Strengthening multi-stakeholder cooperation in the international investment regime: The Brazilian model

The rule of law and dispute avoidance and settlement may not be enough to turn FDI into a means to the realization of the SDGs. Multi-stakeholder dialogue and cooperation should also be a central aspect of any institutional design. In this regard, the Brazilian model, at least in theory, scores better than most existing treaties and reform proposals

Solar tower CSP plants with transcritical cycles based on CO2 mixtures: A sensitivity on storage and power block layouts

In this work three CO2-based binary mixtures, CO2 + C6F6, CO2 + C2H3N and CO2 + C4F8, are compared as innovative working fluids for closed power cycles in CSP plants. Adopted in transcritical cycles, they lead to cycle efficiencies higher than sCO2 cycles at minimum temperatures above 50 degrees C, a typical condition for arid regions with high solar radiation. The analysis considers four plant configurations: the first with direct storage, solar salts as HTF and cycle maximum temperatures of 550 degrees C, while the three other plants adopt sodium as HTF and an indirect storage system, designed for cycle maximum temperatures of 550 degrees C, 625 degrees C and 700 degrees C. Detailed models are used to characterize the solar fields optical performance, the receiver thermal efficiency and the HTF pump consumption, both at design and off-design conditions, for large scale plants located in Las Vegas. Different power block layouts are considered, spanning from the more efficient ones to cycles with a high heat recovery capacity. In addition, the impact of the mixtures on the design of heat exchangers is evidenced, with convincing results with respect to the heat transfer characteristics of CO2. Considering the resulting yearly performances and LCOE of each configuration, the adoption of indirect storage systems is considered a viable solution for high temperature solar plants. The three innovative mixtures allow for a reduction in LCOE with respect to sCO2 cycles (up to 10 $/MWh, depending on the configuration), capacity factors above 70% for the specific location, optimal solar multiples around 2.8 and 12 equivalent hours of TES

Creativity Support in a Serious Game for Dementia Care

This paper advocates the use of computer-based serious games as a form of creativity support tool. Whilst the use of serious games has grown considerably in recent years, support for players to think creatively is often implicit in the game, and does not exploit the wide range of creativity techniques and software tools available. This paper makes the case for explicit creativity support in serious games, explores how implicit creativity support can be delivered in game play, and extends one reported model of serious game play with activities in which players deploy different forms of supported creative thinking. The model is then applied to inform 2 versions of a serious game developed to train carers in creativity techniques to deliver more person-centered care to people with dementia. Each version of the game was delivered as a prototype to support playtesting of the game and its effect on carer training

Arsenic movement and fractionation in agricultural soils which received wastewater from an adjacent industrial site for 50 years

Arsenic (As) is an element with important environmental and human health implications due to its toxic properties. It is naturally occurring since it is contained in minerals, but it can also be enriched and distributed in the environment by anthropogenic activities. This paper reports on the historic As contamination of agricultural soils in one of the most important national relevance site for contamination in Italy, the so-called SIN Brescia-Caffaro, in the city of Brescia, northern Italy. These agricultural areas received As through the use of irrigation waters from wastewater coming from a factory of As-based pesticides (lead and calcium arsenates, sodium arsenite). Pesticide production started in 1920 and ended in the '70. Concentrations in the areas are generally beyond the legal threshold values for different soil uses and are up to >200 mg/kg. Arsenic contamination was studied to assess the long-time trend and the dynamics related to the vertical movement of As down to 1 m depth and its horizontal diffusion with surface irrigation in the entire field. Arsenic fractionation analysis (solid phase speciation by sequential extraction procedure) was also performed on samples collected from these areas and employed in greenhouse experiments with several plant species to evaluate the long-term contamination and the role of plant species in modifying As availability in soil. The results of this work can help in the evaluation of the conditions controlling the vertical transfer of As towards surface aquifers, the bioaccumulation likelihood in the agricultural food chain and the selection of sustainable remediation techniques such as phytoextraction

加强国际投资体系中的多方合作：巴西模式

The rule of law and dispute avoidance and settlement may not be enough to turn FDI into a means to the realization of the SDGs. Multi-stakeholder dialogue and cooperation should also be a central aspect of any institutional design. In this regard, the Brazilian model, at least in theory, scores better than most existing treaties and reform proposals

Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis

Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SSc(Fib+)) with that obtained from six SSc patients without pulmonary fibrosis (SSc(Fib-)) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SSc(Fib+ )patients and SSc(Fib- )patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SSc(Fib+ )patients compared with SSc(Fib- )patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SSc(Fib+ )patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease

In vitro susceptibilities of Neoscytalidium spp. sequence types to antifungal agents and antimicrobial photodynamic treatment with phenothiazinium photosensitizers

Neoscytalidium spp. are ascomycetous fungi consisting of pigmented and hyaline varieties both able to cause skin and nail infection. Their colour-based identification is inaccurate and may compromise the outcome of the studies with these fungi. The aim of this study was to genotype 32 isolates morphologically identified as Neoscytalidium dimidiatum or Neoscytalidium dimidiatum var. hyalinum by multilocus sequence typing (MLST), differentiate the two varieties by their sequence types (STs), evaluate their susceptibility to seven commercial antifungal drugs [amphotericin B (AMB), voriconazole (VOR), terbinafine (TER), 5-flucytosine (5FC), ketoconazole (KET), fluconazole (FLU), and caspofungin (CAS)], and also to the antimicrobial photodynamic treatment (APDT) with the phenothiazinium photosensitizers (PSs) methylene blue (MB), new methylene blue (NMBN), toluidine blue O (TBO), and the pentacyclic derivative S137. The efficacy of each PS was determined, initially, based on its minimal inhibitory concentration (MIC). Additionally, the APDT effects with each PS on the survival of ungerminated and germinated arthroconidia of both varieties were evaluated. Seven loci of Neoscytalidium spp. were sequenced on MLST revealing eight polymorphic sites and six STs. All N. dimidiatum var. hyalinum isolates were clustered in a single ST. AMB, VOR, and TER were the most effective antifungal agents against both varieties. The hyaline variety isolates were much less tolerant to the azoles than the isolates of the pigmented variety. APDT with S137 showed the lowest MIC for all the isolates of both varieties. APDT with all the PSs killed both ungerminated and germinated arthroconidia of both varieties reducing the survival up to 5 logs. Isolates of the hyaline variety were also less tolerant to APDT. APDT with the four PSs also increased the plasma membrane permeability of arthroconidia of both varieties but only NMBN and S137 caused peroxidation of the membrane lipids. © 2017 British Mycological Society

Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression.

Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST