Dos and don’ts in response priming research

Response priming is a well-understood but sparsely employed paradigm in cognitive science. The method is powerful and well-suited for exploring early visuomotor processing in a wide range of tasks and research fields. Moreover, response priming can be dissociated from visual awareness, possibly because it is based on the first sweep of feedforward processing of primes and targets. This makes it a theoretically interesting device for separating conscious and unconscious vision. We discuss the major opportunities of the paradigm and give specific recommendations (e.g., tracing the time-course of priming in parametric experiments). Also, we point out typical confounds, design flaws, and data processing artifacts

Direct-energy-regenerated particulate trap technology. Final report

The objective of this CRADA between Lockheed Martin and Cummins Engine Company was to develop fiber-reinforced silicon carbide (SiC) composite materials for use as diesel engine particulate traps. Chemical vapor deposition techniques were used to partially densify and rigidize a thin fibrous substrate and produce the porous SiC- based filter. Microwave energy was used to directly couple to the deposited SiC to uniformly heat the filter and oxidize the collected carbon particulates. For commercial usage particulate traps must: (1) filter carbon particulates from a high temperature diesel exhaust at an acceptably low backpressure, (2) survive thousands of thermal transients due to regeneration or cleaning of the filter by oxidizing the collected carbon, (3) be durable and reliable over the expected life of the filter (300,000 miles or 10,000 hours), and (4) provide a low overall operating cost which is competitive with other filtering techniques. The development efforts performed as part of this CRADA have resulted in a very promising new technology for Cummins Engine Company. Ceramic fiber based filter papers were developed at Fleetguard, Inc., (a Cummins Subsidiary) and used to produce the spiral wound, corrugated filter cartridges. Optimized SiC coatings were developed at Lockheed Martin which couple with 2.45 GHz microwaves. Prototype particulate filter cartridges fabricated at Fleetguard and rigidized at Lockheed Martin performed well in single cylinder engine tests at Cummins. These prototype filters obtained filtering efficiencies greater than 80% at acceptably low backpressures and could be successfully headed and regenerated using a conventional in-home microwave oven

Blood-based systems biology biomarkers for next-generation clinical trials in Alzheimer’s disease

Alzheimer’s disease (AD)—a complex disease showing multiple pathomechanistic alterations—is triggered by nonlinear dynamic interactions of genetic/epigenetic and environmental risk factors, which, ultimately, converge into a biologically heterogeneous disease. To tackle the burden of AD during early preclinical stages, accessible blood-based biomarkers are currently being developed. Specifically, next-generation clinical trials are expected to integrate positive and negative predictive blood-based biomarkers into study designs to evaluate, at the individual level, target druggability and potential drug resistance mechanisms. In this scenario, systems biology holds promise to accelerate validation and qualification for clinical trial contexts of use—including proof-of-mechanism, patient selection, assessment of treatment efficacy and safety rates, and prognostic evaluation. Albeit in their infancy, systems biology-based approaches are poised to identify relevant AD “signatures” through multifactorial and interindividual variability, allowing us to decipher disease pathophysiology and etiology. Hopefully, innovative biomarker-drug codevelopment strategies will be the road ahead towards effectivedisease-modifying drugs. © 2019, AICH – Servier Grou

Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease

The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer’s disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices. © 2021 Penner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited