Bone substitute effect on vascularization and bone remodeling after application of phVEGF165 transfected BMSC

VEGF (vascular endothelial growth factor) promotes vascularization and remodeling of bone substitutes. The aim of this study was to examine the effect of distinct resorbable ceramic carriers on bone forming capacities of VEGF transfected bone marrow stromal cells (BMSC). A critical size defect of the radius in rabbits was filled either by a low surface scaffold called beta-TCP (tricalciumphsphate) or the high surface scaffold CDHA (calcium deficient hydroxy-apatite) loaded with autologous BMSC, which were either transfected with a control plasmid or a plasmid coding for phVEGF165. They were compared to unloaded scaffolds. Thus, six treatment groups (n = 6 in each group) were followed by X-ray over 16 weeks. After probe retrieval, the volume of new bone was measured by micro-CT scans and vascularization was assessed in histology. While only minor bone formation was found in both carriers when implanted alone, BMSC led to increased osteogenesis in both carriers. VEGF promoted vascularization of the scaffolds significantly in contrast to BMSC alone. Bone formation was increased in the beta-TCP group, whereas it was inhibited in the CDHA group that showed faster scaffold degradation. The results indicate that the interaction of VEGF transfected BMSC with resorbable ceramic carrier influences the ability to promote bone healing

Neuromelanin-Sensitive Magnetic Resonance Imaging in Schizophrenia: A Meta-Analysis of Case-Control Studies

Background: Psychiatry is in urgent need of reliable biomarkers. Novel neuromelanin-sensitive magnetic resonance imaging (NM-MRI) sequences provide a time-efficient and non-invasive way to investigate the human brain in-vivo. This gives insight into the metabolites of dopaminergic signaling and may provide further evidence for potential dopaminergic alterations in patients with schizophrenia (SCZ). The present systematic review provides a meta-analysis of case-control studies using neuromelanin-sensitive sequences in SCZ vs. healthy controls (HC). Methods: According to predefined search terms and inclusion criteria studies were extracted on PubMed. Meta-analyses with a fixed and random-effects model with inverse variance method, DerSimonian-Laird estimator for tau(2), and Cohen's d were calculated. Bias was assessed using funnel plots. The primary study outcome was contrast-to-noise ratio (CNR) in the substantia nigra compared between HC and SCZ. Results: The total sample of k = 6 studies included n = 183 cases and n = 162 controls. Across all studies we found a significant elevation of CNR in the substantia nigra (d = 0.42 [0.187; 0.655], z = 3.521, p < 0.001) in cases compared to controls. We found no significant difference in the control region of locus coeruleus (d = -0.07 [-0.446; 0.302], z = -0.192, p = 0.847), with CNR for the latter only reported in k = 3 studies. Conclusion: CNR in the substantia nigra were significantly elevated in cases compared to controls. Our results support neuromelanin as a candidate biomarker for dopaminergic dysfunction in schizophrenia. Further studies need to assess this candidate marker in large, longitudinal cohorts and address potential effects of disease state, medication and correlations with symptoms

Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect

Both platelet-rich plasma (PRP) and vascular endothelial growth factor (VEGF) can promote regeneration. The aim of this study was to compare the effects of these two elements on bone formation and vascularization in combination with bone marrow stromal cells (BMSC) in a critical-size bone defect in rabbits. The critical-size defects of the radius were filled with: (1) a calcium-deficient hydroxyapatite (CDHA) scaffold + phVEGF(165)-transfected BMSC (VEGF group), (2) CDHA and PRP, or (3) CDHA, autogenous BMSC, and PRP. As controls served: (4) the CDHA scaffold alone and (5) the CDHA scaffold and autogenous BMSC. The volume of new bone was measured by means of micro-CT scans, and vascularization was assessed in histology after 16 weeks. Bone formation was higher in the PRP + CDHA, BMSC + CDHA, and PRP + BMSC + CDHA groups than in the VEGF group (p < 0.05). VEGF transfection significantly promoted vascularization of the scaffolds in contrast to BMSC and PRP (p < 0.05), but was similar to the result of the CDHA + PRP + BMSC group. The results show that VEGF-transfected BMSC as well as the combination of PRP and BMSC improve vascularization, but bone healing was better with the combination of BMSC and PRP than with VEGF-transfected BMSC. Expression of VEGF in BMSC as a single growth factor does not seem to be as effective for bone formation as expanded BMSC alone or PRP which contains a mixture of growth factors. Copyright (C) 2012 S. Karger AG, Base

UKIS-CSMASK: A Python package for multi-sensor cloud and cloud-shadow segmentation

Cloud and cloud shadow segmentation is a crucial pre-processing step for any application that uses multi-spectral satellite images. In particular, time-critical disaster applications, require accurate and immediate cloud and cloud shadow masks while being able to adapt to possibly large variations caused by different sensor characteristics, scene properties or atmospheric conditions. This study introduces the newly developed open-source Python package ukis-csmask for cloud and cloud shadow segmentation in multi-spectral satellite images. Segmentation with ukis-csmask is performed with a pre-trained Convolutional Neural Network based on a U-Net architecture. It works directly on Level-1C data, eliminating the need for prior atmospheric correction. Images need to be in top of atmosphere reflectance and include at least the Blue, Green, Red, NIR, SWIR1 and SWIR2 spectral bands. We provide a performance evaluation on a recent benchmark dataset for cloud and cloud shadow segmentation and proof the generalization ability of our method across multiple satellites (Landsat-5, Landsat-7, Landsat-8, Landsat-9 and Sentinel-2). We also show the influence of augmentation and image bands on the segmentation performance and compare it to the widely used Fmask algorithm and a Random Forest classifier. Compared to previous work in this direction, our study focuses on multi-sensor generalization ability, simplicity and efficiency and provides a ready-to-use software package that has been thoroughly tested

Acute stress alters probabilistic reversal learning in healthy male adults

Behavioural adaptation is a fundamental cognitive ability, ensuring survival by allowing for flexible adjustment to changing environments. In laboratory settings, behavioural adaptation can be measured with reversal learning paradigms requiring agents to adjust reward learning to stimulus–action–outcome contingency changes. Stress is found to alter flexibility of reward learning, but effect directionality is mixed across studies. Here, we used model-based functional MRI (fMRI) in a within-subjects design to investigate the effect of acute psychosocial stress on flexible behavioural adaptation. Healthy male volunteers (n = 28) did a reversal learning task during fMRI in two sessions, once after the Trier Social Stress Test (TSST), a validated psychosocial stress induction method, and once after a control condition. Stress effects on choice behaviour were investigated using multilevel generalized linear models and computational models describing different learning processes that potentially generated the data. Computational models were fitted using a hierarchical Bayesian approach, and model-derived reward prediction errors (RPE) were used as fMRI regressors. We found that acute psychosocial stress slightly increased correct response rates. Model comparison revealed that double-update learning with altered choice temperature under stress best explained the observed behaviour. In the brain, model-derived RPEs were correlated with BOLD signals in striatum and ventromedial prefrontal cortex (vmPFC). Striatal RPE signals for win trials were stronger during stress compared with the control condition. Our study suggests that acute psychosocial stress could enhance reversal learning and RPE brain responses in healthy male participants and provides a starting point to explore these effects further in a more diverse population

Computational mechanisms of belief updating in relation to psychotic-like experiences

Introduction Psychotic-like experiences (PLEs) may occur due to changes in weighting prior beliefs and new evidence in the belief updating process. It is still unclear whether the acquisition or integration of stable beliefs is altered, and whether such alteration depends on the level of environmental and belief precision, which reflects the associated uncertainty. This motivated us to investigate uncertainty-related dynamics of belief updating in relation to PLEs using an online study design. Methods We selected a sample (n = 300) of participants who performed a belief updating task with sudden change points and provided self-report questionnaires for PLEs. The task required participants to observe bags dropping from a hidden helicopter, infer its position, and dynamically update their belief about the helicopter's position. Participants could optimize performance by adjusting learning rates according to inferred belief uncertainty (inverse prior precision) and the probability of environmental change points. We used a normative learning model to examine the relationship between adherence to specific model parameters and PLEs. Results PLEs were linked to lower accuracy in tracking the outcome (helicopter location) (β = 0.26 ± 0.11, p = 0.018) and to a smaller increase of belief precision across observations after a change point (β = −0.003 ± 0.0007, p < 0.001). PLEs were related to slower belief updating when participants encountered large prediction errors (β = −0.03 ± 0.009, p = 0.001). Computational modeling suggested that PLEs were associated with reduced overall belief updating in response to prediction errors (βPE = −1.00 ± 0.45, p = 0.028) and reduced modulation of updating at inferred environmental change points (βCPP = −0.84 ± 0.38, p = 0.023). Discussion We conclude that PLEs are associated with altered dynamics of belief updating. These findings support the idea that the process of balancing prior belief and new evidence, as a function of environmental uncertainty, is altered in PLEs, which may contribute to the development of delusions. Specifically, slower learning after large prediction errors in people with high PLEs may result in rigid beliefs. Disregarding environmental change points may limit the flexibility to establish new beliefs in the face of contradictory evidence. The present study fosters a deeper understanding of inferential belief updating mechanisms underlying PLEs.Peer Reviewe

Computational mechanisms of belief updating in relation to psychotic-like experiences

