Very small deletions within the NESP55 gene in pseudohypoparathyroidism type 1b

Pseudohypoparathyroidism (PHP) is caused by reduced expression of genes within the GNAS cluster, resulting in parathormone resistance. The cluster contains multiple imprinted transcripts, including the stimulatory G protein α subunit (Gs-α) and NESP55 transcript preferentially expressed from the maternal allele, and the paternally expressed XLas, A/B and antisense transcripts. PHP1b can be caused by loss of imprinting affecting GNAS A/B alone (associated with STX16 deletion), or the entire GNAS cluster (associated with deletions of NESP55 in a minority of cases). We performed targeted genomic next-generation sequencing (NGS) of the GNAS cluster to seek variants and indels underlying PHP1b. Seven patients were sequenced by hybridisation-based capture and fourteen more by long-range PCR and transposon-mediated insertion and sequencing. A bioinformatic pipeline was developed for variant and indel detection. In one family with two affected siblings, and in a second family with a single affected individual, we detected maternally inherited deletions of 40 and 33 bp, respectively, within the deletion previously reported in rare families with PHP1b. All three affected individuals presented with atypically severe PHP1b; interestingly, the unaffected mother in one family had the detected deletion on her maternally inherited allele. Targeted NGS can reveal sequence changes undetectable by current diagnostic methods. Identification of genetic mutations underlying epigenetic changes can facilitate accurate diagnosis and counselling, and potentially highlight genetic elements critical for normal imprint settin

Towards Comparing the Robustness of Synchronous and Asynchronous Circuits by Fault Injection

As transient error rates are growing due to smaller feature sizes, designing reliable synchronous circuits becomes increasingly challenging. Asynchronous logic design constitutes a promising alternative with respect to robustness and stability. In particular, delay-insensitive asynchronous circuits provide interesting properties, like an inherent resilience to delay-faults

Alcohol use disorder symptoms are associated with greater relative value ascribed to alcohol, but not greater discounting of costs imposed on alcohol

This is the final version of the article. Available from the publisher via the DOI in this record.Rationale: Alcohol dependence is characterised by persistent drinking despite health, social and economic costs. Behavioural economics has proposed two explanations for the persistence of alcohol use despite costs. Dependent individuals may (a) ascribe excessively high value to alcohol, such that costs associated with alcohol are exceeded, and/or (b) they may discount (neglect) the costs associated with alcohol. Methods: To test these predictions, the current study recruited 127 student drinkers who reported varied alcohol use disorder symptom severity in the Alcohol Use Disorders Inventory Test (AUDIT; mean=11.17, 69% above the hazardous cutoff). Participants made concurrent forced choices between alcohol and food points under conditions that manipulated the magnitude of points (1, 2 or 3) and the delay to receive points (0 or 3 seconds). Alcohol value was indexed by preferential choice of alcohol versus food points, whereas sensitivity to costs was indexed by the decrease in alcohol choice when food points were of greater magnitude (sensitivity to opportunity costs) and when alcohol points were delayed (sensitivity to delay costs). Results: Percent choice of alcohol over food varied consistently with the relative magnitude of points offered (p<.001) and with time delays imposed on these rewards (p<.001). AUDIT scores were associated with greater alcohol versus food choice across all conditions (p=.001). As alcohol use disorder symptom severity increased, the sensitivity of alcohol choice to the relative magnitude of points (p=.29) and time delays (p=.62) remained unchanged, suggesting no differential discounting of opportunity or delay costs imposed on alcohol. In contrasts of AUDIT categories, there was comparable sensitivity to costs across groups defined as low-risk (N=39), hazardous (n=57), harmful (n=20) and possible dependent drinkers (n=11). Conclusions: Alcohol use disorder symptom severity is associated with greater relative value ascribed to alcohol, but not with greater discounting of opportunity or delay costs imposed on alcohol. Despite limitations of the current study, it may be concluded that cost discounting plays a lesser role in dependence than previously thought.This research was supported by an Alcohol Research UK grant (RS17/03) to Lee Hogarth and an ESRC PhD scholarship to Lorna Hard

Amodal processing in human prefrontal cortex

Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e. g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex

A brief review of neural networks based learning and control and their applications for robots

As an imitation of the biological nervous systems, neural networks (NN), which are characterized with powerful learning ability, have been employed in a wide range of applications, such as control of complex nonlinear systems, optimization, system identification and patterns recognition etc. This article aims to bring a brief review of the state-of-art NN for the complex nonlinear systems. Recent progresses of NNs in both theoretical developments and practical applications are investigated and surveyed. Specifically, NN based robot learning and control applications were further reviewed, including NN based robot manipulator control, NN based human robot interaction and NN based behavior recognition and generation