Non-Euclidean principal component analysis by Hebbian learning

Principal component analysis based on Hebbian learning is originally designed for data processing inEuclidean spaces. We present in this contribution an extension of Oja's Hebbian learning approach fornon-Euclidean spaces. We show that for Banach spaces the Hebbian learning can be carried out using theunderlying semi-inner product. Prominent examples for such Banach spaces are the lp-spaces for p≠2.For kernels spaces, as applied in support vector machines or kernelized vector quantization, thisapproach can be formulated as an online learning scheme based on the differentiable kernel. Hence,principal component analysis can be explicitly carried out in the respective data spaces but nowequipped with a non-Euclidean metric. In the article we provide the theoretical framework and giveillustrative examples

Hebbian learning approaches based on general inner products and distance measures in non-Euclidean spaces

The topic of this thesis is to define a unified and generalized scheme for Hebbian approaches in non-Euclidean spaces for unsupervised and supervised learning. This can be realized in different ways. One possibility is the replacement of the inner product by a semi-inner product (SIP). A SIP relaxes the strict properties of an inner product but preserves the linear aspect in the first argument. Thus, these SIPs are natural equivalents of inner products generating Banach spaces instead of Hilbert spaces for inner products. In this work SIPs for Banach spaces are considered for unsupervised Hebbian like learning approaches. Further, the learning scheme of the supervised Learning Vector Quantization (LVQ) network, which is originally designed for applications in Euclidean data space, can be interpreted under specific circumstances as a Hebbian like learning, too. It is shown that, non-Euclidean metrics applied in LVQ can improve the performance of classification learning compared to Euclidean variants. The previously addressed Hebbian learning methods are vectorial approaches. However, if the data space is a vector space of matrices equipped with a respective matrix norm, then matrix approaches for Hebbian like learning methods become of interest. The extension of these methods in non-Euclidean spaces of matrices to process matrix data is the last main point of this thesis

A state-of-the-art review on studies examining the psychological contract

The psychological contract describes the perceived mutual obligations between an employee and the organization (Rousseau, 1989, 2001). Since 1990 numerous studies have been published examining the effects of psychological contracts. Previous reviews on these studies have focused on the history of the term ‘psychological contract’(Roehling, 1997), and on explaining the description, meaning, and usefulness of the psychological contract (Anderson & Schalk, 1998; Taylor & Tekleab, 2004; Van den Brande, 1999). Guest and Conway (2003) published the first review in which an actual overview of studies on psychological contracts was presented. However, the sample of reviewed studies was rather small (k=9) and only operationalizations of the psychological contract and correlations with dependent variables were reported. A review on more specific information, like survey design, sample, and measurement of the psychological contract is still lacking. As a consequence, the aim of this review was to examine the conceptualization and measurement of the psychological contract

Leeftijd, het psychologisch contract, en werkattitudes: een meta-analyse.

The meta-analysis investigated the relations between age and psychological contracts. It was expected that age would be positively related to the employer obligations, and that age would moderate the relations between contract breach and job attitudes. The hypotheses were tested by means of a meta-analysis of 76 studies with in total 28,773 respondents. It was found that age is related negatively but marginally to the psychological contract, and that age moderated the relations between psychological contract breach and job attitudes. The relations between contract breach on the one hand and trust and affective commitment on the other hand were stronger for older workers, whereas the relation between contract breach and job satisfaction was stronger among younger workers. The theoretical and practical implications are discussed

Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation