Primo contributo della fotografia aerea all’individuazione delle strutture materiali del castello di Monte Franco di Pollenza

Lo studio proposto dall’Autore si inserisce nel quadro di un rinnovato interesse per gli insediamenti castellani delle Marche ed espone i primi risultati di una ricerca su un castello poco conosciuto. Si tratta di Monte Franco, struttura difensiva situata lungo la media valle del fiume Potenza, a N di Pollenza (Montemilone nel Medioevo), centro storico a sua volta sede di un castello. La più antica attestazione di Monte Franco sembra risalire alla fine del XII sec., ma a parte pochi e vaghi riferimenti nella letteratura locale, il castello non è mai stato oggetto di uno studio specifico. L’Autore presenta qui una lettura topografica inedita, basata sull’interpretazione di alcune coperture aerofotografiche, dalle quali emerge principalmente l’andamento del circuito difensivo

The Combination Of Rop And Raft Polymerization For The Synthesis Of Polymeric Nanoparticles

Polymeric nanoparticles (NPs) are colloids in the nanometric size that find application in several field, such as optics, coating and medicine. In this latter case, they are used as drug delivery systems for different therapeutics ranging from lipophilic drugs to oligonucleotides. These nano-colloids are generally made up of polyesters as long as they are able to degrade into safe and easy removable compounds, such as lactic acid and hydroxycaproic acid. In this work, starting from a geometrical model developed for the synthesis of NPs with the same NP size and different molecular weight (MW) block copolymers1, a method to independently control the main characteristics of biodegradable NPs stabilized by highly hydrophilic polymers has been developed and here presented. The method consists in the synthesis of block-copolymers with a brush-like structure via the combination of two living polymerizations: the ring opening polymerization (ROP) and the reversible addition-fragmentation chain transfer (RAFT) polymerization. A library of block copolymers has been produced and self-assembled into water to generate NPs with different size and block-copolymer MWs. As long as these NPs are intended for biomedical applications, the degradation behavior of these colloids has been studied and correlated with the structure of the lipophilic part of the block copolymer. It has been found that the number of the lactone units and their geometrical disposition in the block copolymers impact the degradation behavior of the NPs they are composed of. Thanks to this novel method, it is possible to synthesize NPs with the same size, but with different degradation time. References 1. Palmiero, U. C.; Agostini, A.; Gatti, S.; Sponchioni, M.; Valenti, V.; Brunel, L.; Moscatelli, D., Raft macro-surfmers and their use in the ab initio raft emulsion polymerization to decouple nanoparticle size and polymer molecular weight. Macromolecules 2016, 49 (22), 8387-8396

Polyester-based excipients to formulate lipophilic drugs into nanoparticles directly at the bed of the patient

In recent decades there has been an increased interest in polymeric nanoparticles as drug delivery systems thanks to their several advantages, such as continuous maintenance of drug levels in a therapeutically desirable range, and reduction of harmful side effects. These nano-colloids are generally made up of polyesters as long as they are able to easily degrade into the body. However, NP production is often a process that requires complex microfluidic devices. In addition, expensive purification steps are necessary to eliminate the unloaded drug and the high amount of organic solvent used in the NP production step. In the end, a lyophilization step is general adopted to assure a good shelf-life of the final product. All the above-mentioned steps hamper the cost-effective use of a re-formulation of the same therapeutic agent and, in turn, reduce the availability of these treatments among the patient population. For this reason, in this work, a novel NP production protocol that consists only in the use of a syringe and a needle without the need of subsequent purification and freeze-drying steps has been developed. This has been possible by the optimization of the hydrophilic/lipophilic balance of block-copolymers that are able to directly self-assemble in water. The additional degree of freedom necessary for this optimization was introduced via the synthesis of these materials thorough the combination of the reversible addition-fragmentation chain transfer (RAFT) polymerization and the ring opening polymerization (ROP). The NPs has been used to formulate Trabectedin (ET-743), a widely adopted anticancer therapeutic known for its local adverse effect. The pharmacokinetic behavior, antitumor activity and toxicity of this novel NP-based formulation has been compared to the commercially available formulation Yondelis®. NPs have shown the ability to retain the drug into circulation for a longer time in the blood stream compared to the free ET-743 allowing to considerably reduce the local toxic effects. In addition, the shift of the NP preparation step from a specialist to the final user allows to avoid all the purifications and post-processing steps necessary to assure a good shelf-life of the product. In this way, a ET-743 formulation less toxic than the commercially available Yondelis® can be produced at a competitive price taking also into account that this expensive drug is not lost in any of the NP production steps here adopted. In order to prove the versatility of this novel technology, Paclitaxel (PTX), an anticancer therapeutic that it usually formulated with a toxic surfactant (Chremophor EL), have been also formulated into this NPs. In this way, a novel PTX formulation can be produced at a lower cost compared to the ones already approved and present into the market. In particular, it has shown the same advantage in reduction of the toxicity given by the elimination of the Chremophor EL (e.g in Abraxane® and Genexol®)

Synthesis of zwitterionic-functionalized conjugated nanoparticles for targeted drug delivery applications

Polymeric Nanoparticles (NPs) represent a promising pharmacological tool, since their structure can be modified to obtain: i) encapsulation and controlled release of a wide range of active compounds, ranging from small molecules to siRNA or oligonucleotides; ii) selective cell targeting, thus allowing precise drug delivery to the desired site of action. A powerful strategy to achieve selectivity of uptake in specific cell types is to conjugate the nanoparticles to a ligand specific for receptors expressed by the target cell type. This offers the advantage of a potentially improved drug efficacy with limited side effects and toxicity. Polymeric nanoparticles in a range of 20–100 nm have a high potential for in vivo applications, due to their ability to circulate in the blood for a long period of time. In fact, this size range allows to avoid renal and lymphatic clearance, to prevent opsonization and at the same time improves the internalization by cells. In this work we address the synthesis by reversible addition-fragmentation chain transfer (RAFT) of biodegradable, zwitterionic-based nanoparticles. This Zwitterionic nanoparticles act as super non-fouling surfaces that prevent protein adsorption from complex biological media. The nanoparticles were functionalized with different numbers of selective ligands through click chemistry; different dimensions were synthetized changing the length of the hydrophobic part. In vitro studies were performed to evaluate the uptake of functionalized nanoparticles

Magnetic and ground penetrating radar for the research of Medieval buried structures in Marche Region

A magnetic and Ground Penetrating Radar joint survey was carried out in the framework of the R.I.M.E.M. project that has the aim of supporting the archaeological prospections and drive the selection of the excavation areas related to the Late Roman Period and Early Middle Ages in the Central and Southern Italy. In particular, this papers deals with the magnetic surveys acquired near “Madonna della Valle” and GPR and magnetic joint surveys carried out in “Monastero”site. Most of magnetic maps carried out in “Madonna della Valle” site shown the absence of structured magnetic anomalies, despite of the presence of archaeological signs. Several hypothesis were given to explain this evidence. Joint interpretation performed in “Monastero” site shown more intense magnetic anomalies related with shallower reflections due to probably to buried pipes. Other reflections are related with magnetic anomalies compatible with archaeological targets, but some significant reflections do not correspond to any magnetic anomaly, indicating magnetic method could be “blind” respect the archaeological target. New field surveys including the electrical resistivity tomography could be carried out in order to overcome these acquisition and interpretation difficulties

Magnetic and ground penetrating radar for the research of Medieval buried structures in Marche Region

A magnetic and Ground Penetrating Radar joint survey was carried out in the framework of the R.I.M.E.M. project that has the aim of supporting the archaeological prospections and drive the selection of the excavation areas related to the Late Roman Period and Early Middle Ages in the Central and Southern Italy. In particular, this papers deals with the magnetic surveys acquired near \u201cMadonna della Valle\u201d and GPR and magnetic joint surveys carried out in \u201cMonastero\u201dsite. Most of magnetic maps carried out in \u201cMadonna della Valle\u201d site shown the absence of structured magnetic anomalies, despite of the presence of archaeological signs. Several hypothesis were given to explain this evidence. Joint interpretation performed in \u201cMonastero\u201d site shown more intense magnetic anomalies related with shallower reflections due to probably to buried pipes. Other reflections are related with magnetic anomalies compatible with archaeological targets, but some significant reflections do not correspond to any magnetic anomaly, indicating magnetic method could be \u201cblind\u201d respect the archaeological target. New field surveys including the electrical resistivity tomography could be carried out in order to overcome these acquisition and interpretation difficulties

Poly(HPMA)-based copolymers with biodegradable side chains able to self-assemble into nanoparticles

Poly(N-(2-Hydroxypropyl) methacrylamide) (poly(HPMA)) is gaining pharmaceutical attention in replacement to PEG as a hydrophilic stabilizer for polymer nanoparticles (NPs) devoted to systemic administration.[1] This is due to its biocompatibility, prolonged circulation time and, compared to PEG, to the avoidance of allergic reactions and of the accelerated blood clearance effect.[2, 3] In this work, a lipophilic HPMA-based macromonomer with a predetermined and controllable structure is synthesized for the first time attaching a short oligo(caprolactone) chain obtained via Ring Opening Polymerization (ROP) to the HPMA using a succinic acid unit as a spacer. This biodegradable monomer (hereinafter HPMA-CL) was then used to synthesize well-defined amphiphilic block copolymers comprising a hydrophilic poly(HPMA) block and a hydrophobic poly(HPMA-CL) segment via Reversible Addition-Fragmentation Transfer (RAFT) polymerization. The combination of ROP and RAFT allows the production of a library of polymers with a predetermined and controlled structure that are able to self-assemble in water into biodegradable NPs with different size. In particular, such NPs are designed to degrade in aqueous environment into completely water soluble poly(HPMA), with a molecular weight that is below the critical threshold for the renal excretion. This is a very important feature since it allows to avoid polymer accumulation into the body once the NPs are injected.[4] The degradation time is a function of the number of caprolactone units in the HPMA-CL macromonomer and of its degree of polymerization in the NP forming copolymer. Then, the polymer structure can be adjusted to obtain the desired degradation time. Finally, the possibility for such nanoparticles to physically incorporate and mediate the release of a lipophilic antineoplastic drug was evaluated in the case of Trabectedin. The formulation proved to be biocompatible and to sustainedly release the drug for up to 24 hours. Please click Additional Files below to see the full abstract

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe