Engineering robust polar chiral clathrate crystals

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Royal Society of Chemistry 2013.The R-(+)-enantiomeric form of Dianin's compound and the S-(+)-enantiomeric form of its direct thiachroman analogue both obtained chromatographically employing a cellulose tris(3,5-dimethylphenylcarbamate) column, are shown to undergo supramolecular assembly to form a polar clathrate lattice which is stable even in the absence of a consolidating guest component

An Agonist of the CXCR4 Receptor Strongly Promotes Regeneration of Degenerated Motor Axon Terminals

The activation of the G-protein coupled receptor CXCR4 by its ligand CXCL12\u3b1 is involved in a large variety of physiological and pathological processes, including the growth of B cells precursors and of motor axons, autoimmune diseases, stem cell migration, inflammation, and several neurodegenerative conditions. Recently, we demonstrated that CXCL12\u3b1 potently stimulates the functional recovery of damaged neuromuscular junctions via interaction with CXCR4. This result prompted us to test the neuroregeneration activity of small molecules acting as CXCR4 agonists, endowed with better pharmacokinetics with respect to the natural ligand. We focused on NUCC-390, recently shown to activate CXCR4 in a cellular system. We designed a novel and convenient chemical synthesis of NUCC-390, which is reported here. NUCC-390 was tested for its capability to induce the regeneration of motor axon terminals completely degenerated by the presynaptic neurotoxin \u3b1-Latrotoxin. NUCC-390 was found to strongly promote the functional recovery of the neuromuscular junction, as assayed by electrophysiology and imaging. This action is CXCR4 dependent, as it is completely prevented by AMD3100, a well-characterized CXCR4 antagonist. These data make NUCC-390 a strong candidate to be tested in human therapy to promote nerve recovery of function after different forms of neurodegeneratio

Dietary practices in isovaleric acidemia:A European survey

Background: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. Aim: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). Methods: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n=53). The questionnaire comprised 27 questions about the dietary management of IVA. Results: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. Conclusions: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability. (C) 2017 The Authors. Published by Elsevier Inc

Dietary practices in propionic acidemia:A European survey

Background: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. Aim: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. Methods: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. Results: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/ FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. Conclusions: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking

Per una visione integrata del trasporto transfrontaliero nelle regioni alpine

La mobilità transfrontaliera è un tema in forte crescita a livello europeo. Da un lato, i pendolari che giornalmente attraversano i confini nazionali sono triplicati negli ultimi 20 anni; dall’altro il flusso di turisti che attraversano i confini nazionali è significativamente cresciuto, soprattutto nelle regioni alpine. A dispetto di questa crescita della domanda, l’offerta di trasporto pubblico presenta ancora diverse barriere che determinano spostamenti effettuati prevalentemente con mezzi privati, con conseguenti esternalità negative. Questo articolo analizza le barriere tecniche e politiche che interessano l’offerta di trasporto pubblico a livello transfrontaliero (connettività, info-mobilità e tariffazione, multi-modalità). Vengono considerate quattro differenti scale (europea, alpina, euro-regionale e regionale), evidenziando come esistono significativi limiti nello sviluppo di strategie comuni per risolvere il problema a livello sistemico e non puntuale. Lo sviluppo di un approccio strategico capace di tenere insieme tanto i collegamenti transnazionali principali, quanto la rete di connessioni transfrontaliere minori, è possibile attraverso uno strumento integrato quale l’AG4 di Eusalp. Esso può contribuire alla creazione di una rete integrata a livello di macroarea alpina in grado di cambiare i paradigmi di mobilità transfrontaliera

Cross-border commuting in Central Europe: features, trends and policies

Cross-border commuting is a growing phenomenon both in metropolitan and peripheral areas. Its increase is mostly guaranteed by private vehicles, which cause several negative externalities. Among the European macro-areas of cross-border commuting, Central Europe is characterized by relevant flows, which are originated by EU-13 countries and are headed to EU-15 ones. This article first investigates the specificities of transboundary commuting in Central Europe. Thereafter, it analyzes its transport challenges and best practices. Central European specificities are detected through socio-economic, territorial and transport related indicators, which are compared with other commuting areas. A best practice analysis is performed for four thematic fields: connectivity, multimodality, info-mobility tariffs/ticketing, political cooperation. The followed process highlights the rural character of Central European bordering regions, as well as the necessity to address their cross-border challenges by integrating different mobility aspects. In this way, a proper improvement of the quality of cross-border public transport may be an occasion to enforce minor relationships across borders. Further, it may grant a balance with the numerous policies focused on the development of the main centers and corridors

An innovative model to estimate the accessibility of a destination by public transport

Accessibility is a valuable indicator for assessing the effectiveness of a transport network. Nevertheless, its analysis can lead to very heterogeneous results depending on the method adopted, thus still struggling to be considered by policy makers and in planning processes. This article contributes to the development of an accessibility analysis as a planning tool, by proposing an alternative model to estimate the relative accessibility of a destination by public transport (PT). Indeed, PT is a mobility paradigm that has been supported to reduce the negative externalities produced by private transport, especially in environmentally fragile contexts. The model includes a set of eleven factors affecting public transport operation which refer to four macro topics: connectivity, multimodality, tariff/ticketing, and info-mobility. They are integrated into a Public Transport Accessibility index which analyses a series of nodes along a route and detects the progressive variation of accessibility. Eventual shifts are highlighted, including information about the factors feeding them. The model is tested for the Lana-Zurich (IT-CH) connection, showing how the most relevant issues are caused by difficulties in the transnational and transregional integration of the services. Through this process, the model aims at backing policy makers in the detection and understanding of public transport barriers and related causes

Automation and urban transport planning: Policy recommendations and best practices

Although Automation is expected to play a crucial role in the future development of transport, currently it lacks strong relations with urban mobility planning. Most types of plans such as SUMPs do not include operative references to Automation, overlooking strategic guidelines or useful measures to integrate this theme into the future vision of mobility. Such a lack represents a missed opportunity, since Automation could stimulate a more collective-oriented mobility paradigm and reduce most of the negative externalities generated by transport. The aim of this contribution is to highlight the importance for transport planning to start dealing with this process in a more rigorous way. For this purpose, the potential effects that Automation may have on transport and land use are summarized in three main types of scenarios. Then, a series of goals are identified, policy recommendations are provided, and exemplificative best practices as well as virtuous urban mobility plans are described