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  • 2015-2019  (131)
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  • 1
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    Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (2015)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publikationsdatum: 2015-08-07
    Beschreibung: We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10 –3 and MR5 for ratios 〈10 –5 . Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times ( P = .004) or 6.3 times ( P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.
    Schlagwort(e): Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Publiziert von American Society of Hematology (ASH)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype (2015)
    Nature Publishing Group (NPG)
    Details
    Publikationsdatum: 2015-10-17
    Beschreibung: Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype Blood Cancer Journal 5, e358 (October 2015). doi:10.1038/bcj.2015.84 Authors: J E Jang, Y H Min, J Yoon, I Kim, J-H Lee, C W Jung, H-J Shin, W S Lee, J H Lee, D-S Hong, H-J Kim, H-J Kim, S Park, K-H Lee, J H Jang, J S Chung, S M Lee, J Park, S K Park, J-S Ahn, W-S Min & J-W Cheong
    Digitale ISSN: 2044-5385
    Thema: Medizin
    Publiziert von Nature Publishing Group (NPG)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
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    A CaMoO4 Crystal Low Temperature Detector for the AMoRE Neutrinoless Double Beta Decay Search (2015)
    Hindawi
    Details
    Publikationsdatum: 2015-05-13
    Beschreibung: We report the development of a CaMoO4 crystal low temperature detector for the AMoRE neutrinoless double beta decay search experiment. The prototype detector cell was composed of a 216 g CaMoO4 crystal and a metallic magnetic calorimeter. An overground measurement demonstrated FWHM resolution of 6–11 keV for full absorption gamma peaks. Pulse shape discrimination was clearly demonstrated in the phonon signals, and 7.6  of discrimination power was found for the and separation. The phonon signals showed rise-times of about 1 ms. It is expected that the relatively fast rise-time will increase the rejection efficiency of two-neutrino double beta decay pile-up events which can be one of the major background sources in searches.
    Print ISSN: 1687-7357
    Digitale ISSN: 1687-7365
    Thema: Physik
    Publiziert von Hindawi
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida (2018)
    BioMed Central Ltd.
    In:  BMC Biology, 16 (1). Art.Nr. 136.
    Details
    Publikationsdatum: 2021-02-08
    Beschreibung: Background: Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes. Results: We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization. Conclusions: Our study indicates that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution. Based on our results, we hypothesize that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes. The TALE switch then diversified in the several lineages that engage in a complex multicellular organization. © 2018 The Author(s).
    Materialart: Article , PeerReviewed
    Format: text
    Format: text
    DOI: 10.1186/s12915-018-0605-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Surface Glycopolymers Are Crucial for In Vitro Anti-Wall Teichoic Acid IgG-Mediated Complement Activation and Opsonophagocytosis of Staphylococcus aureus [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions] (2015)
    The American Society for Microbiology (ASM)
    Details
    Publikationsdatum: 2015-10-09
    Beschreibung: The cell envelopes of many Gram-positive bacteria contain wall teichoic acids (WTAs). Staphylococcus aureus WTAs are composed of ribitol phosphate (RboP) or glycerol phosphate (GroP) backbones substituted with d -alanine and N -acetyl- d -glucosamine (GlcNAc) or N -acetyl- d -galactosamine (GalNAc). Two WTA glycosyltransferases, TarM and TarS, are responsible for modifying the RboP WTA with α-GlcNAc and β-GlcNAc, respectively. We recently reported that purified human serum anti-WTA IgG specifically recognizes β-GlcNAc of the staphylococcal RboP WTA and then facilitates complement C3 deposition and opsonophagocytosis of S. aureus laboratory strains. This prompted us to examine whether anti-WTA IgG can induce C3 deposition on a diverse set of clinical S. aureus isolates. To this end, we compared anti-WTA IgG-mediated C3 deposition and opsonophagocytosis abilities using 13 different staphylococcal strains. Of note, the majority of S. aureus strains tested was recognized by anti-WTA IgG, resulting in C3 deposition and opsonophagocytosis. A minority of strains was not recognized by anti-WTA IgG, which correlated with either extensive capsule production or an alteration in the WTA glycosylation pattern. Our results demonstrate that the presence of WTAs with TarS-mediated glycosylation with β-GlcNAc in clinically isolated S. aureus strains is an important factor for induction of anti-WTA IgG-mediated C3 deposition and opsonophagocytosis.
    Print ISSN: 0019-9567
    Digitale ISSN: 1098-5522
    Thema: Medizin
    Publiziert von The American Society for Microbiology (ASM)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Highly Conserved Mitochondrial Genomes among Multicellular Red Algae of the Florideophyceae (2015)
    Oxford University Press
    Details
    Publikationsdatum: 2015-08-30
    Beschreibung: Two red algal classes, the Florideophyceae (approximately 7,100 spp.) and Bangiophyceae (approximately 193 spp.), comprise 98% of red algal diversity in marine and freshwater habitats. These two classes form well-supported monophyletic groups in most phylogenetic analyses. Nonetheless, the interordinal relationships remain largely unresolved, in particular in the largest subclass Rhodymeniophycidae that includes 70% of all species. To elucidate red algal phylogenetic relationships and study organelle evolution, we determined the sequence of 11 mitochondrial genomes (mtDNA) from 5 florideophycean subclasses. These mtDNAs were combined with existing data, resulting in a database of 25 florideophytes and 12 bangiophytes (including cyanidiophycean species). A concatenated alignment of mt proteins was used to resolve ordinal relationships in the Rhodymeniophycidae. Red algal mtDNA genome comparisons showed 47 instances of gene rearrangement including 12 that distinguish Bangiophyceae from Hildenbrandiophycidae, and 5 that distinguish Hildenbrandiophycidae from Nemaliophycidae. These organelle data support a rapid radiation and surprisingly high conservation of mtDNA gene syntheny among the morphologically divergent multicellular lineages of Rhodymeniophycidae. In contrast, we find extensive mitochondrial gene rearrangements when comparing Bangiophyceae and Florideophyceae and multiple examples of gene loss among the different red algal lineages.
    Digitale ISSN: 1759-6653
    Thema: Biologie
    Publiziert von Oxford University Press
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
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    Fast and Accurate Large-Scale Detection of {beta}-Lactamase Genes Conferring Antibiotic Resistance [Analytical Procedures] (2015)
    The American Society for Microbiology (ASM)
    Details
    Publikationsdatum: 2015-09-19
    Beschreibung: Fast detection of β-lactamase ( bla ) genes allows improved surveillance studies and infection control measures, which can minimize the spread of antibiotic resistance. Although several molecular diagnostic methods have been developed to detect limited bla gene types, these methods have significant limitations, such as their failure to detect almost all clinically available bla genes. We developed a fast and accurate molecular method to overcome these limitations using 62 primer pairs, which were designed through elaborate optimization processes. To verify the ability of this large-scale bla detection method ( large-scale bla Finder), assays were performed on previously reported bacterial control isolates/strains. To confirm the applicability of the large-scale bla Finder, the assays were performed on unreported clinical isolates. With perfect specificity and sensitivity in 189 control isolates/strains and 403 clinical isolates, the large-scale bla Finder detected almost all clinically available bla genes. Notably, the large-scale bla Finder detected 24 additional unreported bla genes in the isolates/strains that were previously studied, suggesting that previous methods detecting only limited types of bla genes can miss unexpected bla genes existing in pathogenic bacteria, and our method has the ability to detect almost all bla genes existing in a clinical isolate. The ability of large-scale bla Finder to detect bla genes on a large scale enables prompt application to the detection of almost all bla genes present in bacterial pathogens. The widespread use of the large-scale bla Finder in the future will provide an important aid for monitoring the emergence and dissemination of bla genes and minimizing the spread of resistant bacteria.
