2,999 research outputs found

    Linear Toric Fibrations

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    These notes are based on three lectures given at the 2013 CIME/CIRM summer school. The purpose of this series of lectures is to introduce the notion of a toric fibration and to give its geometrical and combinatorial characterizations. Polarized toric varieties which are birationally equivalent to projective toric bundles are associated to a class of polytopes called Cayley polytopes. Their geometry and combinatorics have a fruitful interplay leading to fundamental insight in both directions. These notes will illustrate geometrical phenomena, in algebraic geometry and neighboring fields, which are characterized by a Cayley structure. Examples are projective duality of toric varieties and polyhedral adjunction theory

    HISTORICAL EARTHEN WALLS: FROM KNOWLEDGE TO CONSCIOUS CONSERVATION

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    Abstract. Centuries-old earthen masonry presenting various stages of degradation, earthen walls that have been restored several times: these are the archeological phases of the city walls of Mascarell, on the Spanish Mediterranean coast. Founded in the first half of the 13th century, this town is the only complex in Castellon Province that preserves all its ancient walls, which were built entirely by means of the brick-faced rammed-earth technique (clay with bricks and lime). This article reports the first results of a research project conducted on the multiple information available on these artifacts: bibliographic, archival and iconographic sources and the results of direct material analysis, stratigraphic analysis and archeological analysis. The situation is complex, as these walls have undergone a long sequence of transformations, including interventions carried out since the 18th century and multiple restorations in the period 1942–2015. The research developed and refined architecture archeology tools in order to analyze the rammed-earth techniques adopted during restoration work (similar but not identical to the historical technique), to characterize the materials used in restoration, to evaluate their resistance to degradation over the years, to define a sort of 'critical evolutionary line' of rammed-earth restoration, and to conduct a cross-sectional study of this building technique from the Middle Ages to the present. Finally, we drafted some guidelines for future interventions for conservation and enhancement

    Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging

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    Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production

    Carbonate assimilation in magmas: a reappraisal based on experimental petrology

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    The main effect of magma-carbonate interaction on magma differentiation is the formation of a silica-undersaturated, alkali-rich residual melt. Such a desilication process was explained as the progressive dissolution of CaCO3 in melt by consumption of SiO2 and MgO to form diopside sensu stricto. Magma chambers emplaced in carbonate substrata, however, are generally associated with magmatic skarns containing clinopyroxene with a high Ca-Tschermak activity in their paragenesis. Data are presented from magma-carbonate interaction experiments, demonstrating that carbonate assimilation is a complex process involving more components than so far assumed. Experimental results show that, during carbonate assimilation, a diopside-hedenbergite-Ca-Tschermak clinopyroxene solid solution is formed and that Ca-Tschermak/diopside and hedenbergite/diopside ratios increase as a function of the progressive carbonate assimilation. Accordingly, carbonate assimilation reaction should be written as follows, taking into account all the involved magmatic components: CaCO3solid+SiO2melt+MgOmelt+FeOmelt+Al2O3melt → (Di-Hd-CaTs)sssolid+CO2fluid The texture of experimental products demonstrates that carbonate assimilation produces three-phases (solid, melt, and fluid) whose main products are: i) diopside-hedenbergite-Ca-Tschermak clinopyroxene solid solution; ii) silica-undersaturated CaO-rich melt; and iii) C-O-H fluid phase. The silica undersaturation of the melt and, more importantly, the occurrence of a CO2-rich fluid phase, must be taken into account as they significantly affect partition coefficients and the redox state of carbonated systems, respectively

    Hydrogen Peroxide Induces Heme Degradation and Protein Aggregation in Human Neuroglobin: Roles of the Disulfide Bridge and the H-bonding in the Distal Heme Cavity

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    In this study, human neuroglobin (hNgb) was found to undergo H2O2-induced breakdown of the heme center at a much slower rate than other globins, namely in the timescale of hours against minutes. We studied how the rate of the process is affected by the Cys46/Cys55 disulfide bond and the network of noncovalent interactions in the distal heme side involving Tyr44, Lys67, the His64 heme iron axial ligand and the heme propionate-7. The rate is increased by the Tyr44 to Ala and Phe mutations, however the rate is lowered by Lys67 to Ala swapping. The absence of the disulfide bridge slows down the reaction further. Therefore, the disulfide bond-controlled accessibility of the heme site and the residues at position 44 and 67 affect the activation barrier of the reaction. Wild-type and mutated species form -amyloid aggregates in the presence of H2O2 producing globular structures. Furthermore, the C46A/C55A, Y44A, Y44F and Y44F/C46A/C55A variants yield potentially harmful fibrils. Finally, the nucleation and growth kinetics for the aggregation of the amyloid structures can be successfully described by the Finke-Watzky model

    Open issues in mucopolysaccharidosis type I-hurler

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    Mucopolysaccharidosis I-Hurler (MPS I-H) is the most severe form of a metabolic genetic disease caused by mutations of IDUA gene encoding the lysosomal α-L-iduronidase enzyme. MPS I-H is a rare, life-threatening disease, evolving in multisystem morbidity including progressive neurological disease, upper airway obstruction, skeletal deformity and cardiomyopathy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the gold standard for the treatment of MPS I-H in patients diagnosed and treated before 2-2.5 years of age, having a high rate of success. Beyond the child's age, other factors influence the probability of treatment success, including the selection of patients, of graft source and the donor type employed. Enzyme replacement therapy (ERT) with human recombinant laronidase has also been demonstrated to be effective in ameliorating the clinical conditions of pre-transplant MPS I-H patients and in improving HSCT outcome, by peri-transplant co-administration. Nevertheless the long-term clinical outcome even after successful HSCT varies considerably, with a persisting residual disease burden. Other strategies must then be considered to improve the outcome of these patients: one is to pursue early pre-symptomatic diagnosis through newborn screening and another one is the identification of novel treatments. In this perspective, even though newborn screening can be envisaged as a future attractive perspective, presently the best path to be pursued embraces an improved awareness of signs and symptoms of the disorder by primary care providers and pediatricians, in order for the patients' timely referral to a qualified reference center. Furthermore, sensitive new biochemical markers must be identified to better define the clinical severity of the disease at birth, to support clinical judgement during the follow-up and to compare the effects of the different therapies. A prolonged neuropsychological follow-up of post-transplant cognitive development of children and residual disease burden is needed. In this perspective, the reference center must guarantee a multidisciplinary follow-up with an expert team. Diagnostic and interventional protocols of reference centers should be standardized whenever possible to allow comparison of clinical data and evaluation of results. This review will focus on all these critical issues related to the management of MPS I-H

    Management of patients with lymphoma and COVID-19: Narrative review and evidence-based practical recommendations

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    Patients with hematologic malignancies can be immunocompromized because of their disease, anti-cancer therapy, and concomitant immunosuppressive treatment. Furthermore, these patients are usually older than 60 years and have comorbidities. For all these reasons they are highly vulnerable to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and have an increased risk of developing severe/critical Coronavirus disease 2019 (COVID-19) compared to the general population. Although COVID-19 vaccination has proven effective in reducing the incidence of severe/critical disease, vaccinated patients with lymphoma may not be protected as they often fail to develop a sufficient antiviral immune response. There is therefore an urgent need to address the management of patients with lymphoma and COVID-19 in the setting of the ongoing pandemic. Passive immunization with monoclonal antibodies against SARS-CoV-2 is a currently available complementary drug strategy to active vaccination for lymphoma patients, while monoclonal antibodies and antiviral drugs (remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir) have proven effective in preventing the progression to severe/critical COVID-19. In this narrative review we present the most recent data documenting the characteristics and outcomes of patients with concomitant lymphoma and COVID-19. Our ultimate goal is to provide practice-oriented guidance in the management of these vulnerable patients from diagnosis to treatment and follow-up of lymphoma. To this purpose, we will first provide an overview of the main data concerning prognostic factors and fatality rate of lymphoma patients who develop COVID-19; the outcomes of COVID-19 vaccination will also be addressed. We will then discuss current COVID-19 prophylaxis and treatment options for lymphoma patients. Finally, based on the literature and our multidisciplinary experience, we will summarize a set of indications on how to manage patients with lymphoma according to COVID-19 exposure, level of disease severity and former history of infection, as typically encountered in clinical practice
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