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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 38 (1992), S. 535-543 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A hybrid model is developed and implemented for predicting the limiting bound of the reactant conversion rate in an isotropic turbulent flow under the influence of a reaction of the type A + B Products. This model is based on the amplitude mapping closure of Kraichnan for the molecular mixing of a stochastically distributed scalar, and the eddy-damped quasi-normal Markovian (EDQNM) spectral closure for the two-point scalar covariance. The results predicted by this model compare well with available experimental data in both gaseous and aqueous plug-flow reactors, but point to the need for more detailed measurements in future experimental studies. With the implementation of the mapping closure, a simple analytical expression is obtained for the decay rate of the unmixedness. This expression is very convenient and is recommended for direct practical applications in the modeling and design of plug-flow reactors.
    Additional Material: 9 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 39 (1993), S. 899-903 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 27 (1994), S. 389-401 
    ISSN: 1059-910X
    Keywords: Biomineralization ; Greigite ; Magnetite ; Pyrite ; Single-magnetic-domain ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Electron microscopic studies on magnetosomes in magnetotactic bacteria have revealed much information on their composition, structure, and even the formation of their mineral phase. The mineral phases of the magnetosomes are of two general types: iron oxides and iron sulfides. Iron oxide-type magnetosomes contain particles of the ferrimagnetic mineral magnetite (Fe3O4) while the iron sulfide-type contain ferrimagnetic greigite (Fe3S4), greigite and non-magnetic pyrite (FeS2), or possibly ferrimagnetic pyrrhotite (Fe7S8). Regardless of their composition, the crystalline particles in magnetosomes have a narrow size range: approximately 35 to 120 nm. Magnetite crystals in this size range are single-magnetic-domains and confer a permanent magnetic dipole moment to the cell. The single-domain size range for greigite is not known but is probably similar to that for magnetite.The morphology of the particles in the bacterial magnetosomes appears to be species-specific. Morphologies of magnetite crystals in different species of magnetotactic bacteria include cubooctahedra, parallelepipedal (truncated hexahedral or octahedral prisms), and tooth- or bullet-shaped (anisotropic). Morphologies of greigite particles include cubo-octahedra and rectangular prismatic. The greigite-pyrite particles are generally pleomorphic with no consistent crystalline morphology. A membrane has been shown to surround the particles in some organisms and may be involved in the formation of the crystalline phase while also providing physical constraints on the size and the shape of the crystal. These results clearly indicate that the biomineralization process involved in the bacterial magnetosome, a good example of a self-assembled structure on a nanometer scale, is highly controlled by the organism. © 1994 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
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  • 4
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Developmental Genetics 13 (1992), S. 181-186 
    ISSN: 0192-253X
    Keywords: Inheritance ; non-genic ; pattern-formation ; ciliate ; Stentor coeruleus ; Tartar ; Vance ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The one form of cytoplasmic inheritance that has not been assimilated into the Central Dogma is the inheritance of surface structural patterns, a phenomenon most clearly expressed in cilates. Vance Tartar, although he worked with a genetically undomesticated organism (Stentor coeruleus), provided early evidence for the crucial role of clonally propagated features of the cell cortex. He showed that the capacity for development of cortical organelle systems is associated with a particular relational feature, the “locus of stripe contrast” (LSC), and that clonally inherited cortical variants (homopolar doublets) could be created at will by microsurgical operations that duplicated the LSC. Tartar also hoped to demonstrate the existence of what David Nanney called “cellular architects” by provoking stentors to carry out entirely novel types of morphogenetic performances. He eventually acknowledged failure, although the bizarre juxtapositions by which he attempted to elicit such novel performances did bring about specific and illuminating defects in cortical development. Subsequent analyses of similar defects in other ciliates revealed not the unitary “pattern factor” postulated by Tartar, but rather a hierarchy of distinct patterning mechanisms. Nonetheless, by pursuing an embryological approach toward morphogenesis in a highly regulative ciliate, Tartar uncovered relational aspects of pattern-determination; this, in my view, delineates the major problem that we must solve to gain understanding of intracellular patterning. © 1992 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
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  • 5
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Propellants, Explosives, Pyrotechnics 15 (1990), S. 26-29 
    ISSN: 0721-3115
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Azidodinitromethyl compounds represent a new highly energetic class of propellant ingredients. Preparation of these materials was accomplished by means of electroxidative coupling of azide ions to dinitromethyl carbanions. Thus, anodic coupling of sodium azide with ethyl 4,4-dinitrobutyrate produced ethyl 4-azido-4,4-dinitrobutyrate. Similarly, 4-azido-4,4-dinitrobutyl acetate was prepared from 4,4-dinitrobutyl acetate and converted by way of the corresponding alcohol to the nitrate ester, 4-azido-4,4-dinitrobutyl nitrate.
