I CONTRATTI DERIVATI DI CREDITO

Il presente lavoro tratta del fenomeno dei derivati di credito dal punto di vista del diritto civile, con particolare riferimento agli aspetti contrattuali e ai problemi di compatibilit\ue0 dei modelli negoziali in uso con le norme imperative e i principi dell\u2019ordine pubblico interno. Nella trattazione degli argomenti, pur cercando di affrontare il discorso in termini generali, si \ue8 assunta come ipotesi paradigmatica il credit default swap, ci\uf2 che comporta senza dubbio una certa approssimazione, vista anche l\u2019estrema variet\ue0 e la complessit\ue0 delle tipologie di credit derivative e dei relativi, mutevoli, regolamenti negoziali conosciuti dalla prassi. Nel primo capitolo, dopo una sintetica descrizione del fenomeno, si evidenziano le notevoli similitudini, anche in termini di struttura e di contenuto, esistenti fra derivati finanziari e derivati su credito, tali da giustificare \u2013 ancor prima della novellata definizione di strumento finanziario (cfr. art. 1 TUF, comma 2 , lett. h) - l\u2019uso dell\u2019espressione \u201ccontratti derivati\u201d per intendere una (macro)categoria di strumenti negoziali socialmente ben individuati, comprensiva delle fattispecie comunemente ascritte a entrambe le tipologie contrattuali. La trattazione prosegue evidenziando le particolarit\ue0 di ordine funzionale che caratterizzano i derivati creditizi, i quali sono \u201ctipicamente\u201d intesi a soddisfare esigenze di protezione da un rischio di credito e, come tali, presentano una matrice quasi-assicurativa, piuttosto che strettamente finanziaria o di investimento. Alla luce della ricostruzione di tale funzione tipica, avallata anche dall\u2019espressione utilizzata dal Legislatore nell\u2019ambito dell\u2019analitica vigente definizione di strumento finanziario (\u201cstrumenti per il trasferimento del rischio di credito\u201d), viene quindi messa in discussione la validit\ue0 dei credit derivative meramente speculativi per possibile contrariet\ue0 con i principi dell\u2019ordine pubblico economico interno. Il secondo capitolo apre con una disamina delle principali conseguenze applicative derivanti dalla sussunzione dei derivati di credito nella definizione legislativa di strumento finanziario (riserva di attivit\ue0, applicazione della disciplina speciale in materia di intermediazione finanziaria e disapplicazione dell\u2019art. 1933 cod. civ.), alla quale segue una critica alla diffusa opinione che riconduce tale tipologia negoziale alla scommessa legalmente autorizzata. Vengono infine affrontati i profili della formazione e del contenuto dei contratti derivati di credito con particolare riferimento alle previsioni negoziali che deferiscono al calculation agent la determinazione dell\u2019oggetto del contratto.This study deals with credit derivatives from the perspective of Italian civil law, with particular focus on contractual issues and matters of compliance of the standard agreement forms with public policy and mandatory rules. While trying to approach the subject matter in general terms, the \u201cplain vanilla\u201d credit default swap is taken as a model for the analysis. This undoubtedly is a challenging exercise, considering the wide variety and complexity of credit derivatives. The first chapter begins by highlighting the remarkable similarities of structure and content existing between financial derivatives and credit derivatives and goes on to examine the purpose of the credit derivatives as instruments of protection from a credit risk. The validity of purely speculative credit derivatives is then called into question in light of public policy principles applicable pursuant to Italian law. The second chapter deals with the main consequences deriving from the inclusion of credit derivatives in the definition of \u201cfinancial instruments\u201d provided by Italian law. It then follows a criticism of the opinion that is widespread among Italian scholars, according to which credit derivatives are subject to the same rules applicable to the bets under Italian law. The last part of the study analyses the provisions of credit derivatives agreements relating to the determination of the subject matter thereof, focusing in particular on the role played by the calculation agent

Solvent-Free Synthesis of Quaternary Oxazolidine-2-thione β3-Amino Ester Analogs

A solvent-free organocatalyzed intermolecular cyclization reaction starting from β-substituted γ-hydroxy-α,β-unsaturated esters and aryl isothiocyanates proceeds via an aza-Michael addition to provide previously unknown quaternary oxazolidine-2-thione β3 amino ester analogs. A panel of diversely-substituted esters was investigated, including β,γ-disubstituted examples which provided the target molecules with very high cis diastereoselectivity

hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2-overexpressing breast cancer cells.

Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 in breast cancer patients is indicative of a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA11a and hMENAΔv6 with opposite functions. A novel role for the epithelial-associated hMENA11a isoform in sustaining HER3 activation and pro-survival pathways in HER2-overexpressing breast cancer cells has been identified by reverse phase protein array and validated in vivo in a series of breast cancer tissues. As HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA11a is involved in these resistance mechanisms. The specific hMENA11a depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors, whereas PI3K inhibitors activated hMENA11a phosphorylation and affected its localization. At the functional level, we found that hMENA11a sustains cell proliferation and survival in response to PI3K inhibitor treatment, whereas hMENA11a silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultures, hMENA11a contributes to resistance to PI3K inhibition because its depletion drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235. Altogether, these results indicate that hMENA11a in HER2-overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA11a expression can be proposed as a marker of HER3 activation and resistance to PI3K inhibition therapies, to select patients who may benefit from these combined targeted treatments. hMENA11a activity could represent a new target for antiproliferative therapies in breast cancer

Risk perception and ethnic background in construction workers: Results of a cross-sectional study in a group of trainees of a vocational school in italy

Risk perception can be influenced by cultural background. The study aims to evaluate risk perception, considering different ethnicities of construction workers from vocational schools in Italy. We administered a questionnaire investigating four different dimensions: Perceived behavioral control (PBC), Danger perception (DP), Safety climate (SC), and Attitude towards safe actions (ATSA). 562 workers answered: 72.4% from Italy, 14.2% from eastern Europe, 9.4% from Balkans, and 3.9% from North Africa. The participants indicated quite low control, attributable to the haste in performing the job. The workers perceived their specific job tasks as riskier compared to the tasks of their colleagues. They reported as fundamental the respecting of safety rules, but indicating that supervisors do not adequately promote safety behaviors. Finally, construction workers judged as \u201cbrave\u201d the colleagues working without protective equipment. When compared to Italians, North Africa workers showed a lower perception of the possibility to control their safe behaviors (p = 0.040), while both eastern Europeans and Balkan obtained higher scores at the ATSA dimension, indicating a kind of fatalistic acceptance of the risky situations at work. Eastern Europeans also showed a lower perception of the dangers (p = 0.002), while Balkan demonstrated a perception of SC even better than the Italian group (p = 0.005)

Spastin recovery in hereditary spastic paraplegia by preventing neddylation-dependent degradation

Hereditary Spastic Paraplegia (HSP) is a neurodegenerative disease most commonly caused by autosomal dominant mutations in the SPG4 gene encoding the microtubule-severing protein spastin. We hypothesise that SPG4-HSP is attributable to reduced spastin function because of haploinsufficiency; thus, therapeutic approaches which elevate levels of the wild-type spastin allele may be an effective therapy. However, until now, how spastin levels are regulated is largely unknown. Here, we show that the kinase HIPK2 regulates spastin protein levels in proliferating cells, in differentiated neurons and in vivo. Our work reveals that HIPK2-mediated phosphorylation of spastin at S268 inhibits spastin K48-poly-ubiquitination at K554 and prevents its neddylation-dependent proteasomal degradation. In a spastin RNAi neuronal cell model, overexpression of HIPK2, or inhibition of neddylation, restores spastin levels and rescues neurite defects. Notably, we demonstrate that spastin levels can be restored pharmacologically by inhibiting its neddylation-mediated degradation in neurons derived from a spastin mouse model of HSP and in patient-derived cells, thus revealing novel therapeutic targets for the treatment of SPG4-HSP

Volcanic Risk Management: the Case of Mt. Etna 2006 Eruption

Mt. Etna volcano is located in a very populated area of eastern Sicily (Italy). Its permanent degassing activity from summit craters and frequent eruptions impact significantly on town habitations and cultivated areas. In the latest years Etna has produced copious ash emission causing great losses to local economy and causing serious hazards to national and international air traffic over Mediterranean area and the often closure of Catania airport. In July 2006 eruptive vents opened on the East and South flanks of the summit craters showing irregular explosive and effusive activity lasting 6 months. This eruption represented the opportunity to perform the pre-operative test of FP6 Eurorisk-Preview (Prevention, Information and Early Warning) project aimed to develop tools for monitoring volcanoes. The test was performed during two temporal phases: the first one of early-warning was aimed to measure ground deformation and the second one during the crisis to survey volcanic ash produced during the explosions. The ground deformations were measured through the elaboration of SAR data. Beside the geophysical objectives, the test was also important to check data availability and efficiency of European Space Agency procedures. The pre-operative test has been peculiar to understand and quantify the delivering time of the final satellite products expected from the Volcanological Observatory in operative case. The analysis of July 2005 - July 2006 SAR data showed a pre-eruptive inflation trend in agreement with the ground network of GPS data. The magmatic source, that produced the September - October activity, has been located about 2.7 km below the summit craters. During the crisis phase characterized by paroxysmal activity, the Italian Civil Protection (DPC) in charge of airport closure in case of volcanic hazard, requested the satellite volcanic ash product retrieved from the NASA-MODIS data. An agreement between the industry Telespazio as direct broadcast of satellite data at Matera station and INGV was signed in order to elaborate the data in near-real time. The volcanic ash product provided information about: the presence of volcanic ash in the air; the affected area; the volcanic plume dispersal direction, dimensions and altitude and the volcanic ash loading. The satellite products and the observations report have been successively inserted in a web-interface. At the same time the observations report has been linked to the DPC dedicated Web-GIS interface that allows in a short time the availability of volcanic ash information to DPC in support to their decisions.Published77-811.10. TTC - Telerilevamentoope

Volcanic Risk Management: the Case of Mt. Etna 2006 Eruption

Mt. Etna volcano is located in a very populated area of eastern Sicily (Italy). Its permanent degassing activity from summit craters and frequent eruptions impact significantly on town habitations and cultivated areas. In the latest years Etna has produced copious ash emission causing great losses to local economy and causing serious hazards to national and international air traffic over Mediterranean area and the often closure of Catania airport. In July 2006 eruptive vents opened on the East and South flanks of the summit craters showing irregular explosive and effusive activity lasting 6 months. This eruption represented the opportunity to perform the pre-operative test of FP6 Eurorisk-Preview (Prevention, Information and Early Warning) project aimed to develop tools for monitoring volcanoes. The test was performed during two temporal phases: the first one of early-warning was aimed to measure ground deformation and the second one during the crisis to survey volcanic ash produced during the explosions. The ground deformations were measured through the elaboration of SAR data. Beside the geophysical objectives, the test was also important to check data availability and efficiency of European Space Agency procedures. The pre-operative test has been peculiar to understand and quantify the delivering time of the final satellite products expected from the Volcanological Observatory in operative case. The analysis of July 2005 - July 2006 SAR data showed a pre-eruptive inflation trend in agreement with the ground network of GPS data. The magmatic source, that produced the September - October activity, has been located about 2.7 km below the summit craters. During the crisis phase characterized by paroxysmal activity, the Italian Civil Protection (DPC) in charge of airport closure in case of volcanic hazard, requested the satellite volcanic ash product retrieved from the NASA-MODIS data. An agreement between the industry Telespazio as direct broadcast of satellite data at Matera station and INGV was signed in order to elaborate the data in near-real time. The volcanic ash product provided information about: the presence of volcanic ash in the air; the affected area; the volcanic plume dispersal direction, dimensions and altitude and the volcanic ash loading. The satellite products and the observations report have been successively inserted in a web-interface. At the same time the observations report has been linked to the DPC dedicated Web-GIS interface that allows in a short time the availability of volcanic ash information to DPC in support to their decisions

Wild-type p53-mediated down-modulation of interleukin 15 and interleukin 15 receptors in human rhabdomyosarcoma cells.

We recently reported that rhabdomyosarcoma cell lines express and secrete interleukin 15 (IL-15), a tightly regulated cytokine with IL-2-like activity. To test whether the p53-impaired function that is frequently found in this tumour type could play a role in the IL-15 production, wild-type p53 gene was transduced in the human rhabdomyosarcoma cell line RD (which harbours a mutated p53 gene), and its effect on proliferation and expression of IL-15 was studied. Arrest of proliferation was induced by wild-type p53; increased proportions of G1-arrested cells and of apoptotic cells were observed. A marked down-modulation of IL-15 expression, at both the mRNA and protein level, was found in p53-transduced cells. Because a direct effect of IL-15 on normal muscle cells has been reported, the presence of IL-15 membrane receptors was studied by cytofluorometric analysis. Rhabdomyosarcoma cells showed IL-15 membrane receptors, which are down-modulated by wild-type p53 transfected gene. In conclusion, wild-type p53 transduction in human rhabdomyosarcoma cells induces the down-modulation of both IL-15 production and IL-15 receptor expression

Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996

The impact of KMT2A-AFF1 rearrangement in pediatric-like, minimal residual disease (MRD)-based clinical trials and the effect of transplant in KMT2A-AFF1 ALL are still debated

neuroimaging changes in menkes disease part 1

SUMMARY: Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease