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5.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)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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  • 2019
  • Journal article (peer-reviewed)
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7.
  • Ariyawansa, Hiran A., et al. (author)
  • Fungal diversity notes 111–252—taxonomic and phylogenetic contributions to fungal taxa
  • 2015
  • In: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 75, s. 27-274
  • Journal article (peer-reviewed)abstract
    • This paper is a compilation of notes on 142 fungal taxa, including five new families, 20 new genera, and 100 new species, representing a wide taxonomic and geographic range. The new families, Ascocylindricaceae, Caryosporaceae and Wicklowiaceae (Ascomycota) are introduced based on their distinct lineages and unique morphology. The new Dothideomycete genera Pseudomassariosphaeria (Amniculicolaceae), Heracleicola, Neodidymella and P s e u d o m i c ros p h a e r i o p s i s ( D id y m e l l a c e a e ) , P s e u d o p i t h o m y c e s ( D i d y m o s p h a e r i a c e a e ) , Brunneoclavispora, Neolophiostoma and Sulcosporium (Halotthiaceae), Lophiohelichrysum (Lophiostomataceae), G a l l i i c o l a , Popul o c re s c e n t i a a nd Va g i c o l a (Phaeosphaeriaceae), Ascocylindrica (Ascocylindricaceae), E l o n g a t o p e d i c e l l a t a ( R o u s s o e l l a c e a e ) , Pseudoasteromassaria (Latoruaceae) and Pseudomonodictys (Macrodiplodiopsidaceae) are introduced. The newly described species of Dothideomycetes (Ascomycota) are Pseudomassariosphaeria bromicola (Amniculicolaceae), Flammeascoma lignicola (Anteagloniaceae), Ascocylindrica marina (Ascocylindricaceae) , Lembosia xyliae (Asterinaceae), Diplodia crataegicola and Diplodia galiicola ( B o t r yosphae r i a cea e ) , Caryospor a aquat i c a (Caryosporaceae), Heracleicola premilcurensis and Neodi dymell a thai landi cum (Didymellaceae) , Pseudopithomyces palmicola (Didymosphaeriaceae), Floricola viticola (Floricolaceae), Brunneoclavispora bambusae, Neolophiostoma pigmentatum and Sulcosporium thailandica (Halotthiaceae), Pseudoasteromassaria fagi (Latoruaceae), Keissleriella dactylidicola (Lentitheciaceae), Lophiohelichrysum helichrysi (Lophiostomataceae), Aquasubmersa japonica (Lophiotremataceae) , Pseudomonodictys tectonae (Macrodiplodiopsidaceae), Microthyrium buxicola and Tumidispora shoreae (Microthyriaceae), Alloleptosphaeria clematidis, Allophaeosphaer i a c y t i s i , Allophaeosphae r i a subcylindrospora, Dematiopleospora luzulae, Entodesmium artemisiae, Galiicola pseudophaeosphaeria, Loratospora(Basidiomycota) are introduced together with a new genus Neoantrodiella (Neoantrodiellaceae), here based on both morphology coupled with molecular data. In the class Agaricomycetes, Agaricus pseudolangei, Agaricus haematinus, Agaricus atrodiscus and Agaricus exilissimus (Agaricaceae) , Amanita m e l l e i a l b a , Amanita pseudosychnopyramis and Amanita subparvipantherina (Amanitaceae), Entoloma calabrum, Cora barbulata, Dictyonema gomezianum and Inocybe granulosa (Inocybaceae), Xerocomellus sarnarii (Boletaceae), Cantharellus eucalyptorum, Cantharellus nigrescens, Cantharellus tricolor and Cantharellus variabilicolor (Cantharellaceae), Cortinarius alboamarescens, Cortinarius brunneoalbus, Cortinarius ochroamarus, Cortinarius putorius and Cortinarius seidlii (Cortinariaceae), Hymenochaete micropora and Hymenochaete subporioides (Hymenochaetaceae), Xylodon ramicida (Schizoporaceae), Colospora andalasii (Polyporaceae), Russula guangxiensis and Russula hakkae (Russulaceae), Tremella dirinariae, Tremella graphidis and Tremella pyrenulae (Tremellaceae) are introduced. Four new combinations Neoantrodiella gypsea, Neoantrodiella thujae (Neoantrodiellaceae), Punctulariopsis cremeoalbida, Punctulariopsis efibulata (Punctulariaceae) are also introduced here for the division Basidiomycota. Furthermore Absidia caatinguensis, Absidia koreana and Gongronella koreana (Cunninghamellaceae), Mortierella pisiformis and Mortierella formosana (Mortierellaceae) are newly introduced in the Zygomycota, while Neocallimastix cameroonii and Piromyces irregularis (Neocallimastigaceae) ar e i n t roduced i n the Neocallimastigomycota. Reference specimens or changes in classification and notes are provided for Alternaria ethzedia, Cucurbitaria ephedricola, Austropleospora, Austropleospora archidendri, Byssosphaeria rhodomphala, Lophiostoma caulium, Pseudopithomyces maydicus, Massariosphaeria, Neomassariosphaeria and Pestalotiopsis montellica.
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  • Kanoni, Stavroula, et al. (author)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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9.
  • Arndt, D. S., et al. (author)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Research review (peer-reviewed)
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10.
  • Lee, Chunsik, et al. (author)
  • VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
  • 2023
  • In: SIGNAL TRANSDUCTION AND TARGETED THERAPY. - : SPRINGERNATURE. - 2095-9907 .- 2059-3635. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
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11.
  • Luo, Yifei, et al. (author)
  • Technology Roadmap for Flexible Sensors
  • 2023
  • In: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
  • Research review (peer-reviewed)abstract
    • Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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12.
  • Wang, Zhaoming, et al. (author)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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  • Arndt, D. S., et al. (author)
  • State of the Climate in 2016
  • 2017
  • In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Journal article (peer-reviewed)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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15.
  • Huang, Jing-Jia, et al. (author)
  • Conformal and superconformal chemical vapor deposition of silicon carbide coatings
  • 2022
  • In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : A V S AMER INST PHYSICS. - 0734-2101 .- 1520-8559. ; 40:5
  • Journal article (peer-reviewed)abstract
    • The approaches to conformal and superconformal deposition developed by Abelson and Girolami for a low-temperature, low-pressure chemical vapor deposition (CVD) setting relevant for electronic materials in micrometer or submicrometer scale vias and trenches, are tested here in a high-temperature, moderate pressure CVD setting relevant for hard coatings in millimeter-scale trenches. Conformal and superconformal deposition of polycrystalline silicon carbide (SiC) can be accomplished at deposition temperatures between 950 and 1000 degrees C with precursor partial pressure higher than 20 Pa and an optional minor addition of HCl as a growth inhibitor. The conformal deposition at low temperatures is ascribed to slower kinetics of the precursor consumption along the trench depth, whereas the impact of high precursor partial pressure and addition of inhibitor is attributable to surface site blocking. With the slower kinetics and the site blocking from precursor saturation leading the growth to nearly conformal and the possibly preferential inhibition effect near the opening than at the depth, a superconformal SiC coating with 2.6 times higher thickness at the bottom compared to the top of a 1 mm trench was achieved. Published under an exclusive license by the AVS.
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16.
  • Huang, Jing-Jia, et al. (author)
  • Controlled CVD Growth of Highly ⟨111⟩-Oriented 3C-SiC
  • 2022
  • In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:23, s. 9918-9925
  • Journal article (peer-reviewed)abstract
    • Highly ⟨111⟩-oriented 3C-SiC coatings with a distinct surface morphology consisting of hexagonally shaped pyramidal crystals were prepared by chemical vapor deposition (CVD) using silicon tetrachloride (SiCl4) and toluene (C7H8) at T ≤ 1250 °C and ptot = 10 kPa. In contrast, similar deposition conditions, with methane (CH4) as the carbon precursor, resulted in randomly oriented 3C-SiC coatings with a cauliflower-like surface of SiC crystallites. No excess carbon was detected in the highly ⟨111⟩-oriented 3C-SiC samples despite the use of aromatic hydrocarbons. The difference in the preferred growth orientation of the 3C-SiC coatings deposited by using C7H8 and CH4 as the carbon precursors was explained via quantum chemical calculations of binding energies on various crystal planes. The adsorption energy of C6H6 on the SiC (111) plane was 6 times higher than that on the (110) plane. On the other hand, CH3 exhibited equally strong adsorption on both planes. This suggested that the highly ⟨111⟩-oriented 3C-SiC growth with C7H8 as the carbon precursor, where both C6H6 and CH3 were considered the main active carbon-containing film forming species, was due to the highly preferred adsorption on the (111) plane, while the lower surface energy of the (110) plane controlled the growth orientation in the CH4 process, in which only CH3 contributed to the film deposition. 
