Identification of a widespread Kamchatkan tephra: A middle Pleistocene tie-point between Arctic and Pacific paleoclimatic records

Very few age controls exist for Quaternary deposits over the vast territory of the East Russian Arctic, which hampers dating of major environmental changes in this area and prevents their correlation to climatic changes in the Arctic and Pacific marine domains. We report a newly identified ~177 ka old Rauchua tephra, which has been dispersed over an area of >1,500,000 km2 and directly links terrestrial paleoenvironmental archives from Arctic Siberia with marine cores in the northwest Pacific, thus permitting their synchronization and dating. The Rauchua tephra can help to identify deposits formed in terrestrial and marine environments during the oxygen isotope stage 6.5 warming event. Chemical composition of volcanic glass from the Rauchua tephra points to its island-arc origin, while its spatial distribution singles out the Kamchatka volcanic arc as a source. The Rauchua tephra represents a previously unknown, large (magnitude >6.5) explosive eruption from the Kamchatka volcanic arc

Early Holocene M~6 explosive eruption from Plosky volcanic massif (Kamchatka) and its tephra as a link between terrestrial and marine paleoenvironmental records

We report tephrochronological and geochemical data on early Holocene activity from Plosky volcanic massif in the Kliuchevskoi volcanic group, Kamchatka Peninsula. Explosive activity of this volcano lasted for ~1.5 kyr, produced a series of widely dispersed tephra layers, and was followed by profuse low-viscosity lava flows. This eruptive episode started a major reorganization of the volcanic structures in the western part of the Kliuchevskoi volcanic group. An explosive eruption from Plosky (M~6), previously unstudied, produced tephra (coded PL2) of a volume of 10–12 km3 (11–13 Gt), being one of the largest Holocene explosive eruptions in Kamchatka. Characteristic diagnostic features of the PL2 tephra are predominantly vitric sponge-shaped fragments with rare phenocrysts and microlites of plagioclase, olivine and pyroxenes, medium- to high-K basaltic andesitic bulk composition, high-K, high-Al and high-P trachyandesitic glass composition with SiO2 = 57.5–59.5 wt%, K2O = 2.3–2.7 wt%, Al2O3 = 15.8–16.5 wt%, and P2O5 = 0.5–0.7 wt%. Other diagnostic features include a typical subduction-related pattern of incompatible elements, high concentrations of all REE (>10× mantle values), moderate enrichment in LREE (La/Yb ~ 5.3), and non-fractionated mantle-like pattern of LILE. Geochemical fingerprinting of the PL2 tephra with the help of EMP and LA-ICP-MS analyses allowed us to map its occurrence in terrestrial sections across Kamchatka and to identify this layer in Bering Sea sediment cores at a distance of >600 km from the source. New high-precision 14C dates suggest that the PL2 eruption occurred ~10,200 cal BP, which makes it a valuable isochrone for early Holocene climate fluctuations and permits direct links between terrestrial and marine paleoenvironmental records. The terrestrial and marine 14C dates related to the PL2 tephra have allowed us to estimate an early Holocene reservoir age for the western Bering Sea at 1,410 ± 64 14C years. Another important tephra from the early Holocene eruptive episode of Plosky volcano, coded PL1, was dated at 11,650 cal BP. This marker is the oldest geochemically characterized and dated tephra marker layer in Kamchatka to date and is an important local marker for the Younger Dryas—early Holocene transition. One more tephra from Plosky, coded PL3, can be used as a marker northeast of the source at a distance of ~110 km

Efficacy assessment of SNP sets for genome-wide disease association studies

The power of a genome-wide disease association study depends critically upon the properties of the marker set used, particularly the number and physical spacing of markers, and the level of inter-marker association due to linkage disequilibrium. Extending our previously devised theoretical framework for the entropy-based selection of genetic markers, we have developed a local measure of the efficacy of a marker set, relative to including a maximally polymorphic single nucleotide polymorphism (SNP) at the map position of interest. Using this quantitative criterion, we evaluated five currently available SNP sets, namely Affymetrix 100K and 500K, and Illumina 100K, 300K and 550K in the CEU, YRI and JPT + CHB HapMap populations. At 50% relative efficacy, the commercial marker sets cover between 19 and 68% of the human genome, depending upon the population under study. An optimal technology-independent 500K marker set constructed from HapMap for Caucasians, in contrast, would achieve 73% coverage at the same relative efficacy

Medical student ultrasound education, a WFUMB position paper, Part II. A consensus statement by ultrasound societies

Publisher Copyright: © 2020 Societatea Romana de Ultrasonografie in Medicina si Biologie. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Ultrasound is becoming a fundamental first-line diagnostic tool for most medical specialties and an innovative tool to teach anatomy, physiology and pathophysiology to undergraduate and graduate students. However, availability of structured training programs during medical school is lagging behind and many physicians still acquire all their ultrasound skills during postgraduate training. There is wide variation in medical student ultrasound education worldwide. Sharing successful educational strategies from early adopter medical schools and learning from leading education programs should advance the integration of ultrasound into the university medical school curricula. In this overview, we present current approaches and suggestions by ultrasound societies concerning medical student education throughout the world. Based on these examples, we formulate a consensus statement with suggestions on how to integrate ultrasound teaching into the preclinical and clinical medical curricula.publishersversionPeer reviewe

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis

This document is the Accepted Manuscript version of the following article: Riessland et al., 'Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis', The American Journal of Human Genetics, Vol. 100 (2): 297-315, first published online 26 January 2017. The final, published version is available online at doi: http://dx.doi.org/10.1016/j.ajhg.2017.01.005 © 2017 American Society of Human Genetics.Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca(2+)-dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies.Peer reviewedFinal Accepted Versio

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO