Quantitative full-colour transmitted light microscopy and dyes for concentration mapping and measurement of diffusion coefficients in microfluidic architectures

International audienceA simple and versatile methodology has been developed for the simultaneous measurement of multiple concentration profiles of colourants in transparent microfluidic systems, using a conventional transmitted light microscope, a digital colour (RGB) camera and numerical image processing combined with multicomponent analysis. Rigorous application of the Beer-Lambert law would require monochromatic probe conditions, but in spite of the broad spectral bandwidths of the three colour channels of the camera, a linear relation between the measured optical density and dye concentration is established under certain conditions. An optimised collection of dye solutions for the quantitative optical microscopic characterisation of microfluidic devices is proposed. Using the methodology for optical concentration measurement we then implement and validate a simplified and robust method for the microfluidic measurement of diffusion coefficients using an H-filter architecture. It consists of measuring the ratio of the concentrations of the two output channels of the H-filter. It enables facile determination of the diffusion coefficient, even for non-fluorescent molecules and nanoparticles, and is compatible with non-optical detection of the analyte

Health-related quality of life in facial palsy:translation and validation of the Dutch version Facial Disability Index

Contains fulltext : 229876.pdf (publisher's version ) (Open Access)PURPOSE: Patient-reported outcome measures are essential in the evaluation of facial palsy. Aim of this study was to translate and validate the Facial Disability Index (FDI) for use in the Netherlands. METHODS: The FDI was translated into Dutch according to a forward-backward method. Construct validity was assessed by formulating 22 hypotheses regarding associations of FDI scores with the Facial Clinimetric Evaluation scale, the Synkinesis Assessment Questionnaire, the Short Form-12 and the Sunnybrook Facial Grading System. Validity was considered adequate if at least 75% (i.e. 17 out of 22) of the hypotheses were confirmed. Additionally, confirmatory factor analysis was performed. Cronbach's α was calculated as a measure of internal consistency. Participants were asked to fill out the FDI a second time after 2 weeks to analyse test-retest reliability. Lastly, smallest detectable change was calculated. RESULTS: In total, 19 hypotheses (86.4%) were confirmed. Confirmatory factor analysis showed acceptable fit for the two factor structure of the original FDI (root mean square error of approximation = 0.064, standardized root mean square residual = 0.081, comparative fit index = 0.925, Chi-square = 50.22 with 34 degrees of freedom). Internal consistency for the FDI physical function scale was good (α > 0.720). Internal consistency for the FDI social/well-being scale was slightly less (α > 0.574). Test-retest reliability for both scales was good (intraclass correlation coefficients > 0.786). Smallest detectable change at the level of the individual was 17.6 points for the physical function and 17.7 points for the social/well-being function, and at group level 1.9 points for both scales. CONCLUSION: The Dutch version FDI shows good psychometric properties. The relatively large values for individual smallest detectable change may limit clinical use. The translation and widespread use of the FDI in multiple languages can help to compare treatment results internationally

Nucleon-nucleon bremsstrahlung: An example of the impossibility of measuring off-shell amplitudes

For nearly fifty years theoretical and experimental efforts in nucleon-nucleon bremsstrahlung (NN$\gamma$) have been devoted to measuring off-shell amplitudes and distinguishing among various NN potentials on the basis of their off-shell behavior. New experiments are underway, designed specifically to attain kinematics further off shell than in the past, and thus to be more sensitive to the off-shell behavior. This letter shows that, contrary to these expectations, and due to the invariance of the S-matrix under transformations of the fields, the off-shell NN amplitude is as a matter of principle an unmeasurable quantity in NN$\gamma$.Comment: 9 pages, Latex, using RevTeX; Minor wording changes, title changed, version to be published in Phys. Rev. Letter

Field transformations and simple models illustrating the impossibility of measuring off-shell effects

In the context of simple models illustrating field transformations in Lagrangian field theories we discuss the impossibility of measuring off-shell effects in nucleon-nucleon bremsstrahlung, Compton scattering, and related processes. To that end we introduce a simple phenomenological Lagrangian describing nucleon-nucleon bremsstrahlung and perform an appropriate change of variables leading to different off-shell behavior in the nucleon-nucleon amplitude as well as the photon-nucleon vertex. As a result we obtain a class of equivalent Lagrangians, generating identical S-matrix elements, of which the original Lagrangian is but one representative. We make use of this property in order to show that what appears as an off-shell effect in an S-matrix element for one Lagrangian may originate in a contact term from an equivalent Lagrangian. By explicit calculation we demonstrate for the case of nucleon-nucleon bremsstrahlung as well as nucleon Compton scattering the equivalence of observables from which we conclude that off-shell effects cannot in any unambiguous way be extracted from an S-matrix element. Finally, we also discuss some implications of introducing off-shell effects on a phenomenological basis, resulting from the requirement that the description of one process be consistent with that of other processes described by the same Lagrangian.Comment: 19 pages, Latex, using RevTe

Endocrinologic disorders and optic pathway gliomas in children with neurofibromatosis type 1

Objective. To establish the prevalence of endocrinologic disorders in children with neurofibromatosis type 1 (NF1) and the relationship between these disorders and cerebral abnormalities on magnetic resonance imaging. Design. A prospective follow-up study. Setting. A multidisciplinary neurofibromatosis clinic. Patients. A total of 122 children diagnosed with NF1 according to diagnostic criteria set by the National Institutes of Health. Results. Central precocious puberty (CPP) was diagnosed in 3 children and growth hormone deficiency (GHD) in 3 children. Optic pathway gliomas were observed in 15 children; in 9 of the 15 cases, the optic chiasm was involved. Of the 3 children with CPP, only 1 showed a chiasma glioma on magnetic resonance imaging. In 1 case with GHD, an optic chiasm glioma was detected on neuroimaging. Two of the 9 children with an optic chiasm glioma presented with CPP or GHD. Conclusions. It has been suggested that CPP in children with NF1 is found exclusively in the presence of a chiasma glioma. We conclude that chiasma glioma may not be obligatory in children with NF1 and CPP or GHD. Moreover, we report a prevalence of GHD in children with NF1 of 2.5%, which has not been established earlier

The Chop Gene Contains an Element for the Positive Regulation of the Mitochondrial Unfolded Protein Response

We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR

Optical Mie Scattering by DNA-Assembled Three-Dimensional Gold Nanoparticle Superlattice Crystals

9 pags., 5 figs.Programmable assemblies of gold nanoparticles engineered with DNA have intriguing optical properties such as Coulomb-interaction-driven strong coupling, polaritonic response in the visible range, and ultralow dispersion dielectric response in the infrared spectral range. In this work, we demonstrate the optical Mie resonances of individual microcrystals of DNA-gold nanoparticle superlattices. Broadband hyperspectral mapping of both transmission and dark-field scattering reveal a polarization-insensitive optical response with distinct spectral features in the visible and near-infrared ranges. Experimental observations are supported by numerical simulations of the microcrystals under a resonant effective medium approximation in the regime of capacitively coupled nanoparticles. The study identifies a universal characteristic optical response which is defined by a band of multipolar Mie resonances, which only weakly depend on the crystal size and light polarization. The use of gold superlattice microcrystals as scattering materials is of interest for fields such as complex nanophotonics, thermoplasmonics, photocatalysis, sensing, and nonlinear optics.D.M., H.J.S., A.G.K., and O.L.M. acknowledge financial support by the Leverhulme Trust through Research Grant RPG-2018-251.Peer reviewe

Survival after resection of malignant peripheral nerve sheath tumors:Introducing and validating a novel type-specific prognostic model

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.</p

Active Wnt signaling in response to cardiac injury

Although the contribution of Wnt signaling in infarct healing is suggested, its exact role after myocardial infarction (MI) still needs to be unraveled. We evaluated the cardiac presence of active Wnt signaling in vivo following MI, and investigated in which cell types active Wnt signaling was present by determining Axin2 promoter-driven LacZ expression. C57BL/6 Axin2-LacZ reporter mice were sacrificed at days 0, 1, 3, 7, 14, and 21 after LAD ligation. Hearts were snap-frozen for immunohistochemistry (IHC) or enzymatically digested to obtain a single cell suspension for flow cytometric analysis. For both FACS and IHC, samples were stained for β-galactosidase and antibodies against Sca-1, CD31, ckit, and CD45. Active Wnt signaling increased markedly in the myocardium, from 7 days post-MI onwards. Using Sca-1 and CD31, to identify progenitor and endothelial cells, a significant increase in LacZ+ cells was found at 7 and 14 days post-MI. LacZ+ cells also increased in the ckit+ and CD45+ cell population. IHC revealed LacZ+ cells co-expressing Sca, CD31, CD45, vWF, and αSMA in the border zone and the infarcted area. Wnt signaling increased significantly after MI in Sca+- and CD31+-expressing cells, suggesting involvement of Wnt signaling in resident Sca+ progenitor cells, as well as endothelial cells. Moreover, active Wnt signaling was present in ckit+ cells, leukocytes, and fibroblast. Given its broad role during the healing phase after cardiac injury, additional research seems warranted before a therapeutic approach on Wnt to enhance cardiac regeneration can be carried out safely