Proposta di un criterio di valutazione del rischio di progetto ai fini della procedura di asseverazione delle iniziative di project financing

La valutazione del rischio ai fini della concessione di finanziamenti alle imprese è un passo fondamentale e sempre delicato; la criticità cresce ulteriormente nel caso di iniziative che sfruttino lo strumento del project financing: tale strumento, particolarmente adatto a supportare le imprese di ingegneria nella realizzazione di opere pubbliche, prevede che la concessione del finanziamento non dipenda in via prioritaria dall’affidabilità e dalla capacità di credito dei soggetti ideatori del progetto – ovvero dal valore e dalla consistenza degli asset messi a disposizione dei finanziatori – bensì dalla accertata capacità dell’iniziativa di consentire il rientro del prestito per essa accordato: la copertura del finanziamento si realizza attraverso l’obbligazione, assunta dal promotore, a destinare parte del cash flow generato dal progetto alla graduale estinzione del debito, ed i soggetti finanziatori accettano come garanzia l’assicurazione della redditività dell’iniziativa. In tal senso la verifica dell’attendibilità dei risultati previsti dal promotore risulta essere determinante. A tal fine, in Italia una serie di Atti di Regolazione emanati dall’Autorità di Vigilanza sui Lavori Pubblici e le leggi che disciplinano il project financing indicano che il piano economico-finanziario presentato per una gara di appalto per “costruzione e gestione” di un’opera di pubblica utilità debba essere asseverato da un istituto di credito che ne certifichi la validità; pur sottolineando l’importanza della verifica del profilo di rischio e dell’equilibrio economico-finanziario dell’operazione, purtroppo la legislazione non definisce con la dovuta precisione modalità ed indicatori della procedura di asseverazione; in tal modo all’istituto asseveratore è spesso richiesto un giudizio complessivo, che lo spinge ad assumersi la responsabilità di approvare o respingere la proposta di progetto dovendone valutare anche aspetti tecnici o specifici del contesto in cui il progetto si pone, ciò che va ben al di là delle tradizionali competenze di un Istituto di Credito. In questa sede si riporta il risultato di uno studio condotto in collaborazione con un primario Istituto di Credito nazionale al fine di proporre una metodologia di valutazione del rischio di progetto che superi gli evidenti limiti della analisi degli scenari (tipicamente, average, best e worst) utilizzando congiuntamente il metodo Monte Carlo e l’analisi di sensibilità. La metodologia proposta, specificamente studiata per superare le criticità della procedura di asseverazione, è stata convalidata su un progetto di realizzazione di opere pubbliche con finanziamento privat

LRG1 as a novel therapeutic target in eye disease

Retinal and choroidal diseases are major causes of blindness and visual impairment in the developed world and on the rise due to an ageing population and diabetes epidemic. Standard of care is centred around blockade of vascular endothelial growth factor (VEGF), but despite having halved the number of patients losing sight, a high rate of patient non-response and loss of efficacy over time are key challenges. Dysregulation of vascular homoeostasis, coupled with fibrosis and inflammation, are major culprits driving sight-threatening eye diseases. Improving our knowledge of these pathological processes should inform the development of new drugs to address the current clinical challenges for patients. Leucine-rich α-2 glycoprotein 1 (LRG1) is an emerging key player in vascular dysfunction, inflammation and fibrosis. Under physiological conditions, LRG1 is constitutively expressed by the liver and granulocytes, but little is known about its normal biological function. In pathological scenarios, such as diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD), its expression is ectopically upregulated and it acquires a much better understood pathogenic role. Context-dependent modulation of the transforming growth-factor β (TGFβ) pathway is one of the main activities of LRG1, but additional roles have recently been emerging. This review aims to highlight the clinical and pre-clinical evidence for the pathogenic contribution of LRG1 to vascular retinopathies, as well as extrapolate from other diseases, functions which may be relevant to eye disease. Finally, we will provide a current update on the development of anti-LRG1 therapies for the treatment of nvAMD

A kwashiorkor case due to the use of an exclusive rice milk diet to treat atopic dermatitis.

