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  • 1
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    Development of a one-dimensional ecosystem model including the iron cycle applied to the Oyashio region, western subarctic Pacific (2012)
    AMER GEOPHYSICAL UNION
    In:  EPIC3Journal of Geophysical Research-Oceans, AMER GEOPHYSICAL UNION, 117(C06021), ISSN: 0148-0227
    Details
    Publication Date: 2019-07-17
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , peerRev
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  • 2
    Electronic Resource
    Electronic Resource
    Doppler views of photofragments (1989)
    [s.l.] : Nature Publishing Group
    Nature 339 (1989), S. 259-260 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE past few years have brought remarkable advances in the understanding of how molecules fall apart following absorption of a photon of radiation. A whole armoury of techniques, using all the extraordinary properties of laser radiation have been deployed to look at the subtleties of ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/339259a0
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    The Pharmacokinetics of Pulmonary-Delivered Insulin: A Comparison of Intratracheal and Aerosol Administration to the Rabbit (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 764-768 
    Details
    ISSN: 1573-904X
    Keywords: insulin ; aerosol ; pulmonary ; pharmacokinetics ; gamma scintigraphy ; drug delivery ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pulmonary deposition and pharmacokinetics of insulin, administered via an endotracheal tube as an aerosol and instillate, in formulations containing either 113mIn-DTPA or 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in four male New Zealand White rabbits. Using a randomized crossover design, the pharmacokinetics of intravenous insulin were also characterized. Recovery of immunoreactive insulin after nebulization was greater than 90%, indicating that the aerosolisation procedure did not cause appreciable insulin degradation. Gamma scintigraphy demonstrated that the penetration index (peripheral:central deposition) for the aerosolized formulation (1.52) was much greater than that for the instillate (0.32). Gamma scintigraphy also allowed exact quantification of the dose deposited after aerosol administration and thus permitted accurate determination of bioavailabilities. The bioavailable fraction for aerosolized insulin was 10-fold greater than for instilled insulin (57.2 vs 5.6%). Mucociliary clearance was likely to be greater for the instillate since it showed a preferential central deposition; this may account for the lower bioavailability. Insulin pharmacokinetics from both pulmonary formulations were absorption rate limited, resulting in postpeak half-lives which were approximately 20-fold greater than the intravenous elimination half-life (3 min). The apparent absorption rate constants resulting from instillation and aerosolisation were statistically equivalent (0.015 and 0.011 min−1, respectively). Mucociliary clearance of insulin would result in an overestimation of the true absorption rate constant; hence if mucociliary transport were greater for the instillate, then the true airways to blood transfer rate constant will be higher for the aerosolized formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015851521551
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  • 4
    Electronic Resource
    Electronic Resource
    Investigation into the GC separation of enantiomers on a trifluoroacetylated cyclodextrin. I. Effect of analyte structure on stereoselectivity for alcohols (1992)
    Weinheim : Wiley-Blackwell
    Journal of High Resolution Chromatography 15 (1992), S. 800-806 
    Details
    ISSN: 0935-6304
    Keywords: Gas chromatography ; Resolution of enantiomers ; Chiral stationary phase ; Derivatized cyclodextrin ; Trifluoroacetylated cyclodextrin ; Structural effects ; Thermodynamic properties ; Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: More than 30 enantiomeric alcohols have been analyzed, without prior derivatization, by gas chromatography using a fused silica capillary column coated with octakis(3-O-trifluoro-acetyl-2,6-di-O-n-pentyl)-γ-cyclodextrin. Most were analyzed over a range of isothermal temperatures from 35 to 70°C. Enantiomeric separations were observed for most of the analytes, even at temperatures as low as 35°C.The stereoselectivity of the stationary phase was found to depend on the length of the longest carbon chain attached to the stereogenic centre in 2- and 3-hydroxy alkanes, the relative positions of the methyl and hydroxyl substituents in methylsubstituted alcohols, and the effects of multiple bonds in the analyte molecule. Thermodynamic data calculated from the results suggest that the enantiomers of all the analytes are resolved by a similar process. Retention and thermodynamic data are presented and possible mechanisms discussed.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jhrc.1240151206
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  • 5
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    Doping-enhanced radiative efficiency enables lasing in unpassivated GaAs nanowires (2016)
    Springer Nature
    Details
    Publication Date: 2016-06-19
    Description: Article Until now, efforts to enhance the performance of nanolasers have focused on reducing the rate of non-radiative recombination. Here, Burgess et al. employ controlled impurity doping to increase the rate of radiative recombination. Nature Communications doi: 10.1038/ncomms11927 Authors: Tim Burgess, Dhruv Saxena, Sudha Mokkapati, Zhe Li, Christopher R. Hall, Jeffrey A. Davis, Yuda Wang, Leigh M. Smith, Lan Fu, Philippe Caroff, Hark Hoe Tan, Chennupati Jagadish
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
    Published by Springer Nature
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  • 6
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    Relaxation of HCN (001) using stimulated electronic Raman scattering in Cs vapor as a tunable infrared source (1979)
    American Institute of Physics
    Details
    Publication Date: 1979-10-15
    Print ISSN: 0021-9606
    Electronic ISSN: 1089-7690
    Topics: Chemistry and Pharmacology , Physics
    Published by American Institute of Physics
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  • 7
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    AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML (2006)
    American Society of Hematology
    Details
    Publication Date: 2006-02-01
    Description: The nonobese diabetic/severe combined immunodeficient (NOD/SCID) assay is the current model for assessment of human normal and leukemic stem cells. We explored why 51% of 59 acute myeloid leukemia (AML) patients were unable to initiate leukemia in NOD/SCID mice. Increasing the cell dose, using more permissive recipients, and alternative tissue sources did not cause AML engraftment in most previously nonengrafting AML samples. Homing of AML cells to the marrow was the same between engrafters and nonengrafters. FLT3 internal tandem duplication (ITD) and nucleophosmin mutations occurred at a similar frequency in engrafters and nonengrafters. The only variable that was related to engraftment ability was the karyotypically defined risk stratification of individual AML cases. Of interest, follow-up of younger patients with intermediate-risk AML revealed a significant difference in overall survival between NOD/SCID engrafting and nonengrafting AMLs. Hence, the ability of AML to engraft in the NOD/SCID assay seems to be an inherent property of AML cells, independent of homing, conditioning, or cell frequency/source, which is directly related to prognosis. Our results suggest an important difference between leukemic initiating cells between engrafting and nonengrafting AML cases that correlates with treatment response.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 8
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    Development of a Human Acute Myeloid Leukaemia Screening Panel and Identification of Novel Gene Mutations. (2004)
    American Society of Hematology
    Details
    Publication Date: 2004-11-16
    Description: Mutation studies in Acute Myeloid Leukaemia (AML) are complicated by the existence of distinct morphological and cytogenetic subtypes; consequently although mutations in any one gene may occur in only 5% of AML, the frequency of mutation may differ both between the different FAB-types and cytogenetic risk groups studied. It is important therefore not only to validate the screening methodology used but also the suitability of the patient panel tested. A screening panel was developed allowing detection of novel recurring gene mutations within samples derived from patients with AML. Mutation analysis of 6 previously described genes (RUNX1, FLT3, KIT, CEBPA, PTPN11, NRAS) and 2 candidate genes (CCND3, FES) were carried out in a cohort of 175 AML samples representing all FAB types (except M3) and cytogenetic risk groups using a combination of SSCP, DHPLC and sequence analysis. One hundred and fifteen mutations were identified in 97 (55%) patients comprising 81 patients (46%) with one mutation, 14 patients (8%) with 2 mutations, and 2 patients (1%) with 3 mutations. Fifty-five out of 88 (63%) patients with normal karyotype AML had at least one mutation. There was was a weak negative association between FLT3 ITD and loop mutation (p = 0.095), a positive association between KIT mutation and favourable risk cytogenetics (p = 0.001), CEBPA mutation and intermediate risk/normal cytogenetics (p = 0.045) and PTPN11 mutation and poor risk disease (p = 0.001). The frequency of individual gene mutation was in accordance with previously published studies. Three novel mutations of FLT3 (Y589D, D839G, Y842H) were detected in 4 patients that would have been overlooked by conventional gel electrophoresis techniques. A single in frame 51bp deletion of nucleotide 939 – 990, resulting in a deletion of 17 amino acids at the carboxyl-terminus of the cyclin D3 protein was identified in a single patient. Overall, both the pattern and mutation frequencies reported in this cohort are similar to those in the literature supporting its further use as an investigational tool in the evaluation of candidate genes in the genesis of myeloid malignancy.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 9
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    Wilm’s Tumour 1 (WT1) Mutations Are Associated with FLT3-ITD Mutation and Poor Prognosis in Normal Karyotype AML. (2006)
    American Society of Hematology
    Details
    Publication Date: 2006-11-01
    Description: Our group has previously shown an association between acquired uniparental disomy 11p and homozygous gene mutation of Wilm’s tumour 1 (WT1) in a patient with normal karyotype acute myeloid leukemia (AML). Based on this observation the incidence of WT1 mutation was investigated in a cohort of normal karyotype AMLs. Mutation screening was performed on 70 patients (median age 55 years, range 19–78 years) by a PCR-direct sequencing approach using intronic primers flanking exons 2–10 of WT1. Mutation status was inferred from the resultant traces and confirmed by use of TOPO TA cloning and sequence analysis of the corresponding mutated clones. Mutations were detected in 7/70 (10%) patients; these typically resulted in insertion of 1–16 bp that led to the disruption of the DNA binding domain of the protein. The mutation profile of FLT3-ITD, NPM and CEBPA was also examined in this cohort of patients to compare the additional mutational events present in WT1 mutated and non-mutated cases. A significant positive association was observed between WT1 and FLT3-ITD mutation with 6/7 WT1 mutated cases having a FLT3-ITD compared to 20/63 non mutated cases (p=0.01). There was no association between mutations in WT1 and either of the good prognostic mutational markers, CEBPA and NPM. All 6 patients with both WT1 and FLT3 mutations were refractory to intensive induction chemotherapy with WT1 mutation showing a trend towards a worse overall survival when compared with the non-mutated group (p=0.07). We can conclude therefore that WT1 is mutated in 10% of normal karyotype AML, is positively associated with FLT3-ITD status and identifies a putative subgroup of normal karyotype AML who fail to achieve remission with conventional cytotoxic therapy and have a poor overall survival. Validation of this data in larger series would support the inclusion of WT1 in the current molecular risk stratification of normal karyotype AML based on CEBPA, NPM and FLT3-ITD status.
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    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 10
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    Hoxa9 Suppresses Cellular Senescence and Sustains the Development of Leukemic Stem Cells Induced by Fusion Proteins In the Absence of Bmi1. (2010)
    American Society of Hematology
    Details
    Publication Date: 2010-11-19
    Description: Abstract 1578 While self renewal is an essential feature for the maintenance of both normal hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs), very little is known about the underlying molecular pathways. Here we report a critical functional interplay between Bmi1 and Hox in establishment of HSCs and LSCs. Using Bmi1-/- bone marrow cells, we observe that leukemia-associated fusion proteins have distinctive Bmi1 requirements. AML1-ETO (AE) and PLZF-RARα (PR) fail to transform Bmi1-/- primary hematopoietic cells, and induce expression of p16/Arf leading to oncogene-induced senescence (OIS). In contrast, MLL-AF9 driving expression of multiple Hox genes can bypass oncogene-induced senescence and exhibits modest Bmi1-dependence for establishment of LSCs, which can induce leukemia upon serial transplants. Since members of Hox genes with proclaimed self-renewal property are specifically up-regulated by MLL fusions in patient samples and our murine models, we asked the question if these Hox genes may partly compensate the functions associated with the loss of Bmi1. To this end, we generated compound Bmi1-/-Hoxa9-/- mice, which have even more compromised hematopoietic stem cell/progenitor compartments than those of Bmi1-/- or Hoxa9-/- mice. Bmi1-/-Hoxa9-/- mice have a greater than eight-fold reduction in the absolute number of Lin-Sca+kit+ (LSK) in the bone marrow as compared to Bmi1-/- mice and a very significant forty-fold reduction for long term hematopoietic stem cells (LT-HSC). More importantly, while MAF9 is able to transform wild type, Bmi1-/- and Hoxa9-/-, it fails to transform Bmi1-/-Hoxa9-/- cells for establishment of LSCs, which can however be resurrected by re-expression of either Bmi1 or Hoxa9, indicating a critical functional interplay between these protein in development of MLL LSCs. Consistent with the known function of Bmi1 in suppressing cellular senescence and the expression of p16/Arf loci, we showed that Hoxa9 alone can also inhibit replicative senescence and Ras-induced senescence in primary human fibroblast. Forced expression of Hoxa9 can suppress p16/Arf expression, as well as cellular senescence induced by AE and PR in Bmi1-/- cells. Together, these results reveal a previously unrecognized functional interplay between Hox and Bmi1 in regulating cell senescence and development of LSCs induced by fusion proteins, which also suggests that synergistic targeting of both molecules may be required for certain LSCs. Disclosures: No relevant conflicts of interest to declare.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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