Introduction

This introduction presents an overview of the key concepts discussed in the subsequent chapters of this book. The book explores, inter alia, the strategy employed by Augustine in using Plato as a pseudo-prophet against later Platonists and explores Eusebius’ reception of Porphyry’s daemonology. It examines Plotinus’ claim that matter is absolute badness and focuses on Maximus the Confessor’s doctrine of creation and asks whether one may detect any influence on Maximus from Philoponus. The book addresses Christian receptions of Platonic metaphysics and also examines the philosophy of number in Augustine’s early works. It argues that the aspect of Augustine’s philosophy must be read in context with the intellectual problems that occupied him at the beginning of his career as a writer. It draws on a number of sources to investigate the development of the doctrine and the various intellectual issues it confronted, including Plato’s Timaeus, Philo of Alexandria, Clement of Alexandria, Origen, Plotinus and, finally, Athanasius

Platonism and Christian Thought in Late Antiquity

Platonism and Christian Thought in Late Antiquity examines the various ways in which Christian intellectuals engaged with Platonism both as a pagan competitor and as a source of philosophical material useful to the Christian faith. The chapters are united in their goal to explore transformations that took place in the reception and interaction process between Platonism and Christianity in this period. The contributions in this volume explore the reception of Platonic material in Christian thought, showing that the transmission of cultural content is always mediated, and ought to be studied as a transformative process by way of selection and interpretation. Some chapters also deal with various aspects of the wider discussion on how Platonic, and Hellenic, philosophy and early Christian thought related to each other, examining the differences and common ground between these traditions. Platonism and Christian Thought in Late Antiquity offers an insightful and broad ranging study on the subject, which will be of interest to students of both philosophy and theology in the Late Antique period, as well as anyone working on the reception and history of Platonic thought, and the development of Christian thought

Cognitive-behavioural therapy in medication-treated adults with attention-deficit/hyperactivity disorder and co-morbid psychopathology:a randomized controlled trial using multi-level analysis

Background. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by high rates of co-morbid psychopathology. Randomized controlled trials of multimodal interventions, combining pharmacological and psychological treatments, have shown a robust treatment effect for ADHD symptoms but outcomes for co-morbid symptoms have been mixed. This may be accounted for by the type of intervention selected and/or by methodological problems including lack of follow-up and low power. The current study addressed these limitations in a parallel-group randomized controlled trial conducted in Iceland.  Method. A total of 95 adult ADHD patients who were already being treated with medication (MED) were randomly assigned to receive treatment as usual (TAU/MED) or 15 sessions of cognitive-behavioural therapy (CBT/MED) using the R&R2ADHD intervention which employs both group and individual modalities. Primary measures of ADHD symptoms and severity of illness, and secondary measures of anxiety, depression and quality of life were given at baseline, end of treatment and 3-month follow-up. Primary outcomes were rated by clinicians blind to treatment condition assignment.  Results. CBT/MED showed overall (combined outcome at end of treatment and 3-month follow-up) significantly greater reduction in primary outcomes for clinician-rated and self-rated ADHD symptoms. Treatment effect of primary outcomes was maintained at follow-up, which suggests robust and lasting findings. In contrast to the primary outcomes, the secondary outcomes showed significant improvement over time.  Conclusions. The study provides evidence for the effectiveness of R&R2ADHD and demonstrates that there are differential effects over time for ADHD symptoms versus co-morbid problems, the latter taking longer to show positive effects

Statistical independence of the colocalized association signals for type 1 diabetes and RPS26 gene expression on chromosome 12q13

Following the recent success of genome-wide association studies in uncovering disease-associated genetic variants, the next challenge is to understand how these variants affect downstream pathways. The most proximal trait to a disease-associated variant, most commonly a single nucleotide polymorphism (SNP), is differential gene expression due to the cis effect of SNP alleles on transcription, translation, and/or splicing gene expression quantitative trait loci (eQTL). Several genome-wide SNP–gene expression association studies have already provided convincing evidence of widespread association of eQTLs. As a consequence, some eQTL associations are found in the same genomic region as a disease variant, either as a coincidence or a causal relationship. Cis-regulation of RPS26 gene expression and a type 1 diabetes (T1D) susceptibility locus have been colocalized to the 12q13 genomic region. A recent study has also suggested RPS26 as the most likely susceptibility gene for T1D in this genomic region. However, it is still not clear whether this colocalization is the result of chance alone or if RPS26 expression is directly correlated with T1D susceptibility, and therefore, potentially causal. Here, we derive and apply a statistical test of this hypothesis. We conclude that RPS26 expression is unlikely to be the molecular trait responsible for T1D susceptibility at this locus, at least not in a direct, linear connection

Genetical genomics: spotlight on QTL hotspots

No abstract available

Expression quantitative trait loci are highly sensitive to cellular differentiation state

Blood cell development from multipotent hematopoietic stem cells to specialized blood cells is accompanied by drastic changes in gene expression for which the triggers remain mostly unknown. Genetical genomics is an approach linking natural genetic variation to gene expression variation, thereby allowing the identification of genomic loci containing gene expression modulators (eQTLs). In this paper, we used a genetical genomics approach to analyze gene expression across four developmentally close blood cell types collected from a large number of genetically different but related mouse strains. We found that, while a significant number of eQTLs (365) had a consistent “static” regulatory effect on gene expression, an even larger number were found to be very sensitive to cell stage. As many as 1,283 eQTLs exhibited a “dynamic” behavior across cell types. By looking more closely at these dynamic eQTLs, we show that the sensitivity of eQTLs to cell stage is largely associated with gene expression changes in target genes. These results stress the importance of studying gene expression variation in well-defined cell populations. Only such studies will be able to reveal the important differences in gene regulation between different ce

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

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Coding and regulatory variants are associated with serum protein levels and disease.

Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins' emerging role as biomarkers and potential causative agents of a wide range of diseases

Fingerprint-based Wi-Fi indoor localization using map and inertial sensors

It is a common understanding that the localization accuracy can be improved by indoor maps and inertial sensors. However, there is a lack of concrete and generic solutions that combine these two features together and practically demonstrate its validity. This article aims to provide such a solution based on the mainstream fingerprint-based indoor localization approach. First, we introduce the theorem called reference points placement, which gives a theoretical guide to place reference points. Second, we design a Wi-Fi signal propagation-based cluster algorithm to reduce the amount of computation. The paper gives a parameter called reliability to overcome the skewing of inertial sensors. Then we also present Kalman filter and Markov chain to predict the system status. The system is able to provide high-accuracy real-time tracking by integrating indoor map and inertial sensors with Wi-Fi signal strength. Finally, the proposed work is evaluated and compared with the previous Wi-Fi indoor localization systems. In addition, the effect of inertial sensors’ reliability is also discussed. Results are drawn from a campus office building which is about 80 m×140 m with 57 access points

Characterizing Dynamic Changes in the Human Blood Transcriptional Network

Gene expression data generated systematically in a given system over multiple time points provides a source of perturbation that can be leveraged to infer causal relationships among genes explaining network changes. Previously, we showed that food intake has a large impact on blood gene expression patterns and that these responses, either in terms of gene expression level or gene-gene connectivity, are strongly associated with metabolic diseases. In this study, we explored which genes drive the changes of gene expression patterns in response to time and food intake. We applied the Granger causality test and the dynamic Bayesian network to gene expression data generated from blood samples collected at multiple time points during the course of a day. The simulation result shows that combining many short time series together is as powerful to infer Granger causality as using a single long time series. Using the Granger causality test, we identified genes that were supported as the most likely causal candidates for the coordinated temporal changes in the network. These results show that PER1 is a key regulator of the blood transcriptional network, in which multiple biological processes are under circadian rhythm regulation. The fasted and fed dynamic Bayesian networks showed that over 72% of dynamic connections are self links. Finally, we show that different processes such as inflammation and lipid metabolism, which are disconnected in the static network, become dynamically linked in response to food intake, which would suggest that increasing nutritional load leads to coordinate regulation of these biological processes. In conclusion, our results suggest that food intake has a profound impact on the dynamic co-regulation of multiple biological processes, such as metabolism, immune response, apoptosis and circadian rhythm. The results could have broader implications for the design of studies of disease association and drug response in clinical trials