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Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer
No full textDespite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties
L’argomentazione delle decisioni della Cassazione: tra autorevolezza del precedente ed esigenze di semplificazione.
No full textLa relazione mira ad approfondire il ruolo dell'argomentazione nel ragionamento dei giudici della Corte di Cassazione italiana e processo decisionale, indicando la funzione del vincolo dello stare decisis (precedente) in un sistema di civil law, quale quello italiano, e tenendo conto del carico di ricorsi che ogni anno la Corte deve gestire
Protecting the Faithful City: Disasters and the Cult of the Saints (Naples, 1573-1587)
No full textTraumatic events may instigate a growth in the “devotional demand” by strengthening the role of saints within society. Hagiography offers, in fact, extensive accounts of earthquakes, eruptions, floods, epidemics, invasions, bloody battles and other disasters that may be ascribed to human or natural causes. This paper focuses on the hagiographic texts produced in Naples between the Sixteenth and Seventeenth centuries and deals in particular with Paolo Regio’s works. The first noticeable signs of the Spanish decline become apparent during this chronological period; hence the “disaster” (in its broadest sense) becomes the catalyst of new political and religious alliances and encourages to build, deconstruct and reconstruct social identities which are conveyed by the organizations of rites, ceremonies, processions as well as networks of patronage in support of old and new cults
Petrogenesis and deformation history of the lawsonite-bearing blueschist facies metabasalts of the Diamante-Terranova oceanic unit (southern Italy)
No full textThe Neotethyan oceanic Diamante-Terranova unit (DIATU; southern Apennines-Calabria-Peloritani Terrane system) includes basic rocks that during the Cenozoic were subducted and metamorphosed to lawsonite-blueschist facies conditions. Petrological and structural observations (both at the meso- and micro-scale) show that lawsonite growth was continuous during three distinctive ductile deformation stages (D1-D3). These likely occurred close to the metamorphic peak, estimated at 350-390 °C and 0.9-1.1 GPa, producing an equilibrium assemblage made of blue Na-amphibole, lawsonite, chlorite and pumpellyite. Locally, pods dominated by quartz and epidote (plus chlorite, calcite and green Ca-amphibole), developed at similar conditions (350-370 °C, 0.8-0.9 GPa). Post-peak evolution during the final exhumation of the DIATU along the subduction channel, also consisted of three deformation stages, defined by folding (D4) and normal faulting (D5) and finally by strike-slip faulting (D6), affecting both the blueschist unit and the unconformably overlying Tortonian conglomerates. Vorticity analysis on syn-tectonic lawsonite crystals indicates that severe flattening occurred during the D2 stage, with a significant secondary non-coaxial strain component along the W-E plane. This is associated with an eastward tectonic vergence, consistent with the subsequent D3 and D4 folding stages characterized by a dominant ENE tectonic transport. It is suggested that exhumation started from the D2 stage and continued during D3 at similar HP/LT metamorphic conditions. The widespread occurrence of unreacted lawsonite crystals suggests that exhumation was very fast and supports the idea that concurrent ductile deformation might play a role in its preservation
Ethylene–co–norbornene copolymerization in the presence of a chain transfer agent
No full textEthylene (E)-co-norbornene (N) copolymerizations were conducted by using two ansa-metallocenes, isopropyliden(η5-cyclopentadienyl)(η5-indenyl)zirconium dichloride (1) and isopropyliden(η5-3-methylcyclopentadienyl)(η5-fluorenyl)zirconium dichloride (2), activated with dimethylanilinium tetrakis(pentafluorophenyl)borate, in presence of TIBA and variable amounts of Zn(Et)2 as a potential chain transfer agent (CTA). The study evaluated the effect of CTA on microstructure, molecular weight, chain end group and structural, thermal and mechanical properties of poly(E-co-N)s. The analysis of the data revealed that in all copolymerization reactions with metallocenes 1 and 2 in presence of diethyl zinc chain transfer to zinc alkyl occurs along with the typical chain transfers of E-co-N polymerization. The chain transfer to zinc alkyl is more efficient at low N content in copolymers. The two catalysts show different behavior in copolymerization at high N content: molar masses of copolymers produced by 2 are more affected by CTA concentration, that is, the chain shortening with increasing CTA content is greater in copolymers obtained with catalyst 2. The analysis of mechanical properties revealed that CTA affects the polymer chain structure. An increase of CTA caused a change of ductility, rigidity, and mechanical strength; chains produced in presence of Zn(Et)2 are, at least in part, characterized by segments produced as a result of exchange between different metal centers, possibly jointed through ethylene units
Mimesis in Plato's Meno
No full textAt the beginning of the dialogue, Meno, with his sophistical concept of the teaching process, asks whether excellence is teachable. Socrates claims that there is no teaching, only recollection and that recollection consists in remembering the knowledge of things which already exists in the depths of our souls. The learning process does not require any "teaching" in the sense of "transmission of knowledge". There is nothing that comes from the outside and goes into the soul of the learner. In order to explain his idea, Socrates presents an image which, in its obscurity, is an implicit refutation - albeit not verbally asserted, but mimetically suggested - of the sophistical idea of teaching, according to which truth comes to the soul from the outside.
The image is of a geometric figure which requires being inscribed in a circumference. In that image, we can observe an implicit comparison that establishes an analogy between teaching (didaskein) and inscribing (enteinein). The view of teaching Plato seeks to reject is that excellence is teachable -namely, that it can be inscribed in a soul, in the way that figure can be inscribed in a circumference
On-Line Bayes Estimation of Rotational Inertia for Power Systems with High Penetration of Renewables. Part I: Theoretical Methodology
No full textIn the last years, large-scale deployment of
renewable energy sources has led to the use of significant
shares of generation from intermittent sources. Renewable
energy sources units are notably inverter-connected wind
turbines and photovoltaic that as such do not provide
rotational inertia: this has implications for frequency
dynamics and power system stability and operation.
Frequency dynamics are faster in case of systems with low
rotational inertia, thus making frequency control and power
system operation more challenging. While the impact of low
rotational inertia on power system stability and operation
have been widely investigated in the recent literature, in this
paper a new Bayesian statistical inference approach is
proposed for the on-line estimation of the rotational inertia
of a given system. The need for estimation is based upon the
observation that the amount of renewable energy affecting
the system is a random process. The authors’ researches of
this paper is devoted to the Bayesian on-line recursive
estimation of the amount of the so-called “Renewable Energy
Source Share”. The numerical application reported in the
companion paper [1] confirms that the proposed estimation
technique constitutes a very fast, efficient and, especially, a
robust method for ‘tracking’ the above share in view of an
efficient assessment of rotational inertia