A NEW HIGH-RESOLUTION BI-CENTENNIAL (1800–2003) PRECIPITATION DATASET FOR THE GREATER ALPINE REGION

A new precipitation dataset for the Greater Alpine Region (GAR; 4°E–19°E, 43°N–49°N) has been developed. It provides monthly precipitation totals for the 1800–2003 period on a 10-min resolution grid. The new ‘HISTALP 10-min-grid’ dataset is based on long-term homogenized precipitation series from meteorological stations across the study domain and a high-resolution precipitation climatology dataset for the 1971–1990 period. The effective coverage of the dataset depends on the observations available in the station network which progressively decline back to the early 19th Century (from 192 to 5 stations). To aid the use of these data in other studies, an accompanying dataset has also been developed, which provides a measure of quality of each monthly precipitation estimate over the grid: the explained variance, relative to the 1931–2000 (maximum data availability) period. The computed quality score illustrates the comparatively poorer accuracy of the dataset for regions and months with less coherent precipitation fields (i.e., over the Alps and in summer) and when the number of stations is reduced, particularly before 1840. The derived gridded field has been compared with other independently-developed datasets and is found to provide a similar description of the precipitation in the GAR for places and periods of common coverage

PATTERNS OF PRECIPITATION VARIABILITY IN THE GREATER ALPINE REGION

A recently set up and homogenised new precipitation dataset for the Greater Alpine Region (GAR) is presented here with some first preliminary analyses. Climate change patterns within the study region are analysed in terms of regionally different evolutions, seasonality, and short to long-term trends. It will be shown that precipitation presents pronouncedly different variability patterns in space as well as in terms of seasonality and at different time scales

Multiscale characterisation of the mechanical properties of austenitic stainless steel joints

A multiscale investigation was pursued in order to obtain the strain distribution and evolution during tensile testing both at the macro- and micro-scale for a diffusion bonded 316L stainless steel. The samples were designed for the purpose to demonstrate that the bond line properties were equal or better than the parent material in a sample geometry that was extracted from a larger component. The macroscopic stress-strain curves were coupled to the strain distributions using a camera-based 2D – Digital Image Correlation system. Results showed significant amount of plastic deformation predominantly concentrated in shear bands which were extended over a large region, crossing through the joint area. Yet it was not possible to be certain whether the joint has shown significant plastic deformation. In order to obtain the joints’ mechanical response in more detail, in situ micromechanical testing was conducted in the SEM chamber that allowed areas of 1x1 mm2 and 50x50 mm2 to be investigated. The size of the welded region was rather small to be accurately captured from the camera based DIC system. Therefore a microscale investigation was pursued where the samples were tested within an SEM chamber. Low magnification SEM imaging was utilised in order to cover a viewing area of 1 mm×1 mm while high magnification SEM imaging was employed to provide evidence of the occurrence of plastic deformation within the joint, at an area of just 50 μm×50 μm. The strain evolution over the microstructural level, within the joint and at the base material was obtained. The local strains were highly non-homogeneous through the whole test. Final failure occurred approximately 0.2 mm away from the joint. Large local strains were measured within the joint region, while SEM imaging showed that plastic deformation occurs via the formation of strong slip bands, followed by the activation of additional slip systems upon further plastic deformation which end up in additional slip bands to form on the surface. Plastic deformation occurred by slip and twinning mechanisms. Upon necking, significant out of plane deformations and slip deformation mechanisms were observed which suggested that plastic deformation was also happening at the last stages of damage evolution for the specific alloy. This was also evident from the large difference between the 600 MPa UTS stress value and the low stress values before final failure (which in many cases was below 30 MPa)

PATTERNS OF PRECIPITATION VARIABILITY IN THE GREATER ALPINE REGION

A recently set up and homogenised new precipitation dataset for the Greater Alpine Region (GAR) is presented here with some first preliminary analyses. Climate change patterns within the study region are analysed in terms of regionally different evolutions, seasonality, and short to long-term trends. It will be shown that precipitation presents pronouncedly different variability patterns in space as well as in terms of seasonality and at different time scales

Human PAPS Synthase Isoforms Are Dynamically Regulated Enzymes with Access to Nucleus and Cytoplasm

In higher eukaryotes, PAPS synthases are the only enzymes producing the essential sulphate-donor 3′-phospho-adenosine-5′-phosphosulphate (PAPS). Recently, PAPS synthases have been associated with several genetic diseases and retroviral infection. To improve our understanding of their pathobiological functions, we analysed the intracellular localisation of the two human PAPS synthases, PAPSS1 and PAPSS2. For both enzymes, we observed pronounced heterogeneity in their subcellular localisation. PAPSS1 was predominantly nuclear, whereas PAPSS2 localised mainly within the cytoplasm. Treatment with the nuclear export inhibitor leptomycin B had little effect on their localisation. However, a mutagenesis screen revealed an Arg-Arg motif at the kinase interface exhibiting export activity. Notably, both isoforms contain a conserved N-terminal basic Lys-Lys-Xaa-Lys motif indispensable for their nuclear localisation. This nuclear localisation signal was more efficient in PAPSS1 than in PAPSS2. The activities of the identified localisation signals were confirmed by microinjection studies. Collectively, we describe unusual localisation signals of both PAPS synthase isoforms, mobile enzymes capable of executing their function in the cytoplasm as well as in the nucleus

Potent Inhibition of HIV-1 Replication by a Tat Mutant

Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection

HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis

Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells

Apoptosis in HIV-1-infected CD4+ primary T cells is triggered by the alteration of the PI3K and p53 pathways, which converge on the FOXO3a transcriptional activator. Tat alone can cause activation of FOXO3a and of its proapoptotic target genes. To understand how Tat affects this pathway, we carried out ChIP-Chip experiments with Tat. Tat associates with the promoters of PTEN and two PP2A subunit genes, but not with the FOXO3a promoter. PTEN and PP2A encode phosphatases, whose levels and activity are increased when Tat is expressed. They counteract phosphorylation of Akt1 and FOXO3a, and so activate transcriptional activity of FOXO3a. FOXO3a promotes increased transcription of Egr-1, which can further stimulate the transcription of PTEN, thereby reinforcing the pathway that leads to FOXO3a transcriptional activation. RNAi experiments support the role of PTEN and PP2A in the initiation of the Tat-mediated cascade, which is critical to apoptosis. The increased accumulation of PTEN and PP2A subunit mRNAs during Tat expression is more likely to be the result of increased transcription initiation and not relief of promoter-proximal pausing of RNAPII. The Tat-PTEN and -PP2A promoter interactions provide a mechanistic explanation of Tat-mediated apoptosis in CD4+ T cells

Variability in storm climate along the Gulf of Cadiz: the role of large scale atmospheric forcing and implications to coastal hazards

In the context of increased coastal hazards due to variability in storminess patterns, the danger of coastal damages and/or morphological changes is related to the sum of sea level conditions, storm surge, maximum wave height and run up values. In order to better understand the physical processes that cause the variability of the above parameters a 44 years reanalysis record (HIPOCAS) was used. The HIPOCAS time-series was validated with real wave and sea-level data using linear and vector correlation methods. In the present work changes in the magnitude, duration, frequency and approach direction of the Atlantic storms over the Gulf of Cadiz (SW Iberian Peninsula) were identified by computing various storm characteristics such as maximum wave height, total energy per storm wave direction and storm duration. The obtained time-series were compared with large-scale atmospheric indices such as the North Atlantic Oscillation (NAO) and the East Atlantic pattern. The results show a good correlation between negative NAO values and increased storminess over the entire Gulf of Cadiz. Furthermore, negative NAO values were correlated with high residual sea level values. Finally, a joint probability analysis of storm and sea level analysis resulted in increased probabilities of the two events happening at the same time indicating higher vulnerability of the coast and increased coastal risks. The above results were compared with coastal inundation events that took place over the last winter seasons in the province of Cadiz.info:eu-repo/semantics/publishedVersio