Consensus based optimization with memory effects: random selection and applications

In this work we extend the class of Consensus-Based Optimization (CBO) metaheuristic methods by considering memory effects and a random selection strategy. The proposed algorithm iteratively updates a population of particles according to a consensus dynamics inspired by social interactions among individuals. The consensus point is computed taking into account the past positions of all particles. While sharing features with the popular Particle Swarm Optimization (PSO) method, the exploratory behavior is fundamentally different and allows better control over the convergence of the particle system. We discuss some implementation aspects which lead to an increased efficiency while preserving the success rate in the optimization process. In particular, we show how employing a random selection strategy to discard particles during the computation improves the overall performance. Several benchmark problems and applications to image segmentation and Neural Networks training are used to validate and test the proposed method. A theoretical analysis allows to recover convergence guarantees under mild assumptions on the objective function. This is done by first approximating the particles evolution with a continuous-in-time dynamics, and then by taking the mean-field limit of such dynamics. Convergence to a global minimizer is finally proved at the mean-field level

Investigating the Molecular Mechanisms of Neisseria Meningitidis Antigen Regulation: Determining a Switch between Colonization and Invasion

NHBA is a surface-exposed lipoprotein which is expressed by all N. meningitidis strains in different isoforms. We determined that temperature controlled the expression of NHBA in all strains tested. NHBA expression was significantly increased at 30 compared to 37°C, both at protein and RNA levels and was also reflected by a higher surface exposure. A detailed molecular analysis indicated that multiple molecular mechanisms are responsible for the thermoregulated NHBA expression. RNA stability/translatability resulted to be increased at lower temperatures and, protein stability was also impacted. Increased NHBA expression resulted in more efficient killing as shown by serum bactericidal assay (SBA). We investigated the NHBA expression in response to the presence of serum. The presence of human serum has contrasting effects on NHBA expression, resulting in transient up-regulation of NHBA mRNA, however the protein is rapidly processed. We propose a model in which NHBA regulation in response to temperature downshift might reflect the bacterial adaptation during the initial step of host-bacterial interaction and might also explain higher susceptibility to anti-NHBA antibodies in the nasopharynx niche. On the other hand, the initial up-regulation and the high processing of NHBA might play a role during the first steps of invasive disease. In the second part of the thesis, we compared genetically engineered outer membrane vesicles and recombinant proteins, as delivery systems of protective antigen. Using NadA as model antigen, we determined that OMV overexpressing NadA produced by homologous (MenB) or heterologous (E.coli) bacterial strains, are able to elicit a higher functional antibody response respect to the recombinant protein per se. The differences in functionality might be due to different IgG subclasses distribution. Moreover, OMV overexpressing NadA are able to elicit antibodies that inhibit NadA-mediated adhesion on the host cells surface, in a much more efficient way respect to the recombinant protein formulation

The role of structural inheritance in continental break-up and exhumation of Alpine Tethyan mantle (Canavese Zone, Western Alps)

The Canavese Zone (CZ) in the Western Alps represents the remnant of the distal passive margin of the Adria microplate, which was stretched and thinned during the Jurassic opening of the Alpine Tethys. Through detailed geological mapping, stratigraphic and structural analyses, we document that the continental break-up of Pangea and tectonic dismemberment of the Adria distal margin, up to mantle rocks exhumation and oceanization, did not simply result from the syn-rift Jurassic extension but was strongly favored by older structural inheritances (the Proto-Canavese Shear Zone), which controlled earlier lithospheric weakness. Our findings allowed to redefine in detail (i) the tectono-stratigraphic setting of the Variscan metamorphic basement and the Late Carboniferous to Early Cretaceous CZ succession, (ii) the role played by inherited Late Carboniferous to Early Triassic structures and (iii) the significance of the CZ in the geodynamic evolution of the Alpine Tethys. The large amount of extensional displacement and crustal thinning occurred during different pulses of Late Carboniferous–Early Triassic strike-slip tectonics is well-consistent with the role played by long-lived regional-scale wrench faults (e.g., the East-Variscan Shear Zone), suggesting a re-discussion of models of mantle exhumation driven by low-angle detachment faults as unique efficient mechanism in stretching and thinning continental crust. Keywords: Alpine Tethys, Western Alps, Jurassic ophiolite, Structural inheritance, Continental break-up, Mantle exhumatio

Multilayer regulation of Neisseria meningitidis NHBA at physiologically relevant temperatures