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17.
  • Huang, Jing-Jia, 1990-, et al. (author)
  • Growth of silicon carbide multilayers with varying preferred growth orientation
  • 2022
  • In: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 447
  • Journal article (peer-reviewed)abstract
    • SiC multilayer coatings were deposited via thermal chemical vapor deposition (CVD) using silicon tetrachloride (SiCl4) and various hydrocarbons under identical growth conditions, i.e. at 1100 °C and 10 kPa. The coatings consisted of layers whose preferred growth orientation alternated between random and highly 〈111〉-oriented. The randomly oriented layers were prepared with either methane (CH4) or ethylene (C2H4) as carbon precursor, whereas the highly 〈111〉-oriented layers were grown utilizing toluene (C7H8) as carbon precursor. In this work, we demonstrated how to fabricate multilayer coatings with different growth orientations by merely switching between hydrocarbons. Moreover, the success in depositing multilayer coatings on both flat and structured graphite substrates has strengthened the assumption proposed in our previous study that the growth of highly 〈111〉-oriented SiC coatings using C7H8 was primarily driven by chemical surface reactions.
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18.
  • Huang, Jing-Jia, et al. (author)
  • Superconformal silicon carbide coatings via precursor pulsed chemical vapor deposition
  • 2023
  • In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - : A V S AMER INST PHYSICS. - 0734-2101 .- 1520-8559. ; 41:3
  • Journal article (peer-reviewed)abstract
    • In this work, silicon carbide (SiC) coatings were successfully grown by pulsed chemical vapor deposition (CVD). The precursors silicon tetrachloride (SiCl4) and ethylene (C2H4) were not supplied in a continuous flow but were pulsed alternately into the growth chamber with H-2 as a carrier and a purge gas. A typical pulsed CVD cycle was SiCl4 pulse-H-2 purge-C2H4 pulse-H-2 purge. This led to growth of superconformal SiC coatings, which could not be obtained under similar process conditions using a constant flow CVD process. We propose a two-step framework for SiC growth via pulsed CVD. During the SiCl4 pulse, a layer of Si is deposited. In the following C2H4 pulse, this Si layer is carburized, and SiC is formed. The high chlorine surface coverage after the SiCl4 pulse is believed to enable superconformal growth via a growth inhibition effect.
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19.
  • Huang, Jing-Jia, 1990- (author)
  • Surface-Controlled Chemical Vapor Deposition of Silicon Carbide
  • 2022
  • Doctoral thesis (other academic/artistic)abstract
    • Polycrystalline cubic silicon carbide, 3C-SiC, has long been investigated in the field of hard coating materials. The typical synthesis method for 3C-SiC coatings is thermal chemical vapor deposition (CVD) using either multicomponent precursors, e.g. methyltrichlorosilane, or a combination of single component precursors, e.g. silane and propane. In this thesis, the fabrication of polycrystalline SiC coatings has been explored from the new aspects on the basis of thermal CVD utilizing silicon tetrachloride (SiCl4) and various hydrocarbons, i.e. toluene (C7H8), methane (CH4) and ethylene (C2H4) as the precursors. The goal of this thesis is to control the surface chemistry in the SiCl4-based SiC CVD and has been accomplished by the following three different approaches: In the first approach to control the surface chemistry of SiC CVD, the difference in the adsorption energy of aromatic and aliphatic hydrocarbons on different SiC crystal planes was utilized. Under identical deposition conditions, a highly <111>-oriented 3C-SiC coating was deposited using C7H8 as the carbon precursor, whereas using CH4 resulted in a randomly oriented 3C-SiC. The results from quantum chemical calculation showed that the active film forming carbon species, i.e. C6H6 in the C7H8 process and CH3 in both C7H8 and CH4 processes, behaved differently when they adsorbed on the 3C-SiC (111) and (110) planes. CH3 is strongly chemisorbed on both planes, while C6H6 is chemisorbed on the (111) plane, but only physiosorbed on the other. The significant difference in the adsorption energy of CH3 and C6H6 on the (111) and (110) planes therefore explains the resulting highly <111>-oriented 3C-SiC from the C7H8 process. Furthermore, the ability to deposit 3C-SiC coatings with alternating highly <111>- and randomly oriented layers by merely switching the carbon precursor between C7H8 and CH4 or C2H4 in a single CVD deposition has further proven that the effect of aromatic hydrocarbons on the preferred growth orientation of 3C-SiC was controlled primarily by the surface chemistry.  The second approach to the surface-controlled SiC CVD was based on the reduction of surface reaction probability (β) for conformal film growth via low-temperature, low-pressure CVD, which was originally proposed by Abelson and Girolami. Their strategies in reducing β, including lowering the temperature and increasing the precursor partial pressure, were successfully adapted to the SiC CVD growth using SiCl4 and C2H4 as the precursors in this thesis, where an elevated temperature and a moderate pressure were used. Moreover, the addition of Cl species as a growth inhibitor to the process further reduced the β, leading to a superconformal SiC growth.  The third approach employed in this thesis for the SiC growth was pulsed CVD. Instead of a continuous and simultaneous SiCl4 and C2H4 flow, the precursors were pulsed alternately into the chamber with each precursor pulse being separated by a H2 purge. In this precursor delivery mode, the gas phase reactions between SiCl4 and C2H4 were avoided and hence the SiC growth was mostly controlled by the surface chemistry. Altering the pulse durations of the precursors led to a variation of growth per cycle (GPC), which was explained by a two-step mechanism. During the SiCl4 pulse, a thin layer of Si is deposited, which is carburized by carbon species produced during the C2H4 pulse. Additionally, the separation of precursor pulses should lead to a large increase in the surface coverage of Cl species, further enhancing the inhibition effect and resulting in a superconformal SiC growth. By using this approach, superconformal SiC coatings were achieved at temperatures where conventional CVD only yielded nonconformal SiC coatings. The observed decline in coating conformality with an elongated purge implied that more surface Cl species were replaced by H during the H2 purge and consequently the inhibition effect was diminished. 
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20.
  • Huang, Qiangsheng, et al. (author)
  • LiNbO3 waveguide with embedded Ag nanowire and 3L MoS2 for strong light confinement and ultra-long propagation length in the visible spectral range
  • 2021
  • In: Optics Express. - : The Optical Society. - 1094-4087. ; 29:5, s. 7168-7178
  • Journal article (peer-reviewed)abstract
    • A vertical slot LiNbO3 waveguide with an Ag nanowire and 3L MoS2 embedded in the low-refractive index slot region is proposed for the purpose of improving light confinement. We find that the proposed waveguide has a novel dielectric based plasmonic mode, where local light field is enhanced by the Ag nanowire. The mode exhibits an extremely large figure of merit (FoM) of 6.5x10(6), one order of magnitude larger than that the largest FoM of any plasmonic waveguide reported in the literature to date. The waveguide also has an extremely long propagation length of 84 cm in the visible wavelength at 680 nm. Furthermore, the waveguide has a low sub-micro bending loss and can be directly connected to all-dielectric waveguides with an extremely low coupling loss. The proposed vertical slot LiNbO3 waveguide is a promising candidate for the realization of ultrahigh integration density tunable circuits in the visible spectral range.
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21.
  • Liu, Zongran, et al. (author)
  • The cervical lymph node contributes to peripheral inflammation related to Parkinson’s disease
  • 2023
  • In: Journal of Neuroinflammation. - 1742-2094. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background: Peripheral inflammation is an important feature of Parkinson’s disease (PD). However, if and how CNS pathology is involved in the peripheral inflammation in PD remains to be fully investigated. Recently, the existence of meningeal lymphatics and its involvement in draining cerebral spinal fluid (CSF) to the cervical lymph node has been discovered. It is known that meningeal lymphatic dysfunction exists in idiopathic PD. The deep cervical lymph node (dCLN) substantially contributes to the drainage of the meningeal lymphatics. In addition, one of the lymphatics draining components, CSF, contains abundant α-synuclein (α-syn), a protein critically involved in PD pathogenesis and neuroinflammation. Thus, we began with exploring the possible structural and functional alterations of the dCLN in a PD mouse model (A53T mice) and investigated the role of pathological α-syn in peripheral inflammation and its potential underlying molecular mechanisms. Methods: In this study, the transgenic mice (prnp-SNCA*A53T) which specifically overexpressed A53T mutant α-syn in CNS were employed as the PD animal model. Immunofluorescent and Hematoxylin and eosin staining were used to evaluate structure of dCLN. Inflammation in dCLNs as well as in bone-marrow-derived macrophages (BMDMs) was assessed quantitatively by measuring the mRNA and protein levels of typical inflammatory cytokines (including IL-1β, IL-6 and TNF-α). Intra-cisterna magna injection, flow cytometric sorting and electrochemiluminescence immunoassays were applied to investigate the lymphatic drainage of α-syn from the CNS. RNA-seq and Western blot were used to explore how pathological α-syn mediated the inflammation in PD mice. Results: The results unequivocally revealed substantially enlarged dCLNs, along with slow lymphatic flow, and increased inflammation in the dCLNs of A53T mice. Oligomeric α-syn drained from CSF potently activated macrophages in the dCLN via endoplasmic reticulum (ER) stress. Notably, inhibition of ER stress effectively suppressed peripheral inflammation in PD mice. Conclusions: Our findings indicate that lymph node enlargement is closely related to macrophage activation, induced by meningeal lymphatics draining oligomeric α-syn, and contributes to the peripheral inflammation in PD. In addition, ER stress is a potential therapeutic target to ameliorate PD pathogenesis.
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22.
  • Marouli, Eirini, et al. (author)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Journal article (peer-reviewed)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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23.
  • Schmit, Stephanie L, et al. (author)
  • Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
  • 2019
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
  • Journal article (peer-reviewed)abstract
    • Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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24.
  • Turcot, Valerie, et al. (author)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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25.
  • Yu, Zhang, et al. (author)
  • Distinction between bacterial and viral infections by serum measurement of human neutrophil lipocalin (HNL) and the impact of antibody selection
  • 2016
  • In: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 432, s. 82-86
  • Journal article (peer-reviewed)abstract
    • The distinction between acute infections of bacterial or viral causes is clinically important, but often very difficult even for experienced doctors. Previous studies indicated that serum measurements of HNL (Human Neutrophil Lipocalin) might be a superior diagnostic means in this regard, but also indicated that the antibody conformation of the HNL assay might have an impact on the diagnostic performance. The aim of the present report was to examine this further. Methods: Several different (n = 24) HNL ELISA assays were developed using different combinations of monoclonal and polyclonal HNL antibodies. Sera were collected from healthy persons (n = 188) and from 155 patients with acute infections.before any antibiotics treatment. The patients were diagnosed as having bacterial (n = 69) or viral causes (n = 86) of their infections. Plasma and serum were also examined by Western blotting using HNL-specific polyclonal antibodies. Results: The optimal assay format for the distinction between bacterial and viral infection resulted in an area under the receiver operating characteristics curve (AuROC) for S-HNL of 0.98. (95% CI 0.94-1.00) as compared to 0.83 (0.76-0.88) for blood neutrophil counts and 0.69 (0.61-0.76) for S-CRP. Results also showed that different assay formats of HNL identified monomeric and dimeric HNL differently, the monomeric HNL being elevated in viral infections and the dimeric HNL being elevated in bacterial infections. Conclusion: We conclude that serum theasurement of HNL is a superior diagnostic means to distinguish between acute infections caused by bacteria or virus. For optimal clinical performance the immunoassay should address conformational epitopes in the dimeric HNL.
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26.
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27.
  • Zhou, Weiqi, et al. (author)
  • Urban tree canopy has greater cooling effects in socially vulnerable communities in the US
  • 2021
  • In: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 4:12, s. 1764-1775
  • Journal article (peer-reviewed)abstract
    • Cities are home to around half of the global population but face intensified and unevenly distributed heat stresses. Trees are utilized to adapt to urban heat; however, most tree planting is prioritized by either biophysical or social metrics, rather than an integration of the two. It therefore remains unclear how to maximize ecological and social benefits of tree planting in the context of environmental justice. Here, we analyze social vulnerability to heat and the cooling capacity of trees across 38 of the largest cities in the United States. We find that socially vulnerable people tend to live in hotter neighborhoods with less tree canopy. Furthermore, tree planting in such neighborhoods can achieve greater cooling benefits per unit increase in canopy. Increasing tree cover in these neighborhoods will meet the greatest need for cooling and achieve greater cooling capacity, creating social and ecological co-benefits. Adaptation measures must address both the distributional injustices of urban heat and procedural justice in planning and managing nature-based cooling approaches.
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