LIDAR studies on microbursts

Preliminary analysis of requirements for future airborne windshear detection systems is presented. The following topics are covered: flight mechanics; microbursts modeling; microburst detection with airborne systems (LIDAR, radar, passive IR sensors); microbursts prediction with ground systems (VHF interferometry). A short overview of these studies is presented and some results are discussed

A new pear scab resistance gene Rvp1 from the European pear cultivar ‘Navara’ maps in a genomic region syntenic to an apple scab resistance gene cluster on linkage group 2

Scab, caused by the ascomycete fungus Venturia pirina, leads to severe damage on European pear varieties resulting in a loss of commercial value and requiring frequent use of fungicides. Identifying scab resistance genes, developing molecular markers linked to these genes and establishing marker-assisted selection would be an effective way to improve European pear breeding for scab resistance. Most of the European pear cultivars (Pyrus communis) are currently reported to be sensitive. The pear cultivar ‘Navara’ was shown to carry a major scab resistance gene whose phenotypic expression in seedling progenies was a typical stellate necrosis symptom. The resistance gene was called Rvp1, for resistance to V. pirina, and was mapped on linkage group 2 of the pear genome close to microsatellite marker CH02b10. This genomic region is known to carry a cluster of scab resistance genes in apple indicating a first functional synteny for scab resistance between apple and pear

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors.

Repeat elements can be dysregulated at a genome-wide scale in human diseases. For example, in Ewing sarcoma, hundreds of inert GGAA repeats can be converted into active enhancers when bound by EWS-FLI1. Here we show that fusions between EWS and GGAA-repeat-targeted engineered zinc finger arrays (ZFAs) can function at least as efficiently as EWS-FLI1 for converting hundreds of GGAA repeats into active enhancers in a Ewing sarcoma precursor cell model. Furthermore, a fusion of a KRAB domain to a ZFA can silence GGAA microsatellite enhancers genome wide in Ewing sarcoma cells, thereby reducing expression of EWS-FLI1-activated genes. Remarkably, this KRAB-ZFA fusion showed selective toxicity against Ewing sarcoma cells compared with non-Ewing cancer cells, consistent with its Ewing sarcoma-specific impact on the transcriptome. These findings demonstrate the value of ZFAs for functional annotation of repeats and illustrate how aberrant microsatellite activities might be regulated for potential therapeutic applications

The WULCA consensus characterization model for water scarcity footprints: assessing impacts of water consumption based on available water remaining (AWARE)

Purpose Life cycle assessment (LCA) has been used to assess freshwater-related impacts according to a new water footprint framework formalized in the ISO 14046 standard. To date, no consensus-based approach exists for applying this standard and results are not always comparable when different scarcity or stress indicators are used for characterization of impacts. This paper presents the outcome of a 2-year consensus building process by the Water Use in Life Cycle Assessment (WULCA), a working group of the UNEP-SETAC Life Cycle Initiative, on a water scarcity midpoint method for use in LCA and for water scarcity footprint assessments. Methods In the previous work, the question to be answered was identified and different expert workshops around the world led to three different proposals. After eliminating one proposal showing low relevance for the question to be answered, the remaining two were evaluated against four criteria: stakeholder acceptance, robustness with closed basins, main normative choice, and physical meaning. Results and discussion The recommended method, AWARE, is based on the quantification of the relative available water remaining per area once the demand of humans and aquatic ecosystems has been met, answering the question “What is the potential to deprive another user (human or ecosystem) when consuming water in this area?” The resulting characterization factor (CF) ranges between 0.1 and 100 and can be used to calculate water scarcity footprints as defined in the ISO standard. Conclusions After 8 years of development on water use impact assessment methods, and 2 years of consensus building, this method represents the state of the art of the current knowledge on how to assess potential impacts from water use in LCA, assessing both human and ecosystem users’ potential deprivation, at the midpoint level, and provides a consensus-based methodology for the calculation of a water scarcity footprint as per ISO 14046

Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by Gαi proteins

AbstractHeterotrimeric Gi proteins play a role in lipopolysaccharide (LPS) and Staphylococcus aureus (SA) activated signaling leading to inflammatory mediator production. We hypothesized that genetic deletion of Gi proteins would alter cytokine and chemokine production induced by LPS and SA. LPS- and heat killed SA-induced cytokine and chemokine production in splenocytes from wild type (WT), Gαi2 (−/−) or Gαi1/3 (−/−) mice were investigated. LPS- or SA-induced production of TNFα, IL-6, IFNγ, IL-12, IL-17, GM-CSF, MIP-1α, MCP-1, MIG and IP-10 were significantly increased (1.2 to 33 fold, p<0.05) in splenocytes harvested from Gαi2(−/−) mice compared with WT mice. The effect of Gαi protein depletion was remarkably isoform specific. In splenocytes from Gαi1/3 (−/−) mice relative to WT mice, SA-induced IL-6, IFNγ, GM-CSF, and IP-10 levels were decreased (59% to 86%, p<0.05), whereas other LPS- or SA-stimulated cytokines and chemokines were not different relative to WT mice. LPS- and SA-induced production of KC were unchanged in both groups of the genetic deficient mice. Splenocytes from both Gαi2 (−/−) and Gαi1/3 (−/−) mice did not exhibit changes in TLR2 and TLR4 expression. Also analysis of splenic cellular composition by flow cytometry demonstrated an increase in splenic macrophages and reduced CD4 T cells in both Gαi2 (−/−) and Gαi1/3 (−/−) mice relative to WT mice. The disparate response of splenocytes from the Gαi2 (−/−) relative to Gαi1/3 (−/−) mice therefore cannot be attributed to major differences in spleen cellular composition. These data demonstrate that Gi2 and Gi1/3 proteins are both involved and differentially regulate splenocyte inflammatory cytokine and chemokine production in a highly Gi isoform specific manner in response to LPS and Gram-positive microbial stimuli