A Model of Weekly Labor Participation for a Belgian Synthetic Population

This paper presents a model of labor participation calibrated on a weekly basis; part-time and full-time employments are also considered. By applying the theory of random utility maximization we model households’ choices. In order to have a good temporal and spatial coverage the model is calibrated on three datasets, extracted from both national and regional travel surveys. The results are applied to synthetic households that reproduce the Belgian population. The proposed innovative methodology simulates synthetic agents by accounting both for households’ and individuals’ characteristics, while not suffering from the problem of the “zero cell value”. The results indicate that there is major day-to-day variability in working activity participation; in particular, on Wednesdays and Fridays the number of households working part-time or not working is particularly high. This is consistent with what was expected by the analysts. Working participation is a fundamental component in activity based models where work is considered a skeletal activity. The tools developed here can be useful to study how changes in population characteristics (i.e. increases of flexible working arrangements and of the number of women in the work force) affect activity participation and travel patterns.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

Role of anionic and nonionic surfactants on the control of particle size and latex colloidal stability in the seeded emulsion polymerization of butyl methacrylate

The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · S_S · ΔA/A_S as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (～ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006     

The multimod application framework: a rapid application development tool for computer aided medicine

This paper describes a new application framework (OpenMAF) for rapid development of multimodal applications in computer-aided medicine. MAF applications are multimodal in data, in representation, and in interaction. The framework supports almost any type of biomedical data, including DICOM datasets, motion-capture recordings, or data from computer simulations (e.g. finite element modeling). The interactive visualization approach (multimodal display) helps the user interpret complex datasets, providing multiple representations of the same data. In addition, the framework allows multimodal interaction by supporting the simultaneous use of different input-output devices like 3D trackers, stereoscopic displays, haptics hardware and speech recognition/synthesis systems. The Framework has been designed to run smoothly even on limited power computers, but it can take advantage of all hardware capabilities. The Framework is based on a collection of portable libraries and it can be compiled on any platform that supports OpenGL, including Windows, MacOS X and any flavor of Unix/linux.     

Delineating Purinergic Signaling in Drosophila

Simplistic models can aid in discovering what is important in the context of normal and pathological behavior. First recognized as a genetic model more than 100 years ago, to date, fruit flies (Drosophila melanogaster) still remain an astonishingly good laboratory stand-in for scientists to study development and physiology and to investigate the molecular mechanisms of human diseases. This is because fruit flies indeed represent a simplistic model. Furthermore, about 75% of human disease-related genes have their counterparts in the Drosophila genome, added to the fact that fruit flies are inexpensive and extremely easy to maintain, being invertebrates and, moreover, lacking any ethical concern issues. Purinergic signaling is, by definition, mediated by extracellular purinergic ligands, among which ATP represents the prototype molecule. A key feature that has progressively emerged when dissecting the purinergic mechanisms is the multilayer and dynamic nature of the signaling sustained by purinergic ligands. Indeed, these last are sequentially metabolized by several different ectonucleotidases, which generate the ligands that simultaneously activate several different purinergic receptors. Since significant purinergic actions have also been described in Drosophila, the aim of the present work is to provide a comprehensive picture of the purinergic events occurring in fruit flies.     

Translational Implications for Radiosensitizing Strategies in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence that includes FP-RMS, harboring the fusion oncoprotein PAX3/7-FOXO1 and FN-RMS, often mutant in the RAS pathway. Risk stratifications of RMS patients determine different prognostic groups and related therapeutic treatment. Current multimodal therapeutic strategies involve surgery, chemotherapy (CHT) and radiotherapy (RT), but despite the deeper knowledge of response mechanisms underpinning CHT treatment and the technological improvements that characterize RT, local failures and recurrence frequently occur. This review sums up the RMS classification and the management of RMS patients, with special attention to RT treatment and possible radiosensitizing strategies for RMS tumors. Indeed, RMS radioresistance is a clinical problem and further studies aimed at dissecting radioresistant molecular mechanisms are needed to identify specific targets to hit, thus improving RT-induced cytotoxicity.     

CRISPR/Cas9-Based Knock-Out of the PMR4 Gene Reduces Susceptibility to Late Blight in Two Tomato Cultivars

Phytophthora infestans, the causal agent of late blight (LB) in tomato (Solanum lycopersicum L.), is a devastating disease and a serious concern for plant productivity. The presence of susceptibility (S) genes in plants facilitates pathogen proliferation; thus, disabling these genes may help provide a broad-spectrum and durable type of tolerance/resistance. Previous studies on Arabidopsis and tomato have highlighted that knock-out mutants of the PMR4 susceptibility gene are tolerant to powdery mildew. Moreover, PMR4 knock-down in potato has been shown to confer tolerance to LB. To verify the same effect in tomato in the present study, a CRISPR–Cas9 vector containing four single guide RNAs (sgRNAs: sgRNA1, sgRNA6, sgRNA7, and sgRNA8), targeting as many SlPMR4 regions, was introduced via Agrobacterium-tumefaciens-mediated transformation into two widely grown Italian tomato cultivars: ‘San Marzano’ (SM) and ‘Oxheart’ (OX). Thirty-five plants (twenty-six SM and nine OX) were selected and screened to identify the CRISPR/Cas9-induced mutations. The different sgRNAs caused mutation frequencies ranging from 22.1 to 100% and alternatively precise insertions (sgRNA6) or deletions (sgRNA7, sgRNA1, and sgRNA8). Notably, sgRNA7 induced in seven SM genotypes a −7 bp deletion in the homozygous status, whereas sgRNA8 led to the production of fifteen SM genotypes with a biallelic mutation (−7 bp and −2 bp). Selected edited lines were inoculated with P. infestans, and four of them, fully knocked out at the PMR4 locus, showed reduced disease symptoms (reduction in susceptibility from 55 to 80%) compared to control plants. The four SM lines were sequenced using Illumina whole-genome sequencing for deeper characterization without exhibiting any evidence of mutations in the candidate off-target regions. Our results showed, for the first time, a reduced susceptibility to Phytophtora infestans in pmr4 tomato mutants confirming the role of KO PMR4 in providing broad-spectrum protection against pathogens.