The role of complement in synaptic degeneration

Synapse loss is an early event of many neurodegenerative diseases including Alzheimer?s disease and Parkinson?s disease. The causes and mechanisms that underpin synapse dysfunction and degeneration are poorly understood. Animal models that mimic the major disease pathologies can be used to investigate possible pathways involved. This work describes the use of two models based on the prion disease and genetic deletion of CSP? both of which are characterised by synaptic degeneration.The ME7 model of prion disease is characterised by accumulation of misfolded prion protein, microglia activation and astrocytosis at 8 weeks post disease initiation (p.i), synaptic degeneration in the CA1 of the hippocampus at 13 weeks p.i, and neuronal loss at 16 weeks p.i. Complement proteins have been shown to be upregulated in brains of patients with a neurodegenerative disease. It has been suggested that C1q is involved in synaptic degeneration by „tagging? synapses for selective removal. qRT-PCR of 18 week p.i. hippocampus from ME7-animals reveals a >5 fold induction of C1q mRNA. This was confirmed by quantitative western blotting of 18 week hippocampus showing a disease-associated increase in C1q protein. Although C1q is induced, the time course and spatial expression do not coincide with the initiation of synapse loss in the CA1. The induction is restricted to the later stages of the disease suggesting that C1q and complement does not direct synapse loss but may contribute to the removal of the cellular debris associated with neuronal loss and/or the accumulation of misfolded prion protein.In the second model, Cysteine String Protein ? (CSP?) knockout mice were investigated at time points beyond the P15, when they show synapse loss, but before they show premature death at P40. This model allows investigation of synaptic degeneration in the absence of accumulated misfolded protein. We investigated this in the context of the hippocampus but failed to show synapse loss at the time points investigated. In contrast we identified a robust astrogliosis consistent with an emerging neuronal dysfunction. This is likely related to the loss of parvalbumin-positive interneurones, and synapses, previously shown to be lost at this time point. This astrocytic response, in contrast to the ME7 model, occurs without the associated induction of C1q and other markers of the neuro-immune response.Together the data show that C1q is not selectively „tagging? synapses as previously suggested, and does not contribute to the progression of prion disease. It is more likely that C1q is upregulated in the late stages of disease to aid in the clearance of cellular debris

Ritardata attuazione delle direttive comunitarie e adeguata remunerazione dei medici specializzandi: tra prescrizione del diritto ed effettivit\ue0 della tutela

Nota alla sentenza del Tribunale Roma, sezione II, del 15 marzo 2011, per la quale, in caso di mancato o tardivo recepimento di una direttiva comunitaria, lo Stato \ue8 contrattualmente responsabile per inadempimento di un'obbligazione legale di natura indennitaria per attivit\ue0 non antigiuridica. La sentenza e il commento affrontano le diverse interpretazioni possibili sull'applicabilit\ue0 della prescrizione del diritto al risarcimento del danno al caso dei medici specializzatisi prima della trasposizione della direttiva, con la quale si \ue8 previsto in loro favore il diritto ad un'adeguata remunerazione

Disturbo post traumatico da stress e analisi bioenergetica

Il Disturbo Post-Traumatico da Stress, è la conseguenza sempre più frequente di gravi avvenimenti (singoli e collettivi) che mettono in pericolo l’integrità fisica della persona (o di più persone). Il DPTS è caratterizzato da un corteo sintomatologico codificato dal DSM 5. Tuttavia l’approccio categoriale di questo sistema classificativo, non riesce a rendere conto della molteplicità di presentazione clinica della sindrome, né delle differenti evoluzioni nel tempo (guarigione spontanea, cronicizzazione, altri gravi disturbi psicopatologici). Un approccio psicopatologico permette di evidenziare il rapporto tra evento (evento traumatico) e la risposta dell’organismo (con la sua capacità di resilienza e la sua struttura caratteriale). Viene poi evidenziato come il corpo sia fortemente coinvolto in questa sindrome e proposto l’usi di tecniche a mediazione corporea, l’analisi bioenergetica e suoi derivati, «Tension, Stress and Trauma Releasing Exercices», come strumenti terapeutici

CH of masonry materials via meshless meso-modeling

In the present study a multi-scale computational strategy for the analysis of masonry structures is presented. The structural macroscopic behaviour is obtained making use of the Computational Homogenization (CH) technique based on the solution of the boundary value problem (BVP) of a detailed Unit Cell (UC) chosen at the meso-scale and representative of the heterogeneous material. The smallest UC is composed by a brick and half of its surrounding joints, the former assumed to behave elastically while the latter considered with an elastoplastic softening response. The governing equations at the macroscopic level are formulated in the framework of finite element method while the Meshless Method (MM) is adopted to solve the BVP at the mesoscopic level. The work focuses on the BVP solution. The consistent tangent stiffness matrix at a macroscopic quadrature point is evaluated on the base of BVP results for the UC together with a localisation procedure. Validation of the MM procedure at the meso-scale level is demonstrated by numerical examples that show the results of the BVP for the simple cases of normal and shear loading of the UC

