In the aftermath of the crisis : the EU administrative system between impediments and momentum

The European responses to the financial and public debt crisis have triggered a process of administrative reorganization and growth within two fundamental sectors of the EU, the internal market of financial services and the EMU. This paper argues that the process of reorganization and growth of the EU administrative machinery within the single financial market and the EMU is characterized by a number of inherent tensions. Four of them are prominent and refer, respectively, to the powers conferred to the satellite administrative bodies established in order to tackle the crisis, to the jurisdictions of the new administrations, to the degree of centralization which is sought within the new mechanisms for the implementation of EU laws and policies, to the accountability mechanisms. When assessed in the light of their capability to improve the EU administrative capacities, such tensions appear to be deeply ambivalent. On the one hand, they might operate as «fault lines» of the whole EU administrative machinery, destabilizing its functioning in two important fields of EU action. On the other hand, by pointing to a host of unsolved issues in EU administrative law, they provide an opportunity for opening a genuine institutional and scientific discussion on the ways in which the EU administrative system should be adjusted or reformed

The Folding process of Human Profilin-1, a novel protein associated with familial amyotrophic lateral sclerosis

Human profilin-1 is a novel protein associated with a recently discovered form of familial amyotrophic lateral sclerosis. This urges the characterization of possible conformational states, different from the fully folded state, potentially able to initiate self-assembly. Under native conditions, profilin-1 is monomeric and possesses a well-defined secondary and tertiary structure. When incubated at low pH or with high urea concentrations, profilin-1 remains monomeric but populates unfolded states exhibiting larger hydrodynamic radius and disordered structure, as assessed by dynamic light scattering, far-UV circular dichroism and intrinsic fluorescence. Refolding from the urea-unfolded state was studied at equilibrium and in real-time using a stopped-flow apparatus. The results obtained with intrinsic fluorescence and circular dichroism indicate a single phase without significant changes of the corresponding signals before the major refolding transition. However, such a transition is preceded by a burst phase with an observed increase of ANS fluorescence, which indicates the conversion into a transiently populated collapsed state possessing solvent-exposed hydrophobic clusters. Kinetic analysis reveals that such state has a conformational stability comparable to that of the fully unfolded state. To our knowledge, profilin-1 is the first example of an amyloid-related protein where folding occurs in the absence of thermodynamically stable partially folded states

Image Embeddings Extracted from CNNs Outperform Other Transfer Learning Approaches in Classification of Chest Radiographs

To identify the best transfer learning approach for the identification of the most frequent abnormalities on chest radiographs (CXRs), we used embeddings extracted from pretrained convolutional neural networks (CNNs). An explainable AI (XAI) model was applied to interpret black-box model predictions and assess its performance. Seven CNNs were trained on CheXpert. Three transfer learning approaches were thereafter applied to a local dataset. The classification results were ensembled using simple and entropy-weighted averaging. We applied Grad-CAM (an XAI model) to produce a saliency map. Grad-CAM maps were compared to manually extracted regions of interest, and the training time was recorded. The best transfer learning model was that which used image embeddings and random forest with simple averaging, with an average AUC of 0.856. Grad-CAM maps showed that the models focused on specific features of each CXR. CNNs pretrained on a large public dataset of medical images can be exploited as feature extractors for tasks of interest. The extracted image embeddings contain relevant information that can be used to train an additional classifier with satisfactory performance on an independent dataset, demonstrating it to be the optimal transfer learning strategy and overcoming the need for large private datasets, extensive computational resources, and long training times

The ESM and the Principle of Transparency

This note analyses a peculiar feature of the ESM, namely the lack of an acceptable set of standards for the fundamental democratic principle of transparency. Moving from the particular nature of this mechanism, we will highlight the most critical concerns connected to secrecy, confidentiality and inviolability of documents, looking not only at the ESM Treaty but also at relevant documents approved by its bodies (in particular the Code of Conduct and the By-Laws)

Synthetic prions with novel strain-specified properties

Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrP(Sc). Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrP(Sc) were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties