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Sökning: WFRF:(Lynch Edward P.)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Leisawitz, David, et al. (författare)
  • The origins space telescope
  • 2019
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11115
  • Konferensbidrag (refereegranskat)abstract
    • The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of Herschel, the largest telescope flown in space to date. After a 3 1/2 year study, the Origins Science and Technology Definition Team will recommend to the Decadal Survey a concept for Origins with a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (MISC-T) will measure the spectra of transiting exoplanets in the 2.8-20 μm wavelength range and offer unprecedented sensitivity, enabling definitive biosignature detections. The Far-IR Imager Polarimeter (FIP) will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer (OSS) will cover wavelengths from 25-588 μm, make wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The telescope has a Spitzer-like architecture and requires very few deployments after launch. The cryo-thermal system design leverages JWST technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural backgroundlimited sensitivity.
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4.
  • Soranno, Patricia A., et al. (författare)
  • LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
  • 2017
  • Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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5.
  • Amundadottir, Laufey, et al. (författare)
  • Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41, s. 986-990
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
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6.
  • Andersson, Joel, et al. (författare)
  • Evolution of structures and hydrothermal alteration in a Palaeoproterozoic supracrustal belt : Constraining paired deformation–fluid flow events in an Fe and Cu–Au prospective terrain in northern Sweden
  • 2020
  • Ingår i: Solid Earth. - : Copernicus publications. - 1869-9510 .- 1869-9529. ; 11:2, s. 547-578
  • Tidskriftsartikel (refereegranskat)abstract
    • An approximately 90 km long Palaeoproterozoic supracrustal belt in the northwestern Norrbotten ore province (northernmost Sweden) was investigated to characterize its structural components, assess hydrothermal alteration–structural geology correlations, and constrain a paired deformation–fluid flow evolution for the belt. New geological mapping of five key areas (Eustiljåkk, Ekströmsberg, Tjårrojåkka, Kaitum West, and Fjällåsen–Allavaara) indicates two major compressional events (D1 and D2) have affected the belt, with each associated with hydrothermal alteration types typical for iron oxide–apatite and iron oxide Cu–Au systems in the region. Early D1 generated a regionally distributed, penetrative S1 foliation and oblique reverse shear zones that show a southwest-block-up sense of shear that formed in response to NE–SW crustal shortening. Peak regional metamorphism at epidote–amphibolite facies broadly overlaps with this D1 event. Based on overprinting relationships, D1 is associated with regional scapolite ± albite, magnetite + amphibole, and late calcite alteration of mafic rock types. These hydrothermal mineral associations linked to D1 structures may form part of a regionally pervasive evolving fluid flow event but are separated in this study by crosscutting relationships.During D2 deformation, folding of S0–S1 structures generated F2 folds with steeply plunging fold axes in low-strain areas. NNW-trending D1 shear zones experienced reverse dip-slip reactivation and strike-slip-dominated movements along steep, E–W-trending D2 shear zones, producing brittle-plastic structures. Hydrothermal alteration linked to D2 structures is a predominantly potassic–ferroan association comprising K-feldspar ± epidote ± quartz ± biotite ± magnetite ± sericite ± sulfides. Locally, syn- or post-tectonic calcite is the main alteration mineral in D2 shear zones that intersect mafic rocks. Our results highlight the importance of combining structural geology with the study of hydrothermal alterations at regional to belt scales to understand the temporal–spatial relationship between mineralized systems. Based on the mapping results and microstructural investigations as well as a review of earlier tectonic models presented for adjacent areas, we suggest a new structural model for this part of the northern Fennoscandian Shield. The new model emphasizes the importance of reactivation of early structures, and the model harmonizes with tectonic models presented by earlier workers based mainly on petrology of the northern Norrbotten area.
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7.
