TiMEG: an integrative statistical method for partially missing multi-omics data

Multi-omics data integration is widely used to understand the genetic architecture of disease. In multi-omics association analysis, data collected on multiple omics for the same set of individuals are immensely important for biomarker identification. But when the sample size of such data is limited, the presence of partially missing individual-level observations poses a major challenge in data integration. More often, genotype data are available for all individuals under study but gene expression and/or methylation information are missing for different subsets of those individuals. Here, we develop a statistical model TiMEG, for the identification of disease-associated biomarkers in a case–control paradigm by integrating the above-mentioned data types, especially, in presence of missing omics data. Based on a likelihood approach, TiMEG exploits the inter-relationship among multiple omics data to capture weaker signals, that remain unidentified in single-omic analysis or common imputation-based methods. Its application on a real tuberous sclerosis dataset identified functionally relevant genes in the disease pathway.

The Adaptation Model Offers a Challenge for the Predictive Coding Account of Mismatch Negativity

An unpredictable stimulus elicits a stronger event-related response than a high-probability stimulus. This differential in response magnitude is termed the mismatch negativity (MMN). Over the past decade, it has become increasingly popular to explain the MMN terms of predictive coding, a proposed general principle for the way the brain realizes Bayesian inference when it interprets sensory information. This perspective article is a reminder that the issue of MMN generation is far from settled, and that an alternative model in terms of adaptation continues to lurk in the wings. The adaptation model has been discounted because of the unrealistic and simplistic fashion in which it tends to be set up. Here, simulations of auditory cortex incorporating a modern version of the adaptation model are presented. These show that locally operating short-term synaptic depression accounts both for adaptation due to stimulus repetition and for MMN responses. This happens even in cases where adaptation has been ruled out as an explanation of the MMN (e.g., in the stimulus omission paradigm and the multi-standard control paradigm). Simulation models that would demonstrate the viability of predictive coding in a similarly multifaceted way are currently missing from the literature, and the reason for this is discussed in light of the current results.

A literature review of personalization transparency and control: Introducing the Transparency-Awareness-Control Framework

<p>Through various online activities, individuals produce large amounts of data that are collected by companies for the purpose of providing users with personalized communication. In the light of this mass collection of personal data, the transparency and control paradigm for personalized communication has led to increased attention of legislators and academics. However, in the scientific literature no clear definition of personalization transparency and control exists, which could lead to reliability and validity issues, impeding knowledge accumulation in academic research. In a literature review, we analyzed 31 articles and we observed that 1) no clear definitions of personalization transparency or control exist, 2) they are used interchangeably in the literature, 3) collection, processing, and sharing of data are the three objects of transparency and control, and 4) increased transparency does not automatically increase control because first awareness needs to be raised in the individual. Also, the relationship between awareness and control depends on the ability and the desire to control. This study contributes to the field of algorithmic communication by creating a common understanding of the transparency and control paradigm and thus improves validity of the results. Further, it progresses research on the issue by synthesizing existing studies on the topic, presenting the Transparency-Awareness-Control framework, and formulating propositions to guide future research.</p>

Robust Model Predictive Control Paradigm for Automatic Voltage Regulators against Uncertainty Based on Optimization Algorithms

This paper introduces a robust model predictive controller (MPC) to operate an automatic voltage regulator (AVR). The design strategy tends to handle the uncertainty issue of the AVR parameters. Frequency domain conditions are derived from the Hermite–Biehler theorem to maintain the stability of the perturbed system. The tuning of the MPC parameters is performed based on a new evolutionary algorithm named arithmetic optimization algorithm (AOA), while the expert designers use trial and error methods to achieve this target. The stability constraints are handled during the tuning process. An effective time-domain objective is formulated to guarantee good performance for the AVR by minimizing the voltage maximum overshoot and the response settling time simultaneously. The results of the suggested AOA-based robust MPC are compared with various techniques in the literature. The system response demonstrates the effectiveness and robustness of the proposed strategy with low control effort against the voltage variations and the parameters’ uncertainty compared with other techniques.

Reinforcer Quality and Self-Control

<p>Self-control has been extensively studied using procedures in which subjects chose between two reinforcer alternatives. Traditionally, one of those alternatives delivers a small reinforcer after a short delay (SI), the other, a larger reinforcer after a long delay (LD). Choosing the SI is defined as impulsivity as it requires forfeit of the larger reinforcer; and choosing the LD is termed self-control. Four experiments were conducted to examine behaviour using non-human animal analogues of self-control situations. The subjects used for all four experiments were Norway-hooded rats. Experiment 1 used an SI - LD self-control paradigm to examine the effect of manipulating reinforcer quality on response distribution. Findings were that behaviour became more impulsive as the delay ratio became more extreme and this tendency was more systematic when different quality reinforcers were used for the SI and LD alternatives. Experiments 2 and 3 introduced a novel self-control paradigm designed as an analogue of choice situations in which individuals choose between two competing immediately available reinforcers each associated with a different delayed reinforcer. The procedure used was a concurrent-chains schedule that delivered primary reinforcement in the initial and the terminal links. The initial reinforcers were of equal amount and unequal quality; the terminal reinforcers were of unequal amount and equal quality. An impulsive choice was defined as choosing the alternative that delivered the most-valuable reinforcer in the initial link and the least-valued reinforcer in the terminal link. A self-controlled choice was defined as choosing the alternative that delivered the least-valuable reinforcer in the initial link and the most-valuable reinforcer in the terminal link. The results indicated that behaviour was more self-controlled when the terminal reinforcer quality was ethanol solution and increasing the delay between the initial and terminal links increased subjects' responding on the impulsive choice. Behaviour allocation in Experiment 3 was well described by the Contextual Choice Model (Grace, 1994) when the temporal context scaling parameter (k) was allowed to vary. Subjects that were relatively more impulsive had lower derived k values. The final experiment presented the subjects from Experiment 3 with concurrent variable interval (VI) VI schedules in which one alternative delivered plain-sucrose solution and the other ethanol-sucrose solution. Preference measures obtained from Experiment 4 were negatively correlated with the values obtained for the scaling parameter in Experiment 3, indicating that subjects which were more impulsive in the MN - ML paradigm had a stronger preference for ethanol. In summary, findings indicate that reinforcer quality may change the discriminability of reinforcer alternatives; and the influence of reinforcer quality on response allocation is well described by quantitative models based on the Matching Law.</p>

Reinforcer Quality and Self-Control

<p>Self-control has been extensively studied using procedures in which subjects chose between two reinforcer alternatives. Traditionally, one of those alternatives delivers a small reinforcer after a short delay (SI), the other, a larger reinforcer after a long delay (LD). Choosing the SI is defined as impulsivity as it requires forfeit of the larger reinforcer; and choosing the LD is termed self-control. Four experiments were conducted to examine behaviour using non-human animal analogues of self-control situations. The subjects used for all four experiments were Norway-hooded rats. Experiment 1 used an SI - LD self-control paradigm to examine the effect of manipulating reinforcer quality on response distribution. Findings were that behaviour became more impulsive as the delay ratio became more extreme and this tendency was more systematic when different quality reinforcers were used for the SI and LD alternatives. Experiments 2 and 3 introduced a novel self-control paradigm designed as an analogue of choice situations in which individuals choose between two competing immediately available reinforcers each associated with a different delayed reinforcer. The procedure used was a concurrent-chains schedule that delivered primary reinforcement in the initial and the terminal links. The initial reinforcers were of equal amount and unequal quality; the terminal reinforcers were of unequal amount and equal quality. An impulsive choice was defined as choosing the alternative that delivered the most-valuable reinforcer in the initial link and the least-valued reinforcer in the terminal link. A self-controlled choice was defined as choosing the alternative that delivered the least-valuable reinforcer in the initial link and the most-valuable reinforcer in the terminal link. The results indicated that behaviour was more self-controlled when the terminal reinforcer quality was ethanol solution and increasing the delay between the initial and terminal links increased subjects' responding on the impulsive choice. Behaviour allocation in Experiment 3 was well described by the Contextual Choice Model (Grace, 1994) when the temporal context scaling parameter (k) was allowed to vary. Subjects that were relatively more impulsive had lower derived k values. The final experiment presented the subjects from Experiment 3 with concurrent variable interval (VI) VI schedules in which one alternative delivered plain-sucrose solution and the other ethanol-sucrose solution. Preference measures obtained from Experiment 4 were negatively correlated with the values obtained for the scaling parameter in Experiment 3, indicating that subjects which were more impulsive in the MN - ML paradigm had a stronger preference for ethanol. In summary, findings indicate that reinforcer quality may change the discriminability of reinforcer alternatives; and the influence of reinforcer quality on response allocation is well described by quantitative models based on the Matching Law.</p>

A Yeast RNA-Interference Pesticide Targeting the Irx Gene Functions as a Broad-Based Mosquito Larvicide and Adulticide

Concerns for widespread insecticide resistance and the unintended impacts of insecticides on nontarget organisms have generated a pressing need for mosquito control innovations. A yeast RNAi-based insecticide that targets a conserved site in mosquito Irx family genes, but which has not yet been identified in the genomes of nontarget organisms, was developed and characterized. Saccharomyces cerevisiae constructed to express short hairpin RNA (shRNA) matching the target site induced significant Aedes aegypti larval death in both lab trials and outdoor semi-field evaluations. The yeast also induced high levels of mortality in adult females, which readily consumed yeast incorporated into an attractive targeted sugar bait (ATSB) during simulated field trials. A conserved requirement for Irx function as a regulator of proneural gene expression was observed in the mosquito brain, suggesting a possible mode of action. The larvicidal and adulticidal properties of the yeast were also verified in Aedes albopictus, Anopheles gambiae, and Culexquinquefasciatus mosquitoes, but the yeast larvicide was not toxic to other nontarget arthropods. These results indicate that further development and evaluation of this technology as an ecofriendly control intervention is warranted, and that ATSBs, an emerging mosquito control paradigm, could potentially be enriched through the use of yeast-based RNAi technology.

Frontal Alpha Asymmetry in Posttraumatic Stress Disorder: Group Differences Among Individuals With and Without PTSD During an Inhibitory Control Task

The current study examined frontal alpha asymmetry (FAA) as a marker of approach- and avoidance-related prefrontal activity in participants with and without trauma exposure and posttraumatic stress disorder (PTSD). We investigated FAA in an inhibitory control paradigm (threatening vs nonthreatening cues) under 2 levels of cognitive demand (baseline: images constant within a block of trials; vs filtering: images varied randomly within a block) in 3 groups of participants: individuals with PTSD ( n = 16), exposed to trauma but without PTSD ( n = 14), and a control group without PTSD or trauma exposure ( n = 15). Under low demand (baseline), both PTSD and trauma-exposed participants exhibited significantly greater relative left than right frontal brain activity (approach) to threatening than to nonthreatening images. Under high demand (filtering), no FAA differences were found between threatening and nonthreatening images, but PTSD participants revealed more relative left than right FAA, whereas trauma-exposed participants showed reduced left relative right FAA. In all conditions, healthy controls exhibited reduced left relative to right FAA and no differences between threatening and nonthreatening images. Study findings suggest dysfunctional prefrontal mechanisms of emotion regulation in PTSD, but adaptive prefrontal regulation in trauma-exposed individuals without PTSD.

New directions for inline inspection of automobile laser welds using non-destructive testing

An innovative pilot installation and eddy current testing (ECT) inspection system for laser-brazed joints is presented. The proposed system detects both surface and sub-surface welding defects operating autonomously and integrated with a robotized arm. Customized eddy current probes were designed and experimentally validated detecting pore defects with 0.13 mm diameter and sub-surface defects buried 1 mm deep. The integration of the system and the manufacturing process towards an Industry 4.0 quality control paradigm is also discussed.