A 200-year Sulfate Record from 16 Antarctic Ice Cores and Associations with Southern Ocean Sea Ice Extent

Data from sixteen, 50m- to 115m-deep, sub-annually dated ice cores are used to examine the recent spatial and temporal concentration variability of sea salt (ss)S04 and excess (xs)S04 over West Antarctica for the last 200 years. The preservation of seasonal layers throughout the length of each record results in a dating accuracy of better than one year based on known global scale volcanic events. A dual transport source for West 9 9 Antarctic SSSO4 and XSSO4 is observed: lower tropospheric for areas below 1000m elevation and mid-upper tropospheric/stratospheric for areas located above 1000m. The XSSO4 records with volcanic peaks removed do not display any evidence of an anthropogenic impact on West Antarctic SO4 \u27 concentrations but do reveal that a major climate transition takes place over West Antarctica -1940. Global-scale volcanic eruptions appear as significant peaks in the robust spline residual XSSO4 records from sites located above 1000m elevation but do not appear in the residual records from sites located below 1000m. These high-resolution records show that the controls on ss- and XSSO42 deposition vary from site to site and can only be resolved using the type of framework of ice core records available from the International Trans-Antarctic Scientific Expedition (ITASE). Sources of SO42 from Ross Sea sea ice and Ross Sea Polyna primary production, combined with transport over the Ross Ice Shelf via frequent cyclogenesis, significantly increases the net transport of SSSO42 and XSSO42 aerosols to low elevation sites in western West Antarctica. Based on linear correlation analysis, ssS04 concentrations are higher when sea ice extent (SIE) is greater, and XSSO4 concentrations are higher when SIE is lesser. The South Pole receives the majority of its XSSO4 from different sources than the rest of West Antarctica, and the Weddell region may be a significant source of aerosol chemistry for eastern West Antarctic sites

College Student Development within the Context of Formalized Sport in American Higher Education

Those providing and managing sport in primary, secondary and post-secondary educational settings must be cognizant of the need for sport programs to enhance, rather than detract from, the educational environment. American post-secondary education provides an important context for inquiry in sport for two primary reasons. First, college enrollment marks a significant period of transition for individuals who are at a developmentally impressionable stage of their lives. Second, roughly 80% of all college students participate in some form of physical activity during their time on a college or university campus, with roughly half of them participating in formal sport. Two bodies of literature provide guidance for sport managers in US higher education: 1) sport development theory and 2) student development theory. This paper aims to provide a road map to facilitate the conversation between these two bodies of theory to unpack the potential contribution of sport to the individual development of sport participants at American colleges and universities. &nbsp

Niemann-Pick Type C Disease Reveals a Link between Lysosomal Cholesterol and PtdIns(4,5)P2 That Regulates Neuronal Excitability.

There is increasing evidence that the lysosome is involved in the pathogenesis of a variety of neurodegenerative disorders. Thus, mechanisms that link lysosome dysfunction to the disruption of neuronal homeostasis offer opportunities to understand the molecular underpinnings of neurodegeneration and potentially identify specific therapeutic targets. Here, using a monogenic neurodegenerative disorder, NPC1 disease, we demonstrate that reduced cholesterol efflux from lysosomes aberrantly modifies neuronal firing patterns. The molecular mechanism linking alterations in lysosomal cholesterol egress to intrinsic tuning of neuronal excitability is a transcriptionally mediated upregulation of the ABCA1 transporter, whose PtdIns(4,5)P2-floppase activity decreases plasma membrane PtdIns(4,5)P2. The consequence of reduced PtdIns(4,5)P2 is a parallel decrease in a key regulator of neuronal excitability, the voltage-gated KCNQ2/3 potassium channel, which leads to hyperexcitability in NPC1 disease neurons. Thus, cholesterol efflux from lysosomes regulates PtdIns(4,5)P2 to shape the electrical and functional identity of the plasma membrane of neurons in health and disease

An emerging technique: multi-ice-core multi-parameter correlations with Antarctic sea-ice extent

ABSTRACT. Using results stemming from the International Trans-Antarctic Scientific Expedition (ITASE) ice-core array plus data from ice cores from the South Pole and Siple Dome we investigate the use of sodium (Na+), non-sea-salt sulfate (nssSO4 2–) and methylsulfonate (MS–) as proxies for Antarctic sea-ice extent (SIE). Maximum and mean annual chemistry concentrations for these three species correlate significantly with maximum, mean and minimum annual SIE, offering more information and clarification than single ice-core and single species approaches. Significant correlations greater than 90% exist between Na+ and maximum SIE; nssSO4 2– with minimum and mean SIE; and MS– with mean SIE. Correlations with SIE within large geographic regions are in the same direction for all ice-core sites for Na+ and nssSO4 2– but not MS–. All ice cores display an SIE correlation with nssSO4 2– and MS–, but not all correlate with Na+. This multi-core multi-parameter study provides the initial step in determining which chemical species can be used reliably and in which regions as a building block for embedding other ice-core records. Once established, the resulting temporal and spatial matrix can be used to relate ice extents, atmospheric patterns, biological productivity and site conditions

Curvature formula for the space of 2-d conformal field theories

We derive a formula for the curvature tensor of the natural Riemannian metric on the space of two-dimensional conformal field theories and also a formula for the curvature tensor of the space of boundary conformal field theories.Comment: 36 pages, 1 figure; v2 references adde

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents

Comparison of PBO solvers in a dependency solving domain

Linux package managers have to deal with dependencies and conflicts of packages required to be installed by the user. As an NP-complete problem, this is a hard task to solve. In this context, several approaches have been pursued. Apt-pbo is a package manager based on the apt project that encodes the dependency solving problem as a pseudo-Boolean optimization (PBO) problem. This paper compares different PBO solvers and their effectiveness on solving the dependency solving problem.Comment: In Proceedings LoCoCo 2010, arXiv:1007.083

Uptake, effectiveness and safety of COVID-19 vaccines in individuals at clinical risk due to immunosuppressive drug therapy or transplantation procedures: a population-based cohort study in England

: Background: Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understand and address the unique challenges faced by immunocompromised individuals in the context of COVID-19 vaccination. Methods: We analysed data from 12,274,946 people in the UK aged > 12 years from 01/12/2020 to 11/04/2022. Of these, 583,541 (4.8%) were immunocompromised due to immunosuppressive drugs, organ transplants, dialysis or chemotherapy. We undertook a cohort analysis to determine COVID-19 vaccine uptake, nested case–control analyses adjusted for comorbidities and sociodemographic characteristics to determine effectiveness of vaccination against COVID-19 hospitalisation, ICU admission and death, and a self-controlled case series assessing vaccine safety for pre-specified adverse events of interest. Results: Overall, 93.7% of immunocompromised individuals received at least one COVID-19 vaccine dose, with 80.4% having received three or more doses. Uptake reduced with increasing deprivation (hazard ratio [HR] 0.78 [95%CI 0.77–0.79] in the most deprived quintile compared to the least deprived quintile for the first dose). Estimated vaccine effectiveness against COVID-19 hospitalisation 2–6 weeks after the second and third doses compared to unvaccinated was 78% (95%CI 72–83) and 91% (95%CI 88–93) in the immunocompromised population, versus 85% (95%CI 83–86) and 86% (95%CI 85–89), respectively, for the general population. Results showed COVID-19 vaccines were protective against intensive care unit (ICU) admission and death in both populations, with effectiveness of over 92% against COVID-19-related death and up to 95% in reducing ICU admissions for both populations following the third dose. COVID-19 vaccines were generally safe for immunocompromised individuals, though specific doses of ChAdOx1, mRNA-1273 and BNT162b2 raised risks of specific cardiovascular/neurological conditions. Conclusions: COVID-19 vaccine uptake is high in immunocompromised individuals on immunosuppressive drug therapy or who have undergone transplantation procedures, with documented disparities by deprivation. Findings suggest that COVID-19 vaccines are protective against severe COVID-19 outcomes in this vulnerable population, and show a similar safety profile in immunocompromised individuals and the general population, despite some increased risk of adverse events. These results underscore the importance of ongoing vaccination prioritisation for this clinically at-risk population to maximise protection against severe COVID-19 outcomes