Abrupt vs. gradual visual onsets in go/no-go sustained attention tasks

Two experiments compared both average performance and changes in performance across time in abrupt- and gradual-onset sustained attention tasks. Experiment 1 compared abrupt- and gradual-onset digits. In conditions where the digits onset and offset abruptly and appeared only briefly, similar to typical conditions in the Sustained Attention to Response Task (SART), participants committed more errors on no-go trials and responded faster overall, indicative of a shift in the speed/accuracy tradeoff toward speed. When the digits abruptly onset but remained on-screen for a longer period of time, there were no differences in no-go error rates, hit rates, or reaction time (RT) variability, but participants still emitted faster RTs overall. Experiment 2 compared abrupt- and gradual-onset images. Similar to Experiment 1, abrupt-onset, short-duration images induced more no-go errors and faster RTs, but also more RT variability and reduced hit rates. In the abrupt-onset, long-duration condition, again the only performance difference was a decrease in average RTs. We discuss implications for using these two types of tasks in sustained attention research.

Anomalous Cognition in the Context of Time: Does the Viewer Describe a Probabilistic Future?

In this process-oriented study, we examined the influence of the time dimension on Psi effects in two experimental conditions (present vs. future). For data collection, selected viewers with experience in the remote viewing method gathered information about targets that were distant in space (the present) and time (the future). The present condition was composed of binary truth statements consisting of two possible options related to current world knowledge. The future condition consisted of two options that were not yet determined at the time of viewing, but depended on the outcome of future mixed martial arts fights. According to the associative remote viewing (ARV) method, the binary outcomes of the present and future options were each associated with a photo, which had to be described by the viewers. An independent judge analyzed the viewers’ qualitative reports through binary correspondence ratings amounting to a hit (1) or no hit (0) per trial. Independently of the time condition, a Psi effect could be observed. The hit rates of the judge (0.88 and 0.62 for the present and future, respectively) were significantly higher than the expected value (0.5) under the null hypothesis (present: p < 0.001, ESP = 0.73; future: p = 0.027, ESF = 0.22; binomial distribution). In addition, the hit rates in the two time conditions differed significantly from each other (χ2 = 9.01; df = 1, p < 0.003). The results confirm the hypothesis that Psi is not completely independent of the time dimension and that the hit rate is influenced by a priori target probabilities. With regard to the Informational Psi (IΨ) theory, we will discuss the implications of a probabilistic future for the understanding of Psi effects.

Is Novelty Detection Important in Long-Term Odor Memory?

Memory for odors is believed to be longer-lasting than memory for visual stimuli, as is evidenced by flat forgetting curves. However, performance on memory tasks is typically weaker in olfaction than vision. Studies of odor memory that use forced-choice methods confound responses that are a result of a trace memory and responses that can be obtained through process of elimination. Moreover, odor memory is typically measured with common stimuli, which are more familiar and responses may be confounded by verbal memory, and measure memory in intentional learning conditions, which are ecologically questionable. Here we demonstrate the value of using tests of memory in which hit rate and correct rejection rate are evaluated separately (i.e., not using forced-choice methods) and uncommon stimuli are used. This study compared memory for common and uncommon odors and pictures that were learned either intentionally (Exp. 1) or incidentally (Exp. 2) and tested with either a forced-choice or a one-stimulus-at-a-time (“monadic”) recognition task after delays of 15 min, 48 h or 1 week. As expected, memory declined with delay in most conditions, but depended upon the particular measure of memory and was better for pictures than odors and for common than uncommon stimuli. For common odors, hit rates decreased with delay but correct rejection rates remained constant with delay. For common pictures, we found the opposite result, constant hit rates and decreased correct rejection rates. Our results support the ‘misfit theory of conscious olfactory perception’, which highlights the importance of the detection of novelty in olfactory memory and suggests that olfactory memory should be studied using more ecologically valid methods.

Enabling Service Cache in Edge Clouds

The next-generation 5G cellular networks are designed to support the internet of things (IoT) networks; network components and services are virtualized and run either in virtual machines (VMs) or containers. Moreover, edge clouds (which are closer to end users) are leveraged to reduce end-to-end latency especially for some IoT applications, which require short response time. However, the computational resources are limited in edge clouds. To minimize overall service latency, it is crucial to determine carefully which services should be provided in edge clouds and serve more mobile or IoT devices locally. In this article, we propose a novel service cache framework called S-Cache , which automatically caches popular services in edge clouds. In addition, we design a new cache replacement policy to maximize the cache hit rates. Our evaluations use real log files from Google to form two datasets to evaluate the performance. The proposed cache replacement policy is compared with other policies such as greedy-dual-size-frequency (GDSF) and least-frequently-used (LFU). The experimental results show that the cache hit rates are improved by 39% on average, and the average latency of our cache replacement policy decreases 41% and 38% on average in these two datasets. This indicates that our approach is superior to other existing cache policies and is more suitable in multi-access edge computing environments. In the implementation, S-Cache relies on OpenStack to clone services to edge clouds and direct the network traffic. We also evaluate the cost of cloning the service to an edge cloud. The cloning cost of various real applications is studied by experiments under the presented framework and different environments.

Analyzing Kinase Similarity in Small Molecule and Protein Structural Space to Explore the Limits of Multi-Target Screening

While selective inhibition is one of the key assets for a small molecule drug, many diseases can only be tackled by simultaneous inhibition of several proteins. An example where achieving selectivity is especially challenging are ligands targeting human kinases. This difficulty arises from the high structural conservation of the kinase ATP binding sites, the area targeted by most inhibitors. We investigated the possibility to identify novel small molecule ligands with pre-defined binding profiles for a series of kinase targets and anti-targets by in silico docking. The candidate ligands originating from these calculations were assayed to determine their experimental binding profiles. Compared to previous studies, the acquired hit rates were low in this specific setup, which aimed at not only selecting multi-target kinase ligands, but also designing out binding to anti-targets. Specifically, only a single profiled substance could be verified as a sub-micromolar, dual-specific EGFR/ErbB2 ligand that indeed avoided its selected anti-target BRAF. We subsequently re-analyzed our target choice and in silico strategy based on these findings, with a particular emphasis on the hit rates that can be expected from a given target combination. To that end, we supplemented the structure-based docking calculations with bioinformatic considerations of binding pocket sequence and structure similarity as well as ligand-centric comparisons of kinases. Taken together, our results provide a multi-faceted picture of how pocket space can determine the success of docking in multi-target drug discovery efforts.

Have I Been Here? Sense of Location in People With Alzheimer's Disease

Background: When navigating in a particular space, a sense of being at a current location is of great help for the navigators in reaching their destination or getting back to the start. To accomplish this work, interwoven neural structures and neurons are called into play. This system is called the heading direction cell-place cell-grid cell circuit. Evidence from various neuroscience studies has revealed that the regions responsible for this circuit are damaged in the early stages of Alzheimer's disease (AD). This may explain why wayfinding difficulty is one of the most frequent symptoms in persons with AD. The aim of this study was to examine the sense of location (SoL) in persons with mild AD, persons with prodromal AD (prAD), and those who were cognitively unimpaired (CU).Methods: We invited people with mild AD, prAD, and CU to participate in this study. The venue of the core experiment to assess SoL was a 660-m path located on the university campus. The participants were instructed to take a walk on the path and press a device to indicate their arrival at each of the five carefully chosen targets. The linear deviations from the target site were compared among the groups.Results: A total of 20 AD, 28 prAD, and 29 CU persons completed the study. Their Mini-Mental State Examination scores were on average 20 (SD 3), 24 (SD 3), and 28 (SD 2). The groups were well differentiated regarding several measurements for cognitive ability and spatial navigation. As for the SoL, the hit rates of exact location with linear deviation of 16 m or less were 0.05, 0.54, and 0.86 for AD, prAD, and CU persons, respectively. The hit rates were well correlated with the presence of getting lost. Also, SoL differentiated well among CU, PrAD, and AD in terms of average linear deviation.Conclusions: Our employing linear deviation by utilizing a grid-cell function device as an assessment for SoL showed distinct features among the three groups. This model can be used to develop more delicate devices or instruments to detect, monitor, and aid spatial navigation in persons with prAD and AD.