This research was sponsored by GlaxoSmithKline Biologicals SA. A.F.H. was funded by Marie Sklodowska-Curie Intra-European Fellowships (PIEF-GA-2012-328377).Neisseria meningitidis colonizes the nasopharynx of humans, and pathogenic strains can disseminate into the bloodstream, causing septicemia and meningitis. NHBA is a surface-exposed lipoprotein expressed by all N. meningitidis strains in different isoforms. Diverse roles have been reported for NHBA in heparin-mediated serum resistance, biofilm formation, and adherence to host tissues. We determined that temperature controls the expression of NHBA in all strains tested, with increased levels at 30–32 °C compared to 37 °C. Higher NHBA expression at lower temperatures was measurable both at mRNA and protein levels, resulting in higher surface exposure. Detailed molecular analysis indicated that multiple molecular mechanisms are responsible for the thermoregulated NHBA expression. The comparison of mRNA steady-state levels and half-lives at 30 °C and 37 °C demonstrated an increased mRNA stability/translatability at lower temperatures. Protein stability was also impacted, resulting in higher NHBA stability at lower temperatures. Ultimately, increased NHBA expression resulted in higher susceptibility to complement-mediated killing. We propose that NHBA regulation in response to temperature downshift might be physiologically relevant during transmission and the initial step(s) of interaction within the host nasopharynx. Together these data describe the importance of NHBA both as a virulence factor and as a vaccine antigen during neisserial colonization and invasion.Publisher PDFPeer reviewe

Towards a radiation free numerical modelling framework to predict spring assisted correction of scaphocephaly

Sagittal Craniosynostosis (SC) is a congenital craniofacial malformation, involving premature sagittal suture ossification; spring-assisted cranioplasty (SAC) – insertion of metallic distractors for skull reshaping – is an established method for treating SC. Surgical outcomes are predictable using numerical modelling, however published methods rely on computed tomography (CT) scans availability, which are not routinely performed. We investigated a simplified method, based on radiation-free 3D stereophotogrammetry scans.Eight SAC patients (age 5.1 ± 0.4 months) with preoperative CT and 3D stereophotogrammetry scans were included. Information on osteotomies, spring model and post-operative spring opening were recorded. For each patient, two preoperative models (PREOP) were created: i) CT model and ii) S model, created by processing patient specific 3D surface scans using population averaged skin and skull thickness and suture locations. Each model was imported into ANSYS Mechanical (Analysis System Inc., Canonsburg, PA) to simulate spring expansion. Spring expansion and cranial index (CI - skull width over length) at times equivalent to immediate postop (POSTOP) and follow up (FU) were extracted and compared with in-vivo measurements.Overall expansion patterns were very similar for the 2 models at both POSTOP and FU. Both models had comparable outcomes when predicting spring expansion. Spring induced CI increase was similar, with a difference of 1.2%±0.8% for POSTOP and 1.6%±0.6% for FU.This work shows that a simplified model created from the head surface shape yields acceptable results in terms of spring expansion prediction. Further modelling refinements will allow the use of this predictive tool during preoperative planning

Reliable and Accurate CD4+ T Cell Count and Percent by the Portable Flow Cytometer CyFlow MiniPOC and \u201cCD4 Easy Count Kit-Dry\u201d, as Revealed by the Comparison with the Gold Standard Dual Platform Technology

An accurate and affordable CD4+ T cells count is an essential tool in the fight against HIV/AIDS. Flow cytometry (FCM) is the "gold standard" for counting such cells, but this technique is expensive and requires sophisticated equipment, temperature-sensitive monoclonal antibodies (mAbs) and trained personnel. The lack of access to technical support and quality assurance programs thus limits the use of FCM in resource-constrained countries. We have tested the accuracy, the precision and the carry-over contamination of Partec CyFlow MiniPOC, a portable and economically affordable flow cytometer designed for CD4+ count and percentage, used along with the "CD4% Count Kit-Dry"

Th1 and Th17 pro-inflammatory profile characterizes iNKT cells in virologically suppressed HIV+ patients with low CD4/CD8 ratio

INTRODUCTION:: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV+ patients (pts). METHODS:: By flow cytometry, we studied iNKT cells from 54 HIV+ pts who started combined antiretroviral therapy (cART) and had undetectable viral load for >1 year. Twenty-five maintained a CD4/CD8 ratio <0.4, while 29 reached a ratio >1.1; 32 age- and sex-matched subjects were healthy controls (CTR). RESULTS:: Pts with low ratio had lower percentage of CD4+ iNKT cells compared to pts with high ratio, and higher CD8+ iNKT cell percentage; double negative (DN) iNKT cells were lower in HIV+ pts compared to CTR. Pts with low ratio had higher percentage of CD4+ and DN iNKT cells expressing CD38 and HLA-DR compared to pts with high ratio. CD4+ iNKT cells expressing PD-1 were higher in pts with CD4/CD8 ratio <0.4, while DN iNKT cells expressing PD-1 were lower compared to pts with ratio >1.1. Pts with low ratio had higher CD4+ iNKT cells producing IL-17, CD8+ iNKT cells producing IFN-γ, TNF-α or IFN-γ plus TNF-α, and DN iNKT cells producing IL-17 or IL-17 plus IFN-γ compared to CTR. Activated CD4+ (or CD8+) T cells correlated with activated CD4+ (or CD8+) iNKT cells, as well as the percentages of CD4+ (or CD8+) T cells expressing PD-1 was correlated to that of CD4+ (or CD8+) iNKT cells expressing PD-1. CONCLUSIONS:: Low CD4/CD8 ratio despite effective cART is associated with altered iNKT cell subsets, enhanced activation and prominent Th1/Th17 pro-inflammatory profile