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  • 6
    Publication Date: 1991-09-01
    Description: H65-RTA is an immunoconjugate that consists of the A chain of ricin (RTA), a ribosomal-inhibiting protein, coupled to a murine monoclonal antibody (H65) directed against the pan-T-cell antigen CD5. The CD5 antigen is heterogeneously expressed on cutaneous T-cell lymphoma tumor cells, but is not expressed on normal cells except lymphocytes. A phase I trial was therefore conducted in which 14 patients with cutaneous T- cell lymphoma progressive on other therapies were treated with up to three cycles of H65-RTA. The maximal tolerated dose (MTD) of H65-RTA was 0.33 mg/kg/d administered intravenously for 10 days as defined by dyspnea at rest at higher doses. Other reversible side effects included myalgia, mild hypoalbuminemia with weight gain, pedal edema, fatigue, fevers, and chills. Six patients received more than one cycle of H65- RTA without increased side effects compared with the first cycle. Pharmacokinetic analysis showed that peak serum drug levels were dose- dependent, and ranged from 1.13 to 5.56 micrograms/mL, with a terminal half-life ranging from 1.0 to 2.9 hours. The development of antibodies against the immunoconjugate was associated with a lower peak drug level, but not with enhanced side effects. Partial responses lasting from 3 to 8 months were documented in four patients. Three of the responding patients received more than one cycle of H65-RTA in the presence of anti-immunoconjugate antibodies. The results from this phase I trial suggest that H65-RTA is an active drug in the treatment of cutaneous T-cell lymphoma. The immunoconjugate may be safely administered repeatedly, even in the presence of anti-immunoconjugate antibodies, with responses noted. Additional studies at the MTD are needed to define the response rate in this disease.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 7
    Publication Date: 1993-09-15
    Description: The characteristic reciprocal translocation t(15;17) of acute promyelocytic leukemia (APL) disrupts the PML gene on chromosome 15 and the retinoic acid receptor-alpha (RAR-alpha) gene on chromosome 17. PML/RAR-alpha fusion mRNAs are then transcribed and can be detected by a newly described reverse transcription polymerase chain reaction (RT- PCR) assay. Using RT followed by nested PCR amplification for PML/RAR- alpha, we serially evaluated bone marrow aspirates from patients with APL who were treated with all-trans retinoic acid (RA) for induction, followed by all-trans RA as maintenance or cytotoxic drugs as consolidation. At diagnosis, PML/RAR-alpha mRNA was detected in all patients. After initial therapy with all-trans RA, the RT-PCR assay remained positive after induction of complete remission in 31 of 32 evaluable patients. Maintenance treatment by all-trans RA alone was associated with persistent assay positivity and subsequent clinical relapse in 13 of 13 patients. By contrast, the test became negative in 19 of 20 newly diagnosed patients who received consolidation chemotherapy; the 1 patient who remained positive relapsed at 12 months. Three of the 19 assay-negative patients later converted to positive and subsequently relapsed; the remaining 16 patients have remained RT-PCR negative in sustained first remission, with a median follow-up duration that exceeds 24 months (range, 12+ to 34+ months). Despite induction of complete remission in a high proportion of patients, all-trans RA rarely eradicates molecular evidence of disease in patients with APL; however, subsequent treatment with cytotoxic chemotherapy frequently converts the RT-PCR assay for PML/RAR-alpha to negative. Serial negative tests are associated with prolonged disease- free survival, whereas persistence of a positive test after treatment is highly correlated with subsequent relapse. This test identifies patients in remission at high risk for relapse who may benefit from additional antileukemic therapy.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 8
    Publication Date: 1993-09-15
    Description: The characteristic reciprocal translocation t(15;17) of acute promyelocytic leukemia (APL) disrupts the PML gene on chromosome 15 and the retinoic acid receptor-alpha (RAR-alpha) gene on chromosome 17. PML/RAR-alpha fusion mRNAs are then transcribed and can be detected by a newly described reverse transcription polymerase chain reaction (RT- PCR) assay. Using RT followed by nested PCR amplification for PML/RAR- alpha, we serially evaluated bone marrow aspirates from patients with APL who were treated with all-trans retinoic acid (RA) for induction, followed by all-trans RA as maintenance or cytotoxic drugs as consolidation. At diagnosis, PML/RAR-alpha mRNA was detected in all patients. After initial therapy with all-trans RA, the RT-PCR assay remained positive after induction of complete remission in 31 of 32 evaluable patients. Maintenance treatment by all-trans RA alone was associated with persistent assay positivity and subsequent clinical relapse in 13 of 13 patients. By contrast, the test became negative in 19 of 20 newly diagnosed patients who received consolidation chemotherapy; the 1 patient who remained positive relapsed at 12 months. Three of the 19 assay-negative patients later converted to positive and subsequently relapsed; the remaining 16 patients have remained RT-PCR negative in sustained first remission, with a median follow-up duration that exceeds 24 months (range, 12+ to 34+ months). Despite induction of complete remission in a high proportion of patients, all-trans RA rarely eradicates molecular evidence of disease in patients with APL; however, subsequent treatment with cytotoxic chemotherapy frequently converts the RT-PCR assay for PML/RAR-alpha to negative. Serial negative tests are associated with prolonged disease- free survival, whereas persistence of a positive test after treatment is highly correlated with subsequent relapse. This test identifies patients in remission at high risk for relapse who may benefit from additional antileukemic therapy.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 9
    Publication Date: 1994-07-15
    Description: chromosome band 11q23, the location of the HRX gene, is a site of recurrent translocations in human malignancies. Infants with acute lymphoblastic leukemia (ALL) commonly have 11q23 translocations and have an especially poor prognosis despite intensive chemotherapy. We analyzed 96 cases of infant ALL treated on three consecutive Pediatric Oncology Group protocols to determine the frequency and prognostic significance of molecular rearrangements of HRX. Overall, 78 cases (81%) had HRX rearrangements detected by Southern blot analysis performed with a single HRX cDNA probe, whereas 18 cases (19%) had germline HRX. Of the 78 cases with HRX rearrangements, only 50 had abnormalities of 11q23 detected cytogenetically. Molecular abnormalities of HRX were associated with early treatment failure and a very poor outcome. Estimated event-free survival for patients with HRX rearrangements was 19% (SE, 7%) at 3 years, compared with 46% (SE, 17%) for patients with germline HRX (P = .033 by the two-sided logrank test). Therefore, infants with ALL and molecular abnormalities of HRX represent a group with an extremely high rate of failure who clearly need innovative or experimental treatment. Furthermore, cytogenetic analysis alone failed to detected 36% of HRX rearrangements, suggesting that molecular analysis be performed on all infants with ALL to identify this group of high-risk patients.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 10
    Publication Date: 1992-01-15
    Description: Although all-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), all groups have described clinical relapses despite continued RA treatment. This finding suggests that resistance to the cytodifferentiating effects of the retinoid had been acquired. To investigate potential mechanisms of clinical resistance to RA, we serially evaluated the clinical pharmacology of the drug in APL patients treated with this agent. Leukemic cells from patients relapsing from RA treatment were cultured in the presence of RA and examined for evidence of morphologic maturation. We also studied messenger RNA expression of the newly described gene product of the (15;17) translocation in APL, PML/RA receptor-alpha (PML/RAR-alpha). Serial pharmacokinetic studies showed that continuous daily RA treatment was associated with a marked decrease in plasma drug concentrations at the time of relapse compared with the initial day of therapy. Doubling the RA dose in six patients failed to reinduce response at the time of relapse and also failed to significantly augment plasma RA concentrations. However, leukemic cells obtained at the time of relapse from four patients retained in vitro sensitivity to the differentiating activity of RA (10(-6) mol/L). No change was observed in the pattern of PML/RAR-alpha expression assessed by Northern blot analysis at the time of relapse compared with pretreatment in two patients who were tested. These results indicate that clinical relapse and “resistance” to continuous treatment with all- trans RA in APL is associated with progressive reduction of plasma concentrations, potentially to levels below those that sustain differentiation of leukemic cells in vivo. Long-term success of this treatment will require the development of strategies that circumvent this pharmacologic phenomenon.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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