Benefits from using combined dynamical-statistical downscaling approaches - Lessons from a case study in the Mediterranean region

Abstract. Various downscaling techniques have been developed to bridge the scale gap between global climate models (GCMs) and finer scales required to assess hydrological impacts of climate change. Such techniques may be grouped into two downscaling approaches: the deterministic dynamical downscaling (DD) and the statistical downscaling (SD). Although SD has been traditionally seen as an alternative to DD, recent works on statistical downscaling have aimed to combine the benefits of these two approaches. The overall objective of this study is to assess whether a DD processing performed before the SD permits to obtain more suitable climate scenarios for basin scale hydrological applications starting from GCM simulations. The case study presented here focuses on the Apulia region (South East of Italy, surface area about 20 000 km2), characterised by a typical Mediterranean climate; the monthly cumulated precipitation and monthly mean of daily minimum and maximum temperature distribution were examined for the period 1953–2000. The fifth-generation ECHAM model from the Max-Planck-Institute for Meteorology was adopted as GCM. The DD was carried out with the Protheus system (ENEA), while the SD was performed through a monthly quantile-quantile correction. The SD resulted efficient in reducing the mean bias in the spatial distribution at both annual and seasonal scales, but it was not able to correct the miss-modelled non-stationary components of the GCM dynamics. The DD provided a partial correction by enhancing the spatial heterogeneity of trends and the long-term time evolution predicted by the GCM. The best results were obtained through the combination of both DD and SD approaches

Immunodetection of nmt55/p54(nrb) isoforms in human breast cancer

BACKGROUND: We previously identified and characterized a novel 55 kDa nuclear protein, termed nmt55/p54(nrb), whose expression was decreased in a subset of human breast tumors. The objective of this study was to determine if this reduced expression in human breast tumors was attributed to the regulation of mRNA transcription or the presence of altered forms of this protein. RESULTS: Northern blot analysis and ribonuclease protection assay indicated that nmt55/p54(nrb) mRNA is expressed at varying levels in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) human breast tumors suggesting that reduced expression of nmt55/p54(nrb) protein in ER- tumors was not due to transcriptional regulation. To determine if multiple protein isoforms are expressed in breast cancer, we utilized Western blot and immunohistochemical analyses, which revealed the expression of an nmt55/p54(nrb) protein isoform in a subset of ER+ tumors. This subset of ER+ human breast tumors expressed an altered form of nmt55/p54(nrb) that was undetectable with an amino-terminal specific antibody suggesting that this isoform contains alterations or modifications within the amino terminal domain. CONCLUSIONS: Our study indicates that nmt55/p54(nrb) protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. The potential involvement of nmt55/p54(nrb) in RNA binding and pre-mRNA splicing may be important for normal cell growth and function; thus, loss or alteration of protein structure may contribute to tumor growth and progression

Metabolic synergies in the biotransformation of organic and metallic toxic compounds by a saprotrophic soil fungus

The saprotrophic fungus Penicillium griseofulvum was chosen as model organism to study responses to a mixture of hexachlorocyclohexane (HCH) isomers (α-HCH, β-HCH, γ-HCH, δ-HCH) and of potentially toxic metals (vanadium, lead) in solid and liquid media. The P. griseofulvum FBL 500 strain was isolated from polluted soil containing high concentrations of HCH isomers and potentially toxic elements (Pb, V). Experiments were performed in order to analyse the tolerance/resistance of this fungus to xenobiotics, and to shed further light on fungal potential in inorganic and organic biotransformations. The aim was to examine the ecological and bioremedial potential of this fungus verifying the presence of mechanisms that allow it to transform HCH isomers and metals under different, extreme, test conditions. To our knowledge, this work is the first to provide evidence on the biotransformation of HCH mixtures, in combination with toxic metals, by a saprotrophic non-white-rot fungus and on the metabolic synergies involved

Cell-to-Cell Signaling Influences the Fate of Prostate Cancer Stem Cells and Their Potential to Generate More Aggressive Tumors

An increasing number of malignancies has been shown to be initiated and propelled by small subpopulations of cancer stem cells (CSC). However, whether tumor aggressiveness is driven by CSC and by what extent this property may be relevant within the tumor mass is still unsettled. To address this issue, we isolated a rare tumor cell population on the basis of its CD44+CD24− phenotype from the human androgen-independent prostate carcinoma cell line DU145 and established its CSC properties. The behavior of selected CSC was investigated with respect to the bulk DU145 cells. The injection of CSC in nude mice generated highly vascularized tumors infiltrating the adjacent tissues, showing high density of neuroendocrine cells and expressing low levels of E-cadherin and β-catenin as well as high levels of vimentin. On the contrary, when a comparable number of unsorted DU145 cells were injected the resulting tumors were less aggressive. To investigate the different features of tumors in vivo, the influence of differentiated tumor cells on CSC was examined in vitro by growing CSC in the absence or presence of conditioned medium from DU145 cells. CSC grown in permissive conditions differentiated into cell populations with features similar to those of cells held in aggressive tumors generated from CSC injection. Differently, conditioned medium induced CSC to differentiate into a cell phenotype comparable to cells of scarcely aggressive tumors originated from bulk DU145 cell injection. These findings show for the first time that CSC are able to generate differentiated cells expressing either highly or scarcely aggressive phenotype, thus influencing prostate cancer progression. The fate of CSC was determined by signals released from tumor environment. Moreover, using microarray analysis we selected some molecules which could be involved in this cell-to-cell signaling, hypothesizing their potential value for prognostic or therapeutic applications

Geomorphological map of the area between the Simpson Crags and Nash Ridge, mapped by areial photographs and satellite images (Victoria Land, Antarctica)

Here is shown a multidisciplinary approach for geomorphological analysis using remote sensing data. An image processing method based on principal component analysis and high pass convolution filter, has been applied to Landsat Thematic Mapper MS satellite date to produce an image map where the spectral and spatial infoprmation of different surface units have been enhanced. Differnt morphogenetic processes have been distinguished; morainic deposits results clearly discernible from the "in situ" material

Predicting new snow density in the Italian Alps: A variability analysis based on 10\ua0years of measurements

Despite its strong impact on the time evolution of the snowpack, current estimation of new snow density ((hn)) is usually accomplished either by using local empirical techniques or by assuming a constant snow density. Faced with the lack of an estimation model of (hn) valid for a wide spatial scale and supported by a suitable number of observations, this study aims to develop simple monthly linear regression models at scale of the entire Italian Alpine chain based on 12,112 snowfall observations at 122 stations, using only air temperature as predictor. Moreover, the remaining variance is investigated in both time and space, also considering some qualitative features of the snowfall events. The daily (hn) measurements present a mean value of 115kgm(-3) (105 and 159kgm(-3) for dry and wet conditions, respectively). The mean air temperature of the 24hr preceding the snowfall event has been found to be the best predictor of the (hn), within 31% of uncertainty. The analysis of associated residues allows supporting the idea that the adoption of a more local approach than the one analysed here is not able to substantially increase the predictive capabilities of the model. In fact, the main factor explaining the remaining variance over the air temperature is the wind, but in a complex orography, as mountain regions are, supplying realistic local wind fields is particularly challenging. Therefore, we conclude that using only the daily mean temperature as predictor is a good choice for estimating daily new snow density at scale of Italian Alpine chain, as well as at more regional scale

Antineoplastic effect of a combined mitotane treatment/ionizing radiation in adrenocortical carcinoma: A preclinical study

Mitotane (MTT) is an adrenolytic drug used in adjuvant and advanced treatments of adrenocortical carcinoma (ACC). Ionizing radiation (IR) is also used in adrenal cancer treatment, even though its biological action remains unknown. To provide a reliable in vivo preclinical model of ACC, we used mouse xenografts bearing human ACC to test the effects of MTT and IR alone and in combination. We evaluated tumor growth inhibition by the RECIST criteria and analyzed the cell cycle by flow cytometry (FCM). In the xenograft ACC model treated with MTT/IR in combination, we observed a marked inhibition of tumor growth, with strong tumor regression (p < 0.0001) compared to MTT and IR given alone (p < 0.05). The MTT results confirm its antisteroidogenic activity (p < 0.05) in the xenograft ACC model, revealing its ability to render cancer cells more prone to radiotherapy treatment. In addition, to explain the biological effect of these treatments on the Mismatch Repair System (MMR), we interfered with the MSH2 gene expression in untreated and MTT/IR-treated H295R and SW13 cell lines. Moreover, we observed that upon treatment with MTT/IR to induce DNA damage, MSH2 gene inhibition in both the H295R and SW13 cell lines did not allow DNA damage repair, thus inducing cell death. In conclusion, MTT seems to have a radiosensitizing property and, when given in combination with IR, is able to promote neoplastic growth inhibition, leading to a significant reduction in tumor size due to cell death