ICGA Journal 24(2): special issue on Ken Thompson

This special issue of the ICGA_J focuses on Ken Thompson on the occasion of his retirement from Bell Labs in December 2000. The contents touch on Unix and cover ken's contribution to computer games, computer chess and 'ICCA', the International Computer Chess Association

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model

Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncating AMFR variants, resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families. Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity. Patient-derived fibroblasts, neural stem cells (NSCs), and in vivo zebrafish modeling were used to investigate pathomechanisms, including initial preclinical therapy assessment. The absence of AMFR disturbs lipid homeostasis, causing lipid droplet accumulation in NSCs and patient-derived fibroblasts which is rescued upon AMFR re-expression. Electron microscopy indicates ER morphology alterations in the absence of AMFR. Similar findings are seen in amfra-/- zebrafish larvae, in addition to altered touch-evoked escape response and defects in motor neuron branching, phenocopying the HSP observed in patients. Interestingly, administration of FDA-approved statins improves touch-evoked escape response and motor neuron branching defects in amfra-/- zebrafish larvae, suggesting potential therapeutic implications. Our genetic and functional studies identify bi-allelic truncating variants in AMFR as a cause of a novel autosomal recessive HSP by altering lipid metabolism, which may potentially be therapeutically modulated using precision medicine with statins

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Adaptive Gaze Control for Object Detection

We propose a novel gaze-control model for detecting objects in images. The model, named act-detect, uses the information from local image samples in order to shift its gaze towards object locations. The model constitutes two main contributions. The first contribution is that the model’s setup makes it computationally highly efficient in comparison with existing window-sliding methods for object detection, while retaining an acceptable detection performance. act-detect is evaluated on a face-detection task using a publicly available image set. In terms of detection performance, act-detect slightly outperforms the window-sliding methods that have been applied to the face-detection task. In terms of computational efficiency, act-detect clearly outperforms the window-sliding methods: it requires in the order of hundreds fewer samples for detection. The second contribution of the model lies in its more extensive use of local samples than previous models: instead of merely using them for verifying object presence at the gaze location, the model uses them to determine a direction and distance to the object of interest. The simultaneous adaptation of both the model’s visual features and its gaze-control strategy leads to the discovery of features and strategies for exploiting the local context of objects. For example, the model uses the spatial relations between the bodies of the persons in the images and their faces. The resulting gaze control is a temporal process, in which the object’s context is exploited at different scales and at different image locations relative to the object

A Situated Model for Sensory-motor

This paper shows that sensory-motor coordination contributes to the performance of situated models on the high-level task of artificial gaze control for gender recognition in static natural images. To investigate the advantage of sensory-motor coordination, we compare a non-situated model of gaze control with a situated model. The non-situated model is incapable of sensory-motor coordination. It shifts the gaze according to a fixed set of locations, optimised by an evolutionary algorithm. The situated model determines gaze shifts on the basis of local inputs in a visual scene. An evolutionary algorithm optimises the model&apos;s gaze control policy. In the experiments performed, the situated model outperforms the non-situated model. By adopting a Bayesian framework, we show that the mechanism of sensory-motor coordination is the cause of this performance di#erence. The essence is that the mechanism maximises task-specific information in the observations over time, by establishing dependencies between multiple actions and observations