On the comparability of knowledge transfer activities – a case study at the German Baltic Sea Coast focusing regional climate services

In this article the comparability of knowledge transfer activities is discussed by accounting for external impacts. It is shown that factors which are neither part of the knowledge transfer activity nor part of the participating institution may have significant impact on the potential usefulness of knowledge transfer activities. Differences in the potential usefulness are leading to different initial conditions of the knowledge transfer activities. This needs to be taken into account when comparing different knowledge transfer activities, e.g., in program evaluations. This study is focusing on regional climate services at the German Baltic Sea coast. It is based on two surveys and experiences with two identical web tools applied on two regions with different spatial coverage. The results show that comparability among science based knowledge transfer activities is strongly limited through several external impacts. The potential usefulness and thus the initial condition of a particular knowledge transfer activity strongly depends on (1) the perceived priority of the focused topic, (2) the used information channels, (3) the conformity between the research agenda of service providing institutions and information demands in the public, as well as (4) on the spatial coverage of a service. It is suggested to account for the described external impacts for evaluations of knowledge transfer activities. The results show that the comparability of knowledge transfer activities is limited and challenge the adequacy of quantitative measures in this context. Moreover, as shown in this case study, in particular regional climate services should be individually evaluated on a long term perspective, by potential user groups and/or by its real users. It is further suggested that evaluation criteria should be co-developed with these stakeholder groups

Transferability Intercomparison: An Opportunity for New Insight on the Global Water Cycle and Energy Budget

A new approach, called transferability intercomparisons, is described for advancing both understanding and modeling of the global water cycle and energy budget. Under this approach, individual regional climate models perform simulations with all modeling parameters and parameterizations held constant over a specific period on several prescribed domains representing different climatic regions. The transferability framework goes beyond previous regional climate model intercomparisons to provide a global method for testing and improving model parameterizations by constraining the simulations within analyzed boundaries for several domains. Transferability intercomparisons expose the limits of our current regional modeling capacity by examining model accuracy on a wide range of climate conditions and realizations. Intercomparison of these individual model experiments provides a means for evaluating strengths and weaknesses of models outside their “home domains” (domain of development and testing). Reference sites that are conducting coordinated measurements under the continental-scale experiments under the Global Energy and Water Cycle Experiment (GEWEX) Hydrometeorology Panel provide data for evaluation of model abilities to simulate specific features of the water and energy cycles. A systematic intercomparison across models and domains more clearly exposes collective biases in the modeling process. By isolating particular regions and processes, regional model transferability intercomparisons can more effectively explore the spatial and temporal heterogeneity of predictability. A general improvement of model ability to simulate diverse climates will provide more confidence that models used for future climate scenarios might be able to simulate conditions on a particular domain that are beyond the range of previously observed climates

Integrating the Genetic and Physical Maps of Arabidopsis thaliana: Identification of Mapped Alleles of Cloned Essential (EMB) Genes

The classical genetic map of Arabidopsis includes more than 130 genes with an embryo-defective (emb) mutant phenotype. Many of these essential genes remain to be cloned. Hundreds of additional EMB genes have been cloned and catalogued (www.seedgenes.org) but not mapped. To facilitate EMB gene identification and assess the current level of saturation, we updated the classical map, compared the physical and genetic locations of mapped loci, and performed allelism tests between mapped (but not cloned) and cloned (but not mapped) emb mutants with similar chromosome locations. Two hundred pairwise combinations of genes located on chromosomes 1 and 5 were tested and more than 1100 total crosses were screened. Sixteen of 51 mapped emb mutants examined were found to be disrupted in a known EMB gene. Alleles of a wide range of published EMB genes (YDA, GLA1, TIL1, AtASP38, AtDEK1, EMB506, DG1, OEP80) were discovered. Two EMS mutants isolated 30 years ago, T-DNA mutants with complex insertion sites, and a mutant with an atypical, embryo-specific phenotype were resolved. The frequency of allelism encountered was consistent with past estimates of 500 to 1000 EMB loci. New EMB genes identified among mapped T-DNA insertion mutants included CHC1, which is required for chromatin remodeling, and SHS1/AtBT1, which encodes a plastidial nucleotide transporter similar to the maize Brittle1 protein required for normal endosperm development. Two classical genetic markers (PY, ALB1) were identified based on similar map locations of known genes required for thiamine (THIC) and chlorophyll (PDE166) biosynthesis. The alignment of genetic and physical maps presented here should facilitate the continued analysis of essential genes in Arabidopsis and further characterization of a broad spectrum of mutant phenotypes in a model plant

RBM6 splicing factor promotes homologous recombination repair of double-strand breaks and modulates sensitivity to chemotherapeutic drugs

RNA-binding proteins regulate mRNA processing and translation and are often aberrantly expressed in cancer. The RNA-binding motif protein 6, RBM6, is a known alternative splicing factor that harbors tumor suppressor activity and is frequently mutated in human cancer. Here, we identify RBM6 as a novel regulator of homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Mechanistically, we show that RBM6 regulates alternative splicing-coupled nonstop-decay of a positive HR regulator, Fe65/APBB1. RBM6 knockdown leads to a severe reduction in Fe65 protein levels and consequently impairs HR of DSBs. Accordingly, RBM6-deficient cancer cells are vulnerable to ATM and PARP inhibition and show remarkable sensitivity to cisplatin. Concordantly, cisplatin administration inhibits the growth of breast tumor devoid of RBM6 in mouse xenograft model. Furthermore, we observe that RBM6 protein is significantly lost in metastatic breast tumors compared with primary tumors, thus suggesting RBM6 as a potential therapeutic target of advanced breast cancer. Collectively, our results elucidate the link between the multifaceted roles of RBM6 in regulating alternative splicing and HR of DSBs that may contribute to tumorigenesis, and pave the way for new avenues of therapy for RBM6-deficient tumors

Molecular Foundations of Reproductive Lethality in Arabidopsis thaliana

The SeedGenes database (www.seedgenes.org) contains information on more than 400 genes required for embryo development in Arabidopsis. Many of these EMBRYO-DEFECTIVE (EMB) genes encode proteins with an essential function required throughout the life cycle. This raises a fundamental question. Why does elimination of an essential gene in Arabidopsis often result in embryo lethality rather than gametophyte lethality? In other words, how do mutant (emb) gametophytes survive and participate in fertilization when an essential cellular function is disrupted? Furthermore, why do some mutant embryos proceed further in development than others? To address these questions, we first established a curated dataset of genes required for gametophyte development in Arabidopsis based on information extracted from the literature. This provided a basis for comparison with EMB genes obtained from the SeedGenes dataset. We also identified genes that exhibited both embryo and gametophyte defects when disrupted by a loss-of-function mutation. We then evaluated the relationship between mutant phenotype, gene redundancy, mutant allele strength, gene expression pattern, protein function, and intracellular protein localization to determine what factors influence the phenotypes of lethal mutants in Arabidopsis. After removing cases where continued development potentially resulted from gene redundancy or residual function of a weak mutant allele, we identified numerous examples of viable mutant (emb) gametophytes that required further explanation. We propose that the presence of gene products derived from transcription in diploid (heterozygous) sporocytes often enables mutant gametophytes to survive the loss of an essential gene in Arabidopsis. Whether gene disruption results in embryo or gametophyte lethality therefore depends in part on the ability of residual, parental gene products to support gametophyte development. We also highlight here 70 preglobular embryo mutants with a zygotic pattern of inheritance, which provide valuable insights into the maternal-to-zygotic transition in Arabidopsis and the timing of paternal gene activation during embryo development

Spatio-Temporal Model-Checking of Cyber-Physical Systems Using Graph Queries

We explore the application of graph database technology to spatio-temporal model checking of cooperating cyber-physical systems-of-systems such as vehicle platoons. We present a translation of spatio-temporal automata (STA) and the spatio-temporal logic STAL to semantically equivalent property graphs and graph queries respectively. We prove a sound reduction of the spatio-temporal verification problem to graph database query solving. The practicability and efficiency of this approach is evaluated by introducing NeoMC, a prototype implementation of our explicit model checking approach based on Neo4j. To evaluate NeoMC we consider case studies of verifying vehicle platooning models. Our evaluation demonstrates the effectiveness of our approach in terms of execution time and counterexample detection