Caratteristiche e funzioni delle componente paratestuali nelle edizioni rinascimentali italiane petrarchesche

In virtue of the control carried out on several 15th/16th century Italian editions of the Canzoniere, an explanation is given to a series of editorial choices regarding the presentation of Petrarca’s work, gauged on the potential classification of reading and aimed at knowledgeably influencing the enjoyment of the same semantic message

THE ANTINEOPLASTIC ROLE OF STAT5 INHIBITION IN BCRABL1-POSITIVE CELLS EXPOSED TO PIMOZIDE ALONE AND IN COMBINATION WITH DASATINIB AND PONATINIB

EVEN though the last decades have seen the success of the targeted treatments for BCRABL1-positive Chronic Myeloid Leukemia (CML), with the outstanding achievement of placing selected patients into the so called treatment-free remission, a minor part of these subjects face TKI resistance and/or intolerance. Resistance is a challenging point in the clinical management of CML, occurring in approximately 10–20% of CML cases, due to several mechanisms, among which point mutations of the BCR‐ABL kinase domain, BCRABL overexpression or alternative splicing, sub-efficient plasma concentration of the inhibitor and abnormal drug efflux/influx. The Signal Transducer and Activators of Transcription (STAT) proteins are a family of transcription factors commonly involved in multiple intracellular tasks and pathways, among which survival and proliferation. The STAT family is made up of seven factors, each one with a specific role. In particular, STAT3 and STAT5 (A and B) are strictly involved in cell survival and proliferation and thus are commonly implied in the pathogenesis of many neoplasms. STAT5 is of peculiar interest for its critical role in cellular differentiation, adipogenesis, oncogenesis, immune function and is known to be constitutively activated after the BCRABL1 effect in CML cells. STAT5 expression has been strictly linked to BCRABL1 mutations and disease progression to accelerated and blast phase and may thus represent a significant target to overcome resistance to TKI in CML. In 2011, Nelson et al. evidenced the effect of STAT5 inhibition exerted by a Pimozide, a commonly used neuroleptic drug. As far as we know, literature reports experiments involving STAT5 inhibitors in association with BCRABL inhibition only with first generation inhibitor imatinib. There is no news about the association between STAT5 inhibitors and newer generations of TKIs. The aim of this study is to explore the antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation TKIs, dasatinib and ponatinib respectively, and to identify the cytotoxic in vitro concentrations. For the purpose of the study, K562 cell line was used to simulate the frame of a classical Chronic Myeloid Leukemia disease. The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations. Moreover, an extension of the present study is evaluating the cytotoxic effect on CML leukemic stem cells (LSC), aiming at revealing whether STAT5 inhibition may determine a more profound effect on CML disease and may overcome the LSC escape mechanisms on which TKIs are not active

Hysteresis from dynamically pinned sliding states

We report a surprising hysteretic behavior in the dynamics of a simple one-dimensional nonlinear model inspired by the tribological problem of two sliding surfaces with a thin solid lubricant layer in between. In particular, we consider the frictional dynamics of a harmonic chain confined between two rigid incommensurate substrates which slide with a fixed relative velocity. This system was previously found, by explicit solution of the equations of motion, to possess plateaus in parameter space exhibiting a remarkable quantization of the chain center-of-mass velocity (dynamic pinning) solely determined by the interface incommensurability. Starting now from this quantized sliding state, in the underdamped regime of motion and in analogy to what ordinarily happens for static friction, the dynamics exhibits a large hysteresis under the action of an additional external driving force F_ext. A critical threshold value F_c of the adiabatically applied force F_ext is required in order to alter the robust dynamics of the plateau attractor. When the applied force is decreased and removed, the system can jump to intermediate sliding regimes (a sort of ``dynamic'' stick-slip motion) and eventually returns to the quantized sliding state at a much lower value of F_ext. On the contrary no hysteretic behavior is observed as a function of the external driving velocity.Comment: 12 pages, 5 figures, ECOSS 200

Solitons and exact velocity quantization of incommensurate sliders

We analyze in some detail the recently discovered velocity quantization phenomena in the classical motion of an idealized one-dimensional solid lubricant, consisting of a harmonic chain interposed between two periodic sliders. The ratio w = v_cm/v_ext of the chain center-of-mass velocity to the externally imposed relative velocity of the sliders is pinned to exact ``plateau'' values for wide ranges of parameters, such as sliders corrugation amplitudes, external velocity, chain stiffness and dissipation, and is strictly determined by the commensurability ratios alone. The phenomenon is caused by one slider rigidly dragging the density solitons (kinks/antikinks) that the chain forms with the other slider. Possible consequences of these results for some real systems are discussed.Comment: 12 pages 6 figures. Small fixup after Referee's comments. In print in J. Phys.: Condens. Matte

Follow-up study of over three years of patients with uveitis after cataract phacoemulsification: outcomes and complications

Purpose: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification. Methods: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis. Results: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r = 0.6; p = 0.00) and mostly related to patients who presented more than one postoperative relapse/year (r = 0.2; p = 0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p = 0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY). Conclusion: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are

Gli itinerari turistici in ambito urbano tra accessibilità e informazione

Palermo è una delle città, culturalmente ed economicamente, più importanti dell’intera area del Mediterraneo. Ricca di un notevole patrimonio architettonico e archeologico, è caratterizzata da un elevato potenziale turistico a cui non corrisponde un’adeguata rete di collegamenti e di servizi di trasporto multimodali. Oggi i centri urbani, dalle metropoli ai borghi, rappresentano uno degli anelli più importanti del sistema di offerta turistica, perché sono i luoghi in cui il turista, occasionale e/o di lunga permanenza, si trova di fronte a beni, servizi, cultura ed esperienze, diventandone consumatore. È proprio in questo processo che il visitatore ha necessità di percepire servizi di qualità, specialmente nel campo dei trasporti per rendere accessibili i punti nodali della città. Infatti, per favorire l’organizzazione strutturale del territorio non basta sviluppare i centri urbani in termini di attrattività, ma è necessario assicurare i collegamenti realizzando un sistema infrastrutturale ai vari livelli di connessione e accessibilità. Molte città europee, nel loro programma di rivalutazione dei contesti urbani, hanno sviluppato un sistema di indicatori per valutare la vivibilità delle città, puntando molto sulle interrelazioni tra servizi di trasporto e itinerari turistici, mettendo in primo piano elementi come la qualità dei servizi pubblici, la sicurezza, le aree pedonali e la mobilità, che, sinergicamente, contribuiscono a rendere un centro urbano accogliente e competitivo. Sul piano europeo il programma degli itinerari culturali si fa portatore dei principi insiti nel processo di costruzione comunitaria, in particolar modo per la conoscenza della diversità culturale e del patrimonio storico sotto forma di tradizioni, arte e storia. In questa ottica va prendendo piede la volontà sovranazionale del sostegno per lo sviluppo dell’impresa culturale, anche appartenente al terzo settore, mirato al potenziamento del ruolo delle città siciliane nella promozione dell’europartenariato con realizzazione di circuiti di produzione congiunta. Gli itinerari sono testimonianza della storia e, quindi, fattore di rafforzamento degli ideali e del sentirsi cittadini europei, oltre che costituire di per sé un bene culturale, con le sue complessità sia in termini di individuazione e riconoscimento sia come progettazione e gestione. Connessa all’idea di “itinerario” c’è quella di strada, di via, di movimento e di connessione tra essi. Accessibilità e mobilità assumono rilevanza crescente per qualsiasi politica di sviluppo turistico. I trasporti, infatti, svolgono un ruolo centrale nello sviluppo economico del territorio che trascende le finalità del turismo, anche se è proprio in questo settore che si confermano essenziali. Non solo essenzialità ma anche qualificazione: l’accessibilità di un’area e la componente infrastrutturale del sistema dei trasporti contribuiscono a qualificare l’offerta orientandone i flussi turistici. Il sistema dei trasporti quindi rappresenta un aspetto dinamico dell’offerta turistica, che va formulata attraverso la realizzazione di un quadro organico delle risorse culturali, strutturato in circuiti, reti e itinerari, allo scopo di recuperare i contesti e le identità culturali locali, in una prospettiva di valorizzazione turistica, e di favorire l’emergere dei luoghi di maggiore concentrazione delle risorse (poli attrattori) che costituiranno la struttura portante alla quale saranno agganciate le realtà locali. Il recupero e la valorizzazione di tali contesti potrà avvenire attraverso la creazione di itinerari integrati che, collegando le variegate risorse, potranno attrarre particolari segmenti della domanda turi-stica e attivare occasioni di sviluppo economico e sociale duraturo per le collettività locali, di cui sarà possibile rafforzare l’identità storico-culturale. Da qui l’esigenza dell’individuazione e attivazione di circuiti museali, circuiti delle aree archeologiche, circuiti monumentali, ecc., gestiti in rete attraverso sistemi avanzati di informazione e di comunicazione, anche in funzione del miglioramento dell’integrazione tra i modi di trasporto e dell’interconnessione delle reti di trasporto. Obiettivo dello studio proposto è lo sviluppo di una metodologia progettuale capace di identificare il livello di accessibilità ottimale, dal punto di vista spazio-temporale, ai vari siti tramite la costruzione di itinerari turistici multimodali, basati sullo straordinario patrimonio storico-artistico, di cui dispone la città di Palermo, vero e proprio museo all’aperto (in particolare nel Centro Storico), all’interno del quale sono leggibili le vestigia dei popoli conquistatori, dai palazzi alle antiche mura, dai giardini ai parchi arabo-normanni. Gli itinerari prefigurabili partono da un determinato punto e ripercorrono la città per temi, migliorandone l’accessibilità spaziale e temporale, cosicché il turista possa usufruire qualitativamente del territorio che lo ospita. La ricezione turistica portuale, dal mese di marzo ad ottobre, è molto elevata e, a tal proposito, si potrebbe pensare ad un progetto che proponga di sviluppare una metodologia di accoglienza e gestione dei visitatori. La coniugazione dei tre elementi connessi ad accessibilità, accoglienza e informazione passa attraverso interventi di miglioramento dei collegamenti del porto con il sistema dei trasporti e per la predisposizione di sistemi informativi dei percorsi utili per la fruizione dei luoghi principali dell’offerta turistica, anche al fine del monitoraggio delle attività espositive e culturali per l’attivazione di un sistema integrato regionale ed euromediterraneo. Il piano della segnaletica turistica, la predisposizione di SIT per settore (naturalistico, monumentale, archeologico, museale, ecc.) e per favorire l’accessibilità ai luoghi di interesse turistico (integrazione modale, costi, orari, ecc.), e di siti Web, l’uso del GIS sono ulteriori e importanti strumenti per supportare la mobilità dei flussi turistici nel territorio prescelto come destinazione dei loro viaggi e delle loro vacanze

6. Reading Wittgenstein Between the Texts

Sharing the “historicist challenge to analytic philosophy” (Glock) we investigate the philosophical production (and, to a lesser extent, some non-philosophical works as well) on Ludwig Wittgenstein from a distant reading perspective. First, we provide a description of the “Wittgensteinian field” by analyzing several data provided by the Philosopher’s Index, an electronic bibliographic database especially devoted to philosophy. Then we analyze these data by using statistical tools (such as for example topic modeling) and we interpret the results historically and sociologically, along the lines of Bourdieu on Heidegger, Lamont on Derrida, Gross on Rorty, and Collins on the whole philosophical tradition

Kink plateau dynamics in finite-size lubricant chains

We extend the study of velocity quantization phenomena recently found in the classical motion of an idealized 1D model solid lubricant -- consisting of a harmonic chain interposed between two periodic sliding potentials [Phys. Rev. Lett. 97, 056101 (2006)]. This quantization is due to one slider rigidly dragging the commensurate lattice of kinks that the chain forms with the other slider. In this follow-up work we consider finite-size chains rather than infinite chains. The finite size (i) permits the development of robust velocity plateaus as a function of the lubricant stiffness, and (ii) allows an overall chain-length re-adjustment which spontaneously promotes single-particle periodic oscillations. These periodic oscillations replace the quasi-periodic motion produced by general incommensurate periods of the sliders and the lubricant in the infinite-size model. Possible consequences of these results for some real systems are discussed.Comment: 12 pages, 5 figures, ECOSS 200

Low-thrust transfer to quasi-synchronous Martian elliptic orbit via nonlinear feedback control

This study considers the problem of injecting a spacecraft into an elliptic, repeating-ground-track orbit about Mars, starting from a 4-sol highly elliptical orbit, which is a typical Martian capture orbit, entered at the end of the interplanetary transfer. The final operational orbit has apoares corresponding to the maximum (or minimum) latitude, and nine nodal periods are flown in 5 Martian nodal days. The orbit at hand is proven to guarantee coverage properties similar to the Molniya orbit about Earth; therefore, it is especially suitable for satellites that form constellations. Low-thrust nonlinear orbit control is proposed as an affordable and effective option for orbit injection, capable of attaining significant propellant reduction if compared to alternative strategies based on chemical propulsion. This work introduces a new, saturated feedback law for the low-thrust direction and magnitude that is capable of driving the spacecraft of interest toward the operational orbit. Remarkable stability properties are proven to hold using the Lyapunov stability theory. Because no reference path is to be identified a priori, this technique represents a viable autonomous guidance strategy, even in the case of temporary unavailability of the low-thrust propulsion system or in the presence of widely dispersed initial conditions and errors on estimating orbit perturbations. Monte Carlo simulations prove that the feedback guidance strategy at hand is effective and accurate for injecting a spacecraft into the desired, repeating-ground-track operational orbit without requiring any reference transfer path

Laparoscopic peritoneal lavage. Our experience and review of the literature

NTRODUCTION: Over the years various therapeutic techniques for diverticulitis have been developed. Laparoscopic peritoneal lavage (LPL) appears to be a safe and useful treatment, and it could be an effective alternative to colonic resection in emergency surgery. AIM: This prospective observational study aims to assess the safety and benefits of laparoscopic peritoneal lavage in perforated sigmoid diverticulitis. MATERIAL AND METHODS: We surgically treated 70 patients urgently for complicated sigmoid diverticulitis. Thirty-two (45.7%) patients underwent resection of the sigmoid colon and creation of a colostomy (Hartmann technique); 21 (30%) patients underwent peritoneal laparoscopic lavage; 4 (5.7%) patients underwent colostomy by the Mikulicz technique; and the remaining 13 (18.6%) patients underwent resection of the sigmoid colon and creation of a colorectal anastomosis with a protective ileostomy. RESULTS: The 66 patients examined were divided into 3 groups: 32 patients were treated with urgent surgery according to the Hartmann procedure; 13 patients were treated with resection and colorectal anastomosis; 21 patients were treated urgently with laparoscopic peritoneal lavage. We had no intraoperative complications. The overall mortality was 4.3% (3 patients). In the LPL group the morbidity rate was 33.3%. CONCLUSIONS: Currently it cannot be said that LPL is better in terms of mortality and morbidity than colonic resection. These data may, however, be proven wrong by greater attention in the selection of patients to undergo laparoscopic peritoneal lavage