Experimental analysis of the station keeping response of a double-barge float-over system with an elastically scaled physical model

In this paper, an experimental investigation of the global response to waves relative to a newly developed float-over concept by TechnipFMC Rome Operating Center for transportation, installation and decommissioning of the off-shore platform topside is presented. A flexible scaled model of the float-over system was tested in the wave basin to determine the range of the sea-state conditions for which the response of the catamaran float-over is acceptable for mating operations. The present analysis is part of a more extensive experimental campaign which has involved also the use of a scaled rigid physical model (Dessi et al., 2016) and numerical simulations for which the collected data provide also a validation database

Expression of nuclear survivin in normal skin and squamous cell carcinoma: a possible role in tumor invasion

Background: Survivin is detected in few adult normal cells and it is highly expressed in cancer. Nuclear survivin facilitates cell cycle entry, while the mitochondrial pool protects cells from apoptosis. Survivin is overexpressed in keratinocyte stem cells (KSC) and protects them from apoptosis. Methods: As KSC are at the origin of squamous cell carcinoma (SCC), we evaluated survivin expression in normal and cancerous skin in vivo by immunohistochemistry and western blotting. HaCaT cells overexpressing survivin and wound-healing assay are used. Anova and Student-T tests are used for statistical analysis. Results: Survivin is localized both in the cytoplasm and in the nucleus of normal adult and young keratinocytes. Nuclear survivin is detected in one every 10/11 basal keratinocytes. When present in suprabasal cells, nuclear survivin is co-expressed with K10, but not with K15 or p75-neurotrophin-receptor (p75NTR), a transit amplifying cell marker. Nuclear, but not cytoplasmic survivin expression dramatically increases in actinic keratosis and in SCC in situ, as compared to normal epidermis, and it is highest in poorly differentiated SCC. In SCC tumors, nuclear survivin-positive cells are mainly K10/p75NTR-negative and K15-positive. In poorly differentiated tumors, survivin mostly localizes in the deep infiltrating areas. When overexpressed in keratinocytes, survivin increases cell migration. Conclusion: High survivin expression and the subcellular localization of survivin correlate with keratinocyte differentiation and are associated with undifferentiated and more invasive SCC phenotype

Organ culture and Reflectance Confocal Microscopy as new integrated tools for barrier rescue studies in inflammatory skin diseases

Here we present a new integrated approach to understand skin barrier recovery after physical (tape stripping, TS) or chemical (SDS) injury by combining human skin organ culture and Reflectance Confocal Microscopy (RCM). TS in vitro produced a complete removal of stratum corneum and lipids, a drastic decrease of structural and adhesion proteins, and an increase in cell proliferation. Epidermal recovery with either proliferation or differentiation rescue was observed after 18 hours, with no apoptotic cell detection. On the other hand, when skin organ cultures were exposed to 2% SDS, cellular junctions were disrupted and the expression of late differentiation markers decreased. Junctions repair was detected 24 hours after treatment, with the restoration of epidermal integrity. Both models (TP or SDS) showed the induction of immune-inflammatory markers, such as psoriasin, keratin 16, and the increase in Langerhans cell number. RCM confirmed all the morphological and structural features presented by the organ cultures, thus making this technique fast and easily applicable in the context of dermatological research. These results indicate that combination of skin organ models and RCM can be successfully used for the study of barrier perturbation in skin diseases, for toxicology tests, and for evaluating novel therapies

Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2–4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors

Unsteady aeroelastic analysis of the semi aeroelastic hinge including local geometric nonlinearities

A recent consideration in aircraft design is the use of folding wing tips, with the aim of enabling higher aspect ratio wings with less induced drag but also meeting airport gate limitations. Of particular interest is the concept of using in flight free-floating wing tips in order to reduce aircraft gust and maneuver loads. This study investigates the effects of local geometric nonlinearities on the dynamic stability, postflutter behavior and gust response of floating wing tips. A multibody formulation is introduced to account for finite rotations of rigid folding wing tips attached through hinges on a flexible airframe structure including also aerodynamic follower forces for the folding wing tip components. It is found that the postflutter behavior is characterized by super-critical limit cycle oscillations and no subcritical instability was observed for the analyzed cases. Moreover, the wing tip gust response can vary significantly when geometric nonlinearities are accounted for whereas a small impact was observed on the main airframe structure

New modulated genes in psoriasis-derived keratinocyte subpopulations.

T cells play a crucial role in the pathogenesis of psoriasis, recent data emphasize the key role of keratinocytes that, by carrying intrinsic alterations, could determine the formation of skin lesions resembling psoriasis, without the participation of T-cell derived cytokines. In particular, transit amplifying (TA) cells, the stem cell progeny, seems to be responsible for the psoriatic phenotype. The aim of this study was to analyze the role of keratinocytes sub-populations in the pathogenesis of psoriasis. We analyzed the gene expression profile (GEP) of human keratinocyte sub-populations (stem, “early” TA (ETA) and “late” TA (LTA) cells), derived from healthy skin, lesional and non-lesional psoriatic skin. The total RNA samples, extracted from keratinocyte subpopulations immediately after separation, were hybridized onto the Affymetrix human U133 plus 2.0 GeneChip Array. We identified a small number of up-regulated genes (12 probe sets, corresponding to 8 genes) in keratinocyte subpopulations derived from lesional psoriasis vs. healthy and non-lesional psoriasis. We confirmed the increased expression levels of TCN1, S100A7A, KYNU, SERPINB13, FOXE1, but solely due to the keratinocyte component. We identified for the first time the up-regulation of TMEM171, CLEC7A and NDRG4, which seems to correlate with the pathophysiology of psoriasis. Moreover, GEP analysis of lesional psoriasis sub-populations, as compared to the non-lesional psoriatic counterpart revealed the modulation of 17 probe sets, corresponding to 13 genes. Among these genes, we recognized for the first time the up-regulation of IL13RA1, CCDC109B and CD47. These results indicate the importance of keratinocyte compartment in psoriasis, opening the way to the study of new genes potentially critical in the pathogenesis of psoriasis

Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing

The Notch signaling pathway orchestrates cell fate by either inducing cell differentiation or maintaining cells in an undifferentiated state. This study aims to evaluate Notch expression and function in normal human keratinocytes. Notch1 is expressed in all epidermal layers, though to a different degree of intensity, with a dramatic decrease during ageing. Notch1 intracellular domain (N1ICD) levels are decreased during transit from keratinocyte stem cells (KSC) to transit amplifying (TA) cells, mimicking survivin expression in samples from donors of all ages. Calcium markedly reduces N1ICD levels in keratinocytes. N1ICD overexpression induces the up-regulation of survivin and the down-regulation of keratin 10 and involucrin, while increasing the S phase of the cell cycle. On the other hand, Notch1 inhibition (DAPT) dose-dependently decreases survivin, stimulates differentiation, and reduces keratinocyte proliferation in samples from donors of all ages. Silencing Notch downgrades survivin and increases keratin 10. In addition, Notch1 inhibition decreases survivin levels and proliferation both in KSC and TA cells. Finally, while survivin overexpression decreases keratinocyte differentiation and increases N1ICD expression both in KSC and TA cells, silencing survivin results in N1ICD down-regulation and an increase in differentiation markers. These results suggest that the Notch1/survivin crosstalk contributes to the maintenance of stemness in human keratinocytes

NEW DESIGNS OF YACHT HARBOURS IN ITALY

This paper follows a similar one presented at the VII COPEDEC in Dubai (Noli et al. 2008) with the description of some recent marina projects actually constructed along the Italian coasts. Now attention is devoted to other 8 interesting projects where particular engineering problems have been solved with creativity and scientific rigor by comparing different solutions, even if the small project size, often with private funding and minor economic return, does not allow to spend too much either in the actual works and in the extensive use of sophisticated investigations and advanced design methods

La dignità sospesa

Un gruppo di economisti: la manovra anti-crisi non deve essere un pretesto per tornare indietro sulla limitazione dell’uso arbitrario dei contratti a termine. Ed è anche un’occasione da non sprecare: gli aiuti pubblici alle imprese siano condizionati ad obiettivi di politica industriale