Introduction: Psychotic-like experiences (PLEs) may occur due to changes in weighting prior beliefs and new evidence in the belief updating process. It is still unclear whether the acquisition or integration of stable beliefs is altered, and whether such alteration depends on the level of environmental and belief precision, which reflects the associated uncertainty. This motivated us to investigate uncertainty-related dynamics of belief updating in relation to PLEs using an online study design. Methods: We selected a sample (n = 300) of participants who performed a belief updating task with sudden change points and provided self-report questionnaires for PLEs. The task required participants to observe bags dropping from a hidden helicopter, infer its position, and dynamically update their belief about the helicopter's position. Participants could optimize performance by adjusting learning rates according to inferred belief uncertainty (inverse prior precision) and the probability of environmental change points. We used a normative learning model to examine the relationship between adherence to specific model parameters and PLEs. Results: PLEs were linked to lower accuracy in tracking the outcome (helicopter location) (beta = 0.26 +/- 0.11, p = 0.018) and to a smaller increase of belief precision across observations after a change point (beta = -0.003 +/- 0.0007, p < 0.001). PLEs were related to slower belief updating when participants encountered large prediction errors (beta = -0.03 +/- 0.009, p = 0.001). Computational modeling suggested that PLEs were associated with reduced overall belief updating in response to prediction errors (beta(PE) = -1.00 +/- 0.45, p = 0.028) and reduced modulation of updating at inferred environmental change points (beta(CPP) = -0.84 +/- 0.38, p = 0.023). Discussion: We conclude that PLEs are associated with altered dynamics of belief updating. These findings support the idea that the process of balancing prior belief and new evidence, as a function of environmental uncertainty, is altered in PLEs, which may contribute to the development of delusions. Specifically, slower learning after large prediction errors in people with high PLEs may result in rigid beliefs. Disregarding environmental change points may limit the flexibility to establish new beliefs in the face of contradictory evidence. The present study fosters a deeper understanding of inferential belief updating mechanisms underlying PLEs

Gas phase structures and charge localization in small aluminum oxide anions: Infrared photodissociation spectroscopy and electronic structure calculations

We use cryogenic ion trap vibrational spectroscopy in combination with quantum chemical calculations to study the structure of mono- and dialuminum oxide anions. The infrared photodissociation spectra of D2-tagged AlO1-4 − and Al2O3-6 − are measured in the region from 400 to 1200 cm−1. Structures are assigned based on a comparison to simulated harmonic and anharmonic IR spectra derived from electronic structure calculations. The monoaluminum anions contain an even number of electrons and exhibit an electronic closed-shell ground state. The Al2O3-6 − anions are oxygen-centered radicals. As a result of a delicate balance between localization and delocalization of the unpaired electron, only the BHLYP functional is able to qualitatively describe the observed IR spectra of all species with the exception of AlO3 −. Terminal Al–O stretching modes are found between 1140 and 960 cm−1. Superoxo and peroxo stretching modes are found at higher (1120-1010 cm−1) and lower energies (850-570 cm−1), respectively. Four modes in-between 910 and 530 cm−1 represent the IR fingerprint of the common structural motif of dialuminum oxide anions, an asymmetric four-member Al–(O)2–Al ring

MetaCook: FAIR Vocabularies Cookbook

One of the prerequisites for FAIR data publication is the use of FAIR vocabularies. Currently, tools for the collaborative composition of such vocabularies are missing. For this reason, a universal manual and software for user-friendly vocabulary assembly is being composed in the HMC-funded MetaCook project. The project includes 4 separate test cases from 4 labs across KIT and Hereon, which will help strengthen the software\u27s universality and applicability to various domains. The components described in MetaCook will be implemented in the form of multiple software tools. The first one, a Python-based web application called VocPopuli, is the entry point for domain experts. The software, whose first version is being developed at the time of writing, enables the collaborative definition, and editing of metadata terms. Additionally, it annotates each term, as well as the entire vocabulary, with the help of the PROV Data Model (PROV-DM) - a schema used to describe the provenance of a given object. Finally, it assigns a unique ID to each term in the vocabulary, as well as a hash-based ID the vocabulary itself. The second software tool will facilitate the transformation of the vocabularies developed with the help of VocPopuli into ontologies. It will handle two distinct use cases – the from-scratch conversion of vocabularies into ontologies, and the augmentation of existing ontologies with the terms from a given thesaurus. Both software tools will be used by two semi-overlapping user groups: domain experts will input, edit, and discuss vocabulary terms in their area of interest, while vocabulary and ontology administrators will oversee the vocabulary creation, and ontology transformation. Both the controlled vocabularies and the corresponding ontologies offer the possibility to enrich data documented in Electronic Laboratory Notebooks (ELNs). As the simplest solution, terms used within the ELN are linked to the IDs of the related vocabulary and ontology for an unambiguous definition. Additionally, an export of the defined schemes can be used to automatically create a structured form in the ELNs for documenting the described processes. The output from the developed tools will be exemplarily integrated into the ELNs Herbie and Kadi4Mat