Yale School of Public Health Symposium on tissue imaging mass spectrometry: illuminating phenotypic heterogeneity and drug disposition at the molecular level.

‘A picture is worth a thousand words’ is an idiom from the English language (‘borrowed’ from on old Chinese proverb) that conveys the notion that a complex idea can be succinctly and fully described by a single image. Never has this expression been truer than in the clinical and pharmaceutical arenas. Enormous strides have been made by the scientific community in the evolving field of biomedical imaging with the aim of representing and/or quantifying aspects of disease and drug action by using tools such as radiography, MRI, PET, and ultrasound. Yet linking the phenotypical data generated by these systems to the genome is a challenging task. Identifying the link between the mechanism of disease or failed drug response to the genome of an individual is difficult, because central pieces of information are missing. However, imaging mass spectrometry (IMS) can overcome this issue. IMS aims to detect the molecular constituents of the tissue; these can then be correlated with genome-related characteristics, such as gene expression patterns and possible mutations, and ultimately provide a phenotypic molecular link to the complex disease biology. The big data technology of IMS can generate spatial information of thousands of metabolites and proteins from within a tissue, facilitating a deeper understanding of the connections between the genome, phenotypic characteristics and the biological response. It is a technology that has the potential to serve as a segue between gene expression and observed biological signal

DFM synthesis approach based on product-process interface modelling. Application to the peen forming process.

Engineering design approach are curently CAD-centred design process. Manufacturing information is selected and assessed very late in the design process and above all as a reactive task instead of being proactive to lead the design choices. DFM appraoches are therefore assesment methods that compare several design alternatives and not real design approaches at all. Main added value of this research work concerns the use of a product-process interface model to jointly manage both the product and the manufacturing data in a proactive DFM way. The DFM synthesis approach and the interface model are presented via the description of the DFM software platform

Universal relationship between the penetration depth and the normal-state conductivity in YBaCuO

The absolute values of the conductivity in the normal state sigma_n and of the low temperature penetration depths lambda(0) were measured for a number of different samples of the YBaCuO family. We found a striking correlation between sigma_n and 1/lambda^2, regardless of doping, oxygen reduction or defects, thus providing a simple method to predict the superconducting penetration depth and to have an estimate of the sample quality by measuring the normal-state conductivity.Comment: 7 pages, 1 figure, Europhys. Lett., accepte

Bound States and Critical Behavior of the Yukawa Potential

We investigate the bound states of the Yukawa potential $V(r)=-\lambda \exp(-\alpha r)/ r$, using different algorithms: solving the Schr\"odinger equation numerically and our Monte Carlo Hamiltonian approach. There is a critical $\alpha=\alpha_C$, above which no bound state exists. We study the relation between $\alpha_C$ and $\lambda$ for various angular momentum quantum number $l$, and find in atomic units, $\alpha_{C}(l)= \lambda [A_{1} \exp(-l/ B_{1})+ A_{2} \exp(-l/ B_{2})]$, with $A_1=1.020(18)$, $B_1=0.443(14)$, $A_2=0.170(17)$, and $B_2=2.490(180)$.Comment: 15 pages, 12 figures, 5 tables. Version to appear in Sciences in China

DFM synthesis approach based on product-process interface modelling. Application to the peen forming process.

International audienceEngineering design approach are curently CAD-centred design process. Manufacturing information is selected and assessed very late in the design process and above all as a reactive task instead of being proactive to lead the design choices. DFM appraoches are therefore assesment methods that compare several design alternatives and not real design approaches at all. Main added value of this research work concerns the use of a product-process interface model to jointly manage both the product and the manufacturing data in a proactive DFM way. The DFM synthesis approach and the interface model are presented via the description of the DFM software platform

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

International audienceAbstractRare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP’s is realised

Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex