Question: Whole-genome sequencing identifies tumor-associated copy number alterations in the bloodstream of prostate cancer patients.

This paper delves into the journey of ETS gene fusions in prostate cancer, tracing their evolution from groundbreaking discovery to their emerging role in clinical practice.

CONTEXT
In 2005, a significant breakthrough was made with the identification of fusions between the TMPRSS2 gene, which is regulated by androgens, and ETS transcription factors in prostate cancer.

OBJECTIVE
The aim is to provide an in-depth review of the advancements in our comprehension of ETS gene fusions, with a specific focus on the obstacles impeding their translation into clinical utility.

EVIDENCE ACQUISITION
A comprehensive search of the PubMed database was conducted to compile reports pertaining to ETS fusions in prostate cancer.

EVIDENCE SYNTHESIS
Post the discovery of ETS fusions, a multitude of novel 5' and 3' fusion partners and various splice isoforms have surfaced. The TMPRSS2:ERG fusion, the most prevalent, is found in roughly 50% of localized prostate cancers detected through prostate-specific antigen (PSA) screening, and in 15-35% of population-based studies. Notably, ETS fusions can be identified noninvasively in the urine of men with prostate cancer, boasting a specificity rate exceeding 90% in PSA-screened cohorts. Emerging data from population-based cohorts untreated for prostate cancer suggest a correlation between ETS fusions and cancer-specific mortality and metastatic progression. However, retrospective studies on prostatectomy patients have yielded inconsistent findings regarding the association between ETS fusions and cancer aggressiveness. Apart from their potential as biomarkers, tissue and functional investigations suggest a critical role for ETS fusions in the transition from a benign to a malignant state. Moreover, recent findings indicate that the 5' and 3' ends of ETS fusions, as well as their downstream targets, may be amenable to therapeutic targeting.

CONCLUSIONS
The latest studies suggest that the initial clinical applications of ETS fusions will likely revolve around noninvasive prostate cancer detection and aiding in complex diagnostic scenarios. Further research is warranted to elucidate the relationship between gene fusions and cancer aggressiveness, with a particular emphasis on accounting for the multifocal and heterogeneous nature of localized prostate cancer. A range of promising strategies for targeting ETS fusions have been identified. Collectively, these findings point to the imminent impact of ETS fusions on various aspects of prostate cancer diagnosis and treatment.

The development of the narrow-band imaging (NBI) has been increasing the interest of medical specialists in the study of laryngeal microvascular network to establish diagnosis without biopsy and pathological examination. A possible solution to this challenging problem is presented in this paper, which proposes an automatic method based on anisotropic filtering and matched filter to extract the lesion area and segment blood vessels. Lesion classification is then performed based on a statistical analysis of the blood vessels' characteristics, such as thickness, tortuosity, and density. Here, the presented algorithm is applied to 50 NBI endoscopic images of laryngeal diseases and the segmentation and classification accuracies are investigated. The experimental results show the proposed algorithm provides reliable results, reaching an overall classification accuracy rating of 84.3%. This is a highly motivating preliminary result that proves the feasibility of the new method and supports the investment in further research and development to translate this study into clinical practice. Furthermore, to our best knowledge, this is the first time image processing is used to automatically classify laryngeal tumors in endoscopic videos based on tumor vascularization characteristics. Therefore, the introduced system represents an innovation in biomedical and health informatics.

* Correspondence: momiao.xiong@gmail.com; Momiao.Xiong@uth.tmc.edu; yin.yao@nih.gov; lijin@fudan.edu.cn Equal contributors Human Genetics Center, School of Public Health, University of Texas Houston Health Sciences Center, Houston, TX, USA Unit on Statistical Genomics, Division of Intramural Division Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200433, China Full list of author information is available at the end of the article Abstract

Motivation
The identification of contaminating sequences in a de novo assembly is challenging because of the absence of information on the target species. For sample types where the target organism is impossible to isolate from its matrix, such as endoparasites, endosymbionts and soil-harvested samples, contamination is unavoidable. A few post-assembly decontamination methods are currently available but are based only on alignments to databases, which can lead to poor decontamination.

Results
We present a new decontamination method based on a hierarchical clustering algorithm called MCSC. This method uses frequent patterns found in sequences to create clusters. These clusters are then linked to the target species or tagged as contaminants using classic alignment tools. The main advantage of this decontamination method is that it allows sequences to be tagged correctly even if they are unknown or misaligned to a database.

Availability and Implementation
Scripts and documentation about the MCSC decontamination method are available at https://github.com/Lafond-LapalmeJ/MCSC_Decontamination .

Contact
: benjamin.mimee@agr.gc.ca.

Supplementary information
Supplementary data are available at Bioinformatics online.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

BACKGROUND
The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case. The allelic variants are associated with impaired hydroxylation of S-warfarin in in-vitro expression systems. We have studied the effect of CYP2C9 polymorphism on the in-vivo warfarin dose requirement.

METHODS
Patients with a daily warfarin dose requirement of 1.5 mg or less (low-dose group, n=36), randomly selected patients with a wide range of dose requirements from an anticoagulant clinic in north-east England (clinic control group, n=52), and 100 healthy controls from the community in the same region were studied. Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis. Case notes were reviewed to assess the difficulties encountered during the induction of warfarin therapy and bleeding complications in the low-dose and clinic control groups.

FINDINGS
The odds ratio for individuals with a low warfarin dose requirement having one or more CYP2C9 variant alleles compared with the normal population was 6.21 (95% CI 2.48-15.6). Patients in the low-dose group were more likely to have difficulties at the time of induction of warfarin therapy (5.97 [2.26-15.82]) and have increased risk of major bleeding complications (rate ratio 3.68 [1.43-9.50]) when compared with randomly selected clinic controls.

INTERPRETATION
We have shown that there is a strong association between CYP2C9 variant alleles and low warfarin dose requirement. CYP2C9 genotyping may identify a subgroup of patients who have difficulty at induction of warfarin therapy and are potentially at a higher risk of bleeding complications.

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single-cell expression profiles to sequentially acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. Descending the phylogenetic tree of a PDGF-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type, expressing pro-angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed an up-regulation of pro-invasive genes. An in-frame deletion in a specific dimerization domain of PDGF receptor correlates with an up-regulation of growth pathways in a proneural GBM and enhances proliferation when ectopically expressed in glioma cell lines. In-frame deletions in this domain are frequent in public GBM data.


Question: Identification of tumor-associated copy number alterations in the bloodstream of prostate cancer patients through whole-genome sequencing.

This study explores the genetic alterations that define the genomic landscapes of human breast and colorectal cancers, emphasizing the role of mutations in oncogenes and tumor suppressor genes. To map these genetic changes, researchers analyzed DNA samples from 11 breast and 11 colorectal tumors, sequencing the genes contained in the Reference Sequence database. From an examination of exons representing 20,857 transcripts across 18,191 genes, the study reveals that the genomic profiles of these cancers are characterized by a small number of frequently mutated "mountain" genes and a significantly larger number of "hill" genes mutated at much lower frequencies. The paper introduces statistical and bioinformatic methodologies designed to aid in identifying mutations that contribute to tumorigenesis. The findings have significant implications for understanding the diversity of human cancers and suggest potential avenues for personalized genomics in cancer diagnosis and treatment. These insights could be pivotal in tailoring therapeutic strategies to individual patients based on their unique genetic profiles.

Edit distance has been proven to be an important and frequently-used metric in many human genomic research, with Similar Patient Query (SPQ) being a particularly promising and attractive example. However, due to the widespread privacy concerns on revealing personal genomic data, the scope and scale of many novel use of genome edit distance are substantially limited. While the problem of private genomic edit distance has been studied by the research community for over a decade [6], the state-of-the-art solution [31] is far from even close to be applicable to real genome sequences. In this paper, we propose several private edit distance protocols that feature unprecedentedly high efficiency and precision. Our construction is a combination of a novel genomic edit distance ap- proximation algorithm and new construction of private set difference size protocols. With the private edit distance based secure SPQ primitive, we propose GENSETS, a genome-wide, privacy- preserving similar patient query system. It is able to support search- ing large-scale, distributed genome databases across the nation. We have implemented a prototype of GENSETS. The experimental results show that, with 100 Mbps network connection, it would take GENSETS less than 200 minutes to search through 1 million breast cancer patients (distributed nation-wide in 250 hospitals, each having 4000 patients), based on edit distances between their genomes of lengths about 75 million nucleotides each.

