Identifiers in e-Science platforms for the ecological sciences

In the emerging Web of Data, publishing stable and unique identifiers promises great potential in using the web as common platform to discover and enrich data in the ecologic sciences. With our collaborative e-Science platform “BEFdata”, we generated and published unique identifiers for the data repository of the Biodiversity – Ecosystem Functioning Research Unit of the German Research Foundation (BEF-China; DFG: FOR 891). We linked part of the identifiers to two external data providers, thus creating a virtual common platform including several ecological repositories. We used the Global Biodiversity Facility (GBIF) as well the International Plant Name Index (IPNI) to enrich the data from our own field observations. We conclude in discussing other potential providers for identifiers for the ecological research domain. We demonstrate the ease of making use of existing decentralized and unsupervised identifiers for a data repository, which opens new avenues to collaborative data discovery for learning, teaching, and research in ecology

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid- sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.Integrative Biolog

Identifiers in e-Science platforms for the ecological sciences

In the emerging Web of Data, publishing stable and unique identifiers promises great potential in using the web as common platform to discover and enrich data in the ecologic sciences. With our collaborative e-Science platform “BEFdata”, we generated and published unique identifiers for the data repository of the Biodiversity – Ecosystem Functioning Research Unit of the German Research Foundation (BEF-China; DFG: FOR 891). We linked part of the identifiers to two external data providers, thus creating a virtual common platform including several ecological repositories. We used the Global Biodiversity Facility (GBIF) as well the International Plant Name Index (IPNI) to enrich the data from our own field observations. We conclude in discussing other potential providers for identifiers for the ecological research domain. We demonstrate the ease of making use of existing decentralized and unsupervised identifiers for a data repository, which opens new avenues to collaborative data discovery for learning, teaching, and research in ecology

Identifiers in e-Science platforms for the ecological sciences

In the emerging Web of Data, publishing stable and unique identifiers promises great potential in using the web as common platform to discover and enrich data in the ecologic sciences. With our collaborative e-Science platform “BEFdata”, we generated and published unique identifiers for the data repository of the Biodiversity – Ecosystem Functioning Research Unit of the German Research Foundation (BEF-China; DFG: FOR 891). We linked part of the identifiers to two external data providers, thus creating a virtual common platform including several ecological repositories. We used the Global Biodiversity Facility (GBIF) as well the International Plant Name Index (IPNI) to enrich the data from our own field observations. We conclude in discussing other potential providers for identifiers for the ecological research domain. We demonstrate the ease of making use of existing decentralized and unsupervised identifiers for a data repository, which opens new avenues to collaborative data discovery for learning, teaching, and research in ecology

Identifiers in e-Science platforms for the ecological sciences

In the emerging Web of Data, publishing stable and unique identifiers promises great potential in using the web as common platform to discover and enrich data in the ecologic sciences. With our collaborative e-Science platform “BEFdata”, we generated and published unique identifiers for the data repository of the Biodiversity – Ecosystem Functioning Research Unit of the German Research Foundation (BEF-China; DFG: FOR 891). We linked part of the identifiers to two external data providers, thus creating a virtual common platform including several ecological repositories. We used the Global Biodiversity Facility (GBIF) as well the International Plant Name Index (IPNI) to enrich the data from our own field observations. We conclude in discussing other potential providers for identifiers for the ecological research domain. We demonstrate the ease of making use of existing decentralized and unsupervised identifiers for a data repository, which opens new avenues to collaborative data discovery for learning, teaching, and research in ecology

Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a novel additional molecular marker for disease monitoring

Antileukemic Efficacy in Vitro of Talazoparib and APE1 Inhibitor III Combined with Decitabine in Myeloid Malignancies

Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials

Occurrence of aberrant centrosomal phenotypes in CD34⁺ bone marrow cells.

<p>(A) Centrosome staining and indirect immunofluorescence microscopy was performed on normal bone marrow samples (healthy controls, n = 6) and on specimen derived from patients with MDS (n = 16) and sAML (n = 4). Centrosome alterations in ≤ 5% of the analyzed interphase cells (n = 100) were evaluated as normal. (B) A representative panel of indirect immunofluorescence microscopic images shows normal (regular, n ≤ 2) and aberrant centrosome numbers (n > 2) in interphase cells. Centrosomes were stained using anti-pericentrin antibody (magenta), nuclear DNA is shown in blue (DAPI). Statistical methods: Kruskal-Wallis test. Mann-Whitney U tests followed by Bonferroni-Holm p-value correction were made as post-hoc tests in order to compare the MDS and sAML patients with the control group.</p

Influence of the therapeutic agents azacitidine, lenalidomide and rigosertib on the separase activity distribution (SAD value) in MDS-L cell culture experiments.

<p>(A) Exponentially growing MDS-L cells were treated with azacitidine, lenalidomide and rigosertib, each at concentrations of 500 nM for 48 hours. Subsequently, separase proteolytic activity was analyzed in the remaining vital cell fraction. Untreated MDS-L cells served as negative control (untr). As <i>in vivo</i> benchmark, the mean over the SAD values of all MDS patients under investigation (n = 37) is presented by the very right column. Method: Unpaired two-tailed t test, p = 0.0067 (CI95%: -3.159 to -0.5398). The data are derived from 11 independent assay experiments, each performed in duplicates. (B) The corresponding cell cycle profiles of treated MDS-L cells were analyzed by flow cytometry after propidium iodide (PI) staining. The cell fractions at G1, S and G2/M phase are represented by white, gray and black fillings, respectively. Data are derived from 2 independent assay experiments performed in duplicates. (C) Assessment of apoptosis in treated MDS-L cells by flow cytometry using annexinV / PI staining. Data from early (annexinV positivity only) and late apoptosis (double-positive fraction for annexinV and PI) were combined and are derived from 2 independent assay experiments performed in duplicates. Abbreviations: SAD, separase activity distribution; untr, untreated; AzaC, azacitidine; Lena, lenalidomide; Rigo, rigosertib.</p