Robust postmortem survival of murine vestibular and cochlear stem cells

Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

Dynamic modeling of active regeneration in catalyzed and non-catalyzed diesel particulate filters

Particulate matter (PM) emissions standards set by the US Environmental Protection Agency (EPA) have become increasingly stringent over the years. The EPA regulation for PM in heavy duty diesel engines has been reduced to 0.01 g/bhp-hr for the year 2010. Heavy duty diesel engines make use of an aftertreatment filtration device, the Diesel Particulate Filter (DPF). DPFs are highly efficient in filtering PM (known as soot) and are an integral part of 2010 heavy duty diesel aftertreatment system. PM is accumulated in the DPF as the exhaust gas flows through it. This PM needs to be removed by oxidation periodically for the efficient functioning of the filter. This oxidation process is also known as regeneration. There are 2 types of regeneration processes, namely active regeneration (oxidation of PM by external means) and passive oxidation (oxidation of PM by internal means). Active regeneration occurs typically in high temperature regions, about 500 - 600 °C, which is much higher than normal diesel exhaust temperatures. Thus, the exhaust temperature has to be raised with the help of external devices like a Diesel Oxidation Catalyst (DOC) or a fuel burner. The O2 oxidizes PM producing CO2 as oxidation product. In passive oxidation, one way of regeneration is by the use of NO2. NO2 oxidizes the PM producing NO and CO2 as oxidation products. The passive oxidation process occurs at lower temperatures (200 - 400 °C) in comparison to the active regeneration temperatures. Generally, DPF substrate walls are washcoated with catalyst material to speed up the rate of PM oxidation. The catalyst washcoat is observed to increase the rate of PM oxidation. The goal of this research is to develop a simple mathematical model to simulate the PM depletion during the active regeneration process in a DPF (catalyzed and non-catalyzed). A simple, zero-dimensional kinetic model was developed in MATLAB. Experimental data required for calibration was obtained by active regeneration experiments performed on PM loaded mini DPFs in an automated flow reactor. The DPFs were loaded with PM from the exhaust of a commercial heavy duty diesel engine. The model was calibrated to the data obtained from active regeneration experiments. Numerical gradient based optimization techniques were used to estimate the kinetic parameters of the model.

Surgical suturing of articular cartilage induces osteoarthritis-like changes

INTRODUCTION: In clinical tissue-engineering-based approaches to articular cartilage repair, various types of flap are frequently used to retain an implanted construct within the defect, and they are usually affixed by suturing. We hypothesize that the suturing of articular cartilage is associated with a loss of chondrocytes from, and osteoarthritis-like changes within, the perisutural area. MATERIALS AND METHODS: We established a large, partial-thickness defect model in the femoral groove of adult goats. The defects were filled with bovine fibrinogen to support a devitalized flap of autologous synovial tissue, which was sutured to the surrounding articular cartilage with single, interrupted stitches. The perisutural and control regions were analyzed histologically, histochemically and histomorphometrically shortly after surgery and 3 weeks later. RESULTS: Compared to control regions, chondrocytes were lost from the perisutural area even during the first few hours of surgery. During the ensuing 3 weeks, the numerical density of cells in the perisutural area decreased significantly. The cell losses were associated with a loss of proteoglycans from the extracellular matrix. Shortly after surgery, fissures were observed within the walls of the suture channels. By the third week, their surface density had increased significantly and they were filled with avascular mesenchymal tissue. CONCLUSIONS: The suturing of articular cartilage induces severe local damage, which is progressive and reminiscent of that associated with the early stages of osteoarthritis. This damage could be most readily circumvented by adopting an alternative mode of flap affixation, such as gluing with a biological adhesive.

Modeling of human P450 oxidoreductase structure by in silico mutagenesis and MD simulation

P450 oxidoreductase (POR) is the obligate electron donor for microsomal cytochrome P450s and mutations in POR cause several metabolic disorders. We have modeled the structure of human P450 oxidoreductase by in silico amino acid replacements in the rat POR crystal structure. The rat POR has 94% homology with human POR and 38 amino acids were replaced to make its sequence identical to human POR. Several rounds of molecular dynamic simulations refined the model and removed structural clashes from side chain alterations of replaced amino acids. This approach has the advantage of keeping the cofactor contacts and structural features of the core enzyme intact which could not be achieved by homology based approaches. The final model from our approach was of high quality and compared well with experimentally determined structures of other PORs. This model will be used for analyzing the structural implications of mutations and polymorphisms in human POR.

Multi-Mode Tensor Representation of Motion Data

In this paper, we investigate how a multilinear model can be used to represent human motion data. Based on technical modes (referring to degrees of freedom and number of frames) and natural modes that typically appear in the context of a motion capture session (referring to actor, style, and repetition), the motion data is encoded in form of a high-order tensor. This tensor is then reduced by using N-mode singular value decomposition. Our experiments show that the reduced model approximates the original motion better then previously introduced PCA-based approaches. Furthermore, we discuss how the tensor representation may be used as a valuable tool for the synthesis of new motions.

Transient state estimation in paleoclimatology using data assimilation

Data assimilation methods used for transient atmospheric state estimations in paleoclimatology such as covariance-based approaches, analogue techniques and nudging are briefly introduced. With applications differing widely, a plurality of approaches appears to be the logical way forward.

The assessment of mindfulness with self-report measures: existing scales and open issues

During recent years, mindfulness-based approaches have been gaining relevance for treatment in clinical populations. Correspondingly, the empirical study of mindfulness has steadily grown; thus, the availability of valid measures of the construct is critically important. This paper gives an overview of the current status in the field of self-report assessment of mindfulness. All eight currently available and validated mindfulness scales (for adults) are evaluated, with a particular focus on their virtues and limitations and on differences among them. It will be argued that none of these scales may be a fully adequate measure of mindfulness, as each of them offers unique advantages but also disadvantages. In particular, none of them seems to provide a comprehensive assessment of all aspects of mindfulness in samples from the general population. Moreover, some scales may be particularly indicated in investigations focusing on specific populations such as clinical samples (Cognitive and Affective Mindfulness Scale, Southampton Mindfulness Questionnaire) or meditators (Freiburg Mindfulness Inventory). Three main open issues are discussed: (1) the coverage of aspects of mindfulness in questionnaires; (2) the nature of the relationships between these aspects; and (3) the validity of self-report measures of mindfulness. These issues should be considered in future developments in the self-report assessment of mindfulness.

Food-safety hazards in the pork chain in Nagaland, North East India: implications for human health.

Pork occupies an important place in the diet of the population of Nagaland, one of the North East Indian states. We carried out a pilot study along the pork meat production chain, from live animal to end consumer. The goal was to obtain information about the presence of selected food borne hazards in pork in order to assess the risk deriving from these hazards to the health of the local consumers and make recommendations for improving food safety. A secondary objective was to evaluate the utility of risk-based approaches to food safety in an informal food system. We investigated samples from pigs and pork sourced at slaughter in urban and rural environments, and at retail, to assess a selection of food-borne hazards. In addition, consumer exposure was characterized using information about hygiene and practices related to handling and preparing pork. A qualitative hazard characterization, exposure assessment and hazard characterization for three representative hazards or hazard proxies, namely Enterobacteriaceae, T. solium cysticercosis and antibiotic residues, is presented. Several important potential food-borne pathogens are reported for the first time including Listeria spp. and Brucella suis. This descriptive pilot study is the first risk-based assessment of food safety in Nagaland. We also characterise possible interventions to be addressed by policy makers, and supply data to inform future risk assessments.

Hierarchical segmentation-assisted multimodal registration for MR brain images

Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assisted similarity metric based on point-wise mutual information (PMI). This similarity metric, termed SPMI, enhances the registration accuracy by considering tissue classification probabilities as prior information, which is generated from an expectation maximization (EM) algorithm. Diffeomorphic demons is then adopted as the registration model and is optimized in a hierarchical framework (H-SPMI) based on different levels of anatomical structure as prior knowledge. The proposed method is evaluated using Brainweb synthetic data and clinical fMRI images. Both qualitative and quantitative assessment were performed as well as a sensitivity analysis to the segmentation error. Compared to the pure intensity-based approaches which only maximize mutual information, we show that the proposed algorithm provides significantly better accuracy on both synthetic and clinical data.

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

Protecting Tropical Forests through Public Procurement of Emission Reductions

The rate of destruction of tropical forests continues to accelerate at an alarming rate contributing to an important fraction of overall greenhouse gas emissions. In recent years, much hope has been vested in the emerging REDD+ framework under the UN Framework Convention on Climate Change (UNFCCC), which aims at creating an international incentive system to reduce emissions from deforestation and forest degradation. This paper argues that in the absence of an international consensus on the design of results-based payments, “bottom-up” initiatives should take the lead and explore new avenues. It suggests that a call for tender for REDD+ credits might both assist in leveraging private investments and spending scarce public funds in a cost-efficient manner. The paper discusses the pros and cons of results-based approaches, provides an overview of the goals and principles that govern public procurement and discusses their relevance for the purchase of REDD+ credits, in particular within the ambit of the European Union.

Individual and spousal education, mortality and life expectancy in Switzerland: a national cohort study.

BACKGROUND Household measures of socioeconomic position may better account for the shared nature of material resources, lifestyle, and social position of cohabiting persons, but household measures of education are rarely used. We aimed to evaluate the association of combined educational attainment of married couples on mortality and life expectancy in Switzerland. METHODS The study included 3 496 163 ever-married persons aged ≥30 years. The 2000 census was linked to mortality records through 2008. Mortality by combined educational attainment was assessed by gender-age-specific HRs, with 95% CIs from adjusted models, life expectancy was derived using abridged life tables. RESULTS Having a less educated partner was associated with increased mortality. For example, the HR comparing men aged 50-64 years with tertiary education married to women with tertiary education to men with compulsory education married to women with compulsory education was 2.05 (1.92-2.18). The estimated remaining life expectancy in tertiary educated men aged 30 years married to women with tertiary education was 4.6 years longer than in men with compulsory education married to women with compulsory education. The gradient based on individual education was less steep: the HR comparing men aged 50-64 years with tertiary education with men with compulsory education was 1.74 (1.67-1.81). CONCLUSIONS Using individual educational attainment of married persons is common in epidemiological research, but may underestimate the combined effect of education on mortality and life expectancy. These findings are relevant to epidemiologic studies examining socio-demographic characteristics or aiming to adjust results for these characteristics.

Decoding Delay Minimization in Inter-Session Network Coding

Intra-session network coding has been shown to offer significant gains in terms of achievable throughput and delay in settings where one source multicasts data to several clients. In this paper, we consider a more general scenario where multiple sources transmit data to sets of clients over a wireline overlay network. We propose a novel framework for efficient rate allocation in networks where intermediate network nodes have the opportunity to combine packets from different sources using randomized network coding. We formulate the problem as the minimization of the average decoding delay in the client population and solve it with a gradient-based stochastic algorithm. Our optimized inter-session network coding solution is evaluated in different network topologies and is compared with basic intra-session network coding solutions. Our results show the benefits of proper coding decisions and effective rate allocation for lowering the decoding delay when the network is used by concurrent multicast sessions.

Diminishing risk-taking behavior by modulating activity in the prefrontal cortex: a direct current stimulation study.

Studies have shown increased risk taking in healthy individuals after low-frequency repetitive transcranial magnetic stimulation, known to transiently suppress cortical excitability, over the right dorsolateral prefrontal cortex (DLPFC). It appears, therefore, plausible that differential modulation of DLPFC activity, increasing the right while decreasing the left, might lead to decreased risk taking, which could hold clinical relevance as excessively risky decision making is observed in clinical populations leading to deleterious consequences. The goal of the present study was to investigate whether risk-taking behaviors could be decreased using concurrent anodal transcranial direct current stimulation (tDCS) of the right DLPFC, which allows upregulation of brain activity, with cathodal tDCS of the left DLPCF, which downregulates activity. Thirty-six healthy volunteers performed the risk task while they received either anodal over the right with cathodal over the left DLPFC, anodal over the left with cathodal over the right DLPFC, or sham stimulation. We hypothesized that right anodal/left cathodal would decrease risk-taking behavior compared with left anodal/right cathodal or sham stimulation. As predicted, during right anodal/left cathodal stimulation over the DLPFC, participants chose more often the safe prospect compared with the other groups. Moreover, these participants appeared to be insensitive to the reward associated with the prospects. These findings support the notion that the interhemispheric balance of activity across the DLPFCs is critical in decision-making behaviors. Most importantly, the observed suppression of risky behaviors suggests that populations with boundless risk-taking behaviors leading to negative real-life consequences, such as individuals with addiction, might benefit from such neuromodulation-based approaches.