Pier Francesco Rambaldi: Whole-body FDG PET Imaging in Oncology—Clinical Reports

n/

Use of mannan oligosaccharides during "post-weaning enteric syndrome" in rabbits: effect on in vivo performance from 35 to 60 days

Four groups, each consisting of 684 weaned (35 days) hybrid Hyla rabbits were fed ad libitum the same commercial concentrate supplemented, respectively, with antibiotics (AGP group: colistin sulphate 144 mg/kg; tylosin 100m g/kg and oxytetracyclin 1000 mg/kg) or with mannan oligosac- charides (MOS) at 0.5 (group MOS_0.5), 1.0 (group MOS_1.0) and 1.5 g/kg (group MOS_1.5). Up to 60 days, mortality rate was recorded daily. For each group, 64 rabbits were controlled weekly for live weight to calculate daily weight gain (DWG). Feed intake (and, by consequence, feed conversion ratio) was measured, weekly, per group. No differences were observed for live weight during the trial, while DWG showed an alternate trend, in general, significantly lower for AGP group, exclusive of the third week (49- 56 days). Exclusive of the first week of the trial feed intake was higher for AGP than the other groups and the feed conversion ratio was more favourable for MOS groups. Mortality rate was significantly higher (34.2%) in AGP groups. The lowest mortality was recorded in MOS_1.0 group (7.75%)

Bottom-up manufacturing cost optimisation of composite aircraft structures: Manual layup vs. automated layup

This paper presents a novel methodology for the bottom-up manufacturing cost optimisation of composite aircraft structures for Automated Fibre Placement (AFP) techniques. The proposed bottom-up approach divides the manufacturing process into many individual activities, making it applicable to a wide range of composite aircraft structures. This approach also splits the costs into material, tool, machine, labour, and indirect costs, enabling the precise cost analysis of these structures. A numerical example, featuring a mono-stiff ener composite panel, is investigated. The manufacturing cost of manual layup is compared against that of automated layup. Results indicate that manual layup is superior, in terms of cost, for the manufacture of the mono-stiff ener composite panel, and that the safety of the panel can be signifi cantly improved with only a small 5% increase in manufacturing costs

Structural Analysis of Masonry Square Vaults in the Italian Region of Apulia

This research concerns the introduction and the structural analysis of masonry vaults in Puglia, a region in the south part of Italy, built between the sixteenth and the seventeen centuries. Such vaults have special shapes that make them unique in the overview of the masonry vaults spread all over the world. The present paper intends to shed light on the mechanical behavior of two typical vaults in Puglia, the “volta a spigoli” (edge vault) and the “volta a squadro” (square vault). There are many contributions that explore the mechanical behavior of the classical vaults, but to the authors’ knowledge, this is the first attempt investigating the “volta a squadro”. The paper describes the adopted research methods. First, a building survey is carried out with the integration of previous geometry acquisitions performed by local stakeholders. Then, the analysis is pursued by a non-linear approach that suitably inserts cracks where stress concentrations occur. Two meaningful load conditions are taken into account and numerically investigated. Under vertical loads, numerical results have inferred the surveyed cracks and concluded that the safety factor is much higher than one. On the other hand, under the maximum seismic load, the safety factor is estimated to be about 30%. This work is the very first investigation on the structural performance of a “volta a squadro”

RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load.

The review intends to present and recapitulate the current knowledge on the roles and importance of regulatory RNAs, such as microRNAs and small interfering RNAs, RNA binding proteins and enzymes processing RNAs or activated by RNAs, in cells infected by RNA viruses. The review focuses on how non-coding RNAs are involved in RNA virus replication, pathogenesis and host response, especially in retroviruses HIV, with examples of the mechanisms of action, transcriptional regulation, and promotion of increased stability of their targets or their degradation

Efficient and realistic 3-D Boundary Element simulations of underground construction using isogeometric analysis

The paper outlines some recent developments of the boundary element method (BEM) that makes it more user friendly and suitable for a realistic simulation in geomechanics, especially for underground excavations and tunnelling. The innovations refer to the introduction of isogeometric concepts, elasto-plastic analysis and the simulation of ground support. The introduction of isogeometric concepts for the description of the excavation boundaries results in less user and analysis effort, since complex geometries can be modelled with few parameters and degrees of freedom. No mesh generation is necessary. In order to consider heterogeneous and inelastic ground conditions a domain discretisation is used but the use of isogeometric methods results in a minimum of user effort. Efficient methods are also presented for modelling rock bolts. A comparison of results of test examples with other numerical methods and analytical solutions confirm the efficiency and accuracy of the proposed implementation. A practical example with a complex geometry is presented.Comment: 33 pages, 25 figures. arXiv admin note: text overlap with arXiv:2003.1021

