Absolute and proportional measures of potential markers of rehearsal, and their implications for accounts of its development

PubMed Central

Jarrold, Christopher; Danielsson, Henrik; Wang, Xiaoli

2015-01-01

Previous studies of the development of phonological similarity and word length effects in children have shown that these effects are small or absent in young children, particularly when measured using visual presentation of the memoranda. This has often been taken as support for the view that young children do not rehearse. The current paper builds on recent evidence that instead suggests that absent phonological similarity and word length effects in young children reflects the same proportional cost of these effects in children of all ages. Our aims are to explore the conditions under which this proportional scaling account can reproduce existing developmental data, and in turn suggest ways that future studies might measure and model phonological similarity and word length effects in children. To that end, we first fit a single mathematical function through previously reported data that simultaneously captures absent and negative proportional effects of phonological similarity in young children plus constant proportional similarity effects in older children. This developmental function therefore provides the benchmark that we seek to re-produce in a series of subsequent simulations that test the proportional scaling account. These simulations reproduce the developmental function well, provided that they take into account the influence of floor effects and of measurement error. Our simulations suggest that future empirical studies examining these effects in the context of the development of rehearsal need to take into account proportional scaling. They also provide a demonstration of how proportional costs can be explored, and of the possible developmental functions associated with such an analysis. PMID:25852615

An integrative approach for measuring semantic similarities using gene ontology.

PubMed

Peng, Jiajie; Li, Hongxiang; Jiang, Qinghua; Wang, Yadong; Chen, Jin

2014-01-01

Gene Ontology (GO) provides rich information and a convenient way to study gene functional similarity, which has been successfully used in various applications. However, the existing GO based similarity measurements have limited functions for only a subset of GO information is considered in each measure. An appropriate integration of the existing measures to take into account more information in GO is demanding. We propose a novel integrative measure called InteGO2 to automatically select appropriate seed measures and then to integrate them using a metaheuristic search method. The experiment results show that InteGO2 significantly improves the performance of gene similarity in human, Arabidopsis and yeast on both molecular function and biological process GO categories. InteGO2 computes gene-to-gene similarities more accurately than tested existing measures and has high robustness. The supplementary document and software are available at http://mlg.hit.edu.cn:8082/.

Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions.

PubMed

Mai, Te-Lun; Hu, Geng-Ming; Chen, Chi-Ming

2016-07-01

Research in the recent decade has demonstrated the usefulness of protein network knowledge in furthering the study of molecular evolution of proteins, understanding the robustness of cells to perturbation, and annotating new protein functions. In this study, we aimed to provide a general clustering approach to visualize the sequence-structure-function relationship of protein networks, and investigate possible causes for inconsistency in the protein classifications based on sequences, structures, and functions. Such visualization of protein networks could facilitate our understanding of the overall relationship among proteins and help researchers comprehend various protein databases. As a demonstration, we clustered 1437 enzymes by their sequences and structures using the minimum span clustering (MSC) method. The general structure of this protein network was delineated at two clustering resolutions, and the second level MSC clustering was found to be highly similar to existing enzyme classifications. The clustering of these enzymes based on sequence, structure, and function information is consistent with each other. For proteases, the Jaccard's similarity coefficient is 0.86 between sequence and function classifications, 0.82 between sequence and structure classifications, and 0.78 between structure and function classifications. From our clustering results, we discussed possible examples of divergent evolution and convergent evolution of enzymes. Our clustering approach provides a panoramic view of the sequence-structure-function network of proteins, helps visualize the relation between related proteins intuitively, and is useful in predicting the structure and function of newly determined protein sequences.

Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

PubMed

Ahmed, Rebekah M; Ke, Yazi D; Vucic, Steve; Ittner, Lars M; Seeley, William; Hodges, John R; Piguet, Olivier; Halliday, Glenda; Kiernan, Matthew C

2018-05-01

The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological processes, including eating and metabolism, autonomic nervous system function, sleep, and motor function. Changes in these physiological processes are present in several conditions, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the parkinsonian plus conditions. Key neural structures that mediate physiological changes across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system. In this Review, we highlight the key changes in physiological processing in neurodegenerative syndromes and the similarities in these changes between different progressive neurodegenerative brain conditions. The changes and similarities between disorders might provide novel insights into the human neural correlates of physiological functioning. Given the evidence that physiological changes can arise early in the neurodegenerative process, these changes could provide biomarkers to aid in the early diagnosis of neurodegenerative diseases and in treatment trials.

Self-enhanced catalytic activities of functionalized graphene sheets in the combustion of nitromethane: molecular dynamic simulations by molecular reactive force field.

PubMed

Zhang, Chaoyang; Wen, Yushi; Xue, Xianggui

2014-08-13

Functionalized graphene sheet (FGS) is a promising additive that enhances fuel/propellant combustion, and the determination of its mechanism has attracted much interest. In the present study, a series of molecular dynamic simulations based on a reactive force field (ReaxFF) are performed to explore the catalytic activity (CA) of FGS in the thermal decay of nitromethane (NM, CH3NO2). FGSs and pristine graphene sheets (GSs) are oxidized in hot NM liquid to increase their functionalities and subsequently show self-enhanced CAs during the decay. The CAs result from the interatomic exchanges between the functional groups on the sheets and the NM liquid, i.e., mainly between H and O atoms. CA is dependent on the density of NM, functionalities of sheets, and temperature. The GSs and FGSs that originally exhibit different functionalities tend to possess similar functionalities and consequently similar CAs as temperature increases. Other carbon materials and their oxides can accelerate combustion of other fuels/propellants similar to NM, provided that they can be dispersed and their key reaction steps in combustion are similar to NM.

Resolving protein structure-function-binding site relationships from a binding site similarity network perspective.

PubMed

Mudgal, Richa; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2017-07-01

Functional annotation is seldom straightforward with complexities arising due to functional divergence in protein families or functional convergence between non-homologous protein families, leading to mis-annotations. An enzyme may contain multiple domains and not all domains may be involved in a given function, adding to the complexity in function annotation. To address this, we use binding site information from bound cognate ligands and catalytic residues, since it can help in resolving fold-function relationships at a finer level and with higher confidence. A comprehensive database of 2,020 fold-function-binding site relationships has been systematically generated. A network-based approach is employed to capture the complexity in these relationships, from which different types of associations are deciphered, that identify versatile protein folds performing diverse functions, same function associated with multiple folds and one-to-one relationships. Binding site similarity networks integrated with fold, function, and ligand similarity information are generated to understand the depth of these relationships. Apart from the observed continuity in the functional site space, network properties of these revealed versatile families with topologically different or dissimilar binding sites and structural families that perform very similar functions. As a case study, subtle changes in the active site of a set of evolutionarily related superfamilies are studied using these networks. Tracing of such similarities in evolutionarily related proteins provide clues into the transition and evolution of protein functions. Insights from this study will be helpful in accurate and reliable functional annotations of uncharacterized proteins, poly-pharmacology, and designing enzymes with new functional capabilities. Proteins 2017; 85:1319-1335. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.

PubMed

Almonacid, Daniel E; Yera, Emmanuel R; Mitchell, John B O; Babbitt, Patricia C

2010-03-12

Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.

Quantitative Comparison of Catalytic Mechanisms and Overall Reactions in Convergently Evolved Enzymes: Implications for Classification of Enzyme Function

PubMed Central

Almonacid, Daniel E.; Yera, Emmanuel R.; Mitchell, John B. O.; Babbitt, Patricia C.

2010-01-01

Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation. PMID:20300652

Web service discovery among large service pools utilising semantic similarity and clustering

NASA Astrophysics Data System (ADS)

Chen, Fuzan; Li, Minqiang; Wu, Harris; Xie, Lingli

2017-03-01

With the rapid development of electronic business, Web services have attracted much attention in recent years. Enterprises can combine individual Web services to provide new value-added services. An emerging challenge is the timely discovery of close matches to service requests among large service pools. In this study, we first define a new semantic similarity measure combining functional similarity and process similarity. We then present a service discovery mechanism that utilises the new semantic similarity measure for service matching. All the published Web services are pre-grouped into functional clusters prior to the matching process. For a user's service request, the discovery mechanism first identifies matching services clusters and then identifies the best matching Web services within these matching clusters. Experimental results show that the proposed semantic discovery mechanism performs better than a conventional lexical similarity-based mechanism.

Whole Brain Functional Connectivity Pattern Homogeneity Mapping.

PubMed

Wang, Lijie; Xu, Jinping; Wang, Chao; Wang, Jiaojian

2018-01-01

Mounting studies have demonstrated that brain functions are determined by its external functional connectivity patterns. However, how to characterize the voxel-wise similarity of whole brain functional connectivity pattern is still largely unknown. In this study, we introduced a new method called functional connectivity homogeneity (FcHo) to delineate the voxel-wise similarity of whole brain functional connectivity patterns. FcHo was defined by measuring the whole brain functional connectivity patterns similarity of a given voxel with its nearest 26 neighbors using Kendall's coefficient concordance (KCC). The robustness of this method was tested in four independent datasets selected from a large repository of MRI. Furthermore, FcHo mapping results were further validated using the nearest 18 and six neighbors and intra-subject reproducibility with each subject scanned two times. We also compared FcHo distribution patterns with local regional homogeneity (ReHo) to identify the similarity and differences of the two methods. Finally, FcHo method was used to identify the differences of whole brain functional connectivity patterns between professional Chinese chess players and novices to test its application. FcHo mapping consistently revealed that the high FcHo was mainly distributed in association cortex including parietal lobe, frontal lobe, occipital lobe and default mode network (DMN) related areas, whereas the low FcHo was mainly found in unimodal cortex including primary visual cortex, sensorimotor cortex, paracentral lobule and supplementary motor area. These results were further supported by analyses of the nearest 18 and six neighbors and intra-subject similarity. Moreover, FcHo showed both similar and different whole brain distribution patterns compared to ReHo. Finally, we demonstrated that FcHo can effectively identify the whole brain functional connectivity pattern differences between professional Chinese chess players and novices. Our findings indicated that FcHo is a reliable method to delineate the whole brain functional connectivity pattern similarity and may provide a new way to study the functional organization and to reveal neuropathological basis for brain disorders.

GOMA: functional enrichment analysis tool based on GO modules

PubMed Central

Huang, Qiang; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun

2013-01-01

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results. PMID:23237213

Utility and Limitations of Using Gene Expression Data to Identify Functional Associations

PubMed Central

Peng, Cheng; Shiu, Shin-Han

2016-01-01

Gene co-expression has been widely used to hypothesize gene function through guilt-by association. However, it is not clear to what degree co-expression is informative, whether it can be applied to genes involved in different biological processes, and how the type of dataset impacts inferences about gene functions. Here our goal is to assess the utility and limitations of using co-expression as a criterion to recover functional associations between genes. By determining the percentage of gene pairs in a metabolic pathway with significant expression correlation, we found that many genes in the same pathway do not have similar transcript profiles and the choice of dataset, annotation quality, gene function, expression similarity measure, and clustering approach significantly impacts the ability to recover functional associations between genes using Arabidopsis thaliana as an example. Some datasets are more informative in capturing coordinated expression profiles and larger data sets are not always better. In addition, to recover the maximum number of known pathways and identify candidate genes with similar functions, it is important to explore rather exhaustively multiple dataset combinations, similarity measures, clustering algorithms and parameters. Finally, we validated the biological relevance of co-expression cluster memberships with an independent phenomics dataset and found that genes that consistently cluster with leucine degradation genes tend to have similar leucine levels in mutants. This study provides a framework for obtaining gene functional associations by maximizing the information that can be obtained from gene expression datasets. PMID:27935950

IsoCleft Finder – a web-based tool for the detection and analysis of protein binding-site geometric and chemical similarities

PubMed Central

Najmanovich, Rafael

2013-01-01

IsoCleft Finder is a web-based tool for the detection of local geometric and chemical similarities between potential small-molecule binding cavities and a non-redundant dataset of ligand-bound known small-molecule binding-sites. The non-redundant dataset developed as part of this study is composed of 7339 entries representing unique Pfam/PDB-ligand (hetero group code) combinations with known levels of cognate ligand similarity. The query cavity can be uploaded by the user or detected automatically by the system using existing PDB entries as well as user-provided structures in PDB format. In all cases, the user can refine the definition of the cavity interactively via a browser-based Jmol 3D molecular visualization interface. Furthermore, users can restrict the search to a subset of the dataset using a cognate-similarity threshold. Local structural similarities are detected using the IsoCleft software and ranked according to two criteria (number of atoms in common and Tanimoto score of local structural similarity) and the associated Z-score and p-value measures of statistical significance. The results, including predicted ligands, target proteins, similarity scores, number of atoms in common, etc., are shown in a powerful interactive graphical interface. This interface permits the visualization of target ligands superimposed on the query cavity and additionally provides a table of pairwise ligand topological similarities. Similarities between top scoring ligands serve as an additional tool to judge the quality of the results obtained. We present several examples where IsoCleft Finder provides useful functional information. IsoCleft Finder results are complementary to existing approaches for the prediction of protein function from structure, rational drug design and x-ray crystallography. IsoCleft Finder can be found at: http://bcb.med.usherbrooke.ca/isocleftfinder. PMID:24555058

Distinct Pattern Separation Related Transfer Functions in Human CA3/Dentate and CA1 Revealed Using High-Resolution fMRI and Variable Mnemonic Similarity

ERIC Educational Resources Information Center

Lacy, Joyce W.; Yassa, Michael A.; Stark, Shauna M.; Muftuler, L. Tugan; Stark, Craig E. L.

2011-01-01

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while…

A graph-based semantic similarity measure for the gene ontology.

PubMed

Alvarez, Marco A; Yan, Changhui

2011-12-01

Existing methods for calculating semantic similarities between pairs of Gene Ontology (GO) terms and gene products often rely on external databases like Gene Ontology Annotation (GOA) that annotate gene products using the GO terms. This dependency leads to some limitations in real applications. Here, we present a semantic similarity algorithm (SSA), that relies exclusively on the GO. When calculating the semantic similarity between a pair of input GO terms, SSA takes into account the shortest path between them, the depth of their nearest common ancestor, and a novel similarity score calculated between the definitions of the involved GO terms. In our work, we use SSA to calculate semantic similarities between pairs of proteins by combining pairwise semantic similarities between the GO terms that annotate the involved proteins. The reliability of SSA was evaluated by comparing the resulting semantic similarities between proteins with the functional similarities between proteins derived from expert annotations or sequence similarity. Comparisons with existing state-of-the-art methods showed that SSA is highly competitive with the other methods. SSA provides a reliable measure for semantics similarity independent of external databases of functional-annotation observations.

A new method to improve network topological similarity search: applied to fold recognition

PubMed Central

Lhota, John; Hauptman, Ruth; Hart, Thomas; Ng, Clara; Xie, Lei

2015-01-01

Motivation: Similarity search is the foundation of bioinformatics. It plays a key role in establishing structural, functional and evolutionary relationships between biological sequences. Although the power of the similarity search has increased steadily in recent years, a high percentage of sequences remain uncharacterized in the protein universe. Thus, new similarity search strategies are needed to efficiently and reliably infer the structure and function of new sequences. The existing paradigm for studying protein sequence, structure, function and evolution has been established based on the assumption that the protein universe is discrete and hierarchical. Cumulative evidence suggests that the protein universe is continuous. As a result, conventional sequence homology search methods may be not able to detect novel structural, functional and evolutionary relationships between proteins from weak and noisy sequence signals. To overcome the limitations in existing similarity search methods, we propose a new algorithmic framework—Enrichment of Network Topological Similarity (ENTS)—to improve the performance of large scale similarity searches in bioinformatics. Results: We apply ENTS to a challenging unsolved problem: protein fold recognition. Our rigorous benchmark studies demonstrate that ENTS considerably outperforms state-of-the-art methods. As the concept of ENTS can be applied to any similarity metric, it may provide a general framework for similarity search on any set of biological entities, given their representation as a network. Availability and implementation: Source code freely available upon request Contact: lxie@iscb.org PMID:25717198

Functional Basis of Microorganism Classification.

PubMed

Zhu, Chengsheng; Delmont, Tom O; Vogel, Timothy M; Bromberg, Yana

2015-08-01

Correctly identifying nearest "neighbors" of a given microorganism is important in industrial and clinical applications where close relationships imply similar treatment. Microbial classification based on similarity of physiological and genetic organism traits (polyphasic similarity) is experimentally difficult and, arguably, subjective. Evolutionary relatedness, inferred from phylogenetic markers, facilitates classification but does not guarantee functional identity between members of the same taxon or lack of similarity between different taxa. Using over thirteen hundred sequenced bacterial genomes, we built a novel function-based microorganism classification scheme, functional-repertoire similarity-based organism network (FuSiON; flattened to fusion). Our scheme is phenetic, based on a network of quantitatively defined organism relationships across the known prokaryotic space. It correlates significantly with the current taxonomy, but the observed discrepancies reveal both (1) the inconsistency of functional diversity levels among different taxa and (2) an (unsurprising) bias towards prioritizing, for classification purposes, relatively minor traits of particular interest to humans. Our dynamic network-based organism classification is independent of the arbitrary pairwise organism similarity cut-offs traditionally applied to establish taxonomic identity. Instead, it reveals natural, functionally defined organism groupings and is thus robust in handling organism diversity. Additionally, fusion can use organism meta-data to highlight the specific environmental factors that drive microbial diversification. Our approach provides a complementary view to cladistic assignments and holds important clues for further exploration of microbial lifestyles. Fusion is a more practical fit for biomedical, industrial, and ecological applications, as many of these rely on understanding the functional capabilities of the microbes in their environment and are less concerned with phylogenetic descent.

Functional Basis of Microorganism Classification

PubMed Central

Zhu, Chengsheng; Delmont, Tom O.; Vogel, Timothy M.; Bromberg, Yana

2015-01-01

Correctly identifying nearest “neighbors” of a given microorganism is important in industrial and clinical applications where close relationships imply similar treatment. Microbial classification based on similarity of physiological and genetic organism traits (polyphasic similarity) is experimentally difficult and, arguably, subjective. Evolutionary relatedness, inferred from phylogenetic markers, facilitates classification but does not guarantee functional identity between members of the same taxon or lack of similarity between different taxa. Using over thirteen hundred sequenced bacterial genomes, we built a novel function-based microorganism classification scheme, functional-repertoire similarity-based organism network (FuSiON; flattened to fusion). Our scheme is phenetic, based on a network of quantitatively defined organism relationships across the known prokaryotic space. It correlates significantly with the current taxonomy, but the observed discrepancies reveal both (1) the inconsistency of functional diversity levels among different taxa and (2) an (unsurprising) bias towards prioritizing, for classification purposes, relatively minor traits of particular interest to humans. Our dynamic network-based organism classification is independent of the arbitrary pairwise organism similarity cut-offs traditionally applied to establish taxonomic identity. Instead, it reveals natural, functionally defined organism groupings and is thus robust in handling organism diversity. Additionally, fusion can use organism meta-data to highlight the specific environmental factors that drive microbial diversification. Our approach provides a complementary view to cladistic assignments and holds important clues for further exploration of microbial lifestyles. Fusion is a more practical fit for biomedical, industrial, and ecological applications, as many of these rely on understanding the functional capabilities of the microbes in their environment and are less concerned with phylogenetic descent. PMID:26317871

Analysis of multiplex gene expression maps obtained by voxelation.

PubMed

An, Li; Xie, Hongbo; Chin, Mark H; Obradovic, Zoran; Smith, Desmond J; Megalooikonomou, Vasileios

2009-04-29

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in cortex and corpus callosum. The experimental results confirm the hypothesis that genes with similar gene expression maps might have similar gene functions. The voxelation data takes into account the location information of gene expression level in mouse brain, which is novel in related research. The proposed approach can potentially be used to predict gene functions and provide helpful suggestions to biologists.

DaGO-Fun: tool for Gene Ontology-based functional analysis using term information content measures.

PubMed

Mazandu, Gaston K; Mulder, Nicola J

2013-09-25

The use of Gene Ontology (GO) data in protein analyses have largely contributed to the improved outcomes of these analyses. Several GO semantic similarity measures have been proposed in recent years and provide tools that allow the integration of biological knowledge embedded in the GO structure into different biological analyses. There is a need for a unified tool that provides the scientific community with the opportunity to explore these different GO similarity measure approaches and their biological applications. We have developed DaGO-Fun, an online tool available at http://web.cbio.uct.ac.za/ITGOM, which incorporates many different GO similarity measures for exploring, analyzing and comparing GO terms and proteins within the context of GO. It uses GO data and UniProt proteins with their GO annotations as provided by the Gene Ontology Annotation (GOA) project to precompute GO term information content (IC), enabling rapid response to user queries. The DaGO-Fun online tool presents the advantage of integrating all the relevant IC-based GO similarity measures, including topology- and annotation-based approaches to facilitate effective exploration of these measures, thus enabling users to choose the most relevant approach for their application. Furthermore, this tool includes several biological applications related to GO semantic similarity scores, including the retrieval of genes based on their GO annotations, the clustering of functionally related genes within a set, and term enrichment analysis.

Statistical considerations in the development of injury risk functions.

PubMed

McMurry, Timothy L; Poplin, Gerald S

2015-01-01

We address 4 frequently misunderstood and important statistical ideas in the construction of injury risk functions. These include the similarities of survival analysis and logistic regression, the correct scale on which to construct pointwise confidence intervals for injury risk, the ability to discern which form of injury risk function is optimal, and the handling of repeated tests on the same subject. The statistical models are explored through simulation and examination of the underlying mathematics. We provide recommendations for the statistically valid construction and correct interpretation of single-predictor injury risk functions. This article aims to provide useful and understandable statistical guidance to improve the practice in constructing injury risk functions.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase.