A new approach to predicting the Y-chromosome haplogroup from a set of Y-STR marker values is presented and compared to other approaches. The method has been implemented in an Excel-based program, where an arbitrary number of STR markers may be input and a “goodness of fit” score for 10 haplogroups (E3a, E3b, G, I1a, I1b, I1c, J2, N3, R1a, and R1b) is returned. This method has been applied to 101 R1b haplotypes and 50 I1a haplotypes (all having 37 STR markers available), and the distribution of results is presented. In the case of I1a, the results are compared with the predictions of another method.

The advancement of the next-generation sequencing technology enables mapping gene expression at the single-cell level, capable of tracking cell heterogeneity and determination of cell subpopulations using single-cell RNA sequencing (scRNA-seq). Unlike the objectives of conventional RNA-seq where differential expression analysis is the integral component, the most important goal of scRNA-seq is to identify highly variable genes across a population of cells, to account for the discrete nature of single-cell gene expression and uniqueness of sequencing library preparation protocol for single-cell sequencing. However, there is lack of generic expression variation model for different scRNA-seq data sets. Hence, the objective of this study is to develop a gene expression variation model (GEVM), utilizing the relationship between coefficient of variation (CV) and average expression level to address the over-dispersion of single-cell data, and its corresponding statistical significance to quantify the variably expressed genes (VEGs). We have built a simulation framework that generated scRNA-seq data with different number of cells, model parameters, and variation levels. We implemented our GEVM and demonstrated the robustness by using a set of simulated scRNA-seq data under different conditions. We evaluated the regression robustness using root-mean-square error (RMSE) and assessed the parameter estimation process by varying initial model parameters that deviated from homogeneous cell population. We also applied the GEVM on real scRNA-seq data to test the performance under distinct cases. In this paper, we proposed a gene expression variation model that can be used to determine significant variably expressed genes. Applying the model to the simulated single-cell data, we observed robust parameter estimation under different conditions with minimal root mean square errors. We also examined the model on two distinct scRNA-seq data sets using different single-cell protocols and determined the VEGs. Obtaining VEGs allowed us to observe possible subpopulations, providing further evidences of cell heterogeneity. With the GEVM, we can easily find out significant variably expressed genes in different scRNA-seq data sets.

Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/).

SUMMARY
Plant microRNA prediction tools that use small RNA-sequencing data are emerging quickly. These existing tools have at least one of the following problems: (i) high false-positive rate; (ii) long running time; (iii) work only for genomes in their databases; (iv) hard to install or use. We developed miR-PREFeR (miRNA PREdiction From small RNA-Seq data), which uses expression patterns of miRNA and follows the criteria for plant microRNA annotation to accurately predict plant miRNAs from one or more small RNA-Seq data samples of the same species. We tested miR-PREFeR on several plant species. The results show that miR-PREFeR is sensitive, accurate, fast and has low-memory footprint.

AVAILABILITY AND IMPLEMENTATION
https://github.com/hangelwen/miR-PREFeR

A combination of Gram-Schmidt method and cluster validation algorithm based Bayesian is proposed for nuclei segmentation on microscopic breast cancer image. Gram-Schmidt is applied to identify the cell nuclei on a microscopic breast cancer image and the cluster validation algorithm based Bayesian method is used for separating the touching nuclei. The microscopic image of the breast cancer cells are used as dataset. The segmented cell nuclei results on microscopic breast cancer images using Gram-Schmidt method shows that the most of MSE values are below 0.1 and the average MSE of segmented cell nuclei results is 0.08. The average accuracy of separated cell nuclei counting using cluster validation algorithm is 73% compares with the manual counting.

0957-4174/$ see front matter 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.eswa.2013.05.050 ⇑ Corresponding author at: LT3 Language and Translation Technology Team, University College Ghent, Groot-Brittanniëlaan 45, 9000 Ghent, Belgium. Tel.: +32 9 224 97 53. E-mail addresses: bart.desmet@hogent.be (B. Desmet), veronique.hoste@ hogent.be (V. Hoste). Bart Desmet a,b,⇑, Véronique Hoste a,c

The development of the narrow-band imaging (NBI) has been increasing the interest of medical specialists in the study of laryngeal microvascular network to establish diagnosis without biopsy and pathological examination. A possible solution to this challenging problem is presented in this paper, which proposes an automatic method based on anisotropic filtering and matched filter to extract the lesion area and segment blood vessels. Lesion classification is then performed based on a statistical analysis of the blood vessels' characteristics, such as thickness, tortuosity, and density. Here, the presented algorithm is applied to 50 NBI endoscopic images of laryngeal diseases and the segmentation and classification accuracies are investigated. The experimental results show the proposed algorithm provides reliable results, reaching an overall classification accuracy rating of 84.3%. This is a highly motivating preliminary result that proves the feasibility of the new method and supports the investment in further research and development to translate this study into clinical practice. Furthermore, to our best knowledge, this is the first time image processing is used to automatically classify laryngeal tumors in endoscopic videos based on tumor vascularization characteristics. Therefore, the introduced system represents an innovation in biomedical and health informatics.

BACKGROUND
Physical and psychological symptoms are common during chemotherapy in cancer patients, and real-time monitoring of these symptoms can improve patient outcomes. Sensors embedded in mobile phones and wearable activity trackers could be potentially useful in monitoring symptoms passively, with minimal patient burden.

OBJECTIVE
The aim of this study was to explore whether passively sensed mobile phone and Fitbit data could be used to estimate daily symptom burden during chemotherapy.

METHODS
A total of 14 patients undergoing chemotherapy for gastrointestinal cancer participated in the 4-week study. Participants carried an Android phone and wore a Fitbit device for the duration of the study and also completed daily severity ratings of 12 common symptoms. Symptom severity ratings were summed to create a total symptom burden score for each day, and ratings were centered on individual patient means and categorized into low, average, and high symptom burden days. Day-level features were extracted from raw mobile phone sensor and Fitbit data and included features reflecting mobility and activity, sleep, phone usage (eg, duration of interaction with phone and apps), and communication (eg, number of incoming and outgoing calls and messages). We used a rotation random forests classifier with cross-validation and resampling with replacement to evaluate population and individual model performance and correlation-based feature subset selection to select nonredundant features with the best predictive ability.

RESULTS
Across 295 days of data with both symptom and sensor data, a number of mobile phone and Fitbit features were correlated with patient-reported symptom burden scores. We achieved an accuracy of 88.1% for our population model. The subset of features with the best accuracy included sedentary behavior as the most frequent activity, fewer minutes in light physical activity, less variable and average acceleration of the phone, and longer screen-on time and interactions with apps on the phone. Mobile phone features had better predictive ability than Fitbit features. Accuracy of individual models ranged from 78.1% to 100% (mean 88.4%), and subsets of relevant features varied across participants.

CONCLUSIONS
Passive sensor data, including mobile phone accelerometer and usage and Fitbit-assessed activity and sleep, were related to daily symptom burden during chemotherapy. These findings highlight opportunities for long-term monitoring of cancer patients during chemotherapy with minimal patient burden as well as real-time adaptive interventions aimed at early management of worsening or severe symptoms.


Question: Identification of tumor-associated copy number alterations in the bloodstream of prostate cancer patients through whole-genome sequencing.

Emerging Sequencing Technologies: Innovations and Objectives

Over the past three decades, since the pioneering of electrophoretic methods for DNA sequencing, the field has experienced a significant revolution in terms of cost-effectiveness and efficiency, primarily driven by automation and the continuous refinement of Sanger sequencing techniques. However, the quest for innovation has not been limited to improving existing methods; rather, it has expanded to the exploration of entirely new sequencing technologies. These novel approaches aim to dramatically reduce the costs associated with sequencing, making it feasible to sequence individual human genomes as a routine component of healthcare. In this review, we delve into the details of these emerging technologies and contemplate the potential implications of a 'personal genome project' on both the scientific community and society at large. This paradigm shift, facilitated by advanced sequencing technologies, could redefine the landscape of genetic research and personalized medicine, ushering in a new era of genomic understanding and healthcare delivery.

The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods. Basset predictions for the change in accessibility between variant alleles were far greater for Genome-wide association study (GWAS) SNPs that are likely to be causal relative to nearby SNPs in linkage disequilibrium with them. With Basset, a researcher can perform a single sequencing assay in their cell type of interest and simultaneously learn that cell's chromatin accessibility code and annotate every mutation in the genome with its influence on present accessibility and latent potential for accessibility. Thus, Basset offers a powerful computational approach to annotate and interpret the noncoding genome.

The system design of an integrated microwave imaging radar for the diagnostic screening of breasts cancer is presented. A custom integrated circuit implemented in a 65-nm CMOS technology and a pair of patch antennas realized on a planar laminate are proposed as the basic module of the imaging antenna array. The radar operates on the broad frequency range from 2 to 16 GHz with a dynamic range of 107 dB. Imaging experiments carried out on a realistic breast phantom show that the system is capable of detecting tumor targets with a resolution of 3 mm.

Clustered regularly-interspaced short palindromic repeat (CRISPR) sequences cooperate with CRISPR-associated (Cas) proteins to form the basis of CRISPR-Cas adaptive immune systems in prokaryotes. For more than 20 years, these systems were of interest only to specialists, mainly molecular microbiologists, who tried to understand the properties of this unique defense mechanism. In 2012, the potential of CRISPR-Cas systems was uncovered and these were presented as genome-editing tools with an outstanding capacity to trigger targeted genetic modifications that can be applied to virtually any organism. Shortly thereafter, in early 2013, these tools were shown to efficiently drive specific modification of mammalian genomes. This review attempts to summarize, in a comprehensive manner, the key events and milestones that brought CRISPR-Cas technology from prokaryotes to mammals.

Integrative analysis of multi-omics data is becoming increasingly important to unravel functional mechanisms of complex diseases. However, the currently available multi-omics datasets inevitably suffer from missing values due to technical limitations and various constrains in experiments. These missing values severely hinder integrative analysis of multi-omics data. Current imputation methods mainly focus on using single omics data while ignoring biological interconnections and information imbedded in multi-omics data sets. In this study, a novel multi-omics imputation method was proposed to integrate multiple correlated omics datasets for improving the imputation accuracy. Our method was designed to: 1) combine the estimates of missing value from individual omics data itself as well as from other omics, and 2) simultaneously impute multiple missing omics datasets by an iterative algorithm. We compared our method with five imputation methods using single omics data at different noise levels, sample sizes and data missing rates. The results demonstrated the advantage and efficiency of our method, consistently in terms of the imputation error and the recovery of mRNA-miRNA network structure. We concluded that our proposed imputation method can utilize more biological information to minimize the imputation error and thus can improve the performance of downstream analysis such as genetic regulatory network construction.

Objectives: Electronic health records (EHRs) are only a first step in capturing and utilizing healthrelated data—the challenge is turning that data into useful information. Furthermore, EHRs are increasingly likely to include data relating to patient outcomes, functionality such as clinical decision support, and genetic information as well, and, as such, can be seen as repositories of increasingly valuable information about patients’ health conditions and responses to treatment over time. Methods: We describe a case study of 423 patients treated by Centerstone within Tennessee and Indiana in which we utilized electronic health record data to generate predictive algorithms of individual patient treatment response. Multiple models were constructed using predictor variables derived from clinical, financial and geographic data. Results: For the 423 patients, 101 deteriorated, 223 improved and in 99 there was no change in clinical condition. Based on modeling of various clinical indicators at baseline, the highest accuracy in predicting individual patient response ranged from 70% to 72% within the models tested. In terms of individual predictors, the Centerstone Assessment of Recovery Level—Adult (CARLA) baseline score was most significant in predicting outcome over time (odds ratio 4.1+2.27). Other variables with consistently significant impact on outcome included payer, diagnostic category, location and provision of case management services. Conclusions: This approach represents a promising avenue toward reducing the current gap between research and practice across healthcare, developing data-driven clinical decision support based on real-world populations, and serving as a component of embedded clinical artificial intelligences that ‘‘learn’’ over time. & 2012 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved. 2211-8837/$ see front matter & 2012 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.hlpt.2012.03.001 Corresponding author at: Department of Informatics, Centerstone Research Institute, 365 South Park Ridge Road, Suite 103, Bloomington, IN 47401, United States. Tel.: +1 812 337 2302. E-mail addresses: Casey.Bennett@CenterstoneResearch.org (C.C. Bennett), Tom.Doub@CenterstoneResearch.org (T.W. Doub), RebeccaSelove@CenterstoneResearch.org (R. Selove). Health Policy and Technology (2012) 1, 105–114 Author's personal copy

The proliferation of Electronic Health Records (EHRs) challenges data miners to discover potential and previously unknown patterns from a large collection of medical data. One of the tasks that we address in this paper is to reveal previously unknown effects of drugs on laboratory test results. We propose a method that leverages drug information to find a meaningful list of drugs that have an effect on the laboratory result. We formulate the problem as a convex non smooth function and develop a proximal gradient method to optimize it. The model has been evaluated on two important use cases: lowering low-density lipoproteins and glycated hemoglobin test results. The experimental results provide evidence that the proposed method is more accurate than the state-of-the-art method, rediscover drugs that are known to lower the levels of laboratory test results, and most importantly, discover additional potential drugs that may also lower these levels.

This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. Identification algorithms based on the well-known linear least squares methods of gaussian elimination, Cholesky decomposition, classical Gram-Schmidt, modified Gram-Schmidt, Householder transformation, Givens method, and singular value decomposition are reviewed. The classical Gram-Schmidt, modified Gram-Schmidt,and Householder transformation algorithms are then extended to combine structure determination, or which terms to include in the model, and parameter estimation in a very simple and efficient manner for a class of multivariable discrete-time non-linear stochastic systems which are linear in the parameters.

Alignment-free sequence analysis approaches provide important alternatives over multiple sequence alignment (MSA) in biological sequence analysis because alignment-free approaches have low computation complexity and are not dependent on high level of sequence identity. However, most of the existing alignment-free methods do not employ true full information content of sequences and thus can not accurately reveal similarities and differences among DNA sequences. We present a novel alignment-free computational method for sequence analysis based on Ramanujan-Fourier transform (RFT), in which complete information of DNA sequences is retained. We represent DNA sequences as four binary indicator sequences and apply RFT on the indicator sequences to convert them into frequency domain. The Euclidean distance of the complete RFT coefficients of DNA sequences are used as similarity measures. To address the different lengths of RFT coefficients in Euclidean space, we pad zeros to short DNA binary sequences so that the binary sequences equal the longest length in the comparison sequence data. Thus, the DNA sequences are compared in the same dimensional frequency space without information loss. We demonstrate the usefulness of the proposed method by presenting experimental results on hierarchical clustering of genes and genomes. The proposed method opens a new channel to biological sequence analysis, classification, and structural module identification.

Nearly three decades have passed since the invention of electrophoretic methods for DNA sequencing. The exponential growth in the cost-effectiveness of sequencing has been driven by automation and by numerous creative refinements of Sanger sequencing, rather than through the invention of entirely new methods. Various novel sequencing technologies are being developed, each aspiring to reduce costs to the point at which the genomes of individual humans could be sequenced as part of routine health care. Here, we review these technologies, and discuss the potential impact of such a 'personal genome project' on both the research community and on society.

Motivation
Barcode sequencing (bar-seq) is a high-throughput, and cost effective method to assay large numbers of cell lineages or genotypes in complex cell pools. Because of its advantages, applications for bar-seq are quickly growing-from using neutral random barcodes to study the evolution of microbes or cancer, to using pseudo-barcodes, such as shRNAs or sgRNAs to simultaneously screen large numbers of cell perturbations. However, the computational pipelines for bar-seq clustering are not well developed. Available methods often yield a high frequency of under-clustering artifacts that result in spurious barcodes, or over-clustering artifacts that group distinct barcodes together. Here, we developed Bartender, an accurate clustering algorithm to detect barcodes and their abundances from raw next-generation sequencing data.

Results
In contrast with existing methods that cluster based on sequence similarity alone, Bartender uses a modified two-sample proportion test that also considers cluster size. This modification results in higher accuracy and lower rates of under- and over-clustering artifacts. Additionally, Bartender includes unique molecular identifier handling and a 'multiple time point' mode that matches barcode clusters between different clustering runs for seamless handling of time course data. Bartender is a set of simple-to-use command line tools that can be performed on a laptop at comparable run times to existing methods.

Availability and implementation
Bartender is available at no charge for non-commercial use at https://github.com/LaoZZZZZ/bartender-1.1.

Contact
sasha.levy@stonybrook.edu or song.wu@stonybrook.edu.

Supplementary information
Supplementary data are available at Bioinformatics online.


Question: A concise overview of Soar: An architectural framework for human cognition.

This paper presents TacAir-Soar, an advanced intelligent system designed to emulate human-like behavior in large-scale, distributed military simulations, specifically for combat flight scenarios. The system's novelty lies in its comprehensive approach and ability to scale, making it uniquely suited for the execution of a wide range of airborne missions typically undertaken by the United States military using fixed-wing aircraft. TacAir-Soar integrates a diverse set of intelligent features to achieve its goals, such as the real-time orchestration of complex goals and plans, effective communication and coordination with both human operators and simulated entities, continuous situational awareness, and the capacity to adapt to new orders in-flight. This intelligent pilot system is currently in operation at the Oceana Naval Air Station WISSARD Lab and the Air Force Research Laboratory in Mesa, Arizona. A notable demonstration of its capabilities was during the Synthetic Theater of War 1997, a rigorous operational training exercise that spanned 48 hours continuously, during which TacAir-Soar successfully controlled all U.S. fixed-wing aircraft, showcasing its robustness and adaptability in complex, real-world scenarios.

Good pedagogical actions are key components in all learning-teaching schemes. Automate that is an important Intelligent Tutoring Systems objective. We propose apply Partially Observable Markov Decision Process (POMDP) in order to obtain automatic and optimal pedagogical recommended action patterns in benefit of human students, in the context of Intelligent Tutoring System. To achieve that goal, we need previously create an efficient POMDP solver framework with the ability to work with real world tutoring cases. At present time, there are several Web available POMDP open tool solvers, but their capacity is limited, as experiments showed in this paper exhibit. In this work, we describe and discuss several design ideas toward obtain an efficient POMDP solver, useful in our problem domain.

Hiding and seeking are cognitive abilities frequently demonstrated by humans in both real life and video games. To determine to which extent these abilities can be replicated with AI, we introduce a specialized version of the Turing test for hiding and seeking. We then develop a computer agent that passes the test by appearing indistinguishable from human behavior to a panel of human judges. We analyze the AI techniques that enable the agent to imitate human hide-and-seek behavior and their relative contribution to the agent's performance.

This paper presents a framework for knowledge discovery and concept exploration. In order to enhance the concept exploration capability of knowledge-based systems and to alleviate the limitations of the manual browsing approach, we have developed two spreading activation-based algorithms for concept exploration in large, heterogeneous networks of concepts (e.g., multiple thesauri). One algorithm, which is based on the symbolic Al paradigm, performs a conventional branch-and-bound search on a semantic net representation to identify other highly relevant concepts (a serial, optimal search process). The second algorithm, which is based on the neural network approach, executes the Hopfield net parallel relaxation and convergence process to identify “convergent” concepts for some initial queries (a parallel, heuristic search process). Both algorithms can be adopted for automatic, multiple-thesauri consultation. We tested these two algorithms on a large text-based knowledge network of about 13,000 nodes (terms) and 80,000 directed links in the area of computing technologies. This knowledge network was created from two external thesauri and one automatically generated thesaurus. We conducted experiments to compare the behaviors and performances of the two algorithms with the hypertext-like browsing process. Our experiment revealed that manual browsing achieved higher-term recall but lower-term precision in comparison to the algorithmic systems. However, it was also a much more laborious and cognitively demanding process. In document retrieval, there were no statistically significant differences in document recall and precision between the algorithms and the manual browsing process. In light of the effort required by the manual browsing process, our proposed algorithmic approach presents a viable option for efficiently traversing largescale, multiple thesauri (knowledge network).

This paper describes the software architecture of Stanley, an autonomous land vehicle developed for high-speed desert driving without human intervention. The vehicle recently won the DARPA Grand Challenge, a major robotics competition. The article describes the software architecture of the robot, which relied pervasively on state-of-the-art AI technologies, such as machine learning and probabilistic reasoning.

This article presents a framework for empowering automated cognition and decision making in complex cyber-physical systems (CPS). The key idea is for each cyber-physical component in the system to be able to construct from observations and actions a reduced model of its behavior and respond to external stimuli in the form of a (timed) probabilistic automaton such as a semi-Markov decision process. The reduced order behavioral models of various cyber-physical components can then be integrated into an optimization and decision-making module to determine the best actions for the components under different operating scenarios and cost / payoff functions by solving a bounded-rationality global decision-making problem.1

1. Mental models Since the early 1980s, the notion of mental model has been quite successful in cognitive psychology in general, and in the theory of text processing in particu-Such models have been conceptualized as representations in episodic memory of situations, acts or events spoken or thought about, observed or participated in by human actors, that is of experiences (Ehrlich, Tardieu & Cavazza 1993). In the theory of text processing, such (situation or event) models played a crucial role in establishing the necessary referential basis for the processing of anaphora and other phenomena of coherence (Albrecht & O Brien 1993). They further explained, among many other things, why text recall does not seem to be based on semantic representations of texts, but rather on the mental model construed or updated of the event the text is about (Bower & Morrow 1990). Conversely, mental models also play a role in the much neglected theory of discourse production, viz., as the mental point of departure of all text and talk, from which relevant information may be selected for the strategic construction of their global and local semantic structures. Many experiments have confirmed these hypotheses, and have shown at text comprehension and recall essentially involve a strategic manipulation of models, for instance by matching text information with structures of the The notion of mental space is sometimes also used in formal linguistics as a construct that has similar functions as our notion of a mental model (Faucormier 1985).

We present Project Malmo – an AI experimentation platform built on top of the popular computer game Minecraft, and designed to support fundamental research in artificial intelligence. As the AI research community pushes for artificial general intelligence (AGI), experimentation platforms are needed that support the development of flexible agents that learn to solve diverse tasks in complex environments. Minecraft is an ideal foundation for such a platform, as it exposes agents to complex 3D worlds, coupled with infinitely varied game-play. Project Malmo provides a sophisticated abstraction layer on top of Minecraft that supports a wide range of experimentation scenarios, ranging from navigation and survival to collaboration and problem solving tasks. In this demo we present the Malmo platform and its capabilities. The platform is publicly released as open source software at IJCAI, to support openness and collaboration in AI research.

Humans and other animals often engage in activities for their own sakes rather than as steps toward solving practical problems. Psychologists call these intrinsically motivated behaviors. What we learn during intrinsically motivated behavior is essential for our development as competent autonomous entities able to efficiently solve a wide range of practical problems as they arise. In this paper we present initial results from a computational study of intrinsically motivated learning aimed at allowing artificial agents to construct and extend hierarchies of reusable skills that are needed for competent autonomy. At the core of the model are recent theoretical and algorithmic advances in computational reinforcement learning, specifically, new concepts related to skills and new learning algorithms for learning with skill hierarchies.

