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  • 1
    Online Resource
    Online Resource
    Japan Surgical Association ; 1995
    In:  The journal of the Japanese Practical Surgeon Society Vol. 56, No. 12 ( 1995), p. 2617-2620
    In: The journal of the Japanese Practical Surgeon Society, Japan Surgical Association, Vol. 56, No. 12 ( 1995), p. 2617-2620
    Type of Medium: Online Resource
    ISSN: 0386-9776
    Language: Unknown
    Publisher: Japan Surgical Association
    Publication Date: 1995
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6634 ( 2023-02-24)
    Abstract: The Hayabusa2 spacecraft retrieved surface and subsurface samples from the carbonaceous near-Earth asteroid (162173) Ryugu, which was expected to be enriched in volatile species. The samples were collected from two locations, one undisturbed surface and the other including material excavated by an artificial impact. Unlike meteorites, these samples have experienced minimal alteration by Earth’s atmosphere. Ryugu is thought to have formed from material ejected (by an impact) from a parent body, which had experienced aqueous alteration (reactions with liquid water) ~4.56 billion years (Gyr) ago. Ryugu’s orbit later migrated from the main asteroid belt to become a near-Earth asteroid. RATIONALE Noble gases and nitrogen isotopes in Ryugu grains are inherited from Ryugu’s parent body and potentially provide information about the source of Earth’s volatile elements. Noble gas isotopes can also be used to assess the orbital evolution and recent surface activities of Ryugu. We pelletized ~0.8-mm-diameter Ryugu grains and investigated their mineralogy before carrying out isotope measurements. We measured the concentrations and isotopic compositions of noble gases and nitrogen, extracted by stepped heating, with mass spectrometers. RESULTS The mineralogy of the Ryugu grains is similar to Ivuna-type carbonaceous (CI) chondrite meteorites. Fine-grained hydrous silicates (phyllosilicates), produced through aqueous alteration of primary minerals, compose the major fraction of the samples. This is consistent with infrared spectroscopic observations of the asteroid. Iron oxide, iron sulfides, and carbonates are also found within the matrix. Noble gas isotopes are dominated by primordially trapped gases. Their abundances are mostly similar to the highest found in a CI chondrite, with some grains having several times higher concentrations than the highest CI value. Isotopic compositions and concentrations of nitrogen vary between the Ryugu grains, with divergence from the CI chondrite composition. The nitrogen concentrations in four Ryugu grains are one-half to one-third the CI values, and the 15 N/ 14 N ratio is also lower. The Ryugu grains with compositions farthest from the CI values are similar to the composition of a dehydrated CI chondrite. Only two surface samples, out of the 16 Ryugu grains measured, have clear signs of noble gases derived from solar wind (SW). Their abundances correspond to SW exposure durations of ≳3500 and ≳250 years at the current orbit, whereas most of the grains were exposed for ≳1 to ≳50 years. Cosmic ray–produced 21 Ne concentrations vary, with no systematic difference between the sample collection sites. The estimated cosmic ray exposure (CRE) ages for the surface and subsurface samples are 5.3 ± 0.9 and 5.2 ± 0.8 million years (Myr), assuming irradiations at 2 to 5 g cm −2 and 150 g cm −2 , respectively. This is consistent with the expected surface residence time under near-Earth impact rates. We infer that Ryugu’s orbit migrated from the main asteroid belt to the near-Earth region ~5 Myr ago. About 30% of cosmogenic 21 Ne, corresponding to a CRE age of ~1 Myr, was released in gas-extraction steps at 100°C, indicating that the Ryugu samples have not experienced heating above 100°C within the past 1 Myr. Previous studies have suggested that Ryugu experienced an orbital excursion much closer to the Sun. If this is the case, this excursion must have occurred ≳1 Myr ago. CONCLUSION The mineralogical and noble gas measurements show that the Ryugu samples are similar to CI chondrites. The nitrogen data indicate a heterogeneous distribution of nitrogen-carrying materials with different compositions, one of which has been lost from Ryugu grains to varying degrees. The CRE age of ~5 Myr and the implanted SW are records of the recent irradiation at the current near-Earth orbit of Ryugu. Inferred formation and history of Ryugu. Ryugu’s parent body formed in the early Solar System, incorporating primordial noble gases and nitrogen, followed by aqueous alteration ~4.56 Gyr ago. Ryugu formed from the accumulation of fragments of the parent body ejected by an impact, at an unknown date. Ryugu migrated to its current near-Earth orbit ~5 Myr ago. Ryugu might have experienced another change in orbit, bringing it closer to the Sun (“Path A”), or remained in the same near-Earth orbit (“Path B”).
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 3
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-19)
    Abstract: Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by stimulating the innate immune cells in both direct and indirect manners to produce a variety cytokines, chemokines, and growth factors. It has been developed by empirical methods for decades and considered difficult to choose a single screening method for an ideal vaccine adjuvant, due to their diverse biochemical characteristics, complex mechanisms of, and species specificity for their adjuvanticity. We therefore established a robust adjuvant screening strategy by combining multiparametric analysis of adjuvanticity in vivo and immunological profiles in vitro (such as cytokines, chemokines, and growth factor secretion) of various library compounds derived from hot-water extracts of herbal medicines, together with their diverse distribution of nano-sized physical particle properties with a machine learning algorithm. By combining multiparametric analysis with a machine learning algorithm such as rCCA, sparse-PLS, and DIABLO, we identified that human G-CSF and mouse RANTES, produced upon adjuvant stimulation in vitro , are the most robust biological parameters that can predict the adjuvanticity of various library compounds. Notably, we revealed a certain nano-sized particle population that functioned as an independent negative parameter to adjuvanticity. Finally, we proved that the two-step strategy pairing the negative and positive parameters significantly improved the efficacy of screening and a screening strategy applying principal component analysis using the identified parameters. These novel parameters we identified for adjuvant screening by machine learning with multiple biological and physical parameters may provide new insights into the future development of effective and safe adjuvants for human use.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
    Online Resource
    Online Resource
    Rubber Division, ACS ; 2021
    In:  Rubber Chemistry and Technology Vol. 94, No. 4 ( 2021-10-01), p. 657-668
    In: Rubber Chemistry and Technology, Rubber Division, ACS, Vol. 94, No. 4 ( 2021-10-01), p. 657-668
    Abstract: Effect of protein on vulcanization of NR, obtained from Hevea brasiliensis, was investigated by analyzing the crosslinking structure of the resulting vulcanizates prepared from untreated NR, deproteinized natural rubber (DPNR), and protein-free natural rubber (PFNR) by swelling methods and rubber-state NMR spectroscopy. The proteins present in NR were removed by three methods: deproteinization with enzyme, urea, or urea–acetone in the presence of sodium dodecyl sulfate. The amount of proteins present in NR, approximately 0.238 w/w%, was reduced to 0.000 w/w% by urea–acetone deproteinization, whereas it was reduced to approximately 0.003 and 0.019 w/w% by enzyme and urea deproteinizations, respectively. Hardness, swelling degree, and crosslinking structure depended on the amount of proteins. Changes in mechanical properties for the vulcanizates prepared from not only non-filler compounds but also carbon black–filled and silica-filled compounds were attributed to the amount of proteins.
    Type of Medium: Online Resource
    ISSN: 1943-4804 , 0035-9475
    Language: English
    Publisher: Rubber Division, ACS
    Publication Date: 2021
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  • 5
    Online Resource
    Online Resource
    Japan Society of Histochemistry & Cytochemistry ; 1991
    In:  ACTA HISTOCHEMICA ET CYTOCHEMICA Vol. 24, No. 5 ( 1991), p. 508-516
    In: ACTA HISTOCHEMICA ET CYTOCHEMICA, Japan Society of Histochemistry & Cytochemistry, Vol. 24, No. 5 ( 1991), p. 508-516
    Type of Medium: Online Resource
    ISSN: 0044-5991 , 1347-5800
    Language: English
    Publisher: Japan Society of Histochemistry & Cytochemistry
    Publication Date: 1991
    detail.hit.zdb_id: 2106630-9
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  • 6
    In: Blood, American Society of Hematology, Vol. 125, No. 23 ( 2015-06-04), p. 3527-3535
    Abstract: ATL clones are preserved in a rare CD4+CD45RA+ TSCM population. ATL-TSCM cells unidirectionally produce conventional CD45RO+ ATL cells and show a high potency of repopulating identical ATL clones in vivo.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1010-1010
    Abstract: Background: Histone methylation is one of the major systems of epigenetics and reversibly regulated by lysine (K) specific methyltransferases (KMTs) and demethylases (KDMs). Dysregulation of KMTs such as EZH2 and MLL play a key role in the pathogenesis of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) while the precise function of KDMs remains unclear.KDM1A is the first reported histone demethylase, which mainly catalyzes demethylation of mono- and di-methylated lysine 4 of histone 3 (H3K4me1 and me2 respectively). According to recent reports, the inhibition of KDM1A either alone or in combination of all-trans retinoic acid is effective for AML expressing MLL-AF9 or for several types of AML respectively, suggesting KDM1A could be a therapeutic target of AML. However, other reports argue that KDM1A is essential in hematopoiesis, raising concern that KDM1A-targeted therapy could lead to severe hematological toxicity. Here, we try to clarify what types of leukemia can be ameliorated by the pharmacological inhibition of KDM1A with a possible therapeutic window and what are functional and molecular mechanisms utilizing highly selective KDM1A inhibitors we have newly designed. Results: First we validated the effect of our novel inhibitors on murine leukemia cells harboring MLL-AF9. In accordance with a previous report, our novel KDM1A inhibitors suppressed cell proliferation, diminished clonogenic capacity and induced G1-S cell cycle arrest and myelomonocytic differentiation but not apoptosis in quite low concentration that clonogenicity of normal murine bone marrow cells was spared. Next we examined the effect of these drugs on diverse types of human myeloid leukemia cells and found that our drugs were particularly effective in erythroid leukemia cells (HEL), megakaryocytic leukemia cells (CMK11-5), and a blastic subline from a MDS patient with complex karyotype (MDS-L). MDS-L cells were changed phenotypically and morphologically towards myelomonocytic differentiation such as the increase of CD11b expression level and the induction of neutrophil-like cells. HEL and CMK cells which are negative for myelomonocytic markers also gained CD11b expression and decreased erythroid markers such as CD235a and CD71. These data suggest that the inhibition of KDM1A induces myeloid differentiation across various types of leukemia. To investigate an underlying molecular basis for the cell fate conversion in HEL and myeloid differentiation in MDS-L by the inhibition of KDM1A, we performed gene expression profiling and analyzed a change of gene signatures. The expression pattern of transcriptional factors was changed from the erythroid signature (e.g. GATA1 and TAL1) to the myeloid signature (e.g. SPI1 and CEBPA) in HEL. Gene Set Enrichment Analysis (GSEA) showed that the myeloid differentiation-associated gene signature was positively enriched and the leukemia stem cell-associated gene signature was negatively enriched in both HEL and MDS-L. Finally, we investigated the effect of our KDM1A inhibitors on primary human samples such as AML with MLL-AF9 and MDS in the phase of overt leukemia (MDS/AML) with complex karyotype. The colony formation capacity was clearly impaired in relatively low concentration that normal colonies were spared. We transplanted primary MDS/AML cells with complex karyotype to immunodeficient mice and treated with a KDM1A inhibitor or vehicles after confirming the engraftment. In one MDS/AML case, all mice treated with vehicles (n=4) died of anemia and the increase of human leukemia cells within four months while 3 of 4 mice treated with a KDM1A inhibitor have survived for more than six months. Also in another case, both of two vehicle-treated mice died while all drug-treated mice had survived for more than six months. At day 200 after transplantation, we sacrificed all survived mice treated with a KDM1A inhibitor and found that human blasts were displaced from the bone marrow of treated mice. Those data suggest that our KDM1A inhibitor is effective in vivo and have a possibility for the clinical application. Conclusion: Our study suggests that KDM1A involves with myeloid differentiation and the leukemia stem cell signature and that the pharmacological inhibition of KDM1A by highly selective inhibitors is a promising way to ameliorate AML with poor prognosis such as erythroleukemia and MDS/AML with complex karyotype, without impairing normal hematopoiesis. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Resuscitation, Elsevier BV, Vol. 88 ( 2015-03), p. 63-67
    Type of Medium: Online Resource
    ISSN: 0300-9572
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2010733-X
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  • 9
    In: Therapeutic Apheresis and Dialysis, Wiley, Vol. 10, No. 5 ( 2006-10), p. 430-435
    Type of Medium: Online Resource
    ISSN: 1744-9979 , 1744-9987
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2010864-3
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  • 10
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 4, No. 2 ( 2016-02-01), p. 136-145
    Abstract: Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1. Because of its immunosuppressive property and resistance to treatment, patients with ATL have poor prognoses. ATL cells possess the regulatory T cell (Treg) phenotype, such as CD4 and CD25, and usually express forkhead box P3 (FOXP3). However, the mechanisms of FOXP3 expression and its association with Treg-like characteristics in ATL remain unclear. Selective demethylation of the Treg-specific demethylated region (TSDR) in the FOXP3 gene leads to stable FOXP3 expression and defines natural Tregs. Here, we focus on the functional and clinical relationship between the epigenetic pattern of the TSDR and ATL. Analysis of DNA methylation in specimens from 26 patients with ATL showed that 15 patients (58%) hypomethylated the TSDR. The FOXP3+ cells were mainly observed in the TSDR-hypomethylated cases. The TSDR-hypomethylated ATL cells exerted more suppressive function than the TSDR-methylated ATL cells. Thus, the epigenetic analysis of the FOXP3 gene identified a distinct subtype with Treg properties in heterogeneous ATL. Furthermore, we observed that the hypomethylation of TSDR was associated with poor outcomes in ATL. These results suggest that the DNA methylation status of the TSDR is an important hallmark to define this heterogeneous disease and to predict ATL patient prognosis. Cancer Immunol Res; 4(2); 136–45. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2732517-9
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