A study on the VEGFR2-ligand multi-physics interactions in Angiogenesis.

Tumorgrowthissustainedbyangiogenesis,i.e. theformationofnewbloodvesselsfrompre-existing ones. Angiogenesis is modulated by the interaction between tyrosine kinase receptors (TKRs), expressed by endothelial cells (ECs), and extracellular ligands, produced by tumor cells. This interaction triggers the activation of intracellular signaling cascades and kinetic processes, including cell deformationandadhesion,whicheventuallycausecelldivisionandproliferation. VascularEndothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor expressed on ECs. Ligand stimulation induces the polarization of ECs and the relocation of VEGFR2 in cell protrusion or in the basal aspect in cells plated on ligand enriched extracellular matrix (ECM) [1]. EC response to angiogenic growth factors is regulated by distinct sets of inputs conveyed by TRKs and different co-receptors including integrins, membrane proteins that are responsible of stress fibers formation and cell contractility [2]. Although biochemical pathways following VEGFR2 activation are well established, knowledge about the receptor dynamics on the plasma membrane remains limited. A multi-physics model has been developed [3] to describe: i) the diffusion of VEGFR2 on the cellularmembrane;ii)thechemicalkineticsoftheligand-receptorbindingreaction;iii)themechanical adhesion and spreading of the cell onto a ligand-rich extracellular substrate, in finite strain. The identification of the multi-physics interactions that regulate receptor polarization could open new perspectives to develop innovative anti-angiogenic strategies through the modulation of EC activation

Multi-physics interactions drive VEGFR2 relocation on endothelial cells.

Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) is a pro-angiogenic receptor, expressed on endothelial cells (ECs). Although biochemical pathways that follow the VEGFR2 activation are well established, knowledge about the dynamics of receptors on the plasma membrane remains limited. Ligand stimulation induces the polarization of ECs and the relocation of VEGFR2, either in cell protrusions or in the basal aspect in cells plated on ligand-enriched extracellular matrix (ECM). We develop a mathematical model in order to simulate the relocation of VEGFR2 on the cell membrane during the mechanical adhesion of cells onto a ligand-enriched substrate. Co-designing the in vitro experiments with the simulations allows identifying three phases of the receptor dynamics, which are controlled respectively by the high chemical reaction rate, by the mechanical deformation rate, and by the diffusion of free receptors on the membrane. The identification of the laws that regulate receptor polarization opens new perspectives toward developing innovative anti-angiogenic strategies through the modulation of EC activatio

Applicazioni del Laser Scanner terrestre a temi geologico-tecnici

Laser scanner is an electronic instrument capable to survey the three-dimensional geometry of an object through a laser pulse measuring the distance between the laser head and the objects surface. Accuracy, acquisition time and range varies between several commercial products. Short range (up to 50-70 m) scanners can survey in few minutes at high resolution (ca. ± 2 mm), while long range scanners (up to 2000 m) can provide a decimetric accuracy and need more acquisition time. Laser scanner has the advantage that doesn’t need passive corner reflector on the object but on the other hand the measure accuracy could be dependent on the surface characteristics (material, dielectric constant, etc.). The laser scanner output is a three-dimensional cloud of points colored by reflectance values. Both the cloud of point and the derived mesh model can be textured using a external digital images; the final result is photorealistic model of the object completely measurable. Terrestrial laser scanner technology (hardware and software) is in continues developing and several application are related to the geological survey field of application. In particular laser scanner was applied for geo-mechanical analyses, rock fall monitoring, tunnel and cave survey, glacier monitoring. Further development are planned to simplified the usage and analyses of laser data for geologist trough user friendly software tool

Agreement between physicians and parents in rating functional ability of children with juvenile idiopathic arthritis

<p>Abstract</p> <p>Objective</p> <p>To investigate concordance between physicians and parents in rating the degree of functional ability of children with juvenile idiopathic arthritis (JIA).</p> <p>Methods</p> <p>The attending physician and a parent were asked to rate independently the level of physical functioning of 155 patients with disease duration ≥ 5 years on a 6-point scale ranging from 1 = no disability (i.e. the child can do without difficulty all activities that children of his/her age can do) to 6 = severe disability (i.e. all activities are difficult for the child). At study visit, measures of JIA activity and damage were assessed. Agreement was evaluated with weighted kappa (<0.40 = poor agreement; 0.41–0.60 = moderate agreement; 0.61–0.80 = substantial agreement; >0.80 excellent agreement). Physician/parent evaluations were divided in 3 groups: 1) concordance; 2) parent over-rating = parent assessment over-rated relative to physician assessment; 3) physician over-rating = physician assessment over-rated relative to parent assessment. Factors affecting concordance/discordance were evaluated by means of Kruskal-Wallis or Chi-square/Fisher exact test.</p> <p>Results</p> <p>Concordance, parent over-rating and physician over-rating were observed in 107 (69%), 29 (18.7%) and 19 (12.3%) evaluations, respectively. Kappa value was 0.69. Parent over-rating was associated with greater intensity of pain (p = 0.01) and higher Childhood Health Assessment Questionnaire (C-HAQ) score (p = 0.004), whereas physician over-rating was associated with more severe joint disease (p = 0.04 to <0.001), higher C-reactive protein (p = 0.03) higher frequency of Steinbrocker functional class = II (p < 0.001), and greater articular damage, as measured with the Juvenile Arthritis Damage Index (p < 0.001).</p> <p>Conclusion</p> <p>Physicians and parents revealed fair concordance in rating functional ability of children with JIA. Parent over-rating was associated with greater child's pain and worse C-HAQ score, whereas physician over-rating was associated with greater severity of joint inflammation and damage.</p

Development and validation of a composite disease activity score for juvenile idiopathic arthritis

Objective. To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). Methods. The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on &gt;4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0 \u2013101), 27-joint (range 0 \u201357), or 10-joint (range 0 \u2013 40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). Results. The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. Conclusion. The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials

Cross-cultural adaptation and psychometric evaluation of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) in 54 languages across 52 countries: review of the general methodology

The aim of this project was to cross-culturally adapt and validate the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) questionnaire in 54 languages across 52 different countries that are members of the Paediatric Rheumatology International Trials Organisation (PRINTO). This effort was part of a wider project named Epidemiology and Outcome of Children with Arthritis (EPOCA) to obtain information on the frequency of juvenile idiopathic arthritis (JIA) categories in different geographic areas, the therapeutic approaches adopted, and the disease status of children with JIA currently followed worldwide. A total of 13,843 subjects were enrolled from the 49 countries that took part both in the cross-cultural adaptation phase and in the related validation and data collection: Algeria, Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany, Greece, Hungary, India, Islamic Republic of Iran, Israel, Italy, Latvia, Libya, Lithuania, Mexico, Netherlands, Norway, Oman, Paraguay, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom and United States of America. 9021 patients had JIA (10.7% systemic arthritis, 41.9% oligoarthritis, 23.5% RF negative polyarthritis, 4.2% RF positive polyarthritis, 3.4% psoriatic arthritis, 10.6% enthesitis-related arthritis and 5.7% undifferentiated arthritis) while 4822 were healthy children. This introductory paper describes the overall methodology; results pertaining to each country are fully described in the accompanying manuscripts. In conclusion, the JAMAR translations were found to have satisfactory psychometric properties and it is thus a reliable and valid tool for the multidimensional assessment of children with JIA

Calibration of rotation axes for multi-axis goniometers in macromolecular crystallography

The installation of multi-axis goniometers such as the ESRF/EMBL miniKappa goniometer system has allowed the increased use of sample reorientation in macromolecular crystallography. Old and newly appearing data collection methods require precision and accuracy in crystal reorientation. The proper use of such multi-axis systems has necessitated the development of rapid and easy to perform methods for establishing and evaluating device calibration. A new diffraction-based method meeting these criteria has been developed for the alibration of the motors responsible for rotational motion. This method takes advantage of crystal symmetry by comparing the orientations of a sample rotated about a given axis and checking that the magnitude of the real rotation fits the calculated angle between these two orientations. Hence, the accuracy and precision of rotational motion can be assessed. This rotation calibration procedure has been performed on several beamlines at the ESRF and other synchrotrons. Some resulting data are presented here for reference. © 2018, Wiley-Blackwell. All Rights Reserved