MC& CYC project is the building, over the coming decade, of a large knowledge base (or KB) of real world facts and heuristics and-as a part of the KB itself-methods for efficiently reasoning over the KB. As the title of this article suggests, our hypothesis is that the two major limitations to building large intelligent programs might be overcome by using such a system. We briefly illustrate how common sense reasoning and analogy can widen the knowledge acquisition bottleneck The next section (“How CYC Works”) illustrates how those same two abilities can solve problems of the type that stymie current expert systems. We then report how the project is being conducted currently: its strategic philosophy, its tactical methodology, and a case study of how we are currently putting that into practice. We conclude with a discussion of the project’s feasibility and timetable.

This chapter addresses the challenge of building or authoring an Intelligent Tutoring System (ITS), along with the problems that have arisen and been dealt with, and the solutions that have been tested. We begin by clarifying what building an ITS entails, and then position today's systems in the overall historical context of ITS research. The chapter concludes with a series of open questions and an introduction to the other chapters in this part of the book.


Question: A concise overview of Soar, an architectural framework for human cognition.

This paper delves into the application of information theory to quantify the human motor system's capabilities in regulating movement amplitude, marking an expansion of its use in sensory, perceptual, and perceptual-motor functions. Initially, the focus will be on evaluating the theory's fundamental aspects: information volume, noise, channel capacity, and transmission rate. It is assumed that readers are acquainted with these concepts as outlined by contemporary theorists. However, it's crucial to note that the motor system cannot be studied in isolation from its sensory components at the behavioral level. Instead, our analysis must encompass the entire receptor-neural-effector system as a whole, as the motor system's performance is inherently intertwined with its sensory mechanisms.

In exploring the motor system's information capacity, the paper highlights the intricate relationship between the motor commands and the sensory feedback necessary for controlling movement amplitude. The human body, as a complex system, integrates sensory inputs and motor outputs in a manner that reflects the principles of information theory. The study of this integration provides insights into how the human body optimally utilizes the available information to achieve precise control over movements.

By employing information theory, researchers can better understand the constraints and capabilities of the human motor system. This includes quantifying the amount of information that can be transmitted through motor commands and assessing the impact of noise on the system's performance. Moreover, the concept of channel capacity becomes relevant in understanding the limits of information processing within the motor system, which ultimately influences the control and coordination of movements.

The paper's investigation into the information capacity of the human motor system contributes to a broader understanding of human cognition and behavior. It sheds light on the neural mechanisms underlying motor control and highlights the role of sensory feedback in achieving precise and adaptive motor responses. By examining the motor system within the framework of information theory, the study offers a novel perspective on how humans process and utilize information to execute complex movements with remarkable accuracy and efficiency.

Computer models of emotion inform theories of human intelligence and advance human-centric applications.

Recent advances in deep learning have allowed artificial agents to rival human-level performance on a wide range of complex tasks; however, the ability of these networks to learn generalizable strategies remains a pressing challenge. This critical limitation is due in part to two factors: the opaque information representation in deep neural networks and the complexity of the task environments in which they are typically deployed. Here we propose a novel Hierarchical Q-Network (HQN), motivated by theories of the hierarchical organization of the human prefrontal cortex, that attempts to identify lower dimensional patterns in the value landscape that can be exploited to construct an internal model of rules in simple environments. We draw on combinatorial games, where there exists a single optimal strategy for winning that generalizes across other features of the game, to probe the strategy generalization of the HQN and other reinforcement learning (RL) agents using variations of Wythoff’s game. Traditional RL approaches failed to reach satisfactory performance on variants of Wythoff’s Game; however, the HQN learned heuristic-like strategies that generalized across changes in board configuration. More importantly, the HQN allowed for transparent inspection of the agent’s internal model of the game following training. Our results show how a biologically inspired hierarchical learner can facilitate learning abstract rules to promote robust and flexible action policies in simplified training environments with clearly delineated optimal strategies. 1 ar X iv :1 80 1. 06 68 9v 1 [ cs .A I] 2 0 Ja n 20 18

The General Video Game AI framework and competition pose the problem of creating artificial intelligence that can play a wide, and in principle unlimited, range of games. Concretely, it tackles the problem of devising an algorithm that is able to play any game it is given, even if the game is not known a priori. This area of study can be seen as an approximation of General Artificial Intelligence, with very little room for game-dependent heuristics. This talk summarizes the motivation, infrastructure, results and future plans of General Video Game AI, stressing the findings and first conclusions drawn after two editions of our competition, presenting the tracks that will be held in 2016 and outlining our future plans.

Causal knowledge plays a crucial role in human thought, but the nature of causal representation and inference remains a puzzle. Can human causal inference be captured by relations of probabilistic dependency, or does it draw on richer forms of representation? This article explores this question by reviewing research in reasoning, decision making, various forms of judgment, and attribution. We endorse causal Bayesian networks as the best normative framework and as a productive guide to theory building. However, it is incomplete as an account of causal thinking. On the basis of a range of experimental work, we identify three hallmarks of causal reasoning-the role of mechanism, narrative, and mental simulation-all of which go beyond mere probabilistic knowledge. We propose that the hallmarks are closely related. Mental simulations are representations over time of mechanisms. When multiple actors are involved, these simulations are aggregated into narratives.

As part of the information fusion task we wish to automatically fuse information derived from the text extraction process with data from a structured knowledge base. This process will involve resolving, aggregating, integrating and abstracting information via the methodologies of Knowledge Representation and Reasoning into a single comprehensive description of an individual or event. This report surveys the key principles underlying research in the field of Knowledge Representation and Reasoning. It represents an initial step in deciding upon a Knowledge Representation and Reasoning system for our information fusion task. APPROVED FOR PUBLIC RELEASE

We expect a variety of autonomous systems, from rovers to life-support systems, to play a critical role in the success of manned Mars missions. The crew and ground support personnel will want to control and be informed by these systems at varying levels of detail depending on the situation. Moreover, these systems will need to operate safely in the presence of people and cooperate with them effectively. We call such autonomous systems human-centered in contrast with traditional Òblack-boxÓ autonomous systems. Our goal is to design a framework for human-centered autonomous systems that enables users to interact with these systems at whatever level of control is most appropriate whenever they so choose, but minimize the necessity for such interaction. This paper discusses on-going research at the NASA Ames Research Center and the Johnson Space Center in developing human-centered autonomous systems that can be used for a manned Mars mission.

The paper discusses the augmentation of the Concurrent Individual and Social Learning (CISL) mechanism with a new Human Advice Layer (HAL). The new layer is characterized by a Gaussian Mixture Model (GMM), which is trained on human experience data. The CISL mechanism consists of the Individual Performance and Task Allocation Markov Decision Processes (MDP), and the HAL can provide preferred action selection policies to the individual agents. The data utilized for training the GMM is collected using a heterogeneous team foraging simulation. When leveraging human experience in the multi-agent learning process, the team performance is enhanced significantly.

In our research on Commonsense reasoning, we have found that an especially important kind of knowledge is knowledge about human goals. Especially when applying Commonsense reasoning to interface agents, we need to recognize goals from user actions (plan recognition), and generate sequences of actions that implement goals (planning). We also often need to answer more general questions about the situations in which goals occur, such as when and where a particular goal might be likely, or how long it is likely to take to achieve. In past work on Commonsense knowledge acquisition, users have been directly asked for such information. Recently, however, another approach has emerged—to entice users into playing games where supplying the knowledge is the means to scoring well in the game, thus motivating the players. This approach has been pioneered by Luis von Ahn and his colleagues, who refer to it as Human Computation. Common Consensus is a fun, self-sustaining web-based game, that both collects and validates Commonsense knowledge about everyday goals. It is based on the structure of the TV game show Family Feud1. A small user study showed that users find the game fun, knowledge quality is very good, and the rate of knowledge collection is rapid. ACM Classification: H.3.3 [INFORMATION STORAGE AND RETRIEVAL]: Information Search and Retrieval; I.2.6 [ARTIFICIAL INTELLIGENCE]: Learning

The cognitive dimensions framework is a broad-brush evaluation technique for interactive devices and for non-interactive notations. It sets out a small vocabulary of terms designed to capture the cognitively-relevant aspects of structure, and shows how they can be traded off against each other. The purpose of this paper is to propose the framework as an evaluation technique for visual programming environments. We apply it to two commercially-available dataflow languages (with further examples from other systems) and conclude that it is effective and insightful; other HCI-based evaluation techniques focus on different aspects and would make good complements. Insofar as the examples we used are representative, current VPLs are successful in achieving a good ‘closeness of match’, but designers need to consider the ‘viscosity’ (resistance to local change) and the ‘secondary notation’ (possibility of conveying extra meaning by choice of layout, colour, etc.).

CONSIDER THE FOLLOWING SCEnario. A fleet of unmanned air vehicles undertakes a mission to disable an enemy airfield. Pre-mission intelligence indicates that the airfield is not defended, and mission planning proceeds accordingly. While the UAVs are en route to the target, new intelligence indicates that a mobile surface-to-air missile launcher now guards the airfield. The UAVs autonomously replan their mission, dividing into two groups—a SAM-suppression unit and an airfield-suppression unit—and proceed to accomplish their objectives. During the flight, specialized algorithms for detecting and recognizing SAM launchers automatically upload and are integrated into the SAM-suppression unit’s software. In this scenario, new software components are dynamically inserted into fielded, heterogeneous systems without requiring system restart, or indeed, any downtime. Mission replanning relies on analyses that include feedback from current performance. Furthermore, such replanning can take place autonomously, can involve multiple, distributed, cooperating planners, and where major changes are demanded and require human approval or guidance, can cooperate with mission analysts. Throughout, system integrity requires the assurance of consistency, correctness, and coordination of changes. Other applications for fleets of UAVs might include environment and land-use monitoring, freeway-traffic management, fire fighting, airborne cellular-telephone relay stations, and damage surveys in times of natural disaster. How wasteful to construct afresh a specific software platform for each new UAV application! Far better if software architects can simply adapt the platform to the application at hand, and better yet, if the platform itself adapts on demand even while serving some other purpose. For example, an irborne sensor platform designed for environmental and land-use monitoring could prove useful for damage surveys following an earthquake or hurricane, provided someone could change the software quickly enough and with sufficient assurance that the new system would perform as intended. Software engineering aims for the systematic, principled design and deployment of applications that fulfill software’s original promise—applications that retain full plasticity throughout their lifecycle and that are as easy to modify in the field as they are on the drawing board. Software engineers have pursued many techniques for achieving this goal: specification languages, high-level programming languages, and object-oriented analysis and design, to name just a few. However, while each contributes to the goal, the sum total still falls short. Self-adaptive software will provide the key. Many disciplines will contribute to its progress, but wholesale advances require a sysSELF-ADAPTIVE SOFTWARE REQUIRES HIGH DEPENDABILITY, ROBUSTNESS, ADAPTABILITY, AND AVAILABILITY. THIS ARTICLE DESCRIBES AN INFRASTRUCTURE SUPPORTING TWO SIMULTANEOUS PROCESSES IN SELF-ADAPTIVE SOFTWARE: SYSTEM EVOLUTION, THE CONSISTENT APPLICATION OF CHANGE OVER TIME, AND SYSTEM ADAPTATION, THE CYCLE OF DETECTING CHANGING CIRCUMSTANCES AND PLANNING AND DEPLOYING RESPONSIVE MODIFICATIONS.


Question: A beginner's guide to Soar, a cognitive architecture for human-like thinking.

In this paper, we delve into the evolution of communication theory, particularly in light of recent advancements in modulation techniques such as Pulse Code Modulation (PCM) and Pulse Position Modulation (PPM), which trade bandwidth for signal-to-noise ratio. This has heightened the demand for a comprehensive theory of communication, the groundwork for which was laid by Nyquist and Hartley in their seminal works. We aim to expand upon their theories by incorporating additional elements, notably the impact of channel noise and the efficiency gains derived from the statistical structure of the original message and the nature of the information's end destination. The core challenge in communication is the accurate or approximate reproduction of a message chosen at one location at another. Although messages often carry meaning and are correlated with physical or conceptual entities, these semantic elements are extraneous to the engineering challenge at hand. What matters is that the actual message is selected from a pool of possible messages. The system design must accommodate every possible selection, not just the one that will be chosen, as this is unknown during the design phase. If the pool of messages is finite, the number of messages or any monotonically increasing function of this number can serve as a measure of the information produced when a message is chosen from the set, assuming all choices are equally probable. As Hartley suggested, the most intuitive choice is the logarithmic function. Although this definition requires significant generalization when considering the influence of message statistics and continuous message ranges, we will consistently utilize a logarithmic measure. This choice is more practical for several reasons:

The exploration of communication theory in this context provides a foundation for understanding how information is processed and transmitted, which is crucial for the development of architectures like Soar that aim to emulate human cognition. The use of a logarithmic measure to quantify information, as proposed by Hartley, aligns with the need to efficiently encode and decode messages, a principle that can be extended to the cognitive processing of information within human-like AI systems. This theoretical framework supports the design of architectures capable of handling large volumes of data, akin to human cognitive capabilities, by emphasizing the importance of message statistics and the optimization of information transmission.

MC& CYC project is the building, over the coming decade, of a large knowledge base (or KB) of real world facts and heuristics and-as a part of the KB itself-methods for efficiently reasoning over the KB. As the title of this article suggests, our hypothesis is that the two major limitations to building large intelligent programs might be overcome by using such a system. We briefly illustrate how common sense reasoning and analogy can widen the knowledge acquisition bottleneck The next section (“How CYC Works”) illustrates how those same two abilities can solve problems of the type that stymie current expert systems. We then report how the project is being conducted currently: its strategic philosophy, its tactical methodology, and a case study of how we are currently putting that into practice. We conclude with a discussion of the project’s feasibility and timetable.

Software agents, or softbots, are supposedly intelligent programs that assist the user in performing repetitive , boring, and time-consuming tasks. An overview of software agents, with special attention focused on the so-called personal assistants, is presented as an introduction. Following that, an in-depth look at one of the rst commercially available intelligent agents Open Sesame!, a personal assistant for managing the Macintosh desktop environment, is presented. The existing intelligent agent paradigms, we argue, break down when it comes to actively helping the end user because of aws inherent in the current approaches to intelligent agent design. To that end, we discuss the reasons why this is, particularly with respect to Open Sesame!, and promote the notion of situatedness to be taken into account more seriously for developing software agents that actively support the user for the duration of the task at hand. As an example for a more situated approach to personal assistant design, a quick overview of a project to develop a personal assistant for news ltering is discussed.

system for handling the design of elevator systems that is currently in use at Westinghouse Elevator Company Although VT tries to postpone each decision in creating a design until all information that constrains the decision is known, for many decisions this postponement is not possible In these cases, VT uses the strategy of constructing a plausible approximation and successively refining it VT uses domain-specific knowledge to guide its backtracking search for successful refinements The VT architecture provides the basis for a knowledge representation that is used by SALT, an automated knowledge-acquisition tool SALT was used to build VT and provides an analysis of VT’s knowledge base to assess its potential for convergence on a solution VT: An Expert Elevator Designer That Uses Knowledge-Based Backtracking Sandra Marcus, Jeffrey Stout, John McDermott

This paper describes an effort to model students' changing knowledge state during skill acquisition. Students in this research are learning to write short programs with the ACT Programming Tutor (APT). APT is constructed around a production rule cognitive model of programming knowledge, called theideal student model. This model allows the tutor to solve exercises along with the student and provide assistance as necessary. As the student works, the tutor also maintains an estimate of the probability that the student has learned each of the rules in the ideal model, in a process calledknowledge tracing. The tutor presents an individualized sequence of exercises to the student based on these probability estimates until the student has ‘mastered’ each rule. The programming tutor, cognitive model and learning and performance assumptions are described. A series of studies is reviewed that examine the empirical validity of knowledge tracing and has led to modifications in the process. Currently the model is quite successful in predicting test performance. Further modifications in the modeling process are discussed that may improve performance levels.

The Experimental Study of Adaptive User Interfaces Pat Langley (langley@isle.org) Institute for the Study of Learning and Expertise 2164 Staunton Court, Palo Alto, CA 94306 Michael Fehling (fehling@odc.stanford.edu) Organizational Dynamics Center, EES/OR Department Stanford University, Stanford, CA 94305 Abstract In this paper we examine some issues that arise in the experimental evaluation of adaptive user interfaces, which are computational decision aids that use machine learning to improve their interaction with users. We begin by reviewing the notion of an adaptive interface and presenting examples for a number of application areas. After this, we discuss plausible dependent measures of their behavior, including solution speed, solution quality, user satisfaction, and predictive accuracy. Next we turn to independent variables that are likely to in uence these measures, including the number of user interactions and characteristics of the system, the user, and the task at hand. In closing, we comment on the role that experimentation plays in the larger scienti c process.

How do we learn to think better, and what can we do to promote such metacognitive learning? Here, we propose that cognitive growth proceeds through metacognitive reinforcement learning. We apply this theory to model how people learn how far to plan ahead and test its predictions about the speed of metacognitive learning in two experiments. In the first experiment, we find that our model can discern a reward structure that promotes metacognitive reinforcement learning from one that hinders it. In the second experiment, we show that our model can be used to design a feedback mechanism that enhances metacognitive reinforcement learning in an environment that hinders learning. Our results suggest that modeling metacognitive learning is a promising step towards promoting cognitive growth.

John Boyd recognized in the 1960's the importance of situation awareness for military operations and introduced the notion of the OODA loop (Observe, Orient, Decide, and Act). Today we realize that many applications have to deal with situation awareness: Customer Relationship Management, Human Capital Management, Supply Chain Management, patient care, power grid management, and cloud services management, as well as any IoT (Internet of Things) related application; the list seems to be endless. Situation awareness requires applications to support the management of data, knowledge, processes, and other services such as social networking in an integrated way. These applications additionally require high personalization as well as rapid and continuous evolution. They must provide a wide variety of operational and functional requirements, including real time processing.
 Handcrafting these applications is an almost impossible task requiring exhaustive resources for development and maintenance. Due to the resources and time involved in their development, these applications typically fall way short of the desired functionality, operational characteristics, and ease and speed of evolution. We - the authors - have developed a model enabling the development and maintenance of situation-aware applications in a declarative and therefore economical manner; we call this model KIDS - Knowledge Intensive Data-processing System.

This paper summarizes our ongoing project on developing an architecture for a robot that can acquire new words and their meanings while engaging in multidomain dialogues. These two functions are crucial in making conversational service robots work in real tasks in the real world. Household robots and office robots need to be able to work in multiple task domains and they also need to engage in dialogues in multiple domains corresponding to those task domains. Lexical acquisition is necessary because speech understanding cannot be done without enough knowledge on words that are possibly spoken in the task domain. Our architecture is based on a multi-expert model in which multiple domain experts are employed and one of them is selected based on the user utterance and the situation to engage in the control of the dialogue and physical behaviors. We incorporate experts that have an ability to acquire new lexical entries and their meanings grounded on the physical world through spoken interactions. By appropriately selecting those experts, lexical acquisition in multi-domain dialogues becomes possible. An example robotic system based on this architecture that can acquire object names and location names demonstrates the viability of the architecture.

Emotions have a powerful impact on behavior and beliefs. The goal of our research is to create general computational models of this interplay of emotion, cognition and behavior to inform the design of virtual humans. Here, we address an aspect of emotional behavior that has been studied extensively in the psychological literature but largely ignored by computational approaches, emotion-focused coping. Rather than motivating external action, emotion-focused coping strategies alter beliefs in response to strong emotions. For example an individual may alter beliefs about the importance of a goal that is being threatened, thereby reducing their distress. We present a preliminary model of emotion-focused coping and discuss how coping processes, in general, can be coupled to emotions and behavior. The approach is illustrated within a virtual reality training environment where the models are used to create virtual human characters in high-stress social situations.

We expect a variety of autonomous systems, from rovers to life-support systems, to play a critical role in the success of manned Mars missions. The crew and ground support personnel will want to control and be informed by these systems at varying levels of detail depending on the situation. Moreover, these systems will need to operate safely in the presence of people and cooperate with them effectively. We call such autonomous systems human-centered in contrast with traditional Òblack-boxÓ autonomous systems. Our goal is to design a framework for human-centered autonomous systems that enables users to interact with these systems at whatever level of control is most appropriate whenever they so choose, but minimize the necessity for such interaction. This paper discusses on-going research at the NASA Ames Research Center and the Johnson Space Center in developing human-centered autonomous systems that can be used for a manned Mars mission.


Question: A concise overview of Soar: An architectural framework for human cognition.

The RoboCup Initiative: A Standardized Platform for AI and Robotics Research

The Robot World Cup Initiative, commonly known as RoboCup, is a pioneering effort aimed at advancing AI and robotics by offering a standardized problem set where a broad spectrum of technologies can be integrated and evaluated. The inaugural RoboCup competition took place at IJCAI-97 in Nagoya. To successfully execute a soccer match with robotic teams, a diverse array of technologies must be seamlessly integrated. These include design principles for autonomous agents, multi-agent cooperation, strategy development, real-time decision-making, robotics, and sensor fusion. Contrary to the AAAI robot competition, which is geared towards a solitary, heavy-duty, and relatively slow-moving robot, RoboCup presents a complex challenge for a team of agile, fast-moving robots operating in a dynamic environment. While the ultimate goal of RoboCup is to host a global championship with physical robots, it also provides a software platform to focus on the underlying software challenges. This paper elaborates on the technical hurdles, competition rules, and the simulation environment that are integral to the RoboCup initiative.

This paper describes an architecture that combines the complementary strengths of probabilistic graphical models and declarative programming to enable robots to represent and reason with qualitative and quantitative descriptions of uncertainty and domain knowledge. An action language is used for the architecture’s low-level (LL) and high-level (HL) system descriptions, and the HL definition of recorded history is expanded to allow prioritized defaults. For any given objective, tentative plans created in the HL using commonsense reasoning are implemented in the LL using probabilistic algorithms, and the corresponding observations are added to the HL history. Tight coupling between the levels helps automate the selection of relevant variables and the generation of policies in the LL for each HL action, and supports reasoning with violation of defaults, noisy observations and unreliable actions in complex domains. The architecture is evaluated in simulation and on robots moving objects in indoor domains.

We present a novel multi-robot simulator named ARGoS. ARGoS is designed to simulate complex experiments involving large swarms of robots of different types. ARGoS is the first multi-robot simulator that is at the same time both efficient (fast performance with many robots) and flexible (highly customizable for specific experiments). Novel design choices in ARGoS have enabled this breakthrough. First, in ARGoS, it is possible to partition the simulated space into multiple sub-spaces, managed by different physics engines running in parallel. Second, ARGoS’ architecture is multi-threaded, thus designed to optimize the usage of modern multi-core CPUs. Finally, the architecture of ARGoS is highly modular, enabling easy addition of custom features and appropriate allocation of computational resources. We assess the efficiency of ARGoS and showcase its flexibility with targeted experiments. Experimental results demonstrate that simulation run-time increases linearly with the number of robots. A 2D-dynamics simulation of 10,000 e-puck robots can be performed in 60 % of the time taken by the corresponding real-world experiment. We show how ARGoS can be extended to suit the needs of an experiment in which custom functionality is necessary to achieve sufficient simulation accuracy. ARGoS is open source software licensed under GPL3 and is downloadable free of charge.

Robots assisting humans in complex domains need the ability to represent, reason with, and learn from, different descriptions of incomplete domain knowledge and uncertainty. This paper focuses on the challenge of incrementally and interactively discovering previously unknown axioms governing domain dynamics, and describes an architecture that integrates declarative programming and relational reinforcement learning to address this challenge. Answer Set Prolog (ASP), a declarative programming paradigm, is used to represent and reason with incomplete domain knowledge for planning and diagnostics. For any given goal, unexplained failure of plans created by ASP-based inference is taken to indicate the existence of unknown domain axioms. The task of discovering these axioms is formulated as a reinforcement learning problem, and a relational representation is used to incrementally generalize from specific axioms identified over time. These generic axioms are then added to the ASP-based representation for subsequent inference. The architecture's capabilities are demonstrated and evaluated in two domains, Blocks World and Robot Butler.

This paper discusses the problems of developing versatile adaptive and intelligent learning systems that can be used in the context of practical Web-based education. We argue that versatility is an important feature of successful Web-based education systems. We introduce ELM-ART, an intelligent interactive educational system to support learning programming in LISP. ELM-ART provides all learning material online in the form of an adaptive interactive textbook. Using a combination of an overlay model and an episodic student model, ELM-ART provides adaptive navigation support, course sequencing, individualized diagnosis of student solutions, and example-based problem-solving support. Results of an empirical study show different effects of these techniques on different types of users during the first lessons of the programming course. ELM-ART demonstrates how some interactive and adaptive educational components can be implemented in WWW context and how multiple components can be naturally integrated together in a single system.

Space syntax research has found that spatial configuration alone explains a substantial proportion of the variance between aggregate human movement rates in different locations in both urban and building interior space. Although it seems possible to explain how people move on the basis of these analyses, the question of why they move this way has always seemed problematic because the analysis contains no explicit representations of either motivations or individual cognition. One possible explanation for the method’s predictive power is that some aspects of cognition are implicit in space syntax analysis. This article reviews the contribution made by syntax research to the understanding of environmental cognition. It proposes that cognitive space, defined as that space which supports our understanding of configurations more extensive than our current visual field, is not a metric space, but topological. A hypothetical process for deriving a nonmetric space from the metric visibility graph involving exploratory movement is developed. The resulting space is shown to closely resemble the axial graph. One of the favored assumptions of those dealing with human action is that the “prime mover” is individual motivation or goal-directed behavior. The evidence from space syntax research, however, is that one can get quite a long way in predicting movement behavior without invoking goals and motivations and in fact, without explicitly assuming anything about individuals or their cognitive capacity. This empirical success is sometimes taken to suggest that individuals and their motivations are not considered important or of interest in space syntax research. Here I argue the reverse. I propose that clues to the nature of individual motivation and cognition may be implicit in space 30 ENVIRONMENT AND BEHAVIOR, Vol. 35 No. 1, January 2003 30-65 DOI: 10.1177/0013916502238864 © 2003 Sage Publications © 2003 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at PENNSYLVANIA STATE UNIV on April 16, 2008 http://eab.sagepub.com Downloaded from syntax theory and analysis, and by making these explicit, the field can contribute to a better understanding of individual-level mechanisms. It is important to note that space syntax research started out as research into societies as distinct to individuals, and it is perhaps this way of slicing the cake—taking a view on what is external and common to all individuals and therefore potentially social—that has led us to take a quite fundamentally different approach to those commonly adopted by researchers who start through a consideration of the individual. I will suggest that the light syntax research can throw on issues of cognition stems from taking this social and therefore broadly exosomatic perspective. I will start, however, with an apparently relatively minor outcome of this program of social research, which was probably unforeseen at the outset but which has become central to the broad social theory proposed by space syntax. Space syntax analysis (which represents and quantifies aspects of spatial pattern) has found that spatial configuration correlates powerfully with observed movement by both pedestrians (e.g., Hillier, Burdett, Peponis, & Penn, 1987; Hillier, Hanson, Peponis, Hudson, & Burdett, 1983; Hillier, Penn, Hanson, Grajewski, & Xu, 1993; Peponis, Hadjinikolaou, Livieratos, & Fatouros, 1989; Read, 1999) and drivers (Penn, Hillier, Banister, & Xu, 1998a, 1998b) (Figure 1). This degree of correlation is surprising because the analysis appears not to incorporate many of the factors considered critical in previous efforts to model human movement patterns through the built environment. The analysis incorporates only certain aspects of the geometry of the environment and makes no mention of the motivations or intentions of the movers either explicitly through the use of origin-destination (O-D) information or implicitly by inclusion of land use, development density, or other factors that might act as a proxy for these. Even the geometric descriptions it uses are extremely parsimonious. No direct account is taken of the metric properties of space, and the analysis that to date has shown the most consistent empirical correlation reduces the effects of metric distance to a minimum and places the most emphasis on the average number of changes of direction encountered on routes, not to specific destinations but to all possible destinations. This appears to eliminate a key factor in most modeling approaches based on rational choice, in which the main “cost” associated with travel— and which it is assumed the rational individual will seek to minimize while achieving their goals—is usually taken as travel time judged on the basis of metric distance. It is, however, exactly the parsimony of the representation and the consistent strength of the empirical results that makes for the practical usefulness of syntax analysis as a design tool (see www.spacesyntax.com for a summary of recent applications projects). Few assumptions need to be made about future Penn / SPACE SYNTAX AND SPATIAL COGNITION 31 © 2003 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at PENNSYLVANIA STATE UNIV on April 16, 2008 http://eab.sagepub.com Downloaded from 32 ENVIRONMENT AND BEHAVIOR / January 2003

This paper extends the Function-Behaviour-Structure (FBS) framework, which proposed eight fundamental processes involved in designing. This framework did not explicitly account for the dynamic character of the context in which designing takes place, described by the notion of situatedness. This paper describes this concept as a recursive interrelationship between different environments, which, together with a model of constructive memory, provides the foundation of a situated FBS framework. The eight fundamental processes are then reconstructed within this new framework to represent designing in a dynamic world.

Understanding argumentation and its role in human reasoning has been a continuous subject of investigation for scholars from the ancient Greek philosophers to current researchers in philosophy, logic and artificial intelligence. In recent years, argumentation models have been used in different areas such as knowledge representation, explanation, proof elaboration, commonsense reasoning, logic programming, legal reasoning, decision making, and negotiation. However, these models address quite specific needs and there is need for a conceptual framework that would organize and compare existing argumentation-based models and methods. Such a framework would be very useful especially for researchers and practitioners who want to select appropriate argumentation models or techniques to be incorporated in new software systems with argumentation capabilities. In this paper, we propose such a conceptual framework, based on taxonomy of the most important argumentation models, approaches and systems found in the literature. This framework highlights the similarities and differences between these argumentation models. As an illustration of the practical use of this framework, we present a case study which shows how we used this framework to select and enrich an argumentation model in a knowledge acquisition project which aimed at representing argumentative knowledge contained in texts critiquing military courses of action.

Humans and other animals often engage in activities for their own sakes rather than as steps toward solving practical problems. Psychologists call these intrinsically motivated behaviors. What we learn during intrinsically motivated behavior is essential for our development as competent autonomous entities able to efficiently solve a wide range of practical problems as they arise. In this paper we present initial results from a computational study of intrinsically motivated learning aimed at allowing artificial agents to construct and extend hierarchies of reusable skills that are needed for competent autonomy. At the core of the model are recent theoretical and algorithmic advances in computational reinforcement learning, specifically, new concepts related to skills and new learning algorithms for learning with skill hierarchies.

This chapter addresses the challenge of building or authoring an Intelligent Tutoring System (ITS), along with the problems that have arisen and been dealt with, and the solutions that have been tested. We begin by clarifying what building an ITS entails, and then position today's systems in the overall historical context of ITS research. The chapter concludes with a series of open questions and an introduction to the other chapters in this part of the book.

This article presents a framework for empowering automated cognition and decision making in complex cyber-physical systems (CPS). The key idea is for each cyber-physical component in the system to be able to construct from observations and actions a reduced model of its behavior and respond to external stimuli in the form of a (timed) probabilistic automaton such as a semi-Markov decision process. The reduced order behavioral models of various cyber-physical components can then be integrated into an optimization and decision-making module to determine the best actions for the components under different operating scenarios and cost / payoff functions by solving a bounded-rationality global decision-making problem.1