Modelling shallow landslide susceptibility by means of a subsurface flow path connectivity index and estimates of soil depth spatial distribution

Topographic index-based hydrological models have gained wide use to describe the hydrological control on the triggering of rainfall-induced shallow landslides at the catchment scale. A common assumption in these models is that a spatially continuous water table occurs simultaneously across the catchment. However, during a rainfall event isolated patches of subsurface saturation form above an impeding layer and their hydrological connectivity is a necessary condition for lateral flow initiation at a point on the hillslope. <br><br> Here, a new hydrological model is presented, which allows us to account for the concept of hydrological connectivity while keeping the simplicity of the topographic index approach. A dynamic topographic index is used to describe the transient lateral flow that is established at a hillslope element when the rainfall amount exceeds a threshold value allowing for (a) development of a perched water table above an impeding layer, and (b) hydrological connectivity between the hillslope element and its own upslope contributing area. A spatially variable soil depth is the main control of hydrological connectivity in the model. The hydrological model is coupled with the infinite slope stability model and with a scaling model for the rainfall frequency–duration relationship to determine the return period of the critical rainfall needed to cause instability on three catchments located in the Italian Alps, where a survey of soil depth spatial distribution is available. The model is compared with a quasi-dynamic model in which the dynamic nature of the hydrological connectivity is neglected. The results show a better performance of the new model in predicting observed shallow landslides, implying that soil depth spatial variability and connectivity bear a significant control on shallow landsliding

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

open6noThis work was supported by the University of Pavia [to MA, grant number BSR1744747; 2017] and the Italian Ministry of University and Research [to MA, FFABR2017]. The University of Bologna is acknowledged by MR [Grants from RFO].Age-related macular degeneration (AMD) is a common disease with a multifactorial aetiology, still lacking effective and curative therapies. Among the early events triggering AMD is the deterioration of the retinal pigment epithelium (RPE), whose fundamental functions assure good health of the retina. RPE is physiologically exposed to high levels of oxidative stress during its lifespan; thus, the integrity and well-functioning of its antioxidant systems are crucial to maintain RPE homeostasis. Among these defensive systems, the Nrf2-pathway plays a primary role. Literature evidence suggests that, in aged and especially in AMD RPE, there is an imbalance between the increased pro-oxidant stress, and the impaired endogenous detoxifying systems, finally reverberating on RPE functions and survival. In this in vitro study on wild type (WT) and Nrf2-silenced (siNrf2) ARPE-19 cells exposed to various AMD-related noxae (H2O2, 4-HNE, MG132 + Bafilomycin), we show that the Nrf2-pathway activation is a physiological protective stress response, leading downstream to an up-regulation of the Nrf2-targets HO1 and p62, and that a Nrf2 impairment predisposes the cells to a higher vulnerability to stress. In search of new pharmacologically active compounds potentially useful for AMD, four nature-inspired hybrids (NIH) were individually characterized as Nrf2 activators, and their pharmacological activity was investigated in ARPE-19 cells. The Nrf2 activator dimethyl-fumarate (DMF; 10 μM) was used as a positive control. Three out of the four tested NIH (5 μM) display both direct and indirect antioxidant properties, in addition to cytoprotective effects in ARPE-19 cells under pro-oxidant stimuli. The observed pro-survival effects require the presence of Nrf2, with the exception of the lead compound NIH1, able to exert a still significant, albeit lower, protection even in siNrf2 cells, supporting the concept of the existence of both Nrf2-dependent and independent pathways mediating pro-survival effects. In conclusion, by using some pharmacological tools as well as a reference compound, we dissected the role of the Nrf2-pathway in ARPE-19 stress response, suggesting that the Nrf2 induction represents an efficient defensive strategy to prevent the stress-induced damage.openCatanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M.Catanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M

Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression

The role of p53 in neurodegenerative diseases is essentially associated with neuronal death. Recently an alternative point of view is emerging, as altered p53 conformation and impaired protein function have been found in fibroblasts and blood cells derived from Alzheimer's disease patients. Here, using stable transfected SH-SY5Y cells overexpressing APP751wt (SY5Y-APP) we demonstrated that the expression of an unfolded p53 conformation compromised neuronal functionality. In particular, these cells showed (i) augmented expression of amyloid precursor protein (APP) and its metabolites, including the C-terminal fragments C99 and C83 and β-amyloid peptide (ii) high levels of oxidative markers, such as 4-hydroxy-2-nonenal Michael-adducts and 3-nitro-tyrosine and (iii) altered p53 conformation, mainly due to nitration of its tyrosine residues. The consequences of high-unfolded p53 expression resulted in loss of p53 pro-apoptotic activity, and reduction of growth-associated protein 43 (GAP-43) mRNA and protein levels. The role of unfolded p53 in cell death resistance and lack of GAP-43 transcription was demonstrated by ZnCl(2) treatment. Zinc supplementation reverted p53 wild-type tertiary structure, increased cells sensitivity to acute cytotoxic injury and GAP-43 levels in SY5Y-APP clone

Preliminary definitions for the sonographic features of synovitis in children

Objectives Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process. Methods The decision on which US techniques to use, the components to be included in the definitions as well as the final wording were developed by 31 ultrasound experts in a consensus process. A Likert scale of 1-5 with 1 indicating complete disagreement and 5 complete agreement was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, MCP and tibiotalar joints displaying various degrees of synovitis at various ages. Results B-Mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e. synovial hypertrophy, effusion and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% (range 80-100) of participants scoring it as 4 or 5 on a Likert scale. Conclusions US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web-based still images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research

Zap1 Control of Cell-Cell Signaling in \u3ci\u3eCandida albicans\u3c/i\u3e Biofilms

Biofilms of Candida albicans include both yeast cells and hyphae. Prior studies indicated that a zap1/ mutant, defective in zinc regulator Zap1, has increased accumulation of yeast cells in biofilms. This altered yeast-hypha balance may arise from internal regulatory alterations or from an effect on the production of diffusible quorum-sensing (QS) molecules. Here, we develop biosensor reporter strains that express yeastspecific YWP1-RFP or hypha-specific HWP1-RFP, along with a constitutive TDH3-GFP normalization standard. Seeding these biosensor strains into biofilms allows a biological activity assay of the surrounding biofilm milieu. A zap1/ biofilm induces the yeast-specific YWP1-RFP reporter in a wild-type biosensor strain, as determined by both quantitative reverse transcription-PCR (qRT-PCR) gene expression measurements and confocal microscopy. Remediation of the zap1/ zinc uptake defect through zinc transporter gene ZRT2 overexpression reverses induction of the yeast-specific YWP1-RFP reporter. Gas chromatography-mass spectrometry (GC-MS) measurements of known organic QS molecules show that the zap1/ mutant accumulates significantly less farnesol than wild-type or complemented strains and that ZRT2 overexpression does not affect farnesol accumulation. Farnesol is a well-characterized inhibitor of hypha formation; hence, a reduction in farnesol levels in zap1/ biofilms is unexpected. Our findings argue that a Zap1- and zinc-dependent signal affects the yeast-hypha balance and that it is operative in the low-farnesol environment of the zap1/ biofilm. In addition, our results indicate that Zap1 is a positive regulator of farnesol accumulation

Tests of an environmental and personnel safe cleaning process for BNL accelerator and storage ring components

A large measure of the successful operation of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL) for over a decade can be attributed to the cleaning of its UHV components during and after construction. A new UHV cleaning process, which had to be environmentally and personnel safe, was needed to replace the harsh, unfriendly process which was still in use. Dow Advanced Cleaning Systems was contracted to develop a replacement process without the use of harsh chemicals and which must clean vacuum surfaces as well as the existing process. Acceptance of the replacement process was primarily based on Photon Stimulated Desorption (PSD) measurements of beam tube samples run on NSLS beam line U10B. One meter long beam tube samples were fabricated from aluminum, 304 stainless steel and oxygen free copper. Initially, coupon samples were cleaned and passed preliminary testing for the proposed process. Next, beam tube samples of each material were cleaned, and the PSD measured on beam line U10B using white light with a critical energy of 487 ev. Prior to cleaning, the samples were contaminated with a mixture of cutting oils, lubricants, vacuum oils and vacuum grease. The contaminated samples were then baked. Samples of each material were also cleaned with the existing process after the same preparation. Beam tube samples were exposed to between 10{sup 22} and 10{sup 23} photons per meter for a PSD measurement. Desorption yields for H{sub 2}, CO, CO{sub 2}, CH{sub 4} and H{sub 2}O are reported for both the existing cleaning and for the replacement cleaning process. Preliminary data, residual gas scans, and PSD results are given and discussed. The new process is also compared with new cleaning methods developed in other laboratories

Photon stimulated desorption measurement of an extruded aluminum beam chamber for the Advanced Photon Source

The Advanced Photon Source (APS), presently being commisioned, will produce X-ray s of unprecedented brightness. The high energy ring of the APS is a 7 GeV positron storage ring, 1104 meters in circumference designed to operate at less than 10{sup {minus}9} Torr with 300 ma of beam and a greater than 10 hour lifetime. The storage ring vacuum chamber is constructed from an extruded 6063 aluminum alloy. During the construction phase, a 2.34 m long section of the APS extruded aluminum chamber was set up on National Synchrotron Light Source (NSLS) X-ray Beamlline X28A and Photon Stimulated Desorption (PSD) was measured. Cleaning and preparation of the chamber was identical to that of the APS construction. In addition to the chamber, small samples of M, Be, and Cu were also exposed to white light having a critical energy of 5 keV. In addition to PSD, measurements were made of specular and diffuse scattering of photons. The chamber and samples were each exposed to a dose greater than 10{sup 23} photons per meter. Desorption yields for H{sub 2}, CO, CO{sub 2}, CH{sub 4} and H{sub 2}0 are reported as a function of accumulated flux, critical energy, incidence angle, and preparation. These results are compared with previous results for aluminum on NSLS Beamlline U1OB and PSD results of other laboratories published for aluminum

Standard and Light-Cycler PCR methods for animal DNA species detection in animal feedstuffs

In this work four species-specific primers and probes were designed and evaluated for the detection and quantification of bovine, ovine, swine and chicken mitochondrial DNA in feeds. PCR primers were optimized using conventional and Real Time PCR, to detect short species-specific sequences amplifiable from heat treated material. Both methods confirmed the high specificity of the primers designed. Real time quantitative PCR assay allowed the detection of as few as 0.01 ng and 0.05 ng of ovine and bovine genomic DNA, respectively. The detection limit for swine and chicken genomic DNA was 0.5 ng. Sensitivity levels observed in DNA extracted from meat samples processed according to EU legislation were different compared to those in genomic DNAs previously described. They resulted in swine 5 fg of MBM DNA, in chicken 25 ng, in ovine and bovine 50 ng. We confirmed the efficiency and specificity of primers in RT-PCR to detect 0.5% of bovine, ovine, swine and chicken MBM in contaminated feedstuffs. (C) 2007 Elsevier Ltd. All rights reserved

TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats

Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components