The Atmospheric River Tracking Method Intercomparison Project (ARTMIP): Quantifying Uncertainties in Atmospheric River Climatology

Atmospheric rivers (ARs) are now widely known for their association with high‐impact weather events and long‐term water supply in many regions. Researchers within the scientific community have developed numerous methods to identify and track of ARs—a necessary step for analyses on gridded data sets, and objective attribution of impacts to ARs. These different methods have been developed to answer specific research questions and hence use different criteria (e.g., geometry, threshold values of key variables, and time dependence). Furthermore, these methods are often employed using different reanalysis data sets, time periods, and regions of interest. The goal of the Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is to understand and quantify uncertainties in AR science that arise due to differences in these methods. This paper presents results for key AR‐related metrics based on 20+ different AR identification and tracking methods applied to Modern‐Era Retrospective Analysis for Research and Applications Version 2 reanalysis data from January 1980 through June 2017. We show that AR frequency, duration, and seasonality exhibit a wide range of results, while the meridional distribution of these metrics along selected coastal (but not interior) transects are quite similar across methods. Furthermore, methods are grouped into criteria‐based clusters, within which the range of results is reduced. AR case studies and an evaluation of individual method deviation from an all‐method mean highlight advantages/disadvantages of certain approaches. For example, methods with less (more) restrictive criteria identify more (less) ARs and AR‐related impacts. Finally, this paper concludes with a discussion and recommendations for those conducting AR‐related research to consider.Fil: Rutz, Jonathan J.. National Ocean And Atmospheric Administration; Estados UnidosFil: Shields, Christine A.. National Center for Atmospheric Research; Estados UnidosFil: Lora, Juan M.. University of Yale; Estados UnidosFil: Payne, Ashley E.. University of Michigan; Estados UnidosFil: Guan, Bin. California Institute of Technology; Estados UnidosFil: Ullrich, Paul. University of California at Davis; Estados UnidosFil: O'Brien, Travis. Lawrence Berkeley National Laboratory; Estados UnidosFil: Leung, Ruby. Pacific Northwest National Laboratory; Estados UnidosFil: Ralph, F. Martin. Center For Western Weather And Water Extremes; Estados UnidosFil: Wehner, Michael. Lawrence Berkeley National Laboratory; Estados UnidosFil: Brands, Swen. Meteogalicia; EspañaFil: Collow, Allison. Universities Space Research Association; Estados UnidosFil: Goldenson, Naomi. University of California at Los Angeles; Estados UnidosFil: Gorodetskaya, Irina. Universidade de Aveiro; PortugalFil: Griffith, Helen. University of Reading; Reino UnidoFil: Kashinath, Karthik. Lawrence Bekeley National Laboratory; Estados UnidosFil: Kawzenuk, Brian. Center For Western Weather And Water Extremes; Reino UnidoFil: Krishnan, Harinarayan. Lawrence Berkeley National Laboratory; Estados UnidosFil: Kurlin, Vitaliy. University of Liverpool; Reino UnidoFil: Lavers, David. European Centre For Medium-range Weather Forecasts; Estados UnidosFil: Magnusdottir, Gudrun. University of California at Irvine; Estados UnidosFil: Mahoney, Kelly. Universidad de Lisboa; PortugalFil: Mc Clenny, Elizabeth. University of California at Davis; Estados UnidosFil: Muszynski, Grzegorz. University of Liverpool; Reino Unido. Lawrence Bekeley National Laboratory; Estados UnidosFil: Nguyen, Phu Dinh. University of California at Irvine; Estados UnidosFil: Prabhat, Mr.. Lawrence Bekeley National Laboratory; Estados UnidosFil: Qian, Yun. Pacific Northwest National Laboratory; Estados UnidosFil: Ramos, Alexandre M.. Universidade Nova de Lisboa; PortugalFil: Sarangi, Chandan. Pacific Northwest National Laboratory; Estados UnidosFil: Viale, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentin

Mutations in INPP5K Cause a Form of Congenital Muscular Dystrophy Overlapping Marinesco-Sjögren Syndrome and Dystroglycanopathy.

Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Demonstration of a dynamic bandpass frequency filter in a rare-earth ion-doped crystal

In this paper we propose and demonstrate a dynamic, narrow-bandpass frequency filter. This is generated in a rare-earth ion-doped crystal using a combination of spectral hole burning and Stark shifting. This filter can toggle within one microsecond between absorption and transmission, with ∼60  dB difference in attenuation, in two separate 1 MHz wide spectral regions. The filter demonstrated here is specifically designed as a component in a rare-earth ion-based quantum repeater protocol. However, this is a general technique that could also be applied for amplitude or phase modulation, or switching between more complicated spectral profiles.SEB and MJS acknowledge the support of the Australian Research Council Centre of Excellence for Quantum Computation and Communication Technology (Project No. CE110001027)

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype–phenotype correlation, this cannot yet be confirmed. © The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc

Atmospheric River Tracking Method Intercomparison Project (ARTMIP): Project Goals and Experimental Design

Abstract. The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the MERRA-2 reanalysis from January 1980 to June of 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month proof of concept trial run designed to illustrate the utility and feasibility of the ARTMIP project

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed. © 2014 Wiley Periodicals, Inc