Semidualizing Modules over Numerical Semigroup Rings

A semidualizing module is a generalization of Grothendieck's dualizing module. For a local Cohen-Macaulay ring $R$, the ring itself and its canonical module are always realized as (trivial) semidualizing modules. Reasonably, one might ponder the question; when do nontrivial examples exist? In this paper, we study this question in the realm of numerical semigroup rings and completely classify which of these rings with multiplicity at most 9 possess a nontrivial semidualizing module. Using this classification, we construct numerical semigroup rings in any multiplicity at least 9 possesses a nontrivial semidualizing module.Comment: 22 pages, comments welcom

Normalized Affymetrix expression data are biased by G-quadruplex formation

Probes with runs of four or more guanines (G-stacks) in their sequences can exhibit a level of hybridization that is unrelated to the expression levels of the mRNA that they are intended to measure. This is most likely caused by the formation of G-quadruplexes, where inter-probe guanines form Hoogsteen hydrogen bonds, which probes with G-stacks are capable of forming. We demonstrate that for a specific microarray data set using the Human HG-U133A Affymetrix GeneChip and RMA normalization there is significant bias in the expression levels, the fold change and the correlations between expression levels. These effects grow more pronounced as the number of G-stack probes in a probe set increases. Approximately 14 of the probe sets are directly affected. The analysis was repeated for a number of other normalization pipelines and two, FARMS and PLIER, minimized the bias to some extent. We estimate that ∼15 of the data sets deposited in the GEO database are susceptible to the effect. The inclusion of G-stack probes in the affected data sets can bias key parameters used in the selection and clustering of genes. The elimination of these probes from any analysis in such affected data sets outweighs the increase of noise in the signal. © 2011 The Author(s)

Functional antibody responses targeting the Spike protein of SARS-CoV-2 Omicron XBB.1.5 in elderly nursing home residents following Wuhan-Hu-1-based mRNA booster vaccination

The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.Ángela Sánchez-Simarro has a contract funded by the Carlos III Health Institute (PFIS Contract; FI22/00338). Eliseo Albert holds a contract funded by the Carlos III Health Institute (co-financed by the European Regional Development Fund, ERDF/FEDER): Juan Rodés Contract; JR20/00011. Brayan Grau is supported by a Juan de la Cierva postdoctoral fellowship (FJC2021-046453-I). This study was supported by the Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) granted to David Navarro, by the Spanish National Research Council (CSIC, project numbers 202020E079 and CSIC-COVID19-028), and a grant from the Spanish Ministry of Science and Innovation [(MCIU/AEI/FEDER, EU): PID2020-115506RB-I00 (HTR)]. The CNB also acknowledges financial support from the Spanish State Research Agency, AEI/https://doi.org/10.13039/501100011033, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2013-0347, SEV-2017-0712). D. Fernández Soto is a recipient of a fellowship (PRE2018-083200) from the Spanish Ministry of Science and Innovation and is a graduate student in the Molecular Biosciences doctoral program of the Autonomous University of Madrid. This research work was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through the CSIC's Global Health Platform (PTI Salud Global) to Ron Geller and Hugh Reyburn. The funders had no role in study design, data collection and interpretation, or in the decision to submit the work for publication.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The National Early Warning Score and its subcomponents recorded within ±24 hours of emergency medical admission are poor predictors of hospital-acquired acute kidney injury

YesBackground: Hospital-acquired Acute Kidney Injury (H-AKI) is a common cause of avoidable morbidity and mortality. Aim: To determine if the patients’ vital signs data as defined by a National Early Warning Score (NEWS), can predict H-AKI following emergency admission to hospital. Methods: Analyses of emergency admissions to York hospital over 24-months with NEWS data. We report the area under the curve (AUC) for logistic regression models that used the index NEWS (model A0), plus age and sex (A1), plus subcomponents of NEWS (A2) and two-way interactions (A3). Likewise for maximum NEWS (models B0,B1,B2,B3). Results: 4.05% (1361/33608) of emergency admissions had H-AKI. Models using the index NEWS had the lower AUCs (0.59 to 0.68) than models using the maximum NEWS AUCs (0.75 to 0.77). The maximum NEWS model (B3) was more sensitivity than the index NEWS model (A0) (67.60% vs 19.84%) but identified twice as many cases as being at risk of H-AKI (9581 vs 4099) at a NEWS of 5. Conclusions: The index NEWS is a poor predictor of H-AKI. The maximum NEWS is a better predictor but seems unfeasible because it is only knowable in retrospect and is associated with a substantial increase in workload albeit with improved sensitivity.The Health Foundatio

Minimal Differential Graded Resolutions of Fiber Products

This dissertation is the culmination of my work in [16-18]. These papers add to a body of work focused on rings known as fiber products. A ring $F$ is said to be a fiber product if there exist ring homomorphisms $S \xrightarrow{\pi_S} W \xleftarrow{\pi_T} T$ and we have $F \cong S \times_W T := \{(s,t) \in S \times T: \pi_S(s) = \pi_T(t)\}$. In this set-up, we say that $F$ is the fiber product of $S$ and $T$ over $W$. For our purpose we only consider rings that are commutative, noetherian rings with identity. We further consider the case where $R$ is a regular local (or standard graded polynomial) ring and study fiber products that can be realized as homomorphic images of $R$. To this end, we study quotients $R/\langle \mathcal{I}\u27, \mathcal{I} \mathcal{J}, \mathcal{J}\u27 \rangle$ where $\mathcal{I}\u27$, $\mathcal{I}$, $\mathcal{J}\u27$, and $\mathcal{J}$ are ideals in $R$. In Chapter 3 we impose conditions as these ideals that allow us to realize these quotients as fiber products (see Proposition 3.2.1). We then explicitly construct a minimal resolution of the quotient over $R$. From this, we recover formulas for the Betti numbers of the quotient as well as the Poincar\\u27e series. We further establish sufficient conditions on the four ideals above to impose a differential graded structure on our minimal resolution. In Chapter 4, we address the case $\mathcal{I}\u27 = 0 = \mathcal{J}\u27$ and obtain a minimal differential graded algebra resolution. We then use the techniques of [2,27] to establish further homological properties of the fiber product. In particular, we show that these fiber products are Golod and are Tor-friendly. In Chapter 5, we allow for $\mathcal{I}\u27 \neq 0$ but maintain $\mathcal{J}\u27 = 0$. We obtain minimal differential graded modules and then establish sufficient conditions on $\mathcal{I}\u27$ to extend the module structure to that of an algeba. We again apply techniques from [2,27] to obtain the Golod and Tor-friendly properties for this larger class of fiber products