LigGrep: a tool for filtering docked poses to improve virtual-screening hit rates

Structure-based virtual screening (VS) uses computer docking to prioritize candidate small-molecule ligands for subsequent experimental testing. Docking programs evaluate molecular binding in part by predicting the geometry with which a given compound might bind a target receptor (e.g., the docked “pose” relative to a protein target). Candidate ligands predicted to participate in the same intermolecular interactions typical of known ligands (or ligands that bind related proteins) are arguably more likely to be true binders. Some docking programs allow users to apply constraints during the docking process with the goal of prioritizing these critical interactions. But these programs often have restrictive and/or expensive licenses, and many popular open-source docking programs (e.g., AutoDock Vina) lack this important functionality. We present LigGrep, a free, open-source program that addresses this limitation. As input, LigGrep accepts a protein receptor file, a directory containing many docked-compound files, and a list of user-specified filters describing critical receptor/ligand interactions. LigGrep evaluates each docked pose and outputs the names of the compounds with poses that pass all filters. To demonstrate utility, we show that LigGrep can improve the hit rates of test VS targeting H. sapiens poly(ADPribose) polymerase 1 (HsPARP1), H. sapiens peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (HsPin1p), and S. cerevisiae hexokinase-2 (ScHxk2p). We hope that LigGrep will be a useful tool for the computational biology community. A copy is available free of charge at http://durrantlab.com/liggrep/.

Ultrasensitive Measurable Residual Disease (MRD) Detection in Acute Myeloid Leukemia (AML) Using a Targeted Next Generation Sequencing (NGS) Panel

INTRODUCTION: Assessment of MRD in AML is emerging as an important tool for refining risk classification and improving patient management and outcomes. MRD also shows promise as a surrogate endpoint to accelerate therapeutic development and may facilitate more robust post-transplant surveillance. Highly sensitive digital PCR (dPCR) methods such as BEAMing - which are 50-100X more sensitive than "pan-heme" NGS assays - have generated compelling data for therapeutic response monitoring and clearance of molecular MRD in clinical trials: for example, for both relapsed/refractory as well as newly diagnosed patients, declining levels and eventual clearance of IDH1 mutations correlated with more robust hematologic response (DiNardo CD et al. N Engl J Med. 2018, 378(25):2386-98; Daigle S et al. Presented at ASH 2019). Nevertheless, the complex clonal dynamics of AML demand broader coverage across more genomic regions than are currently able to be interrogated using dPCR. At the same time, NGS pan-heme panels that offer broad genomic coverage lack sufficient sensitivity to detect MRD, as their limits of detection (LoD) are between 1-5% mutant allele frequency (MAF). To overcome these limitations, we developed a highly sensitive assay based on the Safe-SeqS technology (SafeSEQ) to detect de novo mutations across genomic regions with established and emerging clinical validity for AML MRD. This highly sensitive error-corrected NGS-based workflow detects molecular MRD with an LoD comparable to dPCR assays such as BEAMing. METHODS: A multiplexed enrichment panel targeting 68 highly relevant genomic regions was developed for ultra-sensitive mutation detection across 57 exons spanning 20 genes: BCOR, BRAF, CEBPA, FLT3, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, NPM1, NRAS, PRPF8, PTPN11, SETBP1, SF3B1, SRSF2, TP53, U2AF1, and ZRSR2. Initial analytical performance demonstration for the SafeSEQ AML MRD test examined limit of blank (LoB) as well as LoD at the 95% confidence level (LoD95). LoB was measured using wildtype (wt) gDNA prepared from two NIST cell lines run in replicate; LoD was determined through replicate testing of contrived materials containing 30 characterized mutations across different mutant molecule (MM)/ MAF tiers ranging from 20 MM down to &lt;1 MM. Low and high DNA input levels were also tested, from 1,000 genomic equivalents (GE) up to a subset of tiers run at 20,000 GE (3.3-66 ng) to demonstrate performance irrespective of wt DNA amount. Direct evaluation of analytical and clinical performance between the SafeSEQ AML MRD panel and a subset of mutations detected using BEAMing is currently underway. RESULTS: A rank-based approach was used to evaluate the distribution of background signals observed in the wt cell line DNA across all interrogated base positions. Consistent with previous observations of LoB across different SafeSEQ panels, a very low level of background noise was observed, with the vast majority of bases exhibiting signal &lt;1 MM, indicating robust analytical specificity. Importantly, there were no positions affected by elevated noise for which clinically relevant mutations have been characterized for AML. For the variant-positive contrived materials run in replicate across different mutation levels, hit rates were consistent with those observed in other SafeSEQ assays and yielded 95% detection at 5 MM; this corresponds to 0.025% and 0.5% MAF for 20,000 and 1,000 GE inputs, respectively. Hit rates for the different MM tiers were also consistent between low and high DNA input levels, indicating robust performance for mutation detection across a wide range of background wt DNA. CONCLUSIONS: The SafeSEQ AML MRD assay demonstrates ultra-sensitive detection of low frequency mutations, with an LoD95 of 5 MM (0.025% MAF for 20,000 GE DNA input), while specificity remains very high. Similar to other SafeSEQ platform configurations, this performance is comparable with data obtained using the BEAMing dPCR technology; it is also orders of magnitude more sensitive than broad pan-heme NGS tests. With this combination of ultra-high analytical sensitivity paired with clinically-informed genomic coverage, we anticipate the SafeSEQ AML MRD test will play a fundamental role in accelerating therapeutic development. It should also provide clinicians with more reliable MRD information at important decision points, such as pre-transplant, or when considering novel maintenance therapies. Disclosures Sloane: Sysmex Inostics, Inc: Current Employment.

The Continuity MODIS-VIIRS Cloud Mask

This paper introduces the Continuity Moderate Resolution Imaging Spectroradiometer (MODIS)-Visible Infrared Imaging Radiometer Suite (VIIRS) Cloud Mask (MVCM), a cloud detection algorithm designed to facilitate continuity in cloud detection between the MODIS (Moderate Resolution Imaging Spectroradiometer) on the Aqua and Terra platforms and the series of VIIRS (Visible Infrared Imaging Radiometer Suite) instruments, beginning with the Soumi National Polar-orbiting Partnership (SNPP) spacecraft. It is based on the MODIS cloud mask that has been operating since 2000 with the launch of the Terra spacecraft (MOD35) and continuing in 2002 with Aqua (MYD35). The MVCM makes use of fourteen spectral bands that are common to both MODIS and VIIRS so as to create consistent cloud detection between the two instruments and across the years 2000–2020 and beyond. Through comparison data sets, including collocated Aqua MODIS and Cloud-Aerosol LIdar with Orthogonal Polarization (CALIOP) from the A-Train, this study was designed to assign statistical consistency benchmarks between the MYD35 and MVCM cloud masks. It is shown that the MVCM produces consistent cloud detection results between Aqua MODIS, SNPP VIIRS, and NOAA-20 VIIRS and that the quality is comparable to the standard Aqua MODIS cloud mask. Globally, comparisons with collocated CALIOP lidar show combined clear and cloudy sky hit rates of 88.2%, 87.5%, 86.8%, and 86.8% for MYD35, MVCM Aqua MODIS, MVCM SNPP VIIRS, and MVCM NOAA-20 VIIRS, respectively, for June through until August, 2018. For the same months and in the same order for 60S–60N, hit rates are 90.7%, 90.5%, 90.1%, and 90.3%. From the time series constructed from gridded daily means of 60S–60N cloud fractions, we found that the mean day-to-day cloud fraction differences/standard deviations in percent to be 0.68/0.55, 0.94/0.64, −0.20/0.50, and 0.44/0.82 for MVCM Aqua MODIS-MVCM SNPP VIIRS day and night, and MVCM NOAA-20 VIIRS-MVCM SNPP VIIRS day and night, respectively. It is seen that the MODIS and VIIRS 1.38 µm cirrus detection bands perform similarly but with MODIS detecting slightly more clouds in the middle to high levels of the troposphere and the VIIRS detecting more in the upper troposphere above 16 km. In the Arctic, MVCM Aqua MODIS and SNPP VIIRS reported cloud fraction differences of 0–3% during the mid-summer season and −3–4% during the mid-winter.