 2020 to 31 March 2024. The research undertaken for this thesis was also supported by the Research Mobility award given by the St Leonard’s Postgraduate College and Banco Santander SA for 2021-22, as well as the British Society of the History of Science research grant awarded in 2022."--Fundin
CRB2 depletion induces YAP signaling and disrupts mechanosensing in podocytes
Funding: Alexander von Humboldt Foundation: Humboldt Professorship (to MCG); European Research Council (ERC) under the European Union's Horizon Europe research and innovation program: CELL-FORCE, Grant Agreement No. 101113162 (to MCG); Duke Claude D. Pepper Older Americans Independence Center Pilot Award (G.H.) and NIH/NIDDK - K08DK111940 (G.H.).Focal segmental glomerulosclerosis (FSGS) is a histologic lesion caused by a variety of injurious stimuli that lead to dysfunction/loss of glomerular visceral epithelial cells (i.e., podocytes). Pathogenic mutations in crumbs homolog-2 (CRB2), encoding the type 1 transmembrane protein crumbs homolog-2, have been shown to cause early-onset corticosteroid-resistant nephrotic syndrome (SRNS)/FSGS. Here, we identified a two-generation Indian kindred (DUK40595) with biopsy-proven SRNS/FSGS caused by a compound heterozygous mutation in CRB2 comprised of the previously described truncating mutation p.Gly1036_Alafs*43 and a rare 9-bp deletion mutation p.Leu1074_Asp1076del. Because compound heterozygous mutations involving the truncating p.Gly1036_Alafs*43 variant have been associated with reduced CRB2 expression in podocytes and autosomal recessive SRNS/FSGS, we sought to define the pathogenic effects of CRB2 deficiency in podocytes. We show that CRB2 knockdown induces yes-associated protein (YAP) activity and target gene expression in podocytes. It upregulates YAP-mediated mechanosignaling and increases the density of focal adhesion and F-actin. Using elastic resonator interference stress microscopy (ERISM), we demonstrate that CRB2 knockdown also enhances podocyte contractility in a substrate stiffness-dependent manner. The knockdown effect decreases with increasing substrate stiffness, indicating impaired mechanosensing in CRB2 knockdown cells at low substrate stiffness. Although the mechanical activation of CRB2 knockdown cells is associated with increased YAP activity, the enhanced cell contractility is not significantly reduced by the selective YAP inhibitors K-975 and verteporfin, suggesting that multiple pathways may be involved in mechanosignaling downstream of CRB2. Taken together, these studies provide the first evidence that CRB2 deficiency may impair podocyte mechanotransduction via disruption of YAP signaling in podocytes.Peer reviewe