Bayesian inversion with {\alpha}-stable priors

We propose to use L\'evy {\alpha}-stable distributions for constructing priors for Bayesian inverse problems. The construction is based on Markov fields with stable-distributed increments. Special cases include the Cauchy and Gaussian distributions, with stability indices {\alpha} = 1, and {\alpha} = 2, respectively. Our target is to show that these priors provide a rich class of priors for modelling rough features. The main technical issue is that the {\alpha}-stable probability density functions do not have closed-form expressions in general, and this limits their applicability. For practical purposes, we need to approximate probability density functions through numerical integration or series expansions. Current available approximation methods are either too time-consuming or do not function within the range of stability and radius arguments needed in Bayesian inversion. To address the issue, we propose a new hybrid approximation method for symmetric univariate and bivariate {\alpha}-stable distributions, which is both fast to evaluate, and accurate enough from a practical viewpoint. Then we use approximation method in the numerical implementation of {\alpha}-stable random field priors. We demonstrate the applicability of the constructed priors on selected Bayesian inverse problems which include the deconvolution problem, and the inversion of a function governed by an elliptic partial differential equation. We also demonstrate hierarchical {\alpha}-stable priors in the one-dimensional deconvolution problem. We employ maximum-a-posterior-based estimation at all the numerical examples. To that end, we exploit the limited-memory BFGS and its bounded variant for the estimator

Determining collagen distribution in articular cartilage using contrast-enhanced micro-computed tomography

Objective: Collagen distribution within articular cartilage (AC) is typically evaluated from histological sections, e.g., using collagen staining and light microscopy (LM). Unfortunately, all techniques based on histological sections are time-consuming, destructive, and without extraordinary effort, limited to two dimensions. This study investigates whether phosphotungstic acid (PTA) and phosphomolybdic acid (PMA), two collagen-specific markers and X-ray absorbers, could (1) produce contrast for AC X-ray imaging or (2) be used to detect collagen distribution within AC. Method: We labeled equine AC samples with PTA or PMA and imaged them with micro-computed tomography (micro-CT) at pre-defined time points 0, 18, 36, 54, 72, 90, 180, 270 h during staining. The micro-CT image intensity was compared with collagen distributions obtained with a reference technique, i.e., Fourier-transform infrared imaging (FTIRI). The labeling time and contrast agent producing highest association (Pearson correlation, BlandeAltman analysis) between FTIRI collagen distribution and micro-CT -determined PTA distribution was selected for human AC. Results: Both, PTA and PMA labeling permitted visualization of AC features using micro-CT in non-calcified cartilage. After labeling the samples for 36 h in PTA, the spatial distribution of X-ray attenuation correlated highly with the collagen distribution determined by FTIRI in both equine (mean +/- S.D. of the Pearson correlation coefficients, r = 0.96 +/- 0.03, n = 12) and human AC (r = 0.82 +/- 0.15, n = 4). Conclusions: PTA-induced X-ray attenuation is a potential marker for non-destructive detection of AC collagen distributions in 3D. This approach opens new possibilities in development of non-destructive 3D histopathological techniques for characterization of OA. (C) 2015 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.Peer reviewe

In Vivo and In Vitro Study of a Polylactide-Fiber-Reinforced β-Tricalcium Phosphate Composite Cage in an Ovine Anterior Cervical Intercorporal Fusion Model

A poly-70L/30DL-lactide (PLA70)–β-tricalcium phosphate (β-TCP) composite implant reinforced by continuous PLA-96L/4D-lactide (PLA96) fibers was designed for in vivo spinal fusion. The pilot study was performed with four sheep, using titanium cage implants as controls. The composite implants failed to direct bone growth as desired, whereas the bone contact and the proper integration were evident with controls 6 months after implantation. Therefore, the PLA70/β-TCP composite matrix material was further analyzed in the in vitro experiment by human and ovine adipose stem cells (hASCs and oASCs). The composites proved to be biocompatible as confirmed by live/dead assay. The proliferation rate of oASCs was higher than that of hASCs at all times during the 28 d culture period. Furthermore, the composites had only a minor osteogenic effect on oASCs, whereas the hASC osteogenesis on PLA70/β-TCP composites was evident. In conclusion, the composite implant material can be applied with hASCs for tissue engineering but not be evaluated in vivo with sheep

Vertical profiles of volatile organic compounds and fine particles in atmospheric air by using an aerial drone with miniaturized samplers and portable devices

The increase in volatile organic compound (VOC) emissions released into the atmosphere is one of the main threats to human health and climate. VOCs can adversely affect human life through their contribution to air pollution directly and indirectly by reacting via several mechanisms in the air to form secondary organic aerosols. In this study, an aerial drone equipped with miniaturized air-sampling systems including up to four solid-phase microextraction (SPME) Arrows and four in-tube extraction (ITEX) samplers for the collection of VOCs, along with portable devices for the real-time measurement of black carbon (BC) and total particle numbers at high altitudes was exploited. In total, 135 air samples were collected under optimal sampling conditions from 4 to 14 October 2021 at the boreal forest SMEAR II station, Finland. A total of 48 different VOCs, including nitrogen-containing compounds, alcohols, aldehydes, ketones, organic acids, and hydrocarbons, were detected at different altitudes from 50 to 400 m above ground level with concentrations of up to 6898 ng m−3 in the gas phase and 8613 ng m−3 in the particle phase. Clear differences in VOC distributions were seen in samples collected from different altitudes, depending on the VOC sources. It was also possible to collect aerosol particles by the filter accessory attached on the ITEX sampling system, and five dicarboxylic acids were quantified with concentrations of 0.43 to 10.9 µg m−3. BC and total particle number measurements provided similar diurnal patterns, indicating their correlation. For spatial distribution, BC concentrations were increased at higher altitudes, being 2278 ng m−3 at 100 m and 3909 ng m−3 at 400 m. The measurements aboard the drone provided insights into horizontal and vertical variability in BC and aerosol number concentrations above the boreal forest.</p

An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method. One implant type was made of PL-DL-lactide (PLA), the second one was a titanium core partially covered with PLA. Healing period was 2 and 6 months, with 3 sheep per group. Bone samples were evaluated radiologically, histologically and histomorphometrically for bone remodeling and inflammatory reactions. Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone

Efflux Protein Expression in Human Stem Cell-Derived Retinal Pigment Epithelial Cells

Retinal pigment epithelial (RPE) cells in the back of the eye nourish photoreceptor cells and form a selective barrier that influences drug transport from the blood to the photoreceptor cells. At the molecular level, ATP-dependent efflux transporters have a major role in drug delivery in human RPE. In this study, we assessed the relative expression of several ATP-dependent efflux transporter genes (MRP1, -2, -3, -4, -5, -6, p-gp, and BCRP), the protein expression and localization of MRP1, MRP4, and MRP5, and the functionality of MRP1 efflux pumps at different maturation stages of undifferentiated human embryonic stem cells (hESC) and RPE derived from the hESC (hESC-RPE). Our findings revealed that the gene expression of ATP-dependent efflux transporters MRP1, -3, -4, -5, and p-gp fluctuated during hESC-RPE maturation from undifferentiated hESC to fusiform, epithelioid, and finally to cobblestone hESC-RPE. Epithelioid hESC-RPE had the highest expression of MRP1, -3, -4, and P-gp, whereas the most mature cobblestone hESC-RPE had the highest expression of MRP5 and MRP6. These findings indicate that a similar efflux protein profile is shared between hESC-RPE and the human RPE cell line, ARPE-19, and suggest that hESC-RPE cells are suitable in vitro RPE models for drug transport studies. Embryonic stem cell model might provide a novel tool to study retinal cell differentiation, mechanisms of RPE -derived diseases, drug testing and targeted drug therapy

A Combined Synthetic-Fibrin Scaffold Supports Growth and Cardiomyogenic Commitment of Human Placental Derived Stem Cells

Aims: A potential therapy for myocardial infarction is to deliver isolated stem cells to the infarcted site. A key issue with this therapy is to have at one\u27s disposal a suitable cell delivery system which, besides being able to support cell proliferation and differentiation, may also provide handling and elastic properties which do not affect cardiac contractile function. In this study an elastic scaffold, obtained combining a poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating polymeric network (s-IPN) with fibrin, was used as a substrate for in vitro studies of human amniotic mesenchymal stromal cells (hAMSC) growth and differentiation. Methodology/Principal Findings: After hAMSC seeding on the fibrin side of the scaffold, cell metabolic activity and proliferation were evaluated by WST-1 and bromodeoxyuridine assays. Morphological changes and mRNAs expression for cardiac differentiation markers in the hAMSCs were examined using immunofluorescence and RT-PCR analysis. The beginning of cardiomyogenic commitment of hAMSCs grown on the scaffold was induced, for the first time in this cell population, by a nitric oxide (NO) treatment. Following NO treatment hAMSCs show morphological changes, an increase of the messenger cardiac differentiation markers [troponin I (TnI) and NK2 transcription factor related locus 5 (Nkx2.5)] and a modulation of the endothelial markers [vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR)]. Conclusions/Significance: The results of this study suggest that the s-IPN PEtU-PDMS/fibrin combined scaffold allows a better proliferation and metabolic activity of hAMSCs cultured up to 14 days, compared to the ones grown on plastic dishes. In addition, the combined scaffold sustains the beginning of hAMSCs differentiation process towards a cardiomyogenic lineage

Differential Impact of Tetratricopeptide Repeat Proteins on the Steroid Hormone Receptors

Tetratricopeptide repeat (TPR) motif containing co-chaperones of the chaperone Hsp90 are considered control modules that govern activity and specificity of this central folding platform. Steroid receptors are paradigm clients of Hsp90. The influence of some TPR proteins on selected receptors has been described, but a comprehensive analysis of the effects of TPR proteins on all steroid receptors has not been accomplished yet.We compared the influence of the TPR proteins FK506 binding proteins 51 and 52, protein phosphatase-5, C-terminus of Hsp70 interacting protein, cyclophillin 40, hepatitis-virus-B X-associated protein-2, and tetratricopeptide repeat protein-2 on all six steroid hormone receptors in a homogeneous mammalian cell system. To be able to assess each cofactor's effect on the transcriptional activity of on each steroid receptor we employed transient transfection in a reporter gene assay. In addition, we evaluated the interactions of the TPR proteins with the receptors and components of the Hsp90 chaperone heterocomplex by coimmunoprecipitation. In the functional assays, corticosteroid and progesterone receptors displayed the most sensitive and distinct reaction to the TPR proteins. Androgen receptor's activity was moderately impaired by most cofactors, whereas the Estrogen receptors' activity was impaired by most cofactors only to a minor degree. Second, interaction studies revealed that the strongly receptor-interacting co-chaperones were all among the inhibitory proteins. Intriguingly, the TPR-proteins also differentially co-precipitated the heterochaperone complex components Hsp90, Hsp70, and p23, pointing to differences in their modes of action.The results of this comprehensive study provide important insight into chaperoning of diverse client proteins via the combinatorial action of (co)-chaperones. The differential effects of the TPR proteins on steroid receptors bear on all physiological processes related to steroid hormone activity