Emergent Linguistic Structures in Neural Networks are Fragile

Large Language Models (LLMs) have been reported to have strong performance on natural language processing tasks. However, performance metrics such as accuracy do not measure the quality of the model in terms of its ability to robustly represent complex linguistic structure. In this paper, focusing on the ability of language models to represent syntax, we propose a framework to assess the consistency and robustness of linguistic representations. To this end, we introduce measures of robustness of neural network models that leverage recent advances in extracting linguistic constructs from LLMs via probing tasks, i.e., simple tasks used to extract meaningful information about a single facet of a language model, such as syntax reconstruction and root identification. Empirically, we study the performance of four LLMs across six different corpora on the proposed robustness measures by analysing their performance and robustness with respect to syntax-preserving perturbations. We provide evidence that context-free representation (e.g., GloVe) are in some cases competitive with context-dependent representations from modern LLMs (e.g., BERT), yet equally brittle to syntax-preserving perturbations. Our key observation is that emergent syntactic representations in neural networks are brittle. We make the code, trained models and logs available to the community as a contribution to the debate about the capabilities of LLMs

A FE-Meshless Multiscale Approach for Masonry Materials

AbstractA FE-Meshless multiscale computational strategy for the analysis of running bond masonry is presented. The Meshless Method (MM) is adopted to solve the boundary value problem (BVP) at the mesoscopic level. The representative unit cell is composed by the aggregate and the surrounding joints, the former assumed to behave elastically while the latter are simulated as non-associated elastic-plastic zero-thickness interfaces with a softening response. Macroscopic localization of plastic bands is obtained performing a spectral analysis of the tangent stiffness matrix. Localized plastic bands are embedded into the quadrature points area of the macroscopic finite elements

The FE-Meshless multiscale approach applied to masonry structures

Heterogeneous structures have an overall response that is strongly dependent on the inelastic events developing at the local level. In these structures, the most relevant kinematical and mechanical phenomena take place at a scale which is small if compared to the dimensions of the entire structure. In literature, a mesoscopic and a macroscopic scales of interest are distinguished, directly linked to as many theoretical approaches. The mesoscopic approach [1] considers materials and their interfaces individually, but many difficulties arise in the mesh creation and a fine discretization of the structure is needed, which leads to prohibitive computational costs. The macroscopic approach considers the structure as constituted by a fictitious homogeneous and continuous material. The multiscale techniques belong to the second approach and couple different scales of interest by means of apposite transition laws capable to exchange informations between different consecutive scales [2]. This work relates with the multiscale first order computational homogenization technique applied to masonry structures. A unit cell (UC) is assumed constituted by an elastic bulk volume surrounded by weak joints, which are simulated by zero-thickness elasto-plastic interface models. At a single time step, the FE solution of the fictitious homogenized structure provides strains at all quadrature points. The corresponding macrostress field associated to the strain is obtained by solving a Boundary Value Problem (BVP) of the UC at the mesoscale level. The solution of the BVP is approached by means of a meshless strategy [3] instead of a classical finite element procedure, that is usually time-consuming. By imposing Taylor-Voigt type boundary conditions on the UC, the macroscopic stress is evaluated averaging the UC boundary tractions, according to the Hill-Mandel principle. Localization is faced at both the quadrature point level and at the element level. At the quadrature point level plastic bands are localized applying a continuous-discontinuous bifurcation theory [4] based on the spectral analysis of the acoustic tensor associated to the stiffness matrix. At the element level inelastic response is obtained smearing the plastic zones at the quadrature points over the element area, considering the localized and not localized fraction areas. The proposed model has been implemented on a research oriented finite element analysis pro- gram to run 2D simulations in plane-stress conditions for heterogeneous periodic structures. Quali- tatively good results are obtained in comparison with numerical data available in literature

On the use of EMI for the assessment of dental implant stability

The achievement and the maintenance of dental implant stability are prerequisites for the long-term success of the osseointegration process. Since implant stability occurs at different stages, it is clinically required to monitor an implant over time, i.e. between the surgery and the placement of the artificial tooth. In this framework, non-invasive tests able to assess the degree of osseointegration are necessary. In this paper, the electromechanical impedance (EMI) method is proposed to monitor the stability of dental implants. A 3D finite element model of a piezoceramic transducer (PZT) bonded to a dental implant placed into the bone was created, considering the presence of a bone- implant interface subjected to Young’s modulus change. The numerical model was validated experimentally by testing bovine bone samples. The EMI response of a PZT, bonded to the abutment screwed to implants inserted to the bone, was measured. To simulate the osseointegration process a pulp canal sealer was used to secure the implant to the bone. It was found that the PZT’s admittance is sensitive to the stiffness variation of the bone-implant interface. The results are promising because they show the potential of EMI method to (i) evaluate the material properties around dental implant, and (ii) promote a novel non-invasive monitoring of dental implant surgical procedure

L’ascolto del minore alla luce della legge n.219/2012

The aim of the work above is to provide a survey of the most prominent aspects concerning the hearing of minors. After a short introduction to state of art of the national, international and European law concerning the issue above, the hearing will be dealt with as a subjective right acknowledged to the minor, along with the giudicial features related to his/her capacity of discerment. The procedures so far used in courts for the auditions of minors and the related procedural implications will be examined. The memoranda of understanding which were adopted by many courts even before the reform will be briefly described in order to point out how the customary procedures were subsequently incorporated in the reform. The psychological outlines and the recommendations of the Italian Association of Legal Psychology whose aim is to provide the minor with the best care and protection will be finally taken into account