LEARNING FROM THE BUILDING: DIRECT SOURCES FOR THE PRESERVATION PROJECT. THE EXPERIENCE OF BESOZZO'S TOWN HALL (VARESE, ITALY)

The Town Hall of Besozzo (Varese, Italy) is located in the city centre of the village and its first construction phase is dated back to the XIV-XV century. It shows a complex palimpsest which is the result of the numerous transformations occurred during its life: enlargements, super elevations, demolitions, inner spaces subdivisions and use changes. Currently a project has been issued for the reuse of the building which assigns new spaces for the town offices to the northern wing recently acquired. The aim of the research was to provide a diagnostic insight, useful for the development of the conservation project which will necessarily take into account the multitude of values registered on the building. Owing to a lack of meaningful archival documentation, the elevation's stratigraphic reading and the methods for dating historical buildings proved to be an invaluable resource for the comprehension of the building's transformations. Cross-referencing readings of indirect sources carried on the building with the results of the in-depth analysis made it possible to rebuild the growth of the structure from its origin to the present days. Such analysis includes: geometric survey, photographic rectifications of facade and inner sections, non-destructive diagnostic investigations, bricks, mortar and plaster chemical-physical analysis, mensiochronology, study of the building techniques and chronotypology which is a stylistic analysis performed both on the constructive (apertures) and decorative (shelves, graffiti, colourings traces) architectural elements. Blending the results of these dating techniques produced the complexity of the stratigraphic reading which has been conveyed with adequate hatching on the rectified images (U.S. – Stratigraphic Unity) while schematic 3D reconstructions exemplify the chronological sequence of the building activities. Individuation and comprehension of the building constructive phases made also possible to understand which were the different uses of each room inside this domestic architecture thus providing the client and the bodies in charge of protection with valuable data for the preservation project

An overview of molecular mechanisms in fabry disease

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is alpha-galactosidase A (alpha-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers

Antibody binding modulates conformational exchange in domain III of dengue virus E protein

Domain III of dengue virus E protein (DIII) participates in the recognition of cell receptors and in structural rearrangements required for membrane fusion and ultimately viral infection; furthermore, it contains epitopes for neutralizing antibodies and has been considered a potential vaccination agent. In this work, we addressed various structural aspects of DIII and their relevance for both the dengue virus infection mechanism and antibody recognition. We provided a dynamic description of DIII at physiological and endosomal pHs and in complex with the neutralizing human antibody DV32.6. We observed conformational exchange in the isolated DIII, in regions important for the packing of E protein dimers on the virus surface. This conformational diversity is likely to facilitate the partial detachment of DIII from the other E protein domains, which is required to achieve fusion to the host cellular membranes and to expose the epitopes of many anti-DIII antibodies. A comparison of DIII of two dengue virus serotypes revealed many common features but also some possibly unexpected differences. Antibody binding to DIII of dengue virus serotype 4 attenuated the conformational exchange in the epitope region but, surprisingly, generated exchange in other parts of DIII through allosteric effects

Composition and drivers of energy prices and costs: Case studies in selected energy-intensive industries. Final Report. CEPS Special Report, January 2017

Researchers at CEPS, in cooperation with researchers at Ecofys and Economisti Associati, have carried out a comprehensive examination of energy prices in selected EU industries, commissioned by DG Grow of the European Commission. The 309-page study concentrates on three sectors and two sub-sectors of the ceramics industry: Steel Aluminium (primary & downstream) Wall and floor tiles Bricks and roof tiles Refineries For each of these five (sub-)sectors, the study provides an overview of energy price developments, with particular attention paid to i) energy price levels and ii) the structure of energy prices, i.e. the components of energy bills. The analysis was conducted between December 2015 and June 2016, with the primary information collected between February and March 2016 via a questionnaire sent to the selected plants. The questionnaire contains (inter alia) questions on production levels, financial data and energy costs and consumption

Preventive exercise and physical rehabilitation promote long-term potentiation-like plasticity expression in patients with multiple sclerosis

Background and purpose: Loss of long-term potentiation (LTP) expression has been associated with a worse disease course in relapsing-remitting multiple sclerosis (RR-MS) and represents a pathophysiological hallmark of progressive multiple sclerosis (PMS). Exercise and physical rehabilitation are the most prominent therapeutic approaches to promote synaptic plasticity. We aimed to explore whether physical exercise is able to improve the expression of LTP-like plasticity in patients with multiple sclerosis (MS). Methods: In 46 newly diagnosed RR-MS patients, we explored the impact of preventive exercise on LTP-like plasticity as assessed by intermittent theta-burst stimulation. Patients were divided into sedentary or active, based on physical activity performed during the 6 months prior to diagnosis. Furthermore, in 18 patients with PMS, we evaluated the impact of an 8-week inpatient neurorehabilitation program on clinical scores and LTP-like plasticity explored using paired associative stimulation (PAS). Synaptic plasticity expression was compared in patients and healthy subjects. Results: Reduced LTP expression was found in RR-MS patients compared with controls. Exercising RR-MS patients showed a greater amount of LTP expression compared with sedentary patients. In PMS patients, LTP expression was reduced compared with controls and increased after 8 weeks of rehabilitation. In this group of patients, LTP magnitude at baseline predicted the improvement in hand dexterity. Conclusions: Both preventive exercise and physical rehabilitation may enhance the expression of LTP-like synaptic plasticity in MS, with potential beneficial effects on disability accumulation

cis-2-Tri-n-butylstannylvinyl cuprates: a new synthon for the cis-1,2-ethene dianion

Conjugate additions of lower order and higher order cyano cuprates containing the cis-2-tri-n-butylstannylvinyl group to cycloalkenones have been studied. The higher order cuprates were more reactive towards hindered enones such as 4,4- dimethylcyclohexenone and 2,4,4-trimethylcyclohexenone, and produced higher yields with the base-sensitive acetonide of cis-4,5-dihydroxycyclohexenone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30275/1/0000676.pd

Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis

Introduction: Disease course of multiple sclerosis (MS) is negatively influenced by proinflammatory molecules released by activated T and B lymphocytes and local immune cells. The endovanilloid system plays different physiological functions, and preclinical data suggest that transient receptor potential vanilloid type 1 (TRPV1) could modulate neuroinflammation in this disorder.Methods: The effect of TRPV1 activation on the release of two main proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin (IL)-6, was explored in activated microglial cells. Furthermore, in a group of 132 MS patients, the association between the cerebrospinal fluid (CSF) levels of TNF and IL-6 and a single nucleotide polymorphisms (SNP) influencing TRPV1 protein expression and function (rs222747) was assessed.Results: In in vitro experiments, TRPV1 stimulation by capsaicin significantly reduced TNF and IL-6 release by activated microglial cells. Moreover, the anti-inflammatory effect of TRPV1 activation was confirmed by another TRPV1 agonist, the resiniferatoxin (RTX), whose effects were significantly inhibited by the TRPV1 antagonist, 5-iodoresiniferatoxin (5-IRTX). Vice versa, BV2 pre-treatment with 5-IRTX increased the inflammatory response induced by LPS. Moreover, in MS patients, a significant association emerged between TRPV1 SNP rs222747 and CSF TNF levels. In particular, the presence of a G allele, known to result in increased TRPV1 protein expression and function, was associated to lower CSF levels of TNF.Conclusions: Our results indicate that TRPV1 influences central inflammation in MS by regulating cytokine release by activated microglial cells. The modulation of the endovanilloid system may represent a useful approach to contrast neuroinflammation in MS