Although several cases of severe hypoalbuminemia resulting from rice milk have been described in the past, today the use of rice milk without nutritional counseling to treat eczema is still a continuing, poor practice. We describe a kwashiorkor case in an infant with severe eczema exclusively fed with rice milk. It is well documented that rice milk is not a sufficient protein source. Moreover, only a small portion of eczema is triggered by food allergy. In conclusion this case raises the importance of managing dietary changes facing food allergies with responsibility for specialized consensus among pediatricians, nutritionists, endocrinologists and allergists all of them specialist professionals

Bacillus species at the Canberra Airport: A comparison of real-time polymerase chain reaction and massively parallel sequencing for identification

© 2018 Elsevier B.V. Anthrax, caused by the Gram-positive, spore forming bacterium Bacillus anthracis, is a disease with naturally occurring outbreaks in many parts of the world, primarily in domestic and wild herbivores. Due to the movement of people and stock, B. anthracis could, however, be at transportation hubs including airports. The continuous threat to national and international security from a biological agent release, or hoax attack, is a very real concern. Sensitive, robust and rapid (hours-day) methods to identify biological agents, including B. anthracis, and distinguish pathogenic from non-pathogenic species, is an essential cornerstone to national security. The aim of this project was to determine the presence of Bacillus species at the Canberra Airport using two massively parallel sequencing (MPS) approaches and compare with previous results using real-time polymerase chain reaction (qPCR). Samples were collected daily for seven days each month from August 2011–July 2012 targeting movement of people, luggage and freight into and out of the Canberra Airport. Extracted DNA was analysed using qPCR specific for B. anthracis. A subset of samples was analysed using two MPS approaches. Approach one, using the Ion PGM™ (Thermo Fisher Scientific; TFS) and an in-house assay, targeted the two B. anthracis virulence plasmids (cya and capB genes) and a single conserved region of the 16S rRNA gene. Approach two, using the Ion S5™ (TFS) and the commercial Ion 16S™ Metagenomics Kit (TFS), targeted multiple regions within the bacterial 16S rRNA gene. Overall there was consistency between the two MPS approaches and between MPS and qPCR, however, MPS was more sensitive, particularly for plasmid detection. Whilst the broad-range 16S genomic target(s) used in both MPS approaches in this study was able to generate a metagenomic fingerprint of the bacterial community at the Canberra Airport, it could not resolve Bacillus species beyond the level of the Bacillus cereus group. The inclusion of B. anthracis virulence plasmid targets in the in-house assay did allow for the potential presumptive identifications of pathogenic species. No plasmid targets were in the Ion 16S™ Metagenomics Kit. This study shows the choice of target(s) is key in MPS assay development and should be carefully considered to ensure the assay is fit for purpose, whether as an initial screening (presumptive) or a more specific (but not entirely confirmatory) test. Identification approaches may also benefit from a combination of MPS and qPCR as each has benefits and limitations

Edge centrality via the Holevo quantity

In the study of complex networks, vertex centrality measures are used to identify the most important vertices within a graph. A related problem is that of measuring the centrality of an edge. In this paper, we propose a novel edge centrality index rooted in quantum information. More specifically, we measure the importance of an edge in terms of the contribution that it gives to the Von Neumann entropy of the graph. We show that this can be computed in terms of the Holevo quantity, a well known quantum information theoretical measure. While computing the Von Neumann entropy and hence the Holevo quantity requires computing the spectrum of the graph Laplacian, we show how to obtain a simplified measure through a quadratic approximation of the Shannon entropy. This in turns shows that the proposed centrality measure is strongly correlated with the negative degree centrality on the line graph. We evaluate our centrality measure through an extensive set of experiments on real-world as well as synthetic networks, and we compare it against commonly used alternative measures

Differences in the properties of disrupted and surviving satellites of Milky-Way-mass galaxies in relation to their host accretion histories

From the chemo-dynamical properties of tidal debris in the Milky Way, it has been inferred that the dwarf satellites that have been disrupted had different chemical abundances from their present-day counterparts of similar mass that survive today, specifically, they had lower [Fe/H] and higher [Mg/Fe]. Here we use the ARTEMIS simulations to study the relation between the chemical abundances of disrupted progenitors of MW-mass galaxies and their stellar mass, and the evolution of the stellar mass - metallicity relations (MZR) of this population with redshift. We find that these relations have significant scatter, which correlates with the accretion redshifts (zacc) of satellites, and with their cold gas fractions. We investigate the MZRs of dwarf populations accreted at different redshifts and find that they have similar slopes, and also similar with the slope of the MZR of the surviving population (≈0.32). However, the entire population of disrupted dwarfs displays a steeper MZR, with a slope of ≈0.48, which can be explained by the changes in the mass spectrum of accreted dwarf galaxies with redshift. We find strong relations between the (mass-weighted) ⟨zacc⟩ of the disrupted populations and their global chemical abundances (⟨[Fe/H]⟩ and ⟨[Mg/Fe]⟩), which suggests that chemical diagnostics of disrupted dwarfs can be used to infer the types of merger histories of their hosts. For the case of the MW, our simulations predict that the bulk of the disrupted population was accreted at ⟨zacc⟩≈2, in agreement with other findings. We also find that disrupted satellites form and evolve in denser environments, closer to their hosts, than their present-day counterparts

A nucleotide insertion and frameshift cause albumin Kénitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges

Albumin Kenitra is a new type of genetic variant of human serum albumin that has been found in two members of a family of Sephardic Jews from Kenitra (Morocco). The slow-migrating variant and the normal protein were isolated by anion-exchange chromatography and, after treatment with CNBr, the digests were analyzed by two-dimensional electrophoresis in a polyacrylamide gel. The CNBr peptides of the variant were purified by reverse-phase high performance liquid chromatography and submitted to sequence analysis. Albumin Kenitra is peculiar because it has an elongated polypeptide chain, 601 residues instead of 585, and its sequence is modified beginning from residue 575. DNA structural studies showed that the variant is caused by a single-base insertion, an adenine at nucleotide position 15 970 in the genomic sequence, which leads to a frameshift with the subsequent translation to the first termination codon of exon 15. Mass spectrometric analyses revealed that the four additional cysteine residues of the variant form two new S-S bridges and showed that albumin Kenitra is partially O-glycosylated by a monosialylated HexHexNAc structure. This oligosaccharide chain has been located to Thr596 by amino-acid sequence analysis of the tryptic fragment 592-59

Nuclear accumulation of mRNAs underlies G4C2-repeat-induced translational repression in a cellular model of C9orf72 ALS

A common feature of non-coding repeat expansion disorders is the accumulation of RNA repeats as RNA foci in the nucleus and/or cytoplasm of affected cells. These RNA foci can be toxic because they sequester RNA-binding proteins, thus affecting various steps of post-transcriptional gene regulation. However, the precise step that is affected by C9orf72 GGGGCC (G4C2) repeat expansion, the major genetic cause of amyotrophic lateral sclerosis (ALS), is still poorly defined. In this work, we set out to characterise these mechanisms by identifying proteins that bind to C9orf72 RNA. Sequestration of some of these factors into RNA foci was observed when a (G4C2)31 repeat was expressed in NSC34 and HeLa cells. Most notably, (G4C2)31 repeats widely affected the distribution of Pur-alpha and its binding partner fragile X mental retardation protein 1 (FMRP, also known as FMR1), which accumulate in intra-cytosolic granules that are positive for stress granules markers. Accordingly, translational repression is induced. Interestingly, this effect is associated with a marked accumulation of poly(A) mRNAs in cell nuclei. Thus, defective trafficking of mRNA, as a consequence of impaired nuclear mRNA export, might affect translation efficiency and contribute to the pathogenesis of C9orf72 ALS