Optimization of the force and power consumption of a microfabricated magnetic actuator

The force (F) and the power consumption (P ) of a magnetic actuator are modeled, measured and optimized in the context of developing micro-actuators for large arrays, such as in portable tactile displays for the visually impaired. We present a novel analytical approach complemented with finite element simulation (FEM) and experiment validation, showing that the optimization process can be performed considering a single figure of merit. The magnetic actuator is a disc-shaped permanent magnet displaced by planar microcoil. Numerous design parameters are evaluated, including the width and separation of the coil traces, the trace thickness, number of turns and the maximum and minimum radius of the coil. We obtained experimental values ranging from 2 to 12 mN/ sqrt(W) using up to 2-layer coils of both microfabricated and commercial printed circuit board (PCB) technologies. This performance can be further improved by a factor of two by adopting a 6-layer technology. The method can be applied to a wide range of electromagnetic actuators

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic oligolactam analogues show a correlation between ion transport abilities in artificial liposomes and cytotoxic activity on human cancer cell lines. The reported results demonstrate that the versatile cyclic peptoid scaffold, for its remarkable conformational and complexing properties, can morphologically mimic related natural products and elicit powerful biological activities

Transition Metal Complexes as Anion Carriers

La regolazione del trasporto del cloruro attraverso le membrane biologiche \ue8 un processo fondamentale coinvolto in molte vie metaboliche, il cui squilibrio porta a gravi malattie genetiche come la fibrosi cistica. In Natura, il trasporto del cloruro \ue8 regolato da complesse proteine di membrana, tuttavia esistono anche alcuni esempi di piccole molecole che fungono da trasportatori di anioni. I trasportatori di cloruro hanno mostrato attivit\ue0 biologiche interessanti (ad esempio antitumorale ed antibiotica) e ne \ue8 stato proposto l\u2019utilizzo nella terapia di sostituzione dei canali del cloruro per i pazienti affetti da fibrosi cistica. Quindi, la capacit\ue0 di sviluppare molecole semplici che siano in grado di promuovere il trasporto del cloruro in membrane biologiche appare molto promettente. In letteratura sono presenti numerosi esempi di trasportatori di cloruro, che generalmente utilizzano (tio)uree come elementi di riconoscimento per l\u2019anione. Al contrario, nonostante sia il riconoscimento che il trasporto di ioni siano tipici processi supramolecolari, ci sono pochi esempi dell'uso di complessi di coordinazione come trasportatori di anioni. Recentemente il nostro gruppo di ricerca ha dimostrato che il complesso di palladio dpppPdCl2 \ue8 in grado di promuovere il trasporto di cloruro in liposomi e il progetto di ricerca di questa tesi intende approfondire lo studio dell'attivit\ue0 ionoforica di questi complessi. Le due propriet\ue0 principali che influenzano l'efficienza del trasporto sono la lipofilicit\ue0 dei trasportatori e la loro affinit\ue0 per gli anioni. E\u2019 stato quindi condotto uno studio di relazione struttura-attivit\ue0 riguardante questi due parametri sui complessi Pd(II) dppp. La lipofilicit\ue0 dei complessi di Pd(II) \ue8 stata modificata inserendo sostituenti alchilici, mentre l'effetto dell\u2019affinit\ue0 per il cloruro \ue8 stato valutato introducendo gruppi elettron-attrattori e donatori. Inoltre, \ue8 stato preso in considerazione il bite angle del legante, un parametro importante che influisce sulla reattivit\ue0 dei complessi di coordinazione. L'attivit\ue0 ionoforica dei complessi \ue8 stata studiata utilizzando liposomi come modelli di membrane. I risultati ottenuti indicano che il fattore principale che influenza l'efficienza di trasporto degli ioni \ue8 la lipofilicit\ue0. Invece, per quanto riguarda il bite angle e la costante di affinit\ue0, i loro effetti si sono rivelati pi\uf9 complessi da analizzare. Inoltre, \ue8 stato possibile ottenere informazioni sul meccanismo di trasporto promosso da questi ionofori, che \ue8 stato confermato essere di tipo carrier elettrogenico o non elettrogenico, a seconda del saggio di trasporto. Lo studio dell\u2019attivit\ue0 ionoforica \ue8 stato esteso ad altri metalli, come rame, nichel e platino. Tra questi complessi, quello di Cu(I) si \ue8 dimostrato il pi\uf9 efficiente, seppure inferiore a quello di palladio. Ci\uf2 ha dimostrato la validit\ue0 generale dell'approccio aprendo la strada a ulteriori studi. Una seconda parte della tesi si \ue8 concentrata sullo studio delle propriet\ue0 biologiche di questa nuova classe di ionofori. In collaborazione con la dr.ssa M. Benincasa, la loro attivit\ue0 antimicrobica \ue8 stata studiata su batteri Gram-positivi e negativi, mostrando efficacia antibatterica a concentrazioni micromolari contro S. Aureus. Per investigare il meccanismo di interazione degli ionofori con le cellule, sono stati sviluppati ionofori fluorescenti basati su complessi di naftalimmidi o acenaftene con Cu(I) e Pd(II), la cui emissione di fluorescenza sar\ue0 utilizzata per avere informazioni circa la loro localizzazione nelle cellule. Durante il dottorato ho contribuito allo studio dell'attivit\ue0 ionoforica di nuovi peptoidi sintetici preparati dai gruppi di ricerca del prof. F. De Riccardis e la prof.ssa I. Izzo ed ho partecipato allo sviluppo di nuovi materiali elettrocromici basati su naftalimmidi in collaborazione con il prof. J. Parola, dell\u2019Universidade Nova de Lisboa.The regulation of transmembrane chloride transport is a fundamental process involved in many metabolic pathways and its imbalance leads to serious genetic diseases like cystic fibrosis. In Nature, chloride transport is regulated by complex membrane proteins but there are also a few examples of small molecules which act as anion carriers. Chloride transporters have shown interesting biologic activity (e.g. anticancer, antibiotic) and it has been proposed that they could be used in channel replacement therapy for cystic fibrosis patients. In this context, the ability to develop simple molecules able to efficiently promote chloride transport in biological membranes appears really promising. Several examples of artificial chloride carriers are present in literature, usually based on (thio)ureas. On the contrary despite the fact that ion recognition and transport is a typical supramolecular process, there are only a few examples of the use of coordination complexes as anion transporters. Recently our research group reported that a simple bis-phosphine palladium complex, dpppPdCl2, is able to promote chloride transport in liposomes with a carrier mechanism. This represents a completely new class of ionophores and the research project of this Thesis focus on the design and study of the ionophoric activity of Pd(II) based metal complexes. Knowing from literature studies that the lipophilicity of the carrier and its affinity for the anion are the two main properties affecting the transport efficiency, a structure activity relationship study was done on dppp based Pd(II) complexes. The lipophilicity of the Pd(II) complexes was tuned inserting alkyl substituents on the ligands, while the effect of the chloride association constant of the complexes was evaluated by introducing electron-withdrawing and electron-donor substituents on the phenyl rings of the ligand. Moreover, we took into consideration the bite angle of the ligand, which is an important parameter that determines the reactivity of bis-phosphine metal complexes. The ionophoric activity of the compounds was studied with liposomes-based assays. The results indicate that the main factor affecting the ion transport efficiency is lipophilicity. On the other hand, the effects of the bite angle and of the association constant resulted to be more elusive. Moreover, it was possible to gain information on the mechanism of transport promoted by this new class of ionophores, which was confirmed to be an electrogenic or non-electrogenic carrier type mechanism depending on the experimental conditions. The scope of the study was expanded to other transition metals, like copper, nickel and platinum, among which Cu(I) showed the best activity, although lower than palladium. This proved the general validity of the approach and opened the way to further studies on different type of ligands and metal complexes. A second part of the work was focused on the study of the biological properties of this new class of ionophores. In collaboration with dr. M. Benincasa, their antimicrobial activity was tested on Gram-positive and negative bacterias, showing low micromolar efficacy against S. Aureus. With the aim of obtaining information on the mechanism of interaction of the metal-based anionophores with cells, fluorescent ionophores based on naphthalimide or acenaphthene complexes with Cu(I) and Pd(II) were developed. The fluorescence emission of the complexes will be used to localize the complexes inside living cells. Parallel to the development of metal complex based anion carriers, during the course of the Ph.D. period, I have contributed in the study of the ionophoric activity of new synthetic peptoids prepared by professor F. De Riccardis and professor I. Izzo research groups. I have also participated in the development of new electrochromic materials based on naphthalimide phosphine oxides in collaboration with professor J. Parola of the Universidade Nova de Lisboa

Biological Activity of Trans-Membrane Anion Carriers

Natural and synthetic anionophores promote the trans-membrane transport of anions such as chloride and bicarbonate. This process may alter cellular homeostasis with possible effects on internal ions concentration and pH levels triggering several and diverse biological effects. In this article, an overview of the recent results on the study of aniontransporters, mainly acting with a carrier-type mechanism, is given with emphasis on the structure/activity relationship and on their biological activity as antibiotic and anticancer agents and in the development of new drugs for treating conditions derived from dysregulation of natural anion channels

Thalamocortical Projections onto Behaviorally Relevant Neurons Exhibit Plasticity during Adult Motor Learning

Layer 5 neurons of the neocortex receive direct and relatively strong input from the thalamus. However, the intralaminar distribution of these inputs and their capacity for plasticity in adult animals are largely unknown. In slices of the primary motor cortex (M1), we simultaneously recorded from pairs of corticospinal neurons associated with control of distinct motor outputs: distal forelimb versus proximal forelimb. Activation of ChR2-expressing thalamocortical afferents in M1 before motor learning produced equivalent responses in monosynaptic excitation of neurons controlling the distal and proximal forelimb, suggesting balanced thalamic input at baseline. Following skilled grasp training, however, thalamocortical input shifted to bias activation of corticospinal neurons associated with control of the distal forelimb. This increase was associated with a cell-specific increase in mEPSC amplitude but not presynaptic release probability. These findings demonstrate distinct and highly segregated plasticity of thalamocortical projections during adult learning

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker, whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination