Prognostic role of hERG1 Potassium Channels in Neuroendocrine Tumours of the Ileum and Pancreas

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation.     

On the nice behaviour of the Gaussian projection filter with small observation noise

When projecting on the manifold of Gaussian densities, the projection filter has been shown to be equal to a McShane-Fisk-Stratonovich (MFS) derivation of the Gaussian assumed density filter. Starting from this point, we study the asymptotic behaviour of the Gaussian projection filter when the covariance of the observation noise tends to zero. We prove that the mean square difference between the true state of the system and the estimate given by the projection filter is bounded by a constant which is proportional to the magnitude of the observation noise.     

Clotrimazole nanoparticle gel for mucosal administration

In this study a formulation suitable to be applied on oral and/or vaginal mucosa has been developed for the treatment of fungal infections.The aim of the research is a comparison between clotrimazole (CLO) containing semisolid formulations based on monoolein aqueous dispersion (MAD) or nanostructured lipid carrier (NLC). MAD and NLC have been characterized in terms of morphology and dimensional distribution by cryogenic Transmission Electron Microscopy (cryo-TEM) and Photon Correlation Spectroscopy (PCS). CLO was encapsulated with high entrapment efficiency both in MAD and in NLC, according to Sedimentation Field Flow Fractionation (SdFFF) combined with HPLC. CLO recovery in MAD and NLC has been investigated by time.In order to obtain formulations with suitable viscosity for mucosal application, MAD was diluted with a carbomer gel, while NLC was directly viscosized by the addition of poloxamer 407 in the dispersion. The rheological properties of MAD and NLC after viscosizing have been investigated.Franz cell has been employed to study CLO diffusion from the different vehicles, evidencing diffusion rates from MAD and NLC superimposable to that obtained using Canesten^®.An anticandidal activity study demonstrated that both CLO-MAD and CLO-NLC were more active against Candida albicans with respect to the pure drug.     

Class-level Non-Interference

The Information-Flow property of Non-Interference was recently relaxed into Abstract Non-Interference (ANI), a weakened version where attackers can only observe properties of data, rather than their exact value. ANI was originally defined on integers, where a property models the set of numbers satisfying it. The present work proposes an Object-Oriented, Java-based formulation of an instance of ANI where data take the form of objects, and the observed property comes to be their type. The execution of a program is taken to be the invocation of some method by an external user: a class is secure if, for all its (non-private) methods, the type of their low-security data after the execution does not depend on the initial type of its high-security data (i.e., there are no illicit flows). The relation to ANI theory (in its abstract version) can be seen in the representation of abstract domains in terms of class hierarchies: an upper closure operator map an object into the smallest class it is an instance of. An analyzer for a non-trivial subset of Java is illustrated. A sketch of a soundness proof is provided: a program is never misclassified as secure, i.e., it is rejected whenever the absence of illicit ows cannot be guaranteed.     

Integration of absolute ventricular fibrillation voltage correlateswith successful defibrillation

Previous work has suggested that at higher absolute ventricular fibrillation voltages (AVFV), the heart is more amenable to defibrillation. This study investigated in a canine model whether voltage integration of the AVFV is associated with the defibrillation success rate. The moving-average filter was used to process the ventricular fibrillation (VF) waveform recorded from Lead II of the electrocardiogram (ECG). In seven animals, defibrillation trials were analyzed using a DC shock (DCS) successful approximately 50% of the time when delivered randomly. For each of a total of 84 DCS (40% successes, 60% failures), the fibrillation waveform just prior to DCS was analyzed. The integration of the AVPV waveform was performed over various sample sizes including 1, 4, 8, 16, 64, and 128 ms, as well as the time equal to the mean VF cycle length. The results suggest that dc shocks delivered at instants of higher values of integrated AVFV over the various window sizes are associated with successful defibrillation. Window sizes less than 16 ms appeared to offer the best discrimination. The integration of AVFV over the entire VF cycle length was significantly higher for successful rather than unsuccessful DCS. This interesting observation is consistent with the clinical observation that “coarse” VF (high AVFV) is easier to defibrillate than “fine” VF (low AVFV). The use of voltage integration of AVFV may have potential implications in the improvement of defibrillation success in implantable devices     

Use of CGF in Oral and Implant Surgery: From Laboratory Evidence to Clinical Evaluation

Edentulism is the condition of having lost natural teeth, and has serious social, psychological, and emotional consequences. The need for implant services in edentulous patients has dramatically increased during the last decades. In this study, the effects of concentrated growth factor (CGF), an autologous blood-derived biomaterial, in improving the process of osseointegration of dental implants have been evaluated. Here, permeation of dental implants with CGF has been obtained by using a Round up device. These CGF-coated dental implants retained a complex internal structure capable of releasing growth factors (VEGF, TGF-β1, and BMP-2) and matrix metalloproteinases (MMP-2 and MMP-9) over time. The CGF-permeated implants induced the osteogenic differentiation of human bone marrow stem cells (hBMSC) as confirmed by matrix mineralization and the expression of osteogenic differentiation markers. Moreover, CGF provided dental implants with a biocompatible and biologically active surface that significantly improved adhesion of endothelial cells on CGF-coated implants compared to control implants (without CGF). Finally, data obtained from surgical interventions with CGF-permeated dental implants presented better results in terms of optimal osseointegration and reduced post-surgical complications. These data, taken together, highlight new and interesting perspectives in the use of CGF in the dental implantology field to improve osseointegration and promote the healing process.     

Direct design of a velocity controller and load disturbance estimation for a self-balancing industrial manual manipulator

Self-balancing manual manipulators are devices that countervail the weight of a load that must be manually handled and moved by a human operator. Standard manipulators are made of a framework with an electric motor on the top and a spool connected to the motor shaft through a transmission gear. The load is hung by a handling device connected to a metallic rope wound on the spool. The device considered in this paper, in its current layout, is endowed with a load cell that measures the load weight and is controlled in an open loop. A new layout has been designed, which is not including the weighting load cell and is feedback controlled. The load’s counterbalance and movement are obtained by a velocity closed loop control algorithm designed using a direct design method, the Virtual Reference Feedback Tuning (VRFT). VRFT provides controller parameters tuning in a completely automatic way based on a single I/O batch measurement on the plant. Moreover, the elimination of the load weight transducer causes issues to some handling devices that need weight measurements to attach and detach the load. So, a load mass observer has been designed using a gravitational torque estimator, which is an enhanced version of standard disturbance torque observer for electric motors.     

Modeling data protection and privacy: application and experience with GDPR

Software and Systems Modeling - In Europe and indeed worldwide, the General Data Protection Regulation (GDPR) provides protection to individuals regarding their personal data in the face of new...