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    Study of biochemical mechanisms induced by Gluten FriendlyTM in vitro and in vivo on coeliac patients

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    This thesis aimed to investigate the biochemical mechanisms induced by “Gluten FriendlyTM” in vitro and in vivo on coeliac patients. “Gluten FriendlyTM” is a patented technology (Italian patented method n°: 0001414717, also filed under the Patent Cooperation Treaty, application no. PCT/IB2013/000797 and published in Europe as EP 2903453 A1 and titled “Detoxification method of gluten proteins from cereal grains”) that allows the reshaping of gluten proteins directly in the cereal grains, before milling. Thereby it is possible to obtain functional flours suitable for the preparation of bakery products made from wheat. Specifically, “Gluten FriendlyTM” technology involves the application of microwave energy for a few seconds to hydrated wheat kernels before milling to reach a high temperature for a short amount of time. The method aims to combine the nutritional, organoleptic and rheological properties of wheat proteins with a beneficial role for the gut health and microbiota of both celiac and healthy subjects. This innovative technology relies on a wise combination of parameters such as temperature, humidity, resting, and evaporation, clearly described in the registered patent and quoted in this thesis. This temperature-based process does not cause gluten proteins denaturation, but changes in their conformation, even in the so-called antigenic sequences, that make them unrecognizable in vitro by a wide range of antibodies specific for gluten proteins. It has been postulated that “Gluten FriendlyTM” technology induces rearrangements of protein structure that involve the exposure of charges that may allow a new kind of aggregation among different classes of wheat endosperm proteins, only through hydrophobic and/or ionic interactions. The investigation of gluten proteins reshaping induced by Gluten Friendly technology requires tough efforts since the Gluten Friendly molecule shows difficulty in its isolation. However, the molecular structure could be investigated by using an approach based on integrated techniques such as Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy. While the temperature-treated gluten loses its immunogenic properties in vitro on celiac, gut-derived T-cells lines, it is able to act as a bioactive molecule with pleiotropic effects on human health, without losing its technological proprieties and viscoelasticity. The flour can still form dough, leaven and bake into bread. The sensory qualities of Gluten FriendlyTM bread (GFB) are comparable to that of the Control Bread (CB) in terms of appearance, taste, aroma, colour and bread texture. Furthermore, a previous in vitro study carried out on celiac and healthy fecal microbiota pinpointed that GFB prolonged the survival of L. acidophilus La-5 and exerted an antibacterial effect towards S. aureus and S. Typhimurium. GFB was able to positively modulate the composition of celiac gut microbiota in vitro, promoting changes in Lactobacilli and Bifidobacteria members. These results were confirmed in a following in vitro study, performed by a three-stage continuous gut model system, on the intestinal microbiota composition and metabolites production 3 of healthy and celiac subjects for a prolonged period of 30 days. The study showed the ability of GFB to restore even the microbiota of healthy individuals, increasing the number of bifidogenic bacteria and SCFAs levels. Based on this evidence, the technology has been further improved with the registration of a second patent: "Method for the detoxification of gluten proteins from cereal grains and related uses in the medical field" (Italian priority patent no: 102015000084813 also extended to European level PCT/EP2016/0815899). Further in vitro study showed that GFB, in comparison to CB, increased mucus secretion and gut-barrier function in human intestinal goblet cells. These data support the potential effect of GFB to maintain or improve gut homeostasis and cellular barrier integrity by maintaining higher mucin levels. Moreover, another study based on the preparation of synbiotic fermented milk, containing L. acidophilus La-5 and Gluten FriendlyTM flour (GFF), was carried out. The most important result was the positive effect of GFF on the viability of the probiotic, with a prolongation of the shoulder length to 20 days (12–13 days in the control). Based on this evidence, another in vitro study, aiming to produce a synbiotic yogurt containing Bifidobacterium infantis and GFF, was carried out. The results highlighted that GFF prolonged the viability of Bifidobacteria for 14 days instead of 4 days in the control and control flour (CF). Based on the reduced immunoreactivity and the beneficial effects of Gluten FriendlyTM molecule on the gut microbiota in vitro, an in vivo prospective, double-blind, randomized, placebo-controlled study of 12 weeks was performed on 48 celiac volunteers. After 12 weeks on a Gluten FriendlyTM diet, it induced i) symptoms relief in all patients; ii) a clustering of the mucosal histology and inflammation of celiac subjects in 3-zones, as follows: 35% black zone (cluster 1; increase of IELs and injury), 30% grey zone (cluster 2; intermediate trend), 35% white zone (cluster 3; normal serology, no injury and no increase of IELs, trend as the placebo group). Thus, suggesting positive effect in 35% of patients (white zone) and a possible dynamic situation, with a positive modulation of the inflammation, in 30% of patients (grey zone). iii) a shaping of celiac microbiota towards intestinal homeostasis through a bifidogenic effect that Gluten Friendly induced by its digestion on Lactobacilli and other microorganism butyrate-producing species that contribute to the gut “ health ecology” of celiac subjects

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Temperature-treated gluten proteins in Gluten-FriendlyTM bread increase mucus production and gut-barrier function in human intestinal goblet cells

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    The effects of a control bread (CB) and a Gluten Friendly™ bread (GFB) on intestinal epithelium mucus production and barrier function in healthy human mucus-secreting goblet cells HT-29-16E were investigated. Mucus production in cells exposed to digested breads (GFB and CB) was preliminarily investigated using staining techniques, Periodic Acid-Schiff (PAS) and Alcian blue (AB), and MUC2 and MUC3 were also quantified by ELISA assay. The barrier function of the cell monolayer was evaluated by trans-epithelial electrical resistance (TEER) measurements. GFB increased the secretion of mucins, expressed as the level of PAS and AB staining in comparison with the control. MUC3 levels were not affected, whereas higher MUC2 concentrations (P

    The Impact of Gluten Friendly Flour on the Functionality of an Active Drink: Viability of Lactobacillus acidophilus in a Fermented Milk

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    The Gluten FriendlyTM Technology is an innovative method that induces structural changes in gluten proteins. In this paper a synbiotic fermented milk, containing Lactobacillus acidophilus La-5 and Gluten Friendly Flour (GFF), was proposed. A mixture design was used to combine flour, temperature and probiotic to study the effects of these variables on the acidification. The experiments were done on both GFF and control flour (CF). Thus, the following conditions were chosen to produce the fermented milk: L. acidophilus at 6.5 log cfu/ml; flour at 2.5 g/l; temperature at 37°C. Then, the fermented milk was produced and stored at 4°C for 90 days. The most important result was the positive effect of GFF on the viability of the probiotic, with a prolongation of the shoulder length to 20 days (12–13 days in the control). Moreover, GFF did not act on the sensory scores and on the physico-chemical parameters

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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