Role of Gastrokine 1 in Gastric Cancer

Gastric cancer (GC) has high incidence (> 1.000.000 new cases/year) and mortality rate in several countries and is still one of the most frequent and lethal (> 600.000 dead/year) neoplasia with an average surviving of five years (less than 20%) (Pisani et al., 1990; Lands et al., 1998). It is already well known that infection of gastric antrum mucosal with the bacterium Helicobacter pylori is the cause of the chronic inflammation that leads to intestinal-type gastric cancer in the majority of the cases. The H. pylori infection is widespread but only a small number of the total population of infected individuals might eventually develop adenocarcinoma (around 3/10,000 individuals per year or 2.1% for lifetime infection) 27 (Correa & Piazuelo, 2008). Risk factors influencing the outcome of H. pylori–associated pathology include bacterial cytotoxic heterogeneity, diet, and geographic differences. The phenomenon of decreased gastric cancer incidence in Africa compared with other regions where H. pylori is endemic 28 (Holcombe, 1992) is probably due to the different diet of these populations compared to the western countries. This discrepancy has been partially attributed to helminth co-infection that likely modifies the characteristic proinflammatory type 1 T-helper 1 cell response, to a T-helper 2–predominant response 29 (Whary et al., 2005), typified by the release of non-inflammatory cytokines and reduced incidence of H. pylori–associated glandular atrophy, an early marker of cancer development. The identification of novel genes regulated by H. pylori in vivo, particularly those contributing to these early stages of gastric cancer, would facilitate improved understanding of the differential susceptibility to this pathogen. The different susceptibility among individuals to H. pylori infection is still not yet defined. Some works, however, suggested that the polymorphisms in host genetic factors like the proinflammatory cytokines interleukin-1, interleukin-8, and tumor necrosis factor may play a relevant role 30 (El-Omar et al., 2003). The evolution of intestinal tumours is characterized by a progression of several sequential steps that starts with gastritis and then progresses to mucosal atrophy (atrophic gastritis), intestinal metaplasia, dysplasia and carcinoma with subsequent metastatic dissemination (Correa, 1992, 1995). The diffuse-type has instead a poorer prognosis and develops through unknown genetic and morphological events from normal gastric epithelium. No preceding steps have been identi_ed in the pathogenesis of diffuse carcinoma other than the chronic gastritis. The pathogenesis of gastric cancer remains poorly understood although it is evident that several environmental factors, such as H. pylori infection can be one of the causes leading to this disease. In fact, the risk to develop gastric cancer is increased in patients with H. pylori infections probably as the result of a combination of genetic and environmental factors in which the infection by H. pylori is of particular relevance, especially when the inflammation involves the gastric body region with respect to the antrum (Correa, 1995; Goldstone et al., 1996; Nabewera & Logan, 1999). Generally, this condition is associated to different degrees of atrophy and alterations of the secretor function that, in the long term, became associated to gastric carcinoma (Forman et al., 1991; Parsonnet et al., 1997; Watanabe et al., 1998). Diffuse adenocarcinoma shows an increased propensity for intra and transmural spread and is therefore associated with a poorer prognosis. Unfortunately, the histological classification of an individual gastric adenocarcinoma is not clear-cut with a tumour often comprising a mixture of intestinal and diffuse tissue types. Under these considerations, we think that there is an urgent necessity to dispose of an efficient tool for the detection of early stage gastric cancer like the identification of highly sensitive and specific biomarkers that will aid disease diagnosis and ensure early clinical intervention, thereby preventing mortality and reducing morbidity (Boussioutas & Taupin, 2001). Since most of GC (around 73%) is developed at antrum/pylorus, proteins secreted by antrum/pylorus mucosa might play a critical role in maintaining normal gastric mucosa structure and function

