Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

As a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.A multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.These results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies

Feasibility studies for the measurement of time-like proton electromagnetic form factors from p¯ p→ μ+μ- at P ¯ ANDA at FAIR

This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, | GE| and | GM| , using the p¯ p→ μ+μ- reaction at P ¯ ANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at P ¯ ANDA , using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is p¯ p→ π+π-, due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented

Precision resonance energy scans with the PANDA experiment at FAIR: Sensitivity study for width and line shape measurements of the X(3872)

This paper summarises a comprehensive Monte Carlo simulation study for precision resonance energy scan measurements. Apart from the proof of principle for natural width and line shape measurements of very narrow resonances with PANDA, the achievable sensitivities are quantified for the concrete example of the charmonium-like X(3872) state discussed to be exotic, and for a larger parameter space of various assumed signal cross-sections, input widths and luminosity combinations. PANDA is the only experiment that will be able to perform precision resonance energy scans of such narrow states with quantum numbers of spin and parities that differ from J P C = 1 - -

Results from additional measurements carried out within the BIPM.L-K11 ongoing key comparison

Lasers from three national metrological institutes (NMIs) have been measured following the protocol of the BIPM.L-K11 ongoing key comparison initiated by the Comité Consultative des Longueurs (CCL) 11th meeting in 2003. The absolute frequency of the f component of the R(127) 11-5 transition at 633 nm was measured for two of these lasers in their home institutes, AIST/NMIJ and UME, while the b5 component of the R(106) 28-0 transition at 543 nm was measured on a standard from NIM at the BIPM. The results of these measurements are compiled in the present paper. The comparison reports, as communicated by each participant, are included as Appendices