149 research outputs found

    The building materials’ and components’ database for an evidences-based design approach

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    The design process has always to meet, since the preliminary approaching step, every specific requirement which is foreseen for the building to realize. In a certain way, this operation represents an every time different prototype which varies according to the design demands for the considered room and the carried function, but also according to the used building materials: such an approach is already difficult by itself, but if we consider that at present the availability of technical information about building materials, components and systems is often incomplete or lost among many documents or even absent, it is evident that the designer’s activity becomes very uneven. That is the reason why, the definition of a database for building materials in which indicating each informative attribute to be considered becomes fundamental in order to: - provide a correct, univocal, clear and complete information for every building stakeholder; - help manufacturers to individualize the real needed information to join to their products, so to allow an easier comparison among products themselves and, as a consequence, to push towards a better quality of the entire building process (improving production, design, but also management). The paper deals with an analysis of the necessary information for designers and for maintenance planners, providing different levels of deepening according to the intended use. A particular attention will be paid on the so called “evidences-based design” which gives the opportunity to point out and to consider the most meaningful design matters, making an aware choice of building materials, components and systems. The International Service Life Data Base developed by CSTB with Politecnico di Milano will be reported as a tool for service life prediction, and buildings’ management

    Evaluation of gas turbines as alternative energy production systems for a large cruise ship to meet new maritime regulations

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    As a consequence of the new and up-coming regulations imposed by the International Maritime Organization (IMO), polluting emissions produced by large ships are now under strict control. Moreover, specific areas called \u201cEmission Controlled Area\u201d (ECA), which request even lower pollutant emissions, will be extended. To face up to this issue, ships propelled by Internal Combustion Engines (ICEs) burning Heavy Fuel Oil (HFO) can be equipped with abatement devices such as scrubbers and Selective Catalytic Reactor systems. Along with these solutions, which seem to be the route ship-owners will prefer, other methods can be considered, such as the use of Marine Gas Oil (MGO): a more expensive fuel, but with lower sulphur content. The use of MGO allows users to consider a further and more drastic modification of the power system, namely the use of Gas Turbines (GTs) in place of ICEs. GTs, despite being less efficient, are much lighter, more compact, and can more easily reach low NOx emissions than ICEs. Even if these aspects are theoretically well known, there are still difficulties in finding studies reporting quantitative analysis (weight, dimensions, fuel consumption) that compare GT and ICE power systems employed on board. The present paper aims to provide these data by analyzing different solutions applied to a real case. Unlike other studies, the work is focused on a cruise ship rather than on a cargo ship, because a cruise ship's operation profile is more variable during the trip

    Digital Transformation in the Construction Sector: From BIM to Digital Twin

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    In the next years, perhaps more than ever before, a technological revolution will transform the construction sector in all its aspects, greatly affecting services, production, and supplies. With BIM, and even more considering the Digital Twin topic, the innovation of tools has entailed a methodological innovation for the whole sector, owing to virtual reality simulations and actual dynamic real-time monitoring. This research, starting from an integrated analysis between the current research trends and some relevant national and European projects about the digitalization of construction sector, aims at providing a systematic analysis of some of the pillars that are guiding this phenomenon. In detail, the state of the art, activities, and trends of standardization and platform development in construction sector are considered and intersected to provide a clear background towards the future trends in the sector

    La durabilit\ue0 dei componenti edilizi

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    La pubblicazione riporta una sintesi dei risultati della ricerca scientifica nazionale (PRIN-2003) su \u201cMetodologie di progettazione e di valutazione della durabilit\ue0 dei componenti edilizi in processi di produzione sostenibili, finalizzate alla programmazione della manutenzione degli edifici\u201d delle sei unit\ue0 di ricerca (Politecnico di Milano, Politecnico di Torino, Universit\ue0 degli Studi Federico II di Napoli, Universit\ue0 degli Studi di Palermo, Universit\ue0 degli Studi di Catania, Universit\ue0 degli Studi di Brescia). La ricerca \ue8 condotta in coerenza con quanto si sta sviluppando a livello internazionale nell\u2019ambito dell\u2019International Council for Research and Innovation in Buiding and Construction (CIB), in particolare nella Commissione CIB W80 Prediction of Service Life of Building Materials and Components, nonch\ue9 nei correlati lavori dell\u2019ISO TC 59 SC14 per l\u2019elaborazione delle varie parti della norma ISO 15686 \u201cService life planning\u201d. Il lavoro ha portato nel 2006 alla uscita della prima norma italiana UNI 11156 \u201cValutazione della durabilit\ue0 dei componenti edilizi\u201d articolata in tre parti: \u201cTerminologia e definizione dei parametri di valutazione\u201d, \u201dMetodi per la valutazione della propensione all\u2019affidabilit\ue0\u201d, \u201dMetodi per la valutazione della durata\u201d. I risultati finora acquisiti costituiscono gi\ue0 un significativo riferimento per gli operatori di committenza pubblica e privata in interventi edilizi di nuova costruzione ai fini di organizzare per essi una manutenzione programmata atta ad assicurare nel tempo il mantenimento di un livello di qualit\ue0 tecnologica adeguato, con benefico effetto di riduzione dei costi di gestione degli edifici. Ci\uf2 potr\ue0 essere perseguito attraverso la conoscenza della qualit\ue0 tecnologica utile dei componenti edilizi dei componenti edilizi richiedibile attraverso le specifiche di durabilit\ue0 direttamente imponibili da parte dei progettisti nei capitolati speciali d\u2019appalto secondo i dettati della sopra citata norma UNI 11156

    Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI).

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    Abstract Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. Discussion This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25</p

    Early Aggressive Versus Initially Conservative Treatment in Elderly Patients With Non–ST-Segment Elevation Acute Coronary Syndrome A Randomized Controlled Trial

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    ObjectivesThis study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non–ST-segment elevation acute coronary syndromes (NSTEACS).BackgroundElderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS.MethodsA total of 313 patients ≥75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year.ResultsDuring admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03).ConclusionsThe present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185

    B-RAF and N-RAS Mutations Are Preserved during Short Time In Vitro Propagation and Differentially Impact Prognosis

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    In melanoma, the RAS/RAF/MEK/ERK signalling pathway is an area of great interest, because it regulates tumor cell proliferation and survival. A varying mutation rate has been reported for B-RAF and N-RAS, which has been largely attributed to the differential source of tumor DNA analyzed, e.g., fixed tumor tissues or in vitro propagated melanoma cells. Notably, this variation also interfered with interpreting the impact of these mutations on the clinical course of the disease. Consequently, we investigated the mutational profile of B-RAF and N-RAS in biopsies and corresponding cell lines from metastatic tumor lesions of 109 melanoma patients (AJCC stage III/IV), and its respective impact on survival. 97 tissue biopsies and 105 biopsy-derived cell lines were screened for B-RAF and N-RAS mutations by PCR single strand conformation polymorphism and DNA sequencing. Mutations were correlated with patient survival data obtained within a median follow-up time of 31 months. B-RAF mutations were detected in 55% tissues and 51% cell lines, N-RAS mutations in 23% tissues and 25% cell lines, respectively. There was strong concordance between the mutational status of tissues and corresponding cell lines, showing a differing status for B-RAF in only 5% and N-RAS in only 6%, respectively. Patients with tumors carrying mutated B-RAF showed an impaired median survival (8.0 versus 11.8 months, p = 0.055, tissues; 7.1 versus 9.3 months, p = 0.068, cell lines), whereas patients with N-RAS-mutated tumors presented with a favorable prognosis (median survival 12.5 versus 7.9 months, p = 0.084, tissues; 15.4 versus 6.8 months, p = 0.0008, cell lines), each in comparison with wildtype gene status. Multivariate analysis qualified N-RAS (p = 0.006) but not B-RAF mutation status as an independent prognostic factor of overall survival. Our findings demonstrate that B-RAF and N-RAS mutations are well preserved during short term in vitro propagation and, most importantly, differentially impact the outcome of melanoma patients

    Somatic p16INK4a loss accelerates melanomagenesis

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    Loss of p16INK4a–RB and ARF–p53 tumor suppressor pathways, as well as activation of RAS–RAF signaling, is seen in a majority of human melanomas. Although heterozygous germline mutations of p16INK4a are associated with familial melanoma, most melanomas result from somatic genetic events: often p16INK4a loss and N-RAS or B-RAF mutational activation, with a minority possessing alternative genetic alterations such as activating mutations in K-RAS and/or p53 inactivation. To generate a murine model of melanoma featuring some of these somatic genetic events, we engineered a novel conditional p16INK4a-null allele and combined this allele with a melanocyte-specific, inducible CRE recombinase strain, a conditional p53-null allele and a loxP-stop-loxP activatable oncogenic K-Ras allele. We found potent synergy between melanocyte-specific activation of K-Ras and loss of p16INK4a and/or p53 in melanomagenesis. Mice harboring melanocyte-specific activated K-Ras and loss of p16INK4a and/or p53 developed invasive, unpigmented and nonmetastatic melanomas with short latency and high penetrance. In addition, the capacity of these somatic genetic events to rapidly induce melanomas in adult mice suggests that melanocytes remain susceptible to transformation throughout adulthood

    Endothelin-1 Inhibits Prolyl Hydroxylase Domain 2 to Activate Hypoxia-Inducible Factor-1α in Melanoma Cells

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    The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation.Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels.In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF-1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability

    High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays

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    Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level
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