  • Cioaca, Mihaela-Elena, et al. (författare)
  • Mineralogical Setting of Precious Metals at the Assarel Porphyry Copper-Gold Deposit, Bulgaria, as Supporting Information for the Development of New Drill Core 3D XCT-XRF Scanning Technology
  • 2020
  • Ingår i: Minerals. - : MDPI AG. - 2075-163X. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • A petrographic investigation of ore samples from the Assarel porphyry copper deposit in the Srednogorie metallogenic zone (Bulgaria) constrains the setting and character of precious metals (Au, Ag, PGE) and related minerals within the deposit. This work supports renewed interest in understanding the deportment of precious metals and provides mineralogical knowledge during the testing and validation of novel drill core 3D X-ray computed tomography-X-ray fluorescence (XCT-XRF) scanning technology being developed as part of the X-MINE project. Scanning electron microscopy-energy dispersive spectrometry (SEM-EDS) results indicate precious metals occur in their native state (Au, Ag), as sulfides (Ag), sulfosalts (Au), tellurides (Ag, Pd), and selenides (Ag), and typically form micron-sized inclusions in pyrite and chalcopyrite or are disseminated in the groundmass of the rock. Preservation of early Fe oxide-chalcopyrite +/- bornite assemblage as relics in the more dominant pyrite-chalcopyrite mineralization assemblage supports mineral disequilibrium relationships and multi-stage mineralization events. Several rare minerals (e.g., merenskyite, acanthite, sorosite, tetra-auricupride, auricupride, greenokite, bismuthinite, nagyagite, native Ni) are reported for the first time at Assarel and highlight the mineralogical diversity of the ore. The occurrence of precious metals and related minerals at Assarel attest to a complex hydrothermal system that underwent progressive physicochemical changes during the evolution of the mineralizing system (e.g., redox conditions, fluid chemistry).
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8.
  • Högdahl, Karin, et al. (författare)
  • Ore mineralogy, trace element distribution and 3D X-ray tomography of the polymetallic sulphide deposits at Mavres Petres and Piavitsa, Greece
  • 2019
  • Ingår i: LIFE WITH ORE DEPOSITS ON EARTH, PROCEEDINGS OF THE 15TH SGA BIENNIAL MEETING, 2019, VOLS 1-4. - : SOC GEOLOGY APPLIED MINERAL DEPOSITS-SGA. - 9780852619629 ; , s. 279-282
  • Konferensbidrag (refereegranskat)abstract
    • The Mavres Petres mine, operated by Hellas Gold, and the Piavitsa prospect are both located along the Stratoni fault in the Kassandra mining district, northern Greece. These Tertiary deposits are brecciated, carbonate replacement Pb-Zn-Ag-(Au) mineralisations and the Piavitsa deposit is also associated with Au-rich epithermal veins. Both mineralisations were variably overprinted by later fluids as well as ductile and brittle deformation affecting ore mineralogy and trace element distribution. Galena is the main Ag-carrier, contains significant concentrations of Sb and Bi and is locally associated with a suite of Sb-As-Bi phases. Sphalerite is either massive or occurs as a later cockade-textured type. Both varieties are variably enriched in Mn and can exhibit elevated concentrations of In and Ga. In Piavitsa, alabandite is present as small euhedral crystals or in veins in fractured sphalerite. Pyrite is ubiquitous and is either present as disseminations, massive to skeletal aggregates or as a matrix in breccias. It is often arsenic-bearing and even more so towards the later stages. Arsenopyrite appears to be a late phase and occurs interstitial to pyrite and as euhedral crystals. While both arsenopyrite and arsenian pyrite can be enriched in Au, As-minerals are not necessarily associated with Au.
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9.
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10.
  • Kostka, Kristin, et al. (författare)
  • Unraveling COVID-19: A Large-Scale Characterization of 4.5 Million COVID-19 Cases Using CHARYBDIS.
  • 2022
  • Ingår i: Clinical epidemiology. - 1179-1349. ; 14, s. 369-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
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