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  • 1
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    In:  Journal of Earthquake Engineering, Washington, D.C., American Geophysical Union, vol. 7, no. 4, pp. 599-614, pp. L08304, (ISSN: 1340-4202)
    Publication Date: 2003
    Keywords: Site amplification ; Earthquake ; Earthquake engineering, engineering seismology ; JEE ; SPAROLAI ; SRICHWALSKI
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  • 2
    Publication Date: 2016-03-01
    Description: Cancer stem cells (CSCs) have been identified in several solid malignancies and are now emerging as a plausible target for drug discovery. Beside the questionable existence of CSCs specific markers, the expression of CD133 was reported to be responsible for conferring CSC aggressiveness. Here, we identified two G-rich sequences localized within the introns 3 and 7 of the CD133 gene able to form G-quadruplex (G4) structures, bound and stabilized by small molecules. We further showed that treatment of patient-derived colon CSCs with G4-interacting agents triggers alternative splicing that dramatically impairs the expression of CD133. Interestingly, this is strongly associated with a loss of CSC properties, including self-renewing, motility, tumor initiation and metastases dissemination. Notably, the effects of G4 stabilization on some of these CSC properties are uncoupled from DNA damage response and are fully recapitulated by the selective interference of the CD133 expression. In conclusion, we provided the first proof of the existence of G4 structures within the CD133 gene that can be pharmacologically targeted to impair CSC aggressiveness. This discloses a class of potential antitumoral agents capable of targeting the CSC subpopulation within the tumoral bulk.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2019
    Description: Abstract Laboratory brittle deformation experiments have shown that a rapid transition exists in the behavior of porous materials under stress: At a certain point, early formed and spatially distributed tensile cracks interact and coalesce forming a shear plane. In this work, we present and apply a novel image processing tool that is able to quantify this transition between distributed (“stable”) damage accumulation and localized (“unstable”) deformation, in terms of the size, density, and orientation of cracks at the point of strain localization. Our technique, based on a two‐dimensional Morlet wavelet analysis, can recognize, extract, and visually separate the multiscale changes occurring in the crack network during the deformation process. We first performed a series of triaxial experiments (σ1〉σ2=σ3) on core plugs of Hopeman Sandstone (Scotland, UK) at different effective pressures (from 5 to 30 MPa). We then processed high‐resolution backscattered electron microscope images of thin sections of these core plugs and found differences in the strain localization process as effective pressure was increased. The critical length of tensile cracks required before the onset of strain localization was reduced from 0.24 to 0.15 mm as the effective pressure was increased to 30 MPa, resulting in a narrow fracture zone. Critically, by comparing patterns of fractures in these deformed sandstone samples, we can quantitatively explore the relationship between the observed geometry of the cracks and the inferred mechanical processes. This will eventually help us to better understand the physics underlying the initiation of catastrophic events, such as earthquakes, landslides, and volcanic eruptions.
    Print ISSN: 2169-9313
    Electronic ISSN: 2169-9356
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
    Publication Date: 2015-07-02
    Description: Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA) and is widely considered a preneoplastic condition for hepatocellular carcinoma (HCC). 4-Methylumbelliferone (4MU) is an inhibitor of HA synthesis and has anticancer activity in an orthotopic HCC model with underlying fibrosis. Our aim was to explore the effects of HA inhibition by 4MU orally administered on tumor microenvironment. Hepa129 tumor cells were inoculated orthotopically in C3H/HeJ male mice with fibrosis induced by thioacetamide. Mice were orally treated with 4MU. The effects of 4MU on angiogenesis were evaluated by immunostaining of CD31 and quantification of proangiogenic factors (vascular endothelial growth factor, VEGF, interleukin-6, IL-6 and C-X-C motif chemokine 12, CXCL12) . IL-6 was also quantified in Hepa129 cells in vitro after treatment with 4MU. Migration of endothelial cells and tube formation were also analyzed. As a result, 4MU treatment decreases tumor growth and increased animal survival. Systemic levels of VEGF were significantly inhibited in 4MU-treated mice. Expression of CD31 was reduced after 4MU therapy in liver parenchyma in comparison with control group. In addition, mRNA expression and protein levels of IL-6 and VEGF were inhibited both in tumor tissue and in nontumoral liver parenchyma. Interestingly, IL-6 production was dramatically reduced in Kupffer cells isolated from 4MU-treated mice, and in Hepa129 cells in vitro. Besides, 4MU was able to inhibit endothelial cell migration and tube formation. In conclusion, 4MU has antitumor activity in vivo and its mechanisms of action involve an inhibition of angiogenesis and IL-6 production. 4MU is an orally available molecule with potential for HCC treatment.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2017-11-14
    Description: The mechanics of brittle failure is a well-described multi-scale process that involves a rapid transition from distributed microcracks to localisation along a single macroscopic rupture plane. However, considerable uncertainty exists regarding both the length scale at which this transition occurs and the underlying causes that prompt this shift from a distributed to a localised assemblage of cracks or fractures. For the first time, we used an image analysis tool developed to investigate orientation changes at different scales in images of fracture patterns in faulted materials, based on a two-dimensional continuous wavelet analysis. We detected the abrupt change in the fracture pattern from distributed tensile microcracks to localised shear failure in a fracture network produced by triaxial deformation of a sandstone core plug. The presented method will contribute to our ability of unravelling the physical processes at the base of catastrophic rock failure, including the nucleation of earthquakes, landslides and volcanic eruptions.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
    Publication Date: 2015-02-18
    Description: Here, with the aim of obtaining insight into the intriguing selectivity of G-quadruplex (G4) ligands toward cancer compared to normal cells, a genetically controlled system of progressive transformation in human BJ fibroblasts was analyzed. Among the different comparative evaluations, we found a progressive increase of DNA damage response (DDR) markers throughout the genome from normal toward immortalized and transformed cells. More interestingly, sensitivity to G4 ligands strongly correlated with the presence of a basal level of DNA damage, including at the telomeres, where the chromosome ends were exposed to the DDR without concurrent induction of DNA repair activity, as revealed by the lack of 53BP1 recruitment and telomere aberrations. The link between telomere uncapping and the response to G4 stabilization was directly assessed by showing that a partial TRF2 depletion, causing a basal level of telomere localized DDR, rendered telomerized fibroblasts prone to G4-induced telomere damage and anti-proliferative defects. Taken together these data strongly indicate that the presence of a basal level of telomere-associated DDR is a determinant of susceptibility to G4 stabilization.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Comparative Biochemistry and Physiology -- Part B: Biochemistry and 73 (1982), S. 829-833 
    ISSN: 0305-0491
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Comparative Biochemistry and Physiology -- Part B: Biochemistry and 98 (1991), S. 227-232 
    ISSN: 0305-0491
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1095-8649
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Involution and resorption of both postovulatory and atretic follicles were analysed in piau-jejo Leporinus taeniatus(Characiformes, Anostomidae) in order to evaluate the role of apoptosis during ovarian regression. Histological and ultrastructural analyses showed hallmarks of apoptosis in the granulosa: aggregation of compacted chromatin against the nuclear envelope, cell shrinkage, surface blebbing, loss of cell adhesion and cell fragmentation into apoptotic bodies. Protein synthesis activity preceded the onset of the cell death. The breakdown of the basement membrane led to the detachment of the granulosa cells into the follicular lumen. TUNEL-positive reactions were detected in in situ DNA fragmentation of granulosa of both postovulatory and atretic follicles. Apoptosis increased in a time-dependent manner contributing to reduction of the follicular areas. The apoptotic index (per cent of apoptotic cells) of the granulosa increased in postovulatory follicles soon after spawning, then these follicles degenerated and only remnants were observed at 7 days. In contrast, the granulosa cells reabsorbed the yolk during follicular atresia and the apoptotic index increased only in the late stage of regression. The results indicated apoptosis as the major mechanism to rapidly eliminate postovulatory follicles and being an essential process in the ovarian regression after spawning.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of fish biology 61 (2002), S. 0 
    ISSN: 1095-8649
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Eggs of 23 Characiformes and eight Siluriformes, belonging to nine families with diverse reproductive behaviour, were ultrastructurally analysed. The migratory species exhibited non-adhesive eggs, whereas, most of the sedentary species presented some degree of egg adhesiveness. Among the Characiformes, non-adhesive eggs showed zona radiata with pore-canals or a fibrillar net at the surface; weakly adhesive eggs presented only zona radiata with pore-canals while adhesive eggs exhibited zona radiata with apparatus like globules, filaments, villi or honeycomb-like pores depending on the systematic group. The ‘jelly’ coat is strongly related to the Siluriformes eggs apparently without relationship with adhesiveness. A micropylar disc was present in adhesive eggs of a few species of both Characiformes and Siluriformes. Some patterns were characteristic of the animal pole, others of the vegetal pole, and others were common to both poles. The radial ridges converging to the micropyle in Astyanax bimaculatus lacustris appear to be related to fertilization. In general, egg surface structures in the Characiformes varied according to the genus, whereas all Siluriformes showed a similar egg surface pattern, regardless of the group analysed. Multivariate analysis allowed the identification of eight clusters among the Characiformes and three among the Siluriformes showing relationships between reproductive style and egg characteristics. It is suggested that egg surface and adhesiveness may be related to reproductive patterns and to phylogenesis.
    Type of Medium: Electronic Resource
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