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  • 1
    Keywords: breast cancer ; Citizen science ; Crowd science ; Crowdsourcing
    Abstract: BACKGROUND: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. METHODS: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. FINDINGS: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. INTERPRETATION: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.
    Type of Publication: Journal article published
    PubMed ID: 26288840
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  • 2
    ISSN: 0304-4165
    Keywords: Calcium ; Myometrium ; Serum-restriction
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Keywords: Key words Cell cycle ; Antifolate ; GARFT ; Thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Purpose: Cell cycle-related events in CCRF-CEM lymphocytic leukemia cells were examined subsequent to inhibition of thymidylate synthase (TS) or GAR formyltransferase (GARFT) and prior to cell death or stasis. Methods: Cell populations were treated with the GARFT inhibitors 6R-5,10-dideazatetrahydrofolate (lometrexol) or LY309887, the TS inhibitor ZD1694, or the multitargeted antifolate LY231514. DNA content, nucleoside precursor incorporation and proliferating cell nuclear antigen (PCNA) expression as functions of drug treatment were assessed by multiparameter flow cytometry. Cellular respiration was measured by MTT analysis and apoptosis was detected by extraction of DNA fragments. Results: Cell populations treated for up to 96 h with lometrexol or LY309887 did not replicate and maintained a cell cycle distribution with distinct G1, S and G2/M regions. The number of S phase cells in treated populations was slightly elevated relative to control as measured by DNA content and PCNA. However, these cells were unable to incorporate 5-bromodeoxyuridine (BrdU). Throughout treatment, cells incubated with GARFT inhibitors maintained intact membranes and respired at a level comparable to untreated cells. In contrast, ZD1694 as well as LY231514, induced synchronization of the treatment population at the G1/S interface within 12 h of drug addition. This was followed by synchronous entry of the population into S phase. After 24 h of treatment, more than 90% of the cells were capable of incorporating BrdU and stained positive for PCNA. DNA fragmentation occurred in cells treated with ZD1694 or LY231514 but not in those treated with GARFT inhibitors. In addition, the viable cells remaining after 24–48 h of treatment with ZD1694 or LY231514 were respiring at twice the level of untreated cells. Conclusion: These results demonstrate that the distinct endpoints of GARFT and TS inhibition are preceded by distinct cell cycle and metabolic alterations.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0014-5793
    Keywords: Caffeine ; Intracellular calcium ; Myometrial smooth muscle ; Ryanodine
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0013-4686
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Current microbiology 6 (1981), S. 127-130 
    ISSN: 1432-0991
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The kinetics of growth and toxin production by the Hall strain ofClostridium botulinum type A was examined in the presence of various concentrations of iron (0.1 to 10.1 μg/ml, 1.8 to 182 μM) in a chemically defined medium. At concentrations below 0.5 μg/ml, iron insufficiency limited the growth of the organism. The maximum amount of toxin produced varied by only twofold (6×105 to 1.2×106 mouse median lethal doses/ml per A540 unit) over the 100-fold range of iron concentrations used. High concentrations of iron did not reduce the elaboration of botulinum toxin, in contrast with its marked inhibitory effects on the production of many bacterial toxins. Iron is unlikely to be a regulatory effector for the formation of botulinum toxin by the Hall strain of type A.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Molecular genetics and genomics 141 (1975), S. 23-40 
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Transversion mutations can be distinguished from transition mutations by the use of special rII mutants of bacteriophage T4. Methyl methanesulfonate did not induce reversion of the tester mutants along transversion or transition pathways from A:T1 base pair sites, nor along transversion pathways from G:C base pair sites. Ethyl methanesulfonate and N-methyl-N-nitrosourea, however, induced both transversions and transitions at an A:T base pair site; no transversions were detected at G:C-sites. Mn++ induced transversions and transitions at both A:T-and G:C-sites. The influence of temperature-sensitive gene-43 DNA polymerase mutator and antimutator mutations on the reversion of the rII tester mutants was measured: some gene-43 mutants differentially influenced different pathways of reversion. Studies of thymineless mutagenesis demonstrated A:T-site transversion mutations. A synergistic interaction between thymineless mutagenesis and the gene-43 mutator, tsL56, was used to demonstrate thymineless mutagenesis at one site where it was not detected in the presence of the wild type polymerase.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-136X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Robber flies (Diptera: Asilidae) were studied in Panama from May through August. Of the 16 species examined, 5 perched and foraged in the sun and 11 perched and foraged in the shade. Thoracic body temperatures of light-seeking flies ranged from 35.2–40.6°C during foraging. Light-seeking flies regulated body temperature behaviorally by microhabitat selection and postural adjustments, and physiologically by transferring warmed haemolymph from the thorax to the cooler abdomen. Thoracic temperatures of shade-seeking flies passively followed ambient temperature in the shade and these flies did not thermoregulate. None of these robber flies warmed endothermically in the absence of flight. Resting oxygen consumption ( $$\dot V_{O_2 } $$ ) of both groups scaled with body mass to the 0.77 power. The factorial increment in $$\dot V_{O_2 } $$ resulting from hovering flight ranged from 12 to 56. The $$\dot V_{O_2 } $$ increased markedly with body temperature in light-seeking flies and probably explains the greater foraging effort observed in these species. Wing loading of all 16 species of robber flies scaled with body mass to the 0.39 power. Large light-seeking flies had heavier wing loading than large shade-seeking flies. The differences in body temperature and wing loading between light-seeking and shade-seeking robber flies may be related to differences in flight speed and maneuverability during foraging.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Classical “antimutator” DNA polymerases of bacteriophage T4 were examined for their effects upon frameshift mutation rates at a number of positions within rII cistrons. Their antimutagenic activities reduced frameshift frequencies at a number of sites, but at other sites the opposite occurred: the mutant polymerases exhibited clear mutator activities. This dichotomy reveals the operation of two distinct mechanisms of frameshift mutagenesis that are correlated with the DNA sequences at the frameshift sites. Frameshift mutants subject to the antimutator effects of the mutant polymerase lie in A:T-run DNA sequences, where mutations presumably arise by means of the interstrand DNA misalignments postulated by classical theory. The frameshift mutants produced by the mutator activity of these same polymerases lie in quasipalindromic DNA sequences, where mutations are postulated to arise by aberrant metabolism of DNA secondary structures such as hairpins.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A method is described for recognizing many transversion mutations arising within an ochre (UAA) codon in therII gene of bacteriophage T4. Most of therII ochre mutants used revert only by base pair substitution mutations in their DNA. Transition mutations within the UAA codon produce either an amber (UAG) mutant, an opal (UGA) mutant, or a glutamine (CAA) revertant. All three can be isolated and identified when the ochre mutant is treated with a mutagen which produces transitions. On the other hand, many nonsuppressed revertants with phenotypes different from the CAA revertant arose as transversions. The method has been used to score the spontaneous production of transversions at A:T base pair sites.
    Type of Medium: Electronic Resource
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