Around the world in 36 hours - Understanding the dynamics of the global product design relay marathon

In this system paper we will present a learning experiment - a unique three-day global product design relay marathon organized by the Design Factory Global Network (DFGN). The experiment called Rat Relay simulates a real-world situation in product development where very often a person or team is only working on a project for a limited time and not from beginning to end, individuals work in multidisciplinary and multicultural teams around complex problems, and everything is done with a fast pace. Rat Relay is a learning experiment developed by the Design Factory Global Network, a network of innovation hubs in universities and research organizations in five continents of the world aiming to contribute to transformation of learning and research through a passion-based culture of interdisciplinary collaboration and effective problem solving

Osteoarthritis and the Mediterranean Diet: A Systematic Review

Osteoarthritis (OA) affects 240 million people globally. Few studies have examined the links between osteoarthritis and the Mediterranean diet (MD). The aim of this paper was to systematically review and analyze the epidemiological evidence in humans on the MD and its association with OA. A systematic search of EMBASE identified three studies that explored the association between MD and OA. Two of them were cross-sectional and the third one was a 16-week randomized clinical trial. Prisma declaration was followed to carry out this review. These studies described a positive association between a higher adherence to a MD and the quality of life of participants suffering OA. The prevalence of OA was lower in participants with a higher adherence to a Mediterranean diet. Biomarkers of inflammation and cartilage degradation related to OA were also analyzed and significant differences were detected only for IL1-, which decreased in the MD group. Exploring the relationship between MD and OA is complex, moreover, the limited evidence and methodological differences in such studies makes it difficult to compare results. In conclusion, the three studies included in this systematic review demonstrated some relation between osteoarthritis and a Mediterranean diet. However, prospective and longer interventions are required to evaluate the long-term efficacy of the Mediterranean diet to improve symptomatology and preventing osteoarthritis

Dynamic Identification of Damage in Brick Masonry Walls

This paper shows the experimental and numerical analysis developed on a brick masonry wall of 3x2.5x0.2 m to understand the changes on its dynamic behaviour with different stiffness situations: (i) original, (ii) loaded with different load levels, (iii) damaged by horizontal in plane loads, (iv) retrofitted with Textile Reinforced Mortars (TRM) and (v) retrofitted and damaged by horizontal in plane loads. This analysis has been developed at the Civil Engineering Lab at the University of Alicante. On this masonry wall a matrix of 8 seismic accelerometers have been installed to evaluate, in plane and out of plane, changes in the main frequencies, modal damping ratios and modal shapes. By the use of Operational Modal Analysis techniques the results shows that the changes on the stiffness have important influence on the main frequencies and in the modal damping ratios. Very low influence have been detected on the modal shapes due to the low level of external vibrations generated during the tests. Due to the low level of vibrations inside the lab,the classical application of ambient vibrations for OMA has been not possible and an external white noise force has been introduced on the top the wall by the use of a shaker to generate a general level of vibrations on the specimen

Dynamic behaviour of a novel transition wedge composed by prefabricated reinforced concrete slabs

Abrupt variations of track stiffness in transitions from conventional to slab track, e.g., over bridges and tunnels, usually lead to passenger discomfort, vehicle and track damage and even safety issues. Therefore, to minimize this negative effect, it is very convenient to smooth the stiffness changes in such transitions; and wedges arise as a very effective technique. Although granular wedges are commonly suggested by railroad managers as a solution, this typology presents some disadvantages, e.g., high construction time and costs, that should be addressed. In this paper, a new solution based on prefabricated, reinforced concrete slabs is presented and its dynamical performance is assessed by means of a 3D FEM model. Results indicate that track vibrations both on the rail and over a sleeper are considerably reduced when the new slab-based wedge is considered instead of a traditional granular wedge

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells

The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1- expressing cells, by inactivating NF-jB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

<p><b>Objectives</b> The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.</p> <p><b>Methods</b> A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.</p> <p><b>Results</b> A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).</p> <p><b>Conclusions</b> The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.</p&gt

BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells

Chronic myelogenous leukemia (CML) is characterized by the expression of the BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show in both BCR-ABL cells (Mo7e-p210 and BaF/3-p210) and primary CML CD34+ cells that STI571 inhibition of BCR-ABL tyrosine kinase activity results in a G(1) cell cycle arrest mediated by the PI3K pathway. This arrest is associated with a nuclear accumulation of p27(Kip1) and down-regulation of cyclins D and E. As a result, there is a reduction of the cyclin E/Cdk2 kinase activity and of the retinoblastoma protein phosphorylation. By quantitative reverse transcription-PCR we show that BCR-ABL/PI3K regulates the expression of p27(Kip1) at the level of transcription. We further show that BCR-ABL also regulates p27(Kip1) protein levels by increasing its degradation by the proteasome. This degradation depends on the ubiquitinylation of p27(Kip1) by Skp2-containing SFC complexes: silencing the expression of Skp2 with a small interfering RNA results in the accumulation of p27(Kip1). We also demonstrate that BCR-ABL cells show transcriptional up-regulation of Skp2. Finally, expression of a p27(Kip1) mutant unable of being recognized by Skp2 results in inhibition of proliferation of BCR-ABL cells, indicating that the degradation of p27(Kip1) contributes to the pathogenesis of CML. In conclusion, these results suggest that BCR-ABL regulates cell cycle in CML cells at least in part by inducing proteasome-mediated degradation of the cell cycle inhibitor p27(Kip1) and provide a rationale for the use of inhibitors of the proteasome in patients with BCR-ABL leukemias