A Three-Layers Theoretical Framework For Analyzing Public Private Partnerships: The Italian Case

The applications of PPP all over the world vary from country to country. International literature lacks of contributions focusing on cross-country and cross-sector description, analysis and comparison of Public Private Partnerships (PPPs). The present paper aims at developing a framework for characterizing PPPs in various countries. The theoretical framework is divided in three layers: country, sector and project layers. Each layer is characterized by a set of dimensions and each dimension is characterized by a set of variables that are highly relevant to characterize PPPs. The proposed framework has been applied to characterize PPPs implementation in Italy, with a particular focus on the transport sector

Drilling down hotspots of infraspecific diversity to bring them into on-ground conservation of threatened species

Unprecedented rates of biodiversity loss raise the urgency for preserving species ability to cope with ongoing global changes. An approach in this direction is to target intra-specific hotspots of genetic diversity as conservation priorities. However, these hotspots are often identified by sampling at a spatial resolution too coarse to be useful in practical management of threatened species, hindering the long-appealed dialog between conservation stakeholders and conservation genetic researchers. Here, we investigated the spatial and temporal variation in species presence, genetic diversity, as well as potential risk factors, within a previously identified hotspot of genetic diversity for the endangered Apennine yellow-bellied toad Bombina pachypus. Our results show that this hotspot is neither a geographically homogeneous nor a temporally stable unit. Over a time-window spanning 10–40 years since previous assessments, B. pachypus populations declined in large portions of their hotspot, and their genetic diversity levels decreased. Considering the demographic trend, genetic and epidemiological data, and models of current and future climatic suitability, populations at the extreme south of the hotspot area still qualify for urgent in-situ conservation actions, whereas northern populations would be better managed through a mix of in-situ and ex-situ actions. Our results emphasize that identifying hotspots of genetic diversity, albeit an essential step, does not suffice to warrant on-ground conservation of threatened species. Hotspots should be analyzed at finer geographic and temporal scales, to provide conservation stakeholders with key knowledge to best define conservation priorities, and to optimize resource allocation to alternative management practices

Synthesis and preliminary biological profile of new NO-donor tolbutamide analogues.

We describe a new class of NO-donor hypoglycemic products obtained by joining tolbutamide, a typical hypoglycemic sulfonylurea, with a NO-donor moiety through a hard link. As NO-donors we chose either furoxan (1,2,5-oxadiazole 2-oxide) derivatives or the classical nitrooxy function. A preliminary biological characterization of these compounds, including stimulation of insulin release from cultured rat pancreatic b-cells and in vitro vasodilator and anti-aggregatory activities, is reporte

The EGFR family members sustain the neoplastic phenotype of ALK+ lung adenocarcinoma via EGR1.

In non-small cell lung cancer (NSCLC), receptor tyrosine kinases (RTKs) stand out among causal dominant oncogenes, and the ablation of RTK signaling has emerged as a novel tailored therapeutic strategy. Nonetheless, long-term RTK inhibition leads invariably to acquired resistance, tumor recurrence and metastatic dissemination. In ALK+ cell lines, inhibition of ALK signaling was associated with coactivation of several RTKs, whose pharmacological suppression reverted the partial resistance to ALK blockade. Remarkably, ERBB2 signaling synergized with ALK and contributed to the neoplastic phenotype. Moreover, the engagement of wild-type epidermal growth factor receptor or MET receptors could sustain cell viability through early growth response 1 (EGR1) and/or Erk1/2; Akt activation and EGR1 overexpression prevented cell death induced by combined ALK/RTK inhibition. Membrane expression of ERBB2 in a subset of primary naive ALK+ NSCLC could be relevant in the clinical arena. Our data demonstrate that the neoplastic phenotype of ALK-driven NSCLC relays ‘ab initio' on the concomitant activation of multiple RTK signals via autocrine/paracrine regulatory loops. These findings suggest that molecular and functional signatures are required in de novo lung cancer patients for the design of efficacious and multi-targeted ‘patient-specific' therapies

Novel Mechanisms of Tumor Promotion by the Insulin Receptor Isoform A in Triple-Negative Breast Cancer Cells

The insulin receptor isoform A (IR-A) plays an increasingly recognized role in fetal growth and tumor biology in response to circulating insulin and/or locally produced IGF2. This role seems not to be shared by the IR isoform B (IR-B). We aimed to dissect the specific impact of IR isoforms in modulating insulin signaling in triple negative breast cancer (TNBC) cells. We generated murine 4T1 TNBC cells deleted from the endogenous insulin receptor (INSR) gene and expressing comparable levels of either human IR-A or IR-B. We then measured IR isoform-specific in vitro and in vivo biological effects and transcriptome in response to insulin. Overall, the IR-A was more potent than the IR-B in mediating cell migration, invasion, and in vivo tumor growth. Transcriptome analysis showed that approximately 89% of insulin-stimulated transcripts depended solely on the expression of the specific isoform. Notably, in cells overexpressing IR-A, insulin strongly induced genes involved in tumor progression and immune evasion including chemokines and genes related to innate immunity. Conversely, in IR-B overexpressing cells, insulin predominantly induced the expression of genes primarily involved in the regulation of metabolic pathways and, to a lesser extent, tumor growth and angiogenesis

Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19

The established risk factors of coronavirus disease 2019 (COVID-19) are advanced age, male sex and comorbidities, but they do not fully explain the wide spectrum of disease manifestations. Genetic factors implicated in the host antiviral response provide for novel insights into its pathogenesis. We performed an in-depth genetic analysis of chromosome 21 exploiting the genome-wide association study data, including 6,406 individuals hospitalized for COVID-19 and 902,088 controls with European genetic ancestry from the COVID-19 Host Genetics Initiative. We found that five single nucleotide polymorphisms within TMPRSS2 and near MX1 gene show associations with severe COVID-19. The minor alleles of the five SNPs correlated with a reduced risk of developing severe COVID-19 and high level of MX1 expression in blood. Our findings demonstrate that host genetic factors can influence the different clinical presentations of COVID-19 and that MX1 could be a potential therapeutic target

An ontology-based approach supporting holistic structural design with the consideration of safety, environmental impact and cost

Early stage decision-making for structural design critically influences the overall cost and environmental performance of buildings and infrastructure. However, the current approach often fails to consider the multi-perspectives of structural design, such as safety, environmental issues and cost in a comprehensive way. This paper presents a holistic approach based on knowledge processing (ontology) to facilitate a smarter decision-making process for early design stage by informing designers of the environmental impact and cost along with safety considerations. The approach can give a reasoning based quantitative understanding of how the design alternatives using different concrete materials can affect the ultimate overall performance. Embodied CO2 and cost are both considered along with safety criteria as indicative multi-perspectives to demonstrate the novelty of the approach. A case study of a concrete structural frame is used to explain how the proposed method can be used by structural designers when taking multi performance criteria into account. The major contribution of the paper lies on the creation of a holistic knowledge base which links through different knowledge across sectors to enable the structural engineer to come up with much more comprehensive decisions instead of individual single objective targeted delivery