PubMed

Zemla, Adam T; Lang, Dorothy M; Kostova, Tanya; Andino, Raul; Ecale Zhou, Carol L

2011-06-02

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory--still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could help overcome these difficulties by facilitating the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV (structure-alignment sequence variability), a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus, and we demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique, or that share structural similarity with proteins that would be considered distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local structural alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position. StralSV is provided as a web service at http://proteinmodel.org/AS2TS/STRALSV/.

Horizontal functional gene transfer from bacteria to fishes.

PubMed

Sun, Bao-Fa; Li, Tong; Xiao, Jin-Hua; Jia, Ling-Yi; Liu, Li; Zhang, Peng; Murphy, Robert W; He, Shun-Min; Huang, Da-Wei

2015-12-22

Invertebrates can acquire functional genes via horizontal gene transfer (HGT) from bacteria but fishes are not known to do so. We provide the first reliable evidence of one HGT event from marine bacteria to fishes. The HGT appears to have occurred after emergence of the teleosts. The transferred gene is expressed and regulated developmentally. Its successful integration and expression may change the genetic and metabolic repertoire of fishes. In addition, this gene contains conserved domains and similar tertiary structures in fishes and their putative donor bacteria. Thus, it may function similarly in both groups. Evolutionary analyses indicate that it evolved under purifying selection, further indicating its conserved function. We document the first likely case of HGT of functional gene from prokaryote to fishes. This discovery certifies that HGT can influence vertebrate evolution.

17 CFR 240.16a-1 - Definition of terms.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., investment adviser, investment manager, trustee or person or entity performing a similar function; provided... when payable, is calculated based upon net capital gains and/or net capital appreciation generated from... issuer in charge of a principal business unit, division or function (such as sales, administration or...

17 CFR 240.16a-1 - Definition of terms.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., investment adviser, investment manager, trustee or person or entity performing a similar function; provided... when payable, is calculated based upon net capital gains and/or net capital appreciation generated from... issuer in charge of a principal business unit, division or function (such as sales, administration or...

Prediction of microRNAs Associated with Human Diseases Based on Weighted k Most Similar Neighbors

PubMed Central

Guo, Maozu; Guo, Yahong; Li, Jinbao; Ding, Jian; Liu, Yong; Dai, Qiguo; Li, Jin; Teng, Zhixia; Huang, Yufei

2013-01-01

Background The identification of human disease-related microRNAs (disease miRNAs) is important for further investigating their involvement in the pathogenesis of diseases. More experimentally validated miRNA-disease associations have been accumulated recently. On the basis of these associations, it is essential to predict disease miRNAs for various human diseases. It is useful in providing reliable disease miRNA candidates for subsequent experimental studies. Methodology/Principal Findings It is known that miRNAs with similar functions are often associated with similar diseases and vice versa. Therefore, the functional similarity of two miRNAs has been successfully estimated by measuring the semantic similarity of their associated diseases. To effectively predict disease miRNAs, we calculated the functional similarity by incorporating the information content of disease terms and phenotype similarity between diseases. Furthermore, the members of miRNA family or cluster are assigned higher weight since they are more probably associated with similar diseases. A new prediction method, HDMP, based on weighted k most similar neighbors is presented for predicting disease miRNAs. Experiments validated that HDMP achieved significantly higher prediction performance than existing methods. In addition, the case studies examining prostatic neoplasms, breast neoplasms, and lung neoplasms, showed that HDMP can uncover potential disease miRNA candidates. Conclusions The superior performance of HDMP can be attributed to the accurate measurement of miRNA functional similarity, the weight assignment based on miRNA family or cluster, and the effective prediction based on weighted k most similar neighbors. The online prediction and analysis tool is freely available at http://nclab.hit.edu.cn/hdmpred. PMID:23950912

Exotic species enhance response diversity to land-use change but modify functional composition.

PubMed

Stavert, Jamie R; Pattemore, David E; Gaskett, Anne C; Beggs, Jacqueline R; Bartomeus, Ignasi

2017-08-16

Two main mechanisms may buffer ecosystem functions despite biodiversity loss. First, multiple species could share similar ecological roles, thus providing functional redundancy. Second, species may respond differently to environmental change (response diversity). However, ecosystem function would be best protected when functionally redundant species also show response diversity. This linkage has not been studied directly, so we investigated whether native and exotic pollinator species with similar traits (functional redundancy) differed in abundance (response diversity) across an agricultural intensification gradient. Exotic pollinator species contributed most positive responses, which partially stabilized overall abundance of the pollinator community. However, although some functionally redundant species exhibited response diversity, this was not consistent across functional groups and aggregate abundances within each functional group were rarely stabilized. This shows functional redundancy and response diversity do not always operate in concert. Hence, despite exotic species becoming increasingly dominant in human-modified systems, they cannot replace the functional composition of native species. © 2017 The Author(s).

A new definition and properties of the similarity value between two protein structures.

PubMed

Saberi Fathi, S M

2016-10-01

Knowledge regarding the 3D structure of a protein provides useful information about the protein's functional properties. Particularly, structural similarity between proteins can be used as a good predictor of functional similarity. One method that uses the 3D geometrical structure of proteins in order to compare them is the similarity value (SV). In this paper, we introduce a new definition of the SV measure for comparing two proteins. To this end, we consider the mass of the protein's atoms and concentrate on the number of protein's atoms to be compared. This defines a new measure, called the weighted similarity value (WSV), adding physical properties to geometrical properties. We also show that our results are in good agreement with the results obtained by TM-SCORE and DALILITE. WSV can be of use in protein classification and in drug discovery.

Peri-implant and periodontal tissues: a review of differences and similarities.

PubMed

Dhir, Sangeeta; Mahesh, Lanka; Kurtzman, Gregori M; Vandana, K L

2013-01-01

The health and vitality of an osseointegrated implant depends on the surrounding supporting tissues, which not only anchor the implant to the bone but also have the important function of providing a protective seal. The aim of this article is to provide a basic understanding of differences and similarities between the periodontal and peri-implant tissues at the histologic, clinical, and immunologic levels; it is essential to know these differences and similarities during the clinical handling of these similar-looking tissues. The comparative features are of clinical relevance because it is critical to understand the behavior of the soft tissue found around the tooth and implant. This knowledge is vital from the preliminary stage of treatment planning through prosthetic rehabilitation.

76 FR 45270 - Statement of Organization, Functions, and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

... its structure, to align similar functions under common executive leadership, and to reduce and change... span of control for executive leadership and to organize like activities together, not to change the... Commissioner will provide executive oversight, strategic leadership, and policy direction to FDA's domestic and...

Development of Social Functioning in Preschizophrenia Children and Adolescents: A Systematic Review

ERIC Educational Resources Information Center

Tarbox, Sarah I.; Pogue-Geile, Michael F.

2008-01-01

Schizophrenia is associated with severe deficits in social functioning. Similar deficits may be present prior to psychosis onset, in childhood and adolescence. If so, then prepsychosis social deficits could provide clues to the development of pathological processes in preschizophrenia children and could potentially improve early identification of…

Fuzzy measures on the Gene Ontology for gene product similarity.

PubMed

Popescu, Mihail; Keller, James M; Mitchell, Joyce A

2006-01-01

One of the most important objects in bioinformatics is a gene product (protein or RNA). For many gene products, functional information is summarized in a set of Gene Ontology (GO) annotations. For these genes, it is reasonable to include similarity measures based on the terms found in the GO or other taxonomy. In this paper, we introduce several novel measures for computing the similarity of two gene products annotated with GO terms. The fuzzy measure similarity (FMS) has the advantage that it takes into consideration the context of both complete sets of annotation terms when computing the similarity between two gene products. When the two gene products are not annotated by common taxonomy terms, we propose a method that avoids a zero similarity result. To account for the variations in the annotation reliability, we propose a similarity measure based on the Choquet integral. These similarity measures provide extra tools for the biologist in search of functional information for gene products. The initial testing on a group of 194 sequences representing three proteins families shows a higher correlation of the FMS and Choquet similarities to the BLAST sequence similarities than the traditional similarity measures such as pairwise average or pairwise maximum.

Resolving Quasi-Synonym Relationships in Automatic Thesaurus Construction Using Fuzzy Rough Sets and an Inverse Term Frequency Similarity Function

ERIC Educational Resources Information Center

Davault, Julius M., III.

2009-01-01

One of the problems associated with automatic thesaurus construction is with determining the semantic relationship between word pairs. Quasi-synonyms provide a type of equivalence relationship: words are similar only for purposes of information retrieval. Determining such relationships in a thesaurus is hard to achieve automatically. The term…

Functional diversity of fish in tropical estuaries: A traits-based approach of communities in Pernambuco, Brazil

NASA Astrophysics Data System (ADS)

Silva-Júnior, C. A. B.; Mérigot, B.; Lucena-Frédou, F.; Ferreira, B. P.; Coxey, M. S.; Rezende, S. M.; Frédou, T.

2017-11-01

Environmental changes and human activities may have strong impacts on biodiversity and ecosystem functioning. While biodiversity is traditionally based on species richness and composition, there is a growing concern to take into account functional diversity to assess and manage species communities. In spite of their economic importance, functional diversity quantified by a traits-based approach is still poorly documented in tropical estuaries. In this study, the functional diversity of fishes was investigated within four estuaries in Pernambuco state, northeast of Brazil. These areas are subject to different levels of human impact (e.g. mangrove deforestation, shrimp farming, fishing etc.) and environmental conditions. Fishes were collected during 34 scientific surveys. A total of 122 species were identified and 12 functional traits were quantified describing two main functions: food acquisition and locomotion. Fish abundance and functional dissimilarities data were combined into a multivariate analysis, the Double Principal Coordinate Analysis, to identify the functional typology of fish assemblages according to the estuary. Results showed that Itapissuma, the largest estuary with a wider mangrove forest area, differs from the other three estuaries, showing higher mean values per samples of species richness S and quadratic entropy Q. Similarly, it presented a different functional typology (the first two axes of the DPCoA account for 68.7% of total inertia, while those of a traditional PCA based solely on species abundances provided only 17.4%). Conversely, Suape, Sirinhaém, and to a lower extent Rio Formoso, showed more similarity in their diversity. This result was attributed to their predominantly marine influenced hydrological features, and similar levels of species abundances and in morphological traits. Overall, this study, combining diversity indices and a recent multivariate analysis to access species contribution to functional typology, allows to deepen diversity assessment by providing additional information regarding the functional pattern of fish assemblages.

SIMAP--a comprehensive database of pre-calculated protein sequence similarities, domains, annotations and clusters.

PubMed

Rattei, Thomas; Tischler, Patrick; Götz, Stefan; Jehl, Marc-André; Hoser, Jonathan; Arnold, Roland; Conesa, Ana; Mewes, Hans-Werner

2010-01-01

The prediction of protein function as well as the reconstruction of evolutionary genesis employing sequence comparison at large is still the most powerful tool in sequence analysis. Due to the exponential growth of the number of known protein sequences and the subsequent quadratic growth of the similarity matrix, the computation of the Similarity Matrix of Proteins (SIMAP) becomes a computational intensive task. The SIMAP database provides a comprehensive and up-to-date pre-calculation of the protein sequence similarity matrix, sequence-based features and sequence clusters. As of September 2009, SIMAP covers 48 million proteins and more than 23 million non-redundant sequences. Novel features of SIMAP include the expansion of the sequence space by including databases such as ENSEMBL as well as the integration of metagenomes based on their consistent processing and annotation. Furthermore, protein function predictions by Blast2GO are pre-calculated for all sequences in SIMAP and the data access and query functions have been improved. SIMAP assists biologists to query the up-to-date sequence space systematically and facilitates large-scale downstream projects in computational biology. Access to SIMAP is freely provided through the web portal for individuals (http://mips.gsf.de/simap/) and for programmatic access through DAS (http://webclu.bio.wzw.tum.de/das/) and Web-Service (http://mips.gsf.de/webservices/services/SimapService2.0?wsdl).

DaGO-Fun: tool for Gene Ontology-based functional analysis using term information content measures

PubMed Central

2013-01-01

Background The use of Gene Ontology (GO) data in protein analyses have largely contributed to the improved outcomes of these analyses. Several GO semantic similarity measures have been proposed in recent years and provide tools that allow the integration of biological knowledge embedded in the GO structure into different biological analyses. There is a need for a unified tool that provides the scientific community with the opportunity to explore these different GO similarity measure approaches and their biological applications. Results We have developed DaGO-Fun, an online tool available at http://web.cbio.uct.ac.za/ITGOM, which incorporates many different GO similarity measures for exploring, analyzing and comparing GO terms and proteins within the context of GO. It uses GO data and UniProt proteins with their GO annotations as provided by the Gene Ontology Annotation (GOA) project to precompute GO term information content (IC), enabling rapid response to user queries. Conclusions The DaGO-Fun online tool presents the advantage of integrating all the relevant IC-based GO similarity measures, including topology- and annotation-based approaches to facilitate effective exploration of these measures, thus enabling users to choose the most relevant approach for their application. Furthermore, this tool includes several biological applications related to GO semantic similarity scores, including the retrieval of genes based on their GO annotations, the clustering of functionally related genes within a set, and term enrichment analysis. PMID:24067102

Searching for Electrical Properties, Phenomena and Mechanisms in the Construction and Function of Chromosomes

PubMed Central

Kanev, Ivan; Mei, Wai-Ning; Mizuno, Akira; DeHaai, Kristi; Sanmann, Jennifer; Hess, Michelle; Starr, Lois; Grove, Jennifer; Dave, Bhavana; Sanger, Warren

2013-01-01

Our studies reveal previously unidentified electrical properties of chromosomes: (1) chromosomes are amazingly similar in construction and function to electrical transformers; (2) chromosomes possess in their construction and function, components similar to those of electric generators, conductors, condensers, switches, and other components of electrical circuits; (3) chromosomes demonstrate in nano-scale level electromagnetic interactions, resonance, fusion and other phenomena similar to those described by equations in classical physics. These electrical properties and phenomena provide a possible explanation for unclear and poorly understood mechanisms in clinical genetics including: (a) electrically based mechanisms responsible for breaks, translocations, fusions, and other chromosomal abnormalities associated with cancer, intellectual disability, infertility, pregnancy loss, Down syndrome, and other genetic disorders; (b) electrically based mechanisms involved in crossing over, non-disjunction and other events during meiosis and mitosis; (c) mechanisms demonstrating heterochromatin to be electrically active and genetically important. PMID:24688715

Functional clustering of time series gene expression data by Granger causality

PubMed Central

2012-01-01

Background A common approach for time series gene expression data analysis includes the clustering of genes with similar expression patterns throughout time. Clustered gene expression profiles point to the joint contribution of groups of genes to a particular cellular process. However, since genes belong to intricate networks, other features, besides comparable expression patterns, should provide additional information for the identification of functionally similar genes. Results In this study we perform gene clustering through the identification of Granger causality between and within sets of time series gene expression data. Granger causality is based on the idea that the cause of an event cannot come after its consequence. Conclusions This kind of analysis can be used as a complementary approach for functional clustering, wherein genes would be clustered not solely based on their expression similarity but on their topological proximity built according to the intensity of Granger causality among them. PMID:23107425

SIMAP—the database of all-against-all protein sequence similarities and annotations with new interfaces and increased coverage

PubMed Central

Arnold, Roland; Goldenberg, Florian; Mewes, Hans-Werner; Rattei, Thomas

2014-01-01

The Similarity Matrix of Proteins (SIMAP, http://mips.gsf.de/simap/) database has been designed to massively accelerate computationally expensive protein sequence analysis tasks in bioinformatics. It provides pre-calculated sequence similarities interconnecting the entire known protein sequence universe, complemented by pre-calculated protein features and domains, similarity clusters and functional annotations. SIMAP covers all major public protein databases as well as many consistently re-annotated metagenomes from different repositories. As of September 2013, SIMAP contains >163 million proteins corresponding to ∼70 million non-redundant sequences. SIMAP uses the sensitive FASTA search heuristics, the Smith–Waterman alignment algorithm, the InterPro database of protein domain models and the BLAST2GO functional annotation algorithm. SIMAP assists biologists by facilitating the interactive exploration of the protein sequence universe. Web-Service and DAS interfaces allow connecting SIMAP with any other bioinformatic tool and resource. All-against-all protein sequence similarity matrices of project-specific protein collections are generated on request. Recent improvements allow SIMAP to cover the rapidly growing sequenced protein sequence universe. New Web-Service interfaces enhance the connectivity of SIMAP. Novel tools for interactive extraction of protein similarity networks have been added. Open access to SIMAP is provided through the web portal; the portal also contains instructions and links for software access and flat file downloads. PMID:24165881

Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity

PubMed Central

Lacy, Joyce W.; Yassa, Michael A.; Stark, Shauna M.; Muftuler, L. Tugan; Stark, Craig E.L.

2011-01-01

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input. PMID:21164173

Transference and countertransference to medication and its implications for ego function.

PubMed

Marcus, Eric R

2007-01-01

Transference to medication can provide important information about specific ego dysfunction in sicker patients who often need medication. Whether positive or negative or both in content, the organization of the experience provides one example of the illness' effect on the patients' ego and can therefore be a specific diagnostic assessment strategy. Early resistances to medication may reveal the nature of resistances to the therapeutic alliance and to higher-level ego function. Understanding this can guide verbal and pharmacological interventions to strengthen ego function. Countertransference can similarly be helpful because it, too, can be a highly specific diagnostic indicator.

The ZCPR2 System.

ERIC Educational Resources Information Center

Conn, Richard

1983-01-01

The two-part ZCPR2 System (system itself and related utilities) runs in place of CP/M 2.2 CCP. These public domain programs provide functions similar to those provided by CCP, but offer many enhancements. ZCPR2 programs, features, documentation, and uses are discussed. Problems in using ZCPR2 are also discussed. (JN)

A High Throughput Barley Stripe Mosaic Virus Vector for Virus Induced Gene Silencing in Monocots and Dicots

PubMed Central

Yan, Lijie; Jackson, Andrew O.; Liu, Zhiyong; Han, Chenggui; Yu, Jialin; Li, Dawei

2011-01-01

Barley stripe mosaic virus (BSMV) is a single-stranded RNA virus with three genome components designated alpha, beta, and gamma. BSMV vectors have previously been shown to be efficient virus induced gene silencing (VIGS) vehicles in barley and wheat and have provided important information about host genes functioning during pathogenesis as well as various aspects of genes functioning in development. To permit more effective use of BSMV VIGS for functional genomics experiments, we have developed an Agrobacterium delivery system for BSMV and have coupled this with a ligation independent cloning (LIC) strategy to mediate efficient cloning of host genes. Infiltrated Nicotiana benthamiana leaves provided excellent sources of virus for secondary BSMV infections and VIGS in cereals. The Agro/LIC BSMV VIGS vectors were able to function in high efficiency down regulation of phytoene desaturase (PDS), magnesium chelatase subunit H (ChlH), and plastid transketolase (TK) gene silencing in N. benthamiana and in the monocots, wheat, barley, and the model grass, Brachypodium distachyon. Suppression of an Arabidopsis orthologue cloned from wheat (TaPMR5) also interfered with wheat powdery mildew (Blumeria graminis f. sp. tritici) infections in a manner similar to that of the A. thaliana PMR5 loss-of-function allele. These results imply that the PMR5 gene has maintained similar functions across monocot and dicot families. Our BSMV VIGS system provides substantial advantages in expense, cloning efficiency, ease of manipulation and ability to apply VIGS for high throughput genomics studies. PMID:22031834

Family-specific scaling laws in bacterial genomes.

PubMed

De Lazzari, Eleonora; Grilli, Jacopo; Maslov, Sergei; Cosentino Lagomarsino, Marco

2017-07-27

Among several quantitative invariants found in evolutionary genomics, one of the most striking is the scaling of the overall abundance of proteins, or protein domains, sharing a specific functional annotation across genomes of given size. The size of these functional categories change, on average, as power-laws in the total number of protein-coding genes. Here, we show that such regularities are not restricted to the overall behavior of high-level functional categories, but also exist systematically at the level of single evolutionary families of protein domains. Specifically, the number of proteins within each family follows family-specific scaling laws with genome size. Functionally similar sets of families tend to follow similar scaling laws, but this is not always the case. To understand this systematically, we provide a comprehensive classification of families based on their scaling properties. Additionally, we develop a quantitative score for the heterogeneity of the scaling of families belonging to a given category or predefined group. Under the common reasonable assumption that selection is driven solely or mainly by biological function, these findings point to fine-tuned and interdependent functional roles of specific protein domains, beyond our current functional annotations. This analysis provides a deeper view on the links between evolutionary expansion of protein families and the functional constraints shaping the gene repertoire of bacterial genomes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

RBANS memory percentage retention: No evidence of incremental validity beyond RBANS scores for diagnostic classification of mild cognitive impairment and dementia and for prediction of daily function.