A bayesian approach for sensor optimisation in impact identification

This paper presents a Bayesian approach for optimizing the position of sensors aimed at impact identification in composite structures under operational conditions. The uncertainty in the sensor data has been represented by statistical distributions of the recorded signals. An optimisation strategy based on the genetic algorithm is proposed to find the best sensor combination aimed at locating impacts on composite structures. A Bayesian-based objective function is adopted in the optimisation procedure as an indicator of the performance of meta-models developed for different sensor combinations to locate various impact events. To represent a real structure under operational load and to increase the reliability of the Structural Health Monitoring (SHM) system, the probability of malfunctioning sensors is included in the optimisation. The reliability and the robustness of the procedure is tested with experimental and numerical examples. Finally, the proposed optimisation algorithm is applied to a composite stiffened panel for both the uniform and non-uniform probability of impact occurrence

DISSECTING THE ROLE OF THE CYTOPLASMIC MUTANT NUCLEOPHOSMIN IN ACUTE MYELOID LEUKAEMIA DEVELOPMENT

Acute myeloid leukaemia (AML) is a genetic heterogeneous group of diseases, with the largest subgroup showing a mutation in the Nucleophosmin gene (NPM1). Normally the NPM protein localizes mainly in the nucleolus, but in AML blasts it is aberrant localized to the cytoplasm (NPMc+AML). Notably, NPMc+AML patients show peculiar gene expression profiles, treatment response and prognosis. Hence, it has been proposed as an independent category for leukaemia classification according to WHO in 2008. In view of the relevance of NPMc+ mutation to AML pathogenesis and prognosis, understanding its role in leukaemia development represents a major issue in the field. The aim of this PhD project is to get further insight into the relevance of NPMc+ mutations to AML development. To this scope, here it is reported a characterization of a novel mouse model expressing the mutated protein. The hematopoietic restricted expression of the protein induces leukaemia in mice. This data definitively clarify that NPMc+ is an initiating mutation for leukaemia development. However, the long latency and low penetrance of disease onset strongly support the need of cooperating mutations. Since, the high frequency of FLT3-ITD mutations in NPMc+AML, we genetically tested the synergisms between the two abnormalities. To this scope, NPMc+ mice were crossed with FLT3-ITD mice (Lee, 2007). Double mutated mice developed leukaemia with sort latency and full penetrance indicating effective cooperation. Moreover, our data support the two hits model of tumourigenesis, where functional complementary mutations contribute to disease onset. Another major challenge of this project is to understand how NPMc+ affect the biology of normal HSPC and imposes the transition from normal to cancer stem cells. We found that NPMc+ expression perturbs the homeostasis of HSCP and expand the number of LT-HSC by increasing the proliferation rate. However, this enhanced proliferation is not associated to loss of quiescent and functional HSC, which may represent a reservoir of persistent pre-malignant cells available for the accumulation of additional genetic alteration. Further investigation into the biology of per-leukaemic stem cells may give insights into the molecular mechanisms imposed by the oncogene for malignancy transformation and finally may contribute for the development of new therapeutic strategies

Microtubule-dependent Organization of Vaccinia Virus Core-derivd Early mRNAs into Distinct Cytoplasmic Structures.

Vaccinia virus (vv) early transcription can be reconstituted in vitro from purified virions; in this assay mRNAs are made inside the viral core and subsequently extruded. Although the in vitro process has been extensively characterized, relatively little is known about vv early transcription in vivo. In the present study the fate of vv early mRNAs in infected HeLa cells was followed by BrUTP transfection and confocal and electron microscopy. The extruded vv early mRNAs were found to be organized into unique granular cytoplasmic structures that reached a size up to 1 μm. By EM these structures appeared as amorphous electron-dense cytoplasmic aggregates that were surrounded by ribosomes. Confocal images showed that the RNA structures were located some distance away from intracellular cores and that both structures appeared to be aligned on microtubules (MTs), implying that MT tracks connected mRNAs and cores. Accordingly, intact MTs were found to be required for the typical punctate organization of viral mRNAs. Biochemical evidence supported the notion that vv mRNAs were MT associated and that MT depletion severely affected viral (but not cellular) mRNA synthesis and stability. By confocal microscopy the viral mRNA structures appeared to be surrounded by molecules of the translation machinery, showing that they were active in protein synthesis. Finally, our data suggest a role for a MT and RNA-binding viral protein of 25 kDa (gene L4R), in mRNA targeting away from intracellular cores to their sites of cytoplasmic accumulation