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Complication related to prophylactic stunting vescicoureteral anastomosis in kidney transplantation: our experience and literature rewove
No full textPreclinical toxicology and safety pharmacology of the first-in-class GADD45β/MKK7 inhibitor and clinical candidate, DTP3
No full textAberrant NF-κB activity drives oncogenesis and cell survival in multiple myeloma (MM) and many other cancers. However, despite an aggressive effort by the pharmaceutical industry over the past 30 years, no specific IκBα kinase (IKK)β/NF-κB inhibitor has been clinically approved, due to the multiple dose-limiting toxicities of conventional NF-κB-targeting drugs. To overcome this barrier to therapeutic NF-κB inhibition, we developed the first-in-class growth arrest and DNA-damage-inducible (GADD45)β/mitogen-activated protein kinase kinase (MKK)7 inhibitor, DTP3, which targets an essential, cancer-selective cell-survival module downstream of the NF-κB pathway. As a result, DTP3 specifically kills MM cells, ex vivo and in vivo, ablating MM xenografts in mice, with no apparent adverse effects, nor evident toxicity to healthy cells. Here, we report the results from the preclinical regulatory pharmacodynamic (PD), safety pharmacology, pharmacokinetic (PK), and toxicology programmes of DTP3, leading to the approval for clinical trials in oncology. These results demonstrate that DTP3 combines on-target-selective pharmacology, therapeutic anticancer efficacy, favourable drug-like properties, long plasma half-life and good bioavailability, with no target-organs of toxicity and no adverse effects preclusive of its clinical development in oncology, upon daily repeat-dose administration in both rodent and non-rodent species. Our study underscores the clinical potential of DTP3 as a conceptually novel candidate therapeutic selectively blocking NF-κB survival signalling in MM and potentially other NF-κB-driven cancers
I soggetti vulnerabili fra tutela della persona ed esigenze del mercato. Le esperienze italiana e spagnola a confronto
No full textImpedance-based PZT transducer and fuzzy logic to detect damage in multi-point dressers
No full textAlternative techniques such as impedance-based lead zirconate titanate (PZT) transducers has emerged as an innovative approach for manufacturing monitoring process, because its flexibility of using low-cost piezoelectric diaphragms and its simple methodology in terms of apparatus by using the electromechanical impedance (EMI). In addition, this technique has been under several improvements due to the advance of artificial intelligent systems. On this point, the use of fuzzy logic systems has been reported in literature as an attractive combination to improve the process performance. Therefore, this study proposes an approach to detect damage in multi-point dresser based on EMI technique incorporating a fuzzy logic system. To this end, a fuzzy model is built considering the information obtained from representative damage indices corresponding to the different damage cases that are generated at the dresser. At the end, authors expected that the dressing operation can be optimized, preventing the operation from being performed with worn or damaged dressers and ensuring quality standards and precision to the grinding process, which have a high benefit to the manufacturing chain
La forma dell'atto amministrativo al tempo di internet: spunti a margine di uno "strano" apparentamento elettorale
No full textSommario: 1. L'atto amministrativo tra contenuto e forma. 2. Il caso: le elezioni amministrative nel comune di Seregno e gli accordi nella rete. 3. L'impugnazione di un "twitt". 4. Diritto pubblico e diritto privato. 4.1. Utilizzare quello che c'è: il codice dell'amministrazione digitale. 4.2. Ripensare gli istituti: forma e sostanza dell'atto amministrativo nel mondo moderno. 5. Le incognite del nuovo e la ricerca di garanzie diverse
Phosphorene is the new graphene in biomedical applications
No full textNowadays, the research of smart materials is focusing on the allotropics, which have specific characteristics that are useful in several areas, including biomedical applications. In recent years, graphene has revealed interesting antibacterial and physical peculiarities, but it has also shown limitations. Black phosphorus has structural and biochemical properties that make it ideal for biomedical applications: 2D sheets of black phosphorus are called Black Phosphorene (BP), and it could replace graphene in the coming years. BP, similar to other 2D materials, can be used for colorimetric and fluorescent detectors, as well as for biosensing devices. BP also shows high in vivo biodegradability, producing non-toxic agents in the body. This characteristic is promising for pharmacological applications, as well as for scaffold and prosthetic coatings. BP shows low cytotoxicity, thus avoiding the induction of local inflammation or toxicity. As such, BP is a good candidate for different applications in the biomedical sector. Properties such as biocompatibility, biodegradability, and biosafety are essential for use in medicine. In this review, we have exploited all such aspects, also comparing BP with other similar materials, such as the well-known graphene
Separating Electronic from Steric Effects in Ethene/α-Olefin Copolymerization: A Case Study on Octahedral [ONNO] Zr-Catalysts
No full textFour Cl/Me substituted [ONNO] Zr-catalysts have been tested in ethene/α-olefin polymerization. Replacing electron-donating methyl with isosteric but electron-withdrawing chlorine substituents results in a significant increase of comonomer incorporation. Exploration of steric and electronic properties of the ancillary ligand by DFT confirm that relative reactivity ratios are mainly determined by the electrophilicity of the metal center. Furthermore, quantitative DFT modeling of propagation barriers that determine polymerization kinetics reveals that electronic effects observed in these catalysts affect relative barriers for insertion and a capture-like transition state (TS)
Geological analysis and stability assessment of a sea arch in Palinuro, southern Italy
No full textThe study aims to describe the geological and geostructural layouts of an unstable sea arch located in a very attractive tourist area of Southern Italy. On the basis of ad hoc field surveys and laboratory tests, the problems of an in-depth geo-mechanical characterization of the rock mass are discussed in details and its main strength parameters are derived. An indirect assessment of the possible geostati stress field due to the neotectonic events, which affected this sector of Apennine Range during the last 100,000 years, is proposed and validated by means of numerical non-linear FE analyses. The results suggest that the presence of a lateral thrust acting into the promontory located at the back of the arch, is very likely and its effects would agree well with the failures occurred in the past on the arch surfaces. It is concluded that any possible intervention should be carefully designed on the basis of the highlighted factors and further investigations
Crashworthiness of wing leading edges under bird impact event
No full textThe work aims to investigate the capability of a vertical tail leading edge to withstand bird strike and to pro- vide general considerations on the improvement of such capability with respect to the mass saving and to the required structural performances by considering different material systems.
The assessment of the numerical models was ensured by a double check, and therefore considering the two test cases, aimed to calibrate and validate the numerical models against experimental data, coming from liter- ature: 1) bird strike on metallic flat square plate; 2) bird strike on wing leading-edge with the skin made in metallic sandwich structure (both the honeycomb core and the outer and inner face was in aluminum).
Finally, the crashworthy design of several leading-edge configurations, modifying the material and thickness of the skins and the central core of the leading edge, without changing its external geometrical shape, was inves- tigated by adopting the numerical procedures used for the validation test cases. Actually, unidirectional fiber-re- inforced composite material systems were considered for the outer and inner face of the skins, while different materials were adopted for the core. A comparison among the developed configurations, in terms of requirement fulfillment, global deformation parameters and weight, was performed