    Print ISSN: 0066-4804
    Digitale ISSN: 1098-6596
    Thema: Biologie , Medizin
    Publiziert von The American Society for Microbiology (ASM)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
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    Structure of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus in Complex with a Protective Monoclonal Antibody [Vaccines and Antiviral Agents] (2015)
    The American Society for Microbiology (ASM)
    Details
    Publikationsdatum: 2015-03-11
    Beschreibung: The extracellular domain of influenza A virus matrix protein 2 (M2e) is conserved and is being evaluated as a quasiuniversal influenza A vaccine candidate. We describe the crystal structure at 1.6 Å resolution of M2e in complex with the Fab fragment of an M2e-specific monoclonal antibody that protects against influenza A virus challenge. This antibody binds M2 expressed on the surfaces of cells infected with influenza A virus. Five out of six complementary determining regions interact with M2e, and three highly conserved M2e residues are critical for this interaction. In this complex, M2e adopts a compact U-shaped conformation stabilized in the center by the highly conserved tryptophan residue in M2e. This is the first description of the three-dimensional structure of M2e. IMPORTANCE M2e of influenza A is under investigation as a universal influenza A vaccine, but its three-dimensional structure is unknown. We describe the structure of M2e stabilized with an M2e-specific monoclonal antibody that recognizes natural M2. We found that the conserved tryptophan is positioned in the center of the U-shaped structure of M2e and stabilizes its conformation. The structure also explains why previously reported in vivo escape viruses, selected with a similar monoclonal antibody, carried proline residue substitutions at position 10 in M2.
    Print ISSN: 0022-538X
    Digitale ISSN: 1098-5514
    Thema: Medizin
    Publiziert von The American Society for Microbiology (ASM)
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
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    Healthcare utilisation by pregnant patients with asthma in South Korea: a cohort study using nationwide claims data (2015)
    BMJ Publishing
    In: BMJ Open
    Details
    Publikationsdatum: 2015-11-08
    Beschreibung: Objectives Few nationwide population-based studies have examined the burden of asthma during pregnancy. Here, we investigated the burden and medical treatment of asthma during pregnancy requiring healthcare utilisation in South Korea. Design Cohort study. Setting Nationwide insurance claims database. Participants A total of 1 306 281 pregnant women who delivered in South Korea in 2009–2011. Outcomes The prevalence and exacerbation rates of asthma requiring healthcare utilisation, and the prescription of antiasthmatic drugs during pregnancy. Results The prevalence of asthma requiring healthcare utilisation was 0.43% among pregnant women. Among those with asthma requiring healthcare utilisation, 6.9% were hospitalised and treated with systemic steroids and short-acting β 2 -agonists during pregnancy. Oral drugs were prescribed less during the third trimester than during the first trimester (all p values for trends were 〈0.001). A significant number of patients with asthma were likely to stop taking antiasthmatic drugs after becoming pregnant. Conclusions The prevalence of asthma requiring healthcare utilisation during pregnancy was not very high. However, a significant number of women were likely to stop taking antiasthmatic drugs, and those who did tended to experience exacerbations.
    Schlagwort(e): Open access, Respiratory medicine, Obgyn
    Digitale ISSN: 2044-6055
    Thema: Medizin
    Publiziert von BMJ Publishing
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
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    Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers [Clinical Therapeutics] (2015)
    The American Society for Microbiology (ASM)
    Details
    Publikationsdatum: 2015-07-17
    Beschreibung: Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p -aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration ( C max ) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUC ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean C max and AUC , respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.)
    Print ISSN: 0066-4804
    Digitale ISSN: 1098-6596
    Thema: Biologie , Medizin
    Publiziert von The American Society for Microbiology (ASM)
    Standort Signatur Einschränkungen Verfügbarkeit
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