Small bound for birational automorphism groups of algebraic varieties (with an Appendix by Yujiro Kawamata)

We give an effective upper bound of |Bir(X)| for the birational automorphism group of an irregular n-fold (with n = 3) of general type in terms of the volume V = V(X) under an ''albanese smoothness and simplicity'' condition. To be precise, |Bir(X)| < d_3 V^{10}. An optimum linear bound |Bir(X)|-1 < (1/3)(42)^3 V is obtained for those 3-folds with non-maximal albanese dimension. For all n > 2, a bound |Bir(X)| < d_n V^{10} is obtained when alb_X is generically finite, alb(X) is smooth and Alb(X) is simple.Comment: Mathematische Annalen, to appea

Methodological approaches to determining the marine radiocarbon reservoir effect

The marine radiocarbon reservoir effect is an offset in 14C age between contemporaneous organisms from the terrestrial environment and organisms that derive their carbon from the marine environment. Quantification of this effect is of crucial importance for correct calibration of the &lt;sup&gt;14&lt;/sup&gt;C ages of marine-influenced samples to the calendrical timescale. This is fundamental to the construction of archaeological and palaeoenvironmental chronologies when such samples are employed in &lt;sup&gt;14&lt;/sup&gt;C analysis. Quantitative measurements of temporal variations in regional marine reservoir ages also have the potential to be used as a measure of process changes within Earth surface systems, due to their link with climatic and oceanic changes. The various approaches to quantification of the marine radiocarbon reservoir effect are assessed, focusing particularly on the North Atlantic Ocean. Currently, the global average marine reservoir age of surface waters, R(t), is c. 400 radiocarbon years; however, regional values deviate from this as a function of climate and oceanic circulation systems. These local deviations from R(t) are expressed as +R values. Hence, polar waters exhibit greater reservoir ages (&#948;R = c. +400 to +800 &lt;sup&gt;14&lt;/sup&gt;C y) than equatorial waters (&#948;R = c. 0 &lt;sup&gt;14&lt;/sup&gt;C y). Observed temporal variations in &#948;R appear to reflect climatic and oceanographic changes. We assess three approaches to quantification of marine reservoir effects using known age samples (from museum collections), tephra isochrones (present onshore/offshore) and paired marine/terrestrial samples (from the same context in, for example, archaeological sites). The strengths and limitations of these approaches are evaluated using examples from the North Atlantic region. It is proposed that, with a suitable protocol, accelerator mass spectrometry (AMS) measurements on paired, short-lived, single entity marine and terrestrial samples from archaeological deposits is the most promising approach to constraining changes over at least the last 5 ky BP

Children with familial hypercholesterolemia display changes in LDL and HDL function : A cross-sectional study

Publisher Copyright: © 2021 The Association for the Publication of the Journal of Internal Medicine.Background: The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma low-density lipoprotein (LDL) particles to aggregate and the ability of igh-density lipoprotein (HDL) particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations. Hypothesis: We hypothesized that FH children had disrupted lipoprotein functions. Methods: We analyzed LDL aggregation susceptibility and HDL-apoA-I exchange (HAE), and activity of four proteins that regulate lipoprotein metabolism (cholesteryl ester transfer protein, lecithin–cholesterol acyltransferase, phospholipid transfer protein, and paraoxonase-1) in plasma samples derived from children with FH (n = 47) and from normocholesterolemic children (n = 56). Variation in lipoprotein functions was further explored using an nuclear magnetic resonance-based metabolomics profiling approach. Results: LDL aggregation was higher, and HAE was lower in FH children than in normocholesterolemic children. LDL aggregation associated positively with LDL cholesterol (LDL-C) and negatively with triglycerides, and HAE/apoA-I associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was opposite of that of HAE/apoA-I. Conclusions: FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL add further understanding of the risk for atherosclerotic cardiovascular disease in FH children.Peer reviewe

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition

Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases

Simulation Modelling in Ophthalmology : Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom

Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Existence of Kähler–Einstein metrics and multiplier ideal sheaves on del Pezzo surfaces

We apply Nadel’s method of multiplier ideal sheaves to show that every complex del Pezzo surface of degree at most six whose automorphism group acts without fixed points has a Kähler–Einstein metric. In particular, all del Pezzo surfaces of degree 4, 5, or 6 and certain special del Pezzo surfaces of lower degree are shown to have a Kähler–Einstein metric. These existence statements are not new, but the proofs given in the present paper are less involved than earlier ones by Siu, Tian and Tian–Yau