PubMed

Jodouin, Kara A; O'Connell, Megan E; Morgan, Debra G

2017-01-01

RBANS percentage retention scores may be useful for diagnosis, but their incremental validity is unclear. Percentage retention versus RBANS immediate and delayed memory subtests and delayed index scores were compared for diagnostic classification and for prediction of function. Data from 173 memory clinic patients with an interdisciplinary diagnosis (no cognitive impairment, amnestic mild cognitive impairment [aMCI], and dementia due to Alzheimer's disease [AD]) and complete RBANS data were analyzed. Across diagnostic contrasts, list percentage retention classification accuracy was similar to List Learning delayed recall, but below the Delayed Memory Index (DMI). Similarly, for classifying no cognitive impairment versus aMCI or dementia due to AD, story percentage retention was similar to Story Memory subtests and below the DMI. For classifying aMCI versus AD; however, Story Memory exceeded the DMI, but was similar to Story Memory subtest scores. Similarly, for prediction of function percentage retention measures did not predict variance beyond that predicted by the RBANS subtest or index scores. In sum, there is no evidence that calculation of percentage retention for RBANS adds clinical utility beyond those provided by the standard RBANS scores.

High-confidence prediction of global interactomes based on genome-wide coevolutionary networks

PubMed Central

Juan, David; Pazos, Florencio; Valencia, Alfonso

2008-01-01

Interacting or functionally related protein families tend to have similar phylogenetic trees. Based on this observation, techniques have been developed to predict interaction partners. The observed degree of similarity between the phylogenetic trees of two proteins is the result of many different factors besides the actual interaction or functional relationship between them. Such factors influence the performance of interaction predictions. One aspect that can influence this similarity is related to the fact that a given protein interacts with many others, and hence it must adapt to all of them. Accordingly, the interaction or coadaptation signal within its tree is a composite of the influence of all of the interactors. Here, we introduce a new estimator of coevolution to overcome this and other problems. Instead of relying on the individual value of tree similarity between two proteins, we use the whole network of similarities between all of the pairs of proteins within a genome to reassess the similarity of that pair, thereby taking into account its coevolutionary context. We show that this approach offers a substantial improvement in interaction prediction performance, providing a degree of accuracy/coverage comparable with, or in some cases better than, that of experimental techniques. Moreover, important information on the structure, function, and evolution of macromolecular complexes can be inferred with this methodology. PMID:18199838

High-confidence prediction of global interactomes based on genome-wide coevolutionary networks.

PubMed

Juan, David; Pazos, Florencio; Valencia, Alfonso

2008-01-22

Interacting or functionally related protein families tend to have similar phylogenetic trees. Based on this observation, techniques have been developed to predict interaction partners. The observed degree of similarity between the phylogenetic trees of two proteins is the result of many different factors besides the actual interaction or functional relationship between them. Such factors influence the performance of interaction predictions. One aspect that can influence this similarity is related to the fact that a given protein interacts with many others, and hence it must adapt to all of them. Accordingly, the interaction or coadaptation signal within its tree is a composite of the influence of all of the interactors. Here, we introduce a new estimator of coevolution to overcome this and other problems. Instead of relying on the individual value of tree similarity between two proteins, we use the whole network of similarities between all of the pairs of proteins within a genome to reassess the similarity of that pair, thereby taking into account its coevolutionary context. We show that this approach offers a substantial improvement in interaction prediction performance, providing a degree of accuracy/coverage comparable with, or in some cases better than, that of experimental techniques. Moreover, important information on the structure, function, and evolution of macromolecular complexes can be inferred with this methodology.

Pigeon visual short-term memory directly compared to primates.

PubMed

Wright, Anthony A; Elmore, L Caitlin

2016-02-01

Three pigeons were trained to remember arrays of 2-6 colored squares and detect which of two squares had changed color to test their visual short-term memory. Procedures (e.g., stimuli, displays, viewing times, delays) were similar to those used to test monkeys and humans. Following extensive training, pigeons performed slightly better than similarly trained monkeys, but both animal species were considerably less accurate than humans with the same array sizes (2, 4 and 6 items). Pigeons and monkeys showed calculated memory capacities of one item or less, whereas humans showed a memory capacity of 2.5 items. Despite the differences in calculated memory capacities, the pigeons' memory results, like those from monkeys and humans, were all well characterized by an inverse power-law function fit to d' values for the five display sizes. This characterization provides a simple, straightforward summary of the fundamental processing of visual short-term memory (how visual short-term memory declines with memory load) that emphasizes species similarities based upon similar functional relationships. By closely matching pigeon testing parameters to those of monkeys and humans, these similar functional relationships suggest similar underlying processes of visual short-term memory in pigeons, monkeys and humans. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessing the Functional Role of Leptin in Energy Homeostasis and the Stress Response in Vertebrates

PubMed Central

Deck, Courtney A.; Honeycutt, Jamie L.; Cheung, Eugene; Reynolds, Hannah M.; Borski, Russell J.

2017-01-01

Leptin is a pleiotropic hormone that plays a critical role in regulating appetite, energy metabolism, growth, stress, and immune function across vertebrate groups. In mammals, it has been classically described as an adipostat, relaying information regarding energy status to the brain. While retaining poor sequence conservation with mammalian leptins, teleostean leptins elicit a number of similar regulatory properties, although current evidence suggests that it does not function as an adipostat in this group of vertebrates. Teleostean leptin also exhibits functionally divergent properties, however, possibly playing a role in glucoregulation similar to what is observed in lizards. Further, leptin has been recently implicated as a mediator of immune function and the endocrine stress response in teleosts. Here, we provide a review of leptin physiology in vertebrates, with a particular focus on its actions and regulatory properties in the context of stress and the regulation of energy homeostasis. PMID:28439255

Multiple Stressors and the Functioning of Coral Reefs.

PubMed

Harborne, Alastair R; Rogers, Alice; Bozec, Yves-Marie; Mumby, Peter J

2017-01-03

Coral reefs provide critical services to coastal communities, and these services rely on ecosystem functions threatened by stressors. By summarizing the threats to the functioning of reefs from fishing, climate change, and decreasing water quality, we highlight that these stressors have multiple, conflicting effects on functionally similar groups of species and their interactions, and that the overall effects are often uncertain because of a lack of data or variability among taxa. The direct effects of stressors on links among functional groups, such as predator-prey interactions, are particularly uncertain. Using qualitative modeling, we demonstrate that this uncertainty of stressor impacts on functional groups (whether they are positive, negative, or neutral) can have significant effects on models of ecosystem stability, and reducing uncertainty is vital for understanding changes to reef functioning. This review also provides guidance for future models of reef functioning, which should include interactions among functional groups and the cumulative effect of stressors.

Multiple Stressors and the Functioning of Coral Reefs

NASA Astrophysics Data System (ADS)

Harborne, Alastair R.; Rogers, Alice; Bozec, Yves-Marie; Mumby, Peter J.

2017-01-01

Coral reefs provide critical services to coastal communities, and these services rely on ecosystem functions threatened by stressors. By summarizing the threats to the functioning of reefs from fishing, climate change, and decreasing water quality, we highlight that these stressors have multiple, conflicting effects on functionally similar groups of species and their interactions, and that the overall effects are often uncertain because of a lack of data or variability among taxa. The direct effects of stressors on links among functional groups, such as predator-prey interactions, are particularly uncertain. Using qualitative modeling, we demonstrate that this uncertainty of stressor impacts on functional groups (whether they are positive, negative, or neutral) can have significant effects on models of ecosystem stability, and reducing uncertainty is vital for understanding changes to reef functioning. This review also provides guidance for future models of reef functioning, which should include interactions among functional groups and the cumulative effect of stressors.

Monkey Visual Short-Term Memory Directly Compared to Humans

PubMed Central

Elmore, L. Caitlin; Wright, Anthony A.

