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Spin, torsion and violation of null energy condition in traversable wormholes
No full textThe static spherically symmetric traversable wormholes are analysed in the Einstein-Cartan theory of gravitation. In particular, we computed the torsion tensor for matter fields with different spin S=0,1/2,1,3/2. Interestingly, only for certain values of the spin, the torsion contribution to the Einstein-Cartan field equation allows one to satisfy both flaring-out condition and null energy condition. In this scenario, traversable wormholes can be produced by using usual (non-exotic) spinning matter
Influence of FRP wrapping on reinforcement performances at lap splice regions in RC columns
No full textLap-splice regions are amongst the most critical regions of Reinforced Concrete (RC) members, especially in seismic design. The goal of wrapping with Fibre Reinforced Polymer (FRP) is provide confinement to concrete, however, a further important role is either to increase the bond between the reinforcement bars (in pre-cracked conditions) or to provide for bond (in fully cracked cover conditions). The proposed study aims to quantify the beneficial effect of this retrofit technique on the performance of the longitudinal reinforcement with a first attempt to account explicitly for the pointwise variability of confining stresses. For this purpose, both the reinforcement bar working stress and the anchorage length needed to prevent the bar slippage have been analytically assessed. The model has been validated against experimental tests and a good agreement with the model predictions has been found in both the cases of square and rectangular cross sections
Multicollinearity in regression: an efficiency comparison between Lp-norm and least squares estimators
No full textMulticollinearity is one of the most important issues in regression analysis, as it produces unstable coefficients’ estimates and makes the standard errors severely inflated. The regression theory is based on specific assumptions concerning the set of error random variables. In particular, when errors are uncorrelated and have a constant variance, the ordinary least squares estimator produces the best estimates among all linear estimators. If, as often happens in reality, these assumptions are not met, other methods might give more efficient estimates and their use is therefore recommendable. In this paper, after reviewing and briefly describing the salient features of the methods, proposed in the literature, to determine and address the multicollinearity problem, we introduce the Lpmin method, based on Lp-norm estimation, an adaptive robust procedure that is used when the residual distribution has deviated from normality. The major advantage of this approach is that it produces more efficient estimates of the model parameters, for different degrees of multicollinearity, than those generated by the ordinary least squares method. A simulation study and a real-data application are also presented, in order to show the better results provided by the Lpmin method in the presence of multicollinearity
Multicenter Comparison of 22C3 PharmDx (Agilent) and SP263 (Ventana) Assays to Test PD-L1 Expression for NSCLC Patients to Be Treated with Immune Checkpoint Inhibitors
No full textINTRODUCTION:
Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of patients with NSCLC in association with a companion diagnostic assay, the anti-PD-L1 immunohistochemical (IHC) 22C3 PharmDx (Agilent Technologies, Santa Clara, CA) using the Dako Autostainer (Dako, Carpinteria, CA). However, the Dako platform is not present in each pathology department, and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab.
METHODS:
The Italian Society of Anatomic Pathology and Cytopathology and the Italian Association of Medical Oncology in an independent, multicenter study compared the in vitro diagnostics PD-L1 IHC 22C3 pharmDx test (Agilent) on the Dako Autostainer and the in vitro diagnostics Ventana PD-L1 (SP263) test on the Ventana BenchMark platform (Ventana Medical Systems, Tucson, AZ). Using serial sections from tissue microarrays, 100 lung adenocarcinomas were locally stained and scored in four centers with the same antibody batches.
RESULTS:
A high analytical correlation (more than 90% at the lower 95% confidence interval [CI] value) between PD-L1 expression levels obtained with the 22C3 and SP263 assays was observed. At the proposed clinically relevant cutoffs (≥50% and ≥1%), the overall concordances between 22C3 and SP263 data were 0.99 (95% CI: 0.96-1) and 0.80 (95% CI: 0.68-0.91), respectively. The lower agreement between data obtained with the 22C3 and SP263 clones at the cutoff of 1% or higher was mainly related to the lower (about 80%) interrater agreement at this cutoff with each clone.
