Geometry of Faith: a Stereotomic Reconstruction of Sainte-Anne-la-Royale in Paris

Planned during the XVIIth century by the Italian architect Guarino Guarini, the church of Sainte-Anne-la-Royale was supposed to be built in Paris to honor the French Queen Anne of Austria. In an unfortunate twist of fate the church was only partially realized and later destroyed. Present history\u27s only memory comes in three engravings by Guarino Guarini himself: a plan, a transversal section, and the main elevation. An example of Italian Baroque Architecture, the building shines for its intriguing plan and complex system of vaults. Its execution was supposed to be realized according to the refined techniques of French stereotomy. Faithful to its original inspiration, Sainte-Anne is here rebuilt using a rational geometric system that links each element in the composition by projections and squaring of circles. Each of the elements composing the church has been individually analyzed and reconstructed. The main reference for this process has been provided by Guarini\u27s posthumous essay Architettura Civile. Though still unbuilt, Sainte-Anne-la-Royale has been reconstructed by a new set of drawings, both handmade (pencil on mylar, 30\u27\u27x40\u27\u27) and computer generated, and a physical model (3d-printed; about 41 tall)

Effects of Random Mutagenesis and In Vivo Selection on the Specificity and Stability of a Thermozyme

Factors that give enzymes stability, activity, and substrate recognition result from the combination of few weak molecular interactions, which can be difficult to study through rational protein engineering approaches. We used irrational random mutagenesis and in vivo selection to test if a β-glycosidase from the thermoacidophile Saccharolobus solfataricus (Ssβ-gly) could complement an Escherichia coli strain unable to grow on lactose. The triple mutant of Ssβ-gly (S26L, P171L, and A235V) was more active than the wild type at 85 °C, inactivated at this temperature almost 300-fold quicker, and showed a 2-fold higher kcat on galactosides. The three mutations, which were far from the active site, were analyzed to test their effect at the structural level. Improved activity on galactosides was induced by the mutations. The S26L and P171L mutations destabilized the enzyme through the removal of a hydrogen bond and increased flexibility of the peptide backbone, respectively. However, the flexibility added by S26L mutation improved the activity at T > 60 °C. This study shows that random mutagenesis and biological selection allowed the identification of residues that are critical in determining thermal activity, stability, and substrate recognitio

Molecular-dynamics calculations of thermodynamic properties of metastable alloys

In order to improve our current understanding of the microscopic structure of metastable alloys of immiscible elements such as Ag-Cu and Co-Cu, the Helmholtz free energy of several microstructures based on an fcc unit cell has been calculated and compared with that of a reference state. The microstructures considered for the free energy calculations at fixed volume are (1) a structure formed by alternating layers of fixed thickness of metal 1 and metal 2 separated by coherent interfaces; (2) an atomically disordered solid solution; (3) a structure comprising a random distribution of elemental cubic grains separated by coherent interfaces. Numerical results show that the Helmholtz free energy of structure (3) decreases with increasing grain size and that its value calculated for a sufficiently large grain size approaches the free energy of structure (1). Further molecular-dynamics simulations for the Ag-Cu system have allowed the calculation of the enthalpy at the equilibrium volume of several microstructures including some of those listed above. A comparison of the calculated values of the enthalpy with the heat release observed experimentally allows the advancement of an hypothesis concerning the reaction path and the structure of the equiatomic Ag-Cu alloy obtained by ball milling

The Role of Quantic Molecular Resonance (QMR) in the Treatment of Inferior Turbinate Hypertrophy (ITH): Our Experience With Long-Term Follow-Up in Allergic and Nonallergic Rhinitis Refractory to Medical Therapy. Preliminary Results.

Objective: The aim of this study was to assess the long-term effectiveness of quantic molecular resonance (QMR) in the treatment of inferior turbinate hypertrophy (ITH) in allergic and nonallergic rhinitis refractory to medical therapy. Methods: This study enrolled 281 patients, 160 males (56.9%) and 121 females (43.1%), mean age 37.8 ± 4.1 years, range 18 to 71. Fifty-four patients have been lost to follow up and have been therefore excluded from the final analysis. Based on skin prick test results, 69 patients were considered allergic (group A) and 158 nonallergic (group B). All subjects underwent before surgery (T0) and 3 (T1), 12 (T2), 24 (T3), and 36 months (T4) after QMR treatment to: 4-phase rhinomanometric examination, nasal endoscopy evaluation, and visual analogue scale to quantify the subjective feelings about nasal obstruction. Results: Subjective and objective parameters showed statistically significant improvement in both groups. Group B parameters not changed during follow-up, while group A showed significant worsening between T1 and subsequent assessments. T4 outcome indicates a better result in nonallergic patients. Conclusions: In accordance with the literature, our preliminary data validate QMR treatment as a successful therapeutic option for nasal obstruction due to ITH. Nonallergic patients had a very good T4 outcome. Allergic patients showed a worsening trend after 1 year probably due to other causes

Systems engineering approach for pre-conceptual design of DEMO divertor cassette

Abstract This paper presents the pre-conceptual design activities conducted for the European DEMO divertor, focusing on cassette design and Plasma Facing Components (PFC) integration. Following the systems engineering principles, a systematic design method, the Iterative and Participative Axiomatic Design Process (IPADeP), has been adopted. Basing on Axiomatic Design, IPADeP supports the early conceptual design of complex systems. The work moved from the geometrical and interface constraints imposed by the 2015 DEMO configuration model. Then, since different materials will be used for cassette and PFCs, the divertor geometry has been developed taking into account the cooling parameters of the cassette Eurofer steel and the integration of PFCs cooling system. Accordingly, the design process led to a double wall cassette structure with internal reinforcing ribs to withstand cassette coolant pressure and three different kinds of piping schemes for PFCs with dual circuits. These three solutions differs in the feeding pipes layouts and target manifold protection and they have been proposed and evaluated considering heat flux issues, shielding problems, interface requirements with blanket and vacuum vessel and remote maintenance needs. A cassette parametric shell model has been used to perform first structural analyses of the cassette body against coolant pressure. Taking advantages of the parametric surface modelling and its linkage with Finite Element (FE) code, the cassette ribs layout and thickness has been evaluated and optimized, considering at the same time the structural strength needed to withstand the coolant parameters and the maximum stiffness required for cassette preloading and locking needs

Bone Marrow Clonogenic Capability, Cytokine Production, and Thymic Output in Patients with Common Variable Immunodeficiency

AbstractIn patients with primary Ab deficiencies, hematological and immunological abnormalities are frequently observed. A regenerative failure of hemopoietic stem/progenitor cells has been hypothesized. We evaluated in the bone marrow (BM) of 11 patients with common variable immunodeficiency, the phenotype of BM progenitors and their in vitro growth by colony-forming cell (CFC) and long-term culture (LTC) assays. A significant decrease in erythroid and mixed CFC and, to a greater extent, in primitive LTC-CFC progenitors was observed in patients compared with healthy controls. The frequency of BM pre-B and pro-B cells correlated directly with the absolute number of CD19+ lymphocytes. BM cells cultured in vitro produced spontaneously lower amounts of IL-2 and elevated levels of TNF-α compared with controls, indicating a skewing toward a proapoptotic cytokine pattern. In addition, stromal cells generated after BM LTC secreted less IL-7 and displayed by immunohistochemistry an altered phenotype. These findings were associated with a significant decrease in naive Th cells coexpressing CD31 in the peripheral blood. These results indicate an impaired growth and differentiation capacity of progenitor cells in patients with common variable immunodeficiency

The Natural History of Asymptomatic Ventricular Pre-Excitation A Long-Term Prospective Follow-Up Study of 184 Asymptomatic Children

ObjectivesThe aim of this study was to describe the natural history of asymptomatic ventricular pre-excitation in children and to determine predictors of potentially life-threatening arrhythmic events.BackgroundSudden death can be the first clinical manifestation in asymptomatic children with ventricular pre-excitation, but reduction of its incidence by prophylactic ablation requires the identification of subjects at high risk.MethodsBetween 1995 and 2005 we prospectively collected clinical and electrophysiologic data from 184 children (66% male; median age 10 years; range 8 to 12 years) with asymptomatic ventricular pre-excitation on the electrocardiogram. After electrophysiologic testing, subjects were followed as outpatients taking no medications. The primary end point of the study was the occurrence of arrhythmic events. Predictors of potentially life-threatening arrhythmias were analyzed.ResultsOver a median follow-up of 57 months (min/max 32/90 months) after electrophysiologic testing, 133 children (mean age 10 years; range 8 to 12 years) did not experience arrhythmic events, remaining totally asymptomatic, while 51 children had within 20 months (min/max 8/60 months) a first arrhythmic event, which was potentially life-threatening in 19 of them (mean age 10 years; range 10 to 14 years). Life-threatening tachyarrhythmias resulted in cardiac arrest (3 patients), syncope (3 patients), atypical symptoms (8 patients), or minimal symptoms (5 patients). Univariate analysis identified tachyarrhythmia inducibility (p < 0.001), anterograde refractory period of accessory pathways (APERP) ≤240 ms (p < 0.001), and multiple accessory pathways (p < 0.001) as risk factors for potentially life-threatening arrhythmic events. Independent predictors by multivariate analysis were APERP (p = 0.001) and multiple accessory pathway (p = 0.001).ConclusionsThese findings are potentially relevant in terms of early identification of high-risk asymptomatic children with ventricular pre-excitation. Subjects with short APERPs and multiple pathways are at higher risk of developing life-threatening arrhythmic events and are the best candidates for prophylactic ablation

Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut-liver axis

Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P\ua0<\ua00\ub701) and serum cholesterol (P\ua0<\ua00\ub7001), alanine aminotransferase and glucose (P\ua0<\ua00\ub705). Accordingly, liver PPAR- \u3b1 (P\ua0<\ua00\ub705) and acyl-CoA oxidase-1 (P\ua0<\ua00\ub705) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P\ua0<\ua00\ub705) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P\ua0<\ua00\ub705), duodenal claudin (P\ua0<\ua00\ub705) and duodenal peptide YY (P\ua0<\ua00\ub705) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P\ua0<\ua00\ub705). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota