Homing of placenta-derived mesenchymal stem cells after perinatal intracerebral transplantation in a rat model

The aim of this study is to assess early homing of placenta-derived stem cells after perinatal intracerebral transplantation in rats.

Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model

The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.

FUNCTIONAL PRINCIPAL COMPONENTS MODEL FOR HIGH-DIMENSIONAL BRAIN IMAGING

We establish a fundamental equivalence between singular value decomposition (SVD) and functional principal components analysis (FPCA) models. The constructive relationship allows to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a functional mixed effect model is fitted to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed.

How Minds Work: A Cognitive Theory of Everything - a Tutorial on the IDA Model of Cognition

The IDA model of cognition is a fully integrated artificial cognitive system reaching across the full spectrum of cognition, from low-level perception/action to high-level reasoning. Extensively based on empirical data, it accurately reflects the full range of cognitive processes found in natural cognitive systems. As a source of plausible explanations for very many cognitive processes, the IDA model provides an ideal tool to think with about how minds work. This online tutorial offers a reasonably full account of the IDA conceptual model, including background material. It also provides a high-level account of the underlying computational “mechanisms of mind” that constitute the IDA computational model.

Voter Participation in the 1998 Bundestag Elections: A Theoretical Modification and Empirical Application of Downs’ Theory of Voter Participation

This article seeks to contribute to the illumination of the so-called 'paradox of voting' using the German Bundestag elections of 1998 as an empirical case. Downs' model of voter participation will be extended to include elements of the theory of subjective expected utility (SEU). This will allow a theoretical and empirical exploration of the crucial mechanisms of individual voters' decisions to participate, or abstain from voting, in the German general election of 1998. It will be argued that the infinitely low probability of an individual citizen's vote to decide the election outcome will not necessarily reduce the probability of electoral participation. The empirical analysis is largely based on data from the ALLBUS 1998. It confirms the predictions derived from SEU theory. The voters' expected benefits and their subjective expectation to be able to influence government policy by voting are the crucial mechanisms to explain participation. By contrast, the explanatory contribution of perceived information and opportunity costs is low.

A new model construction by making a detour via intuitionistic theories I: Operational set theory without choice is Π1-equivalent to KP

We introduce a version of operational set theory, OST−, without a choice operation, which has a machinery for Δ0Δ0 separation based on truth functions and the separation operator, and a new kind of applicative set theory, so-called weak explicit set theory WEST, based on Gödel operations. We show that both the theories and Kripke–Platek set theory KPKP with infinity are pairwise Π1Π1 equivalent. We also show analogous assertions for subtheories with ∈-induction restricted in various ways and for supertheories extended by powerset, beta, limit and Mahlo operations. Whereas the upper bound is given by a refinement of inductive definition in KPKP, the lower bound is by a combination, in a specific way, of realisability, (intuitionistic) forcing and negative interpretations. Thus, despite interpretability between classical theories, we make “a detour via intuitionistic theories”. The combined interpretation, seen as a model construction in the sense of Visser's miniature model theory, is a new way of construction for classical theories and could be said the third kind of model construction ever used which is non-trivial on the logical connective level, after generic extension à la Cohen and Krivine's classical realisability model.

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

Integrating attentional control theory and the strength model of self-control

In the present article, we argue that it may be fruitful to incorporate the ideas of the strength model of self-control into the core assumptions of the well-established attentional control theory (ACT). In ACT, it is assumed that anxiety automatically leads to attention disruption and increased distractibility, which may impair subsequent cognitive or perceptual-motor performance, but only if individuals do not have the ability to counteract this attention disruption. However, ACT does not clarify which process determines whether one can volitionally regulate attention despite experiencing high levels of anxiety. In terms of the strength model of self-control, attention regulation can be viewed as a self-control act depending on the momentary availability of self-control strength. We review literature that has revealed that self-control strength moderates the anxiety-performance relationship, discuss how to integrate these two theoretical models, and offer practical recommendations of how to counteract negative anxiety effects.

Development and characterization of a scaffold-free 3D spheroid model of iPSC-derived human cardiomyocytes

Purpose: Cardiomyocytes are terminally differentiated cells in the adult heart and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSC) from human origin was developed and characterized. Methods: Human cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. 2D cultures were examined using immunofluorescence microscopy and Western blotting while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. Results: iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell-cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to pro-hypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived cardiomyocytes formed spheroidal MTs within 4 days showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature, and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium-transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca2+-release, extracellular calcium levels. Conclusions: 3D culture using iPSC-derived human cardiomyocytes provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.

MEMLS3&a: Microwave Emission Model of Layered Snowpacks adapted to include backscattering

The Microwave Emission Model of Layered Snowpacks (MEMLS) was originally developed for microwave emissions of snowpacks in the frequency range 5–100 GHz. It is based on six-flux theory to describe radiative transfer in snow including absorption, multiple volume scattering, radiation trapping due to internal reflection and a combination of coherent and incoherent superposition of reflections between horizontal layer interfaces. Here we introduce MEMLS3&a, an extension of MEMLS, which includes a backscatter model for active microwave remote sensing of snow. The reflectivity is decomposed into diffuse and specular components. Slight undulations of the snow surface are taken into account. The treatment of like- and cross-polarization is accomplished by an empirical splitting parameter q. MEMLS3&a (as well as MEMLS) is set up in a way that snow input parameters can be derived by objective measurement methods which avoid fitting procedures of the scattering efficiency of snow, required by several other models. For the validation of the model we have used a combination of active and passive measurements from the NoSREx (Nordic Snow Radar Experiment) campaign in Sodankylä, Finland. We find a reasonable agreement between the measurements and simulations, subject to uncertainties in hitherto unmeasured input parameters of the backscatter model. The model is written in Matlab and the code is publicly available for download through the following website: http://www.iapmw.unibe.ch/research/projects/snowtools/memls.html.

Calibrating a CGE model with NTBs that Incorporates Standard Models of Modern Trade Theory

We propose a way to incorporate NTBs for the four workhorse models of the modern trade literature in computable general equilibrium models (CGEs). CGE models feature intermediate linkages and thus allow us to study global value chains (GVCs). We show that the Ethier-Krugman monopolistic competition model, the Melitz firm heterogeneity model and the Eaton and Kortum model can be defined as an Armington model with generalized marginal costs, generalized trade costs and a demand externality. As already known in the literature in both the Ethier-Krugman model and the Melitz model generalized marginal costs are a function of the amount of factor input bundles. In the Melitz model generalized marginal costs are also a function of the price of the factor input bundles. Lower factor prices raise the number of firms that can enter the market profitably (extensive margin), reducing generalized marginal costs of a representative firm. For the same reason the Melitz model features a demand externality: in a larger market more firms can enter. We implement the different models in a CGE setting with multiple sectors, intermediate linkages, non-homothetic preferences and detailed data on trade costs. We find the largest welfare effects from trade cost reductions in the Melitz model. We also employ the Melitz model to mimic changes in Non tariff Barriers (NTBs) with a fixed cost-character by analysing the effect of changes in fixed trade costs. While we work here with a model calibrated to the GTAP database, the methods developed can also be applied to CGE models based on the WIOD database.