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  • 1
    Publication Date: 2013-06-05
    Description: Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder with wide variation in clinical phenotype and is caused by heterogeneous germline mutations in two of the Ext genes, EXT-1 and EXT-2 , which encode ubiquitously expressed glycosyltransferases involved in the polymerization of heparan sulfate (HS) chains. To examine whether the Ext mutation could affect HS structures and amounts in HME patients being heterozygous for the Ext genes, we collected blood from patients and healthy individuals, separated it into plasma and cellular fractions and then isolated glycosaminoglycans (GAGs) from those fractions. A newly established method consisting of a combination of selective ethanol precipitation of GAGs, digestion of GAGs recovered on the filter-cup by direct addition of heparitinase or chondroitinase reaction solution and subsequent high-performance liquid chromatography of the unsaturated disaccharide products enabled the analysis using the least amount of blood (200 µL). We found that HS structures of HME patients were almost similar to those of controls in both plasma and cellular fractions. However, interestingly, although both the amounts of HS and chondroitin sulfate (CS) varied depending on the different individuals, the amounts of HS in both the plasma and cellular fractions of HME patient samples were decreased and the ratios of HS to CS (HS/CS) of HME patient samples were almost half those of healthy individuals. The results suggest that HME patients' blood exhibited reduced HS amounts and HS/CS ratios, which could be used as a diagnostic biomarker for HME.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2012-04-05
    Description: A lectin was purified from the mushroom Hygrophorus russula by affinity chromatography on a Sephadex G-50 column and BioAssist S cation exchange chromatography and designated H. russula lectin (HRL). The results of sodium dodecyl sulfate–polyaclylamidegel electrophoresis, gel filtration and matrix-assisted laser desorption ionization time-of-flight mass spectrometry of HRL indicated that it was composed of four identical 18.5 kDa subunits with no S-S linkage. Isoelectric focusing of the lectin showed bands near pI 6.40. The complete sequence of 175 amino acid residues was determined by amino acid sequencing of intact or enzyme-digested HRL. The sequence showed homology with Grifola frondosa lectin. The cDNA of HRL was cloned from RNA extracted from the mushroom. The open reading frame of the cDNA consisted of 528 bp encoding 176 amino acids. In hemagglutination inhibition assay, α1-6 mannobiose was the strongest inhibitor and isomaltose, Glcα1-6Glc, was the second strongest one, among mono- and oligosaccharides tested. Frontal affinity chromatography indicated that HRL had the highest affinity for Manα1-6(Manα1-3)Manβ1-4GlcNAcβ1-4GlcNAc, and non-reducing terminal Manα1-6 was essential for the binding of HRL to carbohydrate chains. The sugar-binding specificity of HRL was also analyzed by using BIAcore. The result from the analysis exhibited positive correlations with that of the hemagglutination inhibition assay. All the results suggested that HRL recognized the α1-6 linkage of mannose and glucose, especially the Manα1-6 bond. HRL showed a mitogenic activity against spleen lymph cells of an F344 rat. Furthermore, an enzyme-linked immunosorbent assay showed strong binding of HRL to human immunodeficiency virus type-1 gp120.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2012-02-18
    Description: Author(s): M. Alvioli, C. Ciofi degli Atti, L. P. Kaptari, C. B. Mezzetti, H. Morita, and S. Scopetta Using realistic wave functions, the proton-neutron and proton-proton momentum distributions in 3 He and 4 He are calculated as a function of the relative, k rel , and center of mass, K c.m. , momenta and the angle between them. For large values of k rel ≳ 2 fm −1 and small values of K c.m. ≲1.0 fm −1 , both dist... [Phys. Rev. C 85, 021001] Published Fri Feb 17, 2012
    Keywords: Nucleon-Nucleon Interaction, Few-Body Systems
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
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  • 4
    Publication Date: 2011-08-10
    Description: Major bacterial small RNAs (sRNAs) regulate the translation and stability of target mRNAs through base pairing with the help of the RNA chaperone Hfq. The Hfq-dependent sRNAs consist of three basic elements, mRNA base-pairing region, Hfq-binding site, and rho-independent terminator. Although the base-pairing region and the terminator are well documented in many sRNAs, the Hfq-binding site is less well-defined except that Hfq binds RNA with a preference for AU-rich sequences. Here, we performed mutational and biochemical studies to define the sRNA site required for Hfq action using SgrS as a model sRNA. We found that shortening terminator polyU tail eliminates the ability of SgrS to bind to Hfq and to silence ptsG mRNA. We also demonstrate that the SgrS terminator can be replaced with any foreign rho-independent terminators possessing a polyU tail longer than 8 without losing the ability to silence ptsG mRNA in an Hfq-dependent manner. Moreover, we found that shortening the terminator polyU tail of several other sRNAs also eliminates the ability to bind to Hfq and to regulate target mRNAs. We conclude that the polyU tail of sRNAs is essential for Hfq action in general. The data also indicate that the terminator polyU tail plays a role in Hfq-dependent stabilization of sRNAs.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2015-03-18
    Description: Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720436/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720436/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Porazinski, Sean -- Wang, Huijia -- Asaoka, Yoichi -- Behrndt, Martin -- Miyamoto, Tatsuo -- Morita, Hitoshi -- Hata, Shoji -- Sasaki, Takashi -- Krens, S F Gabriel -- Osada, Yumi -- Asaka, Satoshi -- Momoi, Akihiro -- Linton, Sarah -- Miesfeld, Joel B -- Link, Brian A -- Senga, Takeshi -- Castillo-Morales, Atahualpa -- Urrutia, Araxi O -- Shimizu, Nobuyoshi -- Nagase, Hideaki -- Matsuura, Shinya -- Bagby, Stefan -- Kondoh, Hisato -- Nishina, Hiroshi -- Heisenberg, Carl-Philipp -- Furutani-Seiki, Makoto -- P30 EY001931/EY/NEI NIH HHS/ -- R01 EY014167/EY/NEI NIH HHS/ -- R01 EY016060/EY/NEI NIH HHS/ -- R01EY014167/EY/NEI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2015 May 14;521(7551):217-21. doi: 10.1038/nature14215. Epub 2015 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. ; Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan. ; IST Austria, Am Campus 1, A-3400 Klosterneuburg, Austria. ; Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan. ; Department of Molecular Biology, School of Medicine, Keio University, Tokyo 160-8582, Japan. ; Japan Science and Technology Agency (JST), ERATO-SORST Kondoh Differentiation Signaling Project, Kyoto 606-8305, Japan. ; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. ; Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. ; Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, UK. ; 1] Japan Science and Technology Agency (JST), ERATO-SORST Kondoh Differentiation Signaling Project, Kyoto 606-8305, Japan [2] Graduate School of Frontier Bioscience, Osaka University, Osaka 565-0871, Japan [3] Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan. ; 1] Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK [2] Japan Science and Technology Agency (JST), ERATO-SORST Kondoh Differentiation Signaling Project, Kyoto 606-8305, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25778702" target="_blank"〉PubMed〈/a〉
    Keywords: Actomyosin/metabolism ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; Body Size/*genetics ; Embryo, Nonmammalian/anatomy & histology/embryology/metabolism ; Fish Proteins/genetics/*metabolism ; GTPase-Activating Proteins/metabolism ; Genes, Essential/genetics ; Gravitation ; Humans ; Morphogenesis/*genetics ; Mutation/genetics ; Organ Size/genetics ; Oryzias/*anatomy & histology/*embryology/genetics ; Phenotype ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Signal Transduction ; Spheroids, Cellular/cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2011-01-29
    Description: The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuda, Shinji -- Toh, Hidehiro -- Hase, Koji -- Oshima, Kenshiro -- Nakanishi, Yumiko -- Yoshimura, Kazutoshi -- Tobe, Toru -- Clarke, Julie M -- Topping, David L -- Suzuki, Tohru -- Taylor, Todd D -- Itoh, Kikuji -- Kikuchi, Jun -- Morita, Hidetoshi -- Hattori, Masahira -- Ohno, Hiroshi -- England -- Nature. 2011 Jan 27;469(7331):543-7. doi: 10.1038/nature09646.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Epithelial Immunobiology, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270894" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates/*metabolism ; Animals ; Bifidobacterium/genetics/*metabolism ; Cercopithecus aethiops ; Escherichia coli Infections/microbiology/*prevention & control ; Escherichia coli O157/*physiology ; Gene Expression Profiling ; Genome, Bacterial ; Mice ; Molecular Sequence Data ; Vero Cells
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2013-06-28
    Description: Obesity has become more prevalent in most developed countries over the past few decades, and is increasingly recognized as a major risk factor for several common types of cancer. As the worldwide obesity epidemic has shown no signs of abating, better understanding of the mechanisms underlying obesity-associated cancer is urgently needed. Although several events were proposed to be involved in obesity-associated cancer, the exact molecular mechanisms that integrate these events have remained largely unclear. Here we show that senescence-associated secretory phenotype (SASP) has crucial roles in promoting obesity-associated hepatocellular carcinoma (HCC) development in mice. Dietary or genetic obesity induces alterations of gut microbiota, thereby increasing the levels of deoxycholic acid (DCA), a gut bacterial metabolite known to cause DNA damage. The enterohepatic circulation of DCA provokes SASP phenotype in hepatic stellate cells (HSCs), which in turn secretes various inflammatory and tumour-promoting factors in the liver, thus facilitating HCC development in mice after exposure to chemical carcinogen. Notably, blocking DCA production or reducing gut bacteria efficiently prevents HCC development in obese mice. Similar results were also observed in mice lacking an SASP inducer or depleted of senescent HSCs, indicating that the DCA-SASP axis in HSCs has key roles in obesity-associated HCC development. Moreover, signs of SASP were also observed in the HSCs in the area of HCC arising in patients with non-alcoholic steatohepatitis, indicating that a similar pathway may contribute to at least certain aspects of obesity-associated HCC development in humans as well. These findings provide valuable new insights into the development of obesity-associated cancer and open up new possibilities for its control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshimoto, Shin -- Loo, Tze Mun -- Atarashi, Koji -- Kanda, Hiroaki -- Sato, Seidai -- Oyadomari, Seiichi -- Iwakura, Yoichiro -- Oshima, Kenshiro -- Morita, Hidetoshi -- Hattori, Masahira -- Honda, Kenya -- Ishikawa, Yuichi -- Hara, Eiji -- Ohtani, Naoko -- England -- Nature. 2013 Jul 4;499(7456):97-101. doi: 10.1038/nature12347. Epub 2013 Jun 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23803760" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/metabolism ; Bile Acids and Salts/metabolism ; Carcinoma, Hepatocellular/complications/etiology/metabolism/prevention & control ; *Cell Aging/drug effects ; Cells, Cultured ; Cytokines/metabolism/secretion ; DNA Damage/drug effects ; Deoxycholic Acid/blood/*metabolism ; Dietary Fats/adverse effects/pharmacology ; Disease Models, Animal ; Fatty Liver/complications/pathology ; Gastrointestinal Tract/drug effects/*metabolism/*microbiology ; Hepatic Stellate Cells/cytology/drug effects/metabolism/*secretion ; Humans ; Interleukin-1beta/deficiency ; Liver Neoplasms/complications/etiology/*metabolism/prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease ; Obesity/chemically induced/*metabolism ; Phenotype ; Risk Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2013-07-12
    Description: Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4(+)FOXP3(+) regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human faecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory molecules--including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)--in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-beta-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Atarashi, Koji -- Tanoue, Takeshi -- Oshima, Kenshiro -- Suda, Wataru -- Nagano, Yuji -- Nishikawa, Hiroyoshi -- Fukuda, Shinji -- Saito, Takuro -- Narushima, Seiko -- Hase, Koji -- Kim, Sangwan -- Fritz, Joelle V -- Wilmes, Paul -- Ueha, Satoshi -- Matsushima, Kouji -- Ohno, Hiroshi -- Olle, Bernat -- Sakaguchi, Shimon -- Taniguchi, Tadatsugu -- Morita, Hidetoshi -- Hattori, Masahira -- Honda, Kenya -- England -- Nature. 2013 Aug 8;500(7461):232-6. doi: 10.1038/nature12331. Epub 2013 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN Center for Integrative Medical Sciences (IMS-RCAI), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23842501" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Cell Proliferation ; Clostridium/classification/genetics/*immunology ; Colitis/microbiology/pathology ; Colon/immunology/microbiology ; Disease Models, Animal ; Feces/microbiology ; Germ-Free Life ; Humans ; Inducible T-Cell Co-Stimulator Protein/metabolism ; Interleukin-10/metabolism ; Male ; Metagenome/genetics/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Inbred F344 ; T-Lymphocytes, Regulatory/cytology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2006-06-03
    Description: The locations of the pole and rotation axis of asteroid 25143 Itokawa were derived from Asteroid Multiband Imaging Camera data on the Hayabusa spacecraft. The retrograde pole orientation had a right ascension of 90.53 degrees and a declination of -66.30 degrees (52000 equinox) or equivalently 128.5 degrees and -89.66 degrees in ecliptic coordinates with a 3.9 degrees margin of error. The surface area is 0.393 square kilometers, the volume is 0.018378 cubic kilometers with a 5% margin of error, and the three axis lengths are 535 meters by 294 meters by 209 meters. The global Itokawa revealed a boomerang-shaped appearance composed of two distinct parts with partly faceted regions and a constricted ring structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Demura, Hirohide -- Kobayashi, Shingo -- Nemoto, Etsuko -- Matsumoto, Naoya -- Furuya, Motohiro -- Yukishita, Akira -- Muranaka, Noboru -- Morita, Hideo -- Shirakawa, Ken -- Maruya, Makoto -- Ohyama, Hiroshi -- Uo, Masashi -- Kubota, Takashi -- Hashimoto, Tatsuaki -- Kawaguchi, Jun'ichiro -- Fujiwara, Akira -- Saito, Jun -- Sasaki, Sho -- Miyamoto, Hideaki -- Hirata, Naru -- New York, N.Y. -- Science. 2006 Jun 2;312(5778):1347-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Software, University of Aizu, Ikki-machi, Aizu-Wakamatsu City, Fukushima 965-8580, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16741112" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2016-10-12
    Description: Author(s): M. Alvioli, C. Ciofi degli Atti, and H. Morita Background: The two-nucleon momentum distributions of nucleons N 1 and N 2 in a nucleus A ,   n A N 1 N 2 ( k rel , K c . m . ) , is a relevant quantity that determines the probability of finding two nucleons with relative momentum k rel and center-of-mass (c.m.) momentum K c . m . ; at high values of the relative momentum an… [Phys. Rev. C 94, 044309] Published Tue Oct 11, 2016
    Keywords: Nuclear Structure
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
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