CONCLUSIONS:
These results indicate a high correlation between PD-L1 IHC expression data obtained with the Agilent PD-L1 IHC 22C3 pharmDx and the Ventana PD-L1 (SP263) tests in NSCLC and suggest that the two assays could be utilized interchangeably as an aid to select patients for first-line and second-line treatment with pembrolizumab and potentially with other anti-PD-1/PD-L1 checkpoint inhibitors
Dietary Polyphenols and Chromatin Remodelling
No full textPolyphenols are the most abundant phytochemicals in fruits, vegetables and plant-derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and post transcriptional gene regulation by non-coding RNAs. Sinergistically and cooperatively these processes regulate gene expression by changing chromatin organization and DNA accessibility. Such induced epigenetic changes can be inherited during cell division, resulting in permanent maintenance of the acquired phenotype, but they may also occur throughout an individual life-course and may ultimately influence phenotypic outcomes (health and disease risk). In the last decade, a number of studies have shown that nutrients can affect metabolic traits by altering the structure of chromatin and directly regulate both transcription and translational processes. In this context, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. Here, we will review how polyphenols, including flavonoids, curcuminoids and stilbenes, modulate the establishment and maintenance of key epigenetic marks, thereby influencing gene expression and, hence, disease risk and health
Assessment of Glycolytic Flux and Mitochondrial Respiration in the Course of Autophagic Responses
No full textAutophagy is an evolutionarily conserved process that mediates prominent homeostatic functions, both at the cellular and organismal level. Indeed, baseline autophagy not only ensures the disposal of cytoplasmic entities that may become cytotoxic upon accumulation, but also contributes to the maintenance of metabolic fitness in physiological conditions. Likewise, autophagy plays a fundamental role in the cellular and organismal adaptation to homeostatic perturbations of metabolic, physical, or chemical nature. Thus, the molecular machinery for autophagy is functionally regulated by a broad panel of sensors that detect indicators of metabolic homeostasis. Moreover, increases in autophagic flux have a direct impact on core metabolic circuitries including (but not limited to) glycolysis and mitochondrial respiration. Here, we detail a simple methodological approach to monitor these two processes in cultured cancer cells that mount a proficient autophagic response to stress
Relazione introduttiva
No full textLa relazione ha tratteggiato, in chiave storica, i rapporti tra giurisdizione civile e religiosa
Obblighi di protezione ed effetti del contratto rispetto a terzi
No full textUn’indagine sulla dottrina degli obblighi di protezione e sugli effetti del contratto rispetto a terzi nei principali diritti continentali. Dal raffronto tra i diversi ordinamenti emerge che le Corti, in alcuni Paesi, hanno esteso gli effetti di protezione del contratto nei riguardi di determinati “terzi” al fine di fornire alla vittima una tutela (contrattuale) maggiormente vantaggiosa di quella delittuale. Da un lato si è estesa l’area dei danni risarcibili, tutelando interessi non protetti ai sensi della responsabilità extracontrattuale. Dall'altro, si è applicato un regime di imputazione della responsabilità più favorevole (sotto i profili dell’onere della prova e del suo oggetto) rispetto alla disciplina della responsabilità delittuale per colpa. In Francia, la stipulation pour autrui tacite ha consentito di estendere al terzo il regime di responsabilità oggettiva contrattuale conseguente all’inadempimento di un’obbligazione di sécurité “di risultato”. Ma la scienza giuridica d'oltralpe, tendenzialmente fedele al principio de l’effet relatif des contrats, ha drasticamente ridimensionato la stipulation pour autrui tacite e si caratterizza, oggi, per un collegamento sistematico con le regole della responsabilità extracontrattuale, propendendo, nei riguardi dei terzi, per una forma di responsabilità “delittuale da inadempimento” anche nel settore dei groupes de contrats. In Germania la dottrina degli obblighi di protezione e l’itinerario del Vertrag mit Schutzwirkung für Dritte hanno permesso sia di rimediare alle incongruenze del BGB in tema di responsabilità degli ausiliari (anche indipendenti) “nell’adempimento” e “nell’attività” (§§ 278 e 831 BGB), sia di invertire l’onere della prova a vantaggio del creditore e/o del terzo vittime del danno (§ 280, comma 1, BGB), sia di proteggere rapporti che altrimenti sarebbero risultati sforniti di una tutela extracontrattuale (ad es., danni meramente economici, danni da culpa in contrahendo e da contratti nulli, danni da inesatte informazioni, ecc.), sulla base della convinzione che debba essere proprio il contratto – e non la responsabilità delittuale – il tipico strumento di protezione degli interessi patrimoniali. Tuttavia, se si esamina il diritto delle obbligazioni sotto il profilo dei criteri di imputazione della responsabilità, anziché sotto l’aspetto, tradizionale, delle fonti, la summa divisio è non più tra le responsabilità delittuale e contrattuale, bensì tra responsabilità oggettiva e responsabilità per colpa, nella consapevolezza della persistenza di regimi intermedi che coinvolgono, parallelamente, sia il torto sia il contratto
Social Media Literacy
No full textThe raising of the "platform society" and UGC 2.0 focusing on more and more practices happening in online social media environments brings about new opportunities but also new concerns for the increasing amount of information people share online. Personal information that people share online is becoming a contemporary treasure that feeds the phenomenon of "big data" commodification. The book offers a critical introduction to the logic of social media platforms by developing a clear and critical understanding aimed at improving the reader's "digital literacy"
