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Recent efforts to build computer simulation models of mental imagery have suggested that imagery is not a unitary phenomenon. Rather, such efforts have led to a modular analysis of the image generation process, with separate modules that can activate visual memories, inspect parts of imaged patterns, and arrange separate parts into a composite image. This idea was supported by the finding of functional dissociations between the kinds of imagery tasks that could be performed in the left and right cerebral hemispheres of two patients who had had their corpus collosa surgically severed. The left hemisphere in both subjects could inspect imaged patterns and could generate single and multi-part images. In contrast, although the right hemisphere could inspect imaged patterns and could generate images of overall shape, it had difficulty in generating multi-part images. the results support the computational model, and suggest a deficit in the module that arranges parts into a composite. The observed pattern of deficits and abilities implied that this module is not used in language, perception, or drawing.

Recent efforts to build computer simulation models of mental imagery have suggested that imagery is not a unitary phenomenon. Rather, such efforts have led to a modular analysis of the image generation process, with separate modules that can activate visual memories, inspect parts of imaged patterns, and arrange separate parts into a composite image. This idea was supported by the finding of functional dissociations between the kinds of imagery tasks that could be performed in the left and right cerebral hemispheres of two patients who had had their corpus collosa surgically severed. The left hemisphere in both subjects could inspect imaged patterns and could generate single and multi-part images. In contrast, although the right hemisphere could inspect imaged patterns and could generate images of overall shape, it had difficulty in generating multi-part images. the results support the computational model, and suggest a deficit in the module that arranges parts into a composite. The observed pattern of deficits and abilities implied that this module is not used in language, perception, or drawing.

Inflammation is a complex process driven by the coordinated action of a vast number of pro- and anti-inflammatory molecular mediators. While experimental studies have provided an abundance of information about the properties and mechanisms of action of individual mediators, essential system level regulatory patterns that determine the time-course of inflammation are not sufficiently understood. In particular, it is not known how the contributions from distinct signaling pathways involved in cytokine regulation combine to shape the overall inflammatory response over different time scales. We investigated the kinetics of the intra- and extra cellular signaling network controlling the production of the essential pro-inflammatory cytokine, tumor necrosis factor (TNF), and its anti-inflammatory counterpart, interleukin10 (IL-10), in a macrophage culture. To tackle the intrinsic complexity of the network, we employed a computational modeling approach using the available literature data about specific molecular interactions. Our computational model successfully captured experimentally observed short- and long-term kinetics of key inflammatory mediators. Subsequent model analysis showed that distinct subnetworks regulate IL-10 production by impacting different temporal phases of the cAMP response element-binding protein (CREB) phosphorylation. Moreover, the model revealed that functionally similar inhibitory control circuits regulate the early and late activation phases of nuclear factor kB and CREB. Finally, we identified and investigated distinct signaling subnetworks that independently control the peak height and tail height of the TNF temporal trajectories. The knowledge of such subnetwork-specific regulatory effects may facilitate therapeutic interventions aimed at precise modulation of the inflammatory response.

This article is from PLoS ONE , volume 9 . Abstract Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3′UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3′UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.

This article is from PLoS ONE , volume 9 . Abstract Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3′UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3′UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.

This article is from PLoS ONE , volume 9 . Abstract Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans and play a major role in the genetics of human phenotype variation and the genetic basis of human complex diseases. Recently, there is considerable interest in understanding the possible role of the CYP11B2 gene with corticosterone methyl oxidase deficiency, primary aldosteronism, and cardio-cerebro-vascular diseases. Hence, the elucidation of the function and molecular dynamic behavior of CYP11B2 mutations is crucial in current genomics. In this study, we investigated the pathogenic effect of 51 nsSNPs and 26 UTR SNPs in the CYP11B2 gene through computational platforms. Using a combination of SIFT, PolyPhen, I-Mutant Suite, and ConSurf server, four nsSNPs (F487V, V129M, T498A, and V403E) were identified to potentially affect the structure, function, and activity of the CYP11B2 protein. Furthermore, molecular dynamics simulation and structure analyses also confirmed the impact of these nsSNPs on the stability and secondary properties of the CYP11B2 protein. Additionally, utilizing the UTRscan, MirSNP, PolymiRTS and miRNASNP, three SNPs in the 3′UTR region were predicted to exhibit a pattern change in the upstream open reading frames (uORF), and eight microRNA binding sites were found to be highly affected due to 3′UTR SNPs. This cataloguing of deleterious SNPs is essential for narrowing down the number of CYP11B2 mutations to be screened in genetic association studies and for a better understanding of the functional and structural aspects of the CYP11B2 protein.

This technical report is the Final Deliverable for Grant No.: N00244-15-1-0051 from the Naval Postgraduate School (NPS) with funding via the NAVSUP Fleet Logistics Center San Diego, on the topic of Advancing Human-Machine Symbiosis Using Hybrid Methods for Collaborative Problem-Solving. This effort was a basic and applied research study program involving thorough reviews and assessments of applicable state of the art research and methods, and the development of a detailed functional design for an advanced-capability intelligence analysis computer-based support system. The technical areas studied involved principles of argumentation including especially computational support aspects for enabling argumentation-based analysis, story-based analysis, uncertainty aspects of analysis in an open-world environment, human-machine symbiosis, hard and soft information fusion, and computational methods for narrative development. Our effort cumulates in a top-level functional design of a notional prototype capability for providing computational support to a hybrid argumentation plus story-based analysis capability. This research was further vetted in the presentation and writing of a paper on the project at the 13th International Conference on Distributed Computing and Artificial Intelligence (DCAI'16) in Seville, Spain in June of 2016

BACKGROUND: Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated gene. The computational identification of such motifs is made easier by the fact that they often appear several times in the upstream region of the regulated genes, so that the number of occurrences of relevant motifs is often significantly larger than expected by pure chance. RESULTS: To exploit this fact, we construct sets of genes characterized by the statistical overrepresentation of a certain motif in their upstream regions. Then we study the functional characterization of these sets by analyzing their annotation to Gene Ontology terms. For the sets showing a statistically significant specific functional characterization, we conjecture that the upstream motif characterizing the set is a binding site for a transcription factor involved in the regulation of the genes in the set. CONCLUSIONS: The method we propose is able to identify many known binding sites in S. cerevisiae and new candidate targets of regulation by known transcription factors. Its application to less well studied organisms is likely to be valuable in the exploration of their regulatory interaction network.

In this paper, we highlight a new computational aspect of Nonstandard Analysis relating to higher-order computability theory. In particular, we prove that the Gandy-Hyland functional equals a primitive recursive functional involving nonstandard numbers inside Nelson's internal set theory. From this classical and ineffective proof in Nonstandard Analysis, a term from Goedel's system T is extracted which computes the Gandy-Hyland functional in terms of a modulus-of-continuity functional and a special case of the fan functional. We obtain several similar relative computability results not involving Nonstandard Analysis from their associated nonstandard theorems, in particular involving the weak continuity functional. By way of reversal, we show that certain relative computability results, called Herbrandisations, also imply the nonstandard theorem from whence they were obtained. Thus, we establish a direct two-way connection between the field Computability (in particular theoretical computer science) and the field Nonstandard Analysis.