2015-01-01

Two adult rhesus monkeys were trained to detect which item in an array of memory items had changed using the same stimuli, viewing times, and delays as used with humans. Although the monkeys were extensively trained, they were less accurate than humans with the same array sizes (2, 4, & 6 items), with both stimulus types (colored squares, clip art), and showed calculated memory capacities of about one item (or less). Nevertheless, the memory results from both monkeys and humans for both stimulus types were well characterized by the inverse power-law of display size. This characterization provides a simple and straightforward summary of a fundamental process of visual short-term memory (how VSTM declines with memory load) that emphasizes species similarities based upon similar functional relationships. By more closely matching of monkey testing parameters to those of humans, the similar functional relationships strengthen the evidence suggesting similar processes underlying monkey and human VSTM. PMID:25706544

CLIPS interface development tools and their application

NASA Technical Reports Server (NTRS)

Engel, Bernard A.; Rewerts, Chris C.; Srinivasan, Raghavan; Rogers, Joseph B.; Jones, Don D.

1990-01-01

A package of C-based PC user interface development functions has been developed and integrated into CLIPS. The primary function is ASK which provides a means to ask the user questions via multiple choice menus or the keyboard and then returns the user response to CLIPS. A parameter-like structure supplies information for the interface. Another function, SHOW, provides a means to paginate and display text. A third function, TITLE, formats and displays title screens. A similar set of C-based functions that are more general and thus will run on UNIX and machines have also been developed. Seven expert system applications were transformed from commercial development environments into CLIPS and utilize ASK, SHOW, and TITLE. Development of numerous new expert system applications using CLIPS and these interface functions has started. These functions greatly reduce the time required to build interfaces for CLIPS applications.

Functional Illiteracy: What Public Libraries Can Do To Help People with Reading and Writing Problems. An Ideas Pamphlet.

ERIC Educational Resources Information Center

International Federation of Library Associations, The Hague (Netherlands).

This pamphlet describes literacy programs currently in effect in Scandinavian countries and provides guidelines for the development of similar programs. Reasons for functional illiteracy in the industrialized world are discussed, and current and potential roles for public libraries in improving the situation are considered. Persons who are…

'The genetic analysis of functional connectomics in Drosophila'

PubMed Central

Meinertzhagen, Ian A.; Lee, Chi-Hon

2014-01-01

Fly and vertebrate nervous systems share many organization characteristics, such as layers, columns and glomeruli, and utilize similar synaptic components, such ion channels and receptors. Both also exhibit similar network features. Recent technological advances, especially in electron microscopy, now allow us to determine synaptic circuits and identify pathways cell-by-cell, as part of the fly’s connectome. Genetic tools provide the means to identify synaptic components, as well as to record and manipulate neuronal activity, adding function to the connectome. This review discusses technical advances in these emerging areas of functional connectomics, offering prognoses in each and identifying the challenges in bridging structural connectomics to molecular biology and synaptic physiology, thereby determining fundamental computation mechanisms that underlie behaviour. PMID:23084874

Kernel approach to molecular similarity based on iterative graph similarity.

PubMed

Rupp, Matthias; Proschak, Ewgenij; Schneider, Gisbert

2007-01-01

Similarity measures for molecules are of basic importance in chemical, biological, and pharmaceutical applications. We introduce a molecular similarity measure defined directly on the annotated molecular graph, based on iterative graph similarity and optimal assignments. We give an iterative algorithm for the computation of the proposed molecular similarity measure, prove its convergence and the uniqueness of the solution, and provide an upper bound on the required number of iterations necessary to achieve a desired precision. Empirical evidence for the positive semidefiniteness of certain parametrizations of our function is presented. We evaluated our molecular similarity measure by using it as a kernel in support vector machine classification and regression applied to several pharmaceutical and toxicological data sets, with encouraging results.

The ALMA software architecture

NASA Astrophysics Data System (ADS)

Schwarz, Joseph; Farris, Allen; Sommer, Heiko

2004-09-01

The software for the Atacama Large Millimeter Array (ALMA) is being developed by many institutes on two continents. The software itself will function in a distributed environment, from the 0.5-14 kmbaselines that separate antennas to the larger distances that separate the array site at the Llano de Chajnantor in Chile from the operations and user support facilities in Chile, North America and Europe. Distributed development demands 1) interfaces that allow separated groups to work with minimal dependence on their counterparts at other locations; and 2) a common architecture to minimize duplication and ensure that developers can always perform similar tasks in a similar way. The Container/Component model provides a blueprint for the separation of functional from technical concerns: application developers concentrate on implementing functionality in Components, which depend on Containers to provide them with services such as access to remote resources, transparent serialization of entity objects to XML, logging, error handling and security. Early system integrations have verified that this architecture is sound and that developers can successfully exploit its features. The Containers and their services are provided by a system-orienteddevelopment team as part of the ALMA Common Software (ACS), middleware that is based on CORBA.

Neural Similarity Between Encoding and Retrieval is Related to Memory Via Hippocampal Interactions

PubMed Central

Ritchey, Maureen; Wing, Erik A.; LaBar, Kevin S.; Cabeza, Roberto

2013-01-01

A fundamental principle in memory research is that memory is a function of the similarity between encoding and retrieval operations. Consistent with this principle, many neurobiological models of declarative memory assume that memory traces are stored in cortical regions, and the hippocampus facilitates the reactivation of these traces during retrieval. The present investigation tested the novel prediction that encoding–retrieval similarity can be observed and related to memory at the level of individual items. Multivariate representational similarity analysis was applied to functional magnetic resonance imaging data collected during encoding and retrieval of emotional and neutral scenes. Memory success tracked fluctuations in encoding–retrieval similarity across frontal and posterior cortices. Importantly, memory effects in posterior regions reflected increased similarity between item-specific representations during successful recognition. Mediation analyses revealed that the hippocampus mediated the link between cortical similarity and memory success, providing crucial evidence for hippocampal–cortical interactions during retrieval. Finally, because emotional arousal is known to modulate both perceptual and memory processes, similarity effects were compared for emotional and neutral scenes. Emotional arousal was associated with enhanced similarity between encoding and retrieval patterns. These findings speak to the promise of pattern similarity measures for evaluating memory representations and hippocampal–cortical interactions. PMID:22967731

Similarity-Based Fusion of MEG and fMRI Reveals Spatio-Temporal Dynamics in Human Cortex During Visual Object Recognition

PubMed Central

Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2016-01-01

Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG–fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50–80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG–fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions. PMID:27235099

GEsture: an online hand-drawing tool for gene expression pattern search.

PubMed

Wang, Chunyan; Xu, Yiqing; Wang, Xuelin; Zhang, Li; Wei, Suyun; Ye, Qiaolin; Zhu, Youxiang; Yin, Hengfu; Nainwal, Manoj; Tanon-Reyes, Luis; Cheng, Feng; Yin, Tongming; Ye, Ning

2018-01-01

Gene expression profiling data provide useful information for the investigation of biological function and process. However, identifying a specific expression pattern from extensive time series gene expression data is not an easy task. Clustering, a popular method, is often used to classify similar expression genes, however, genes with a 'desirable' or 'user-defined' pattern cannot be efficiently detected by clustering methods. To address these limitations, we developed an online tool called GEsture. Users can draw, or graph a curve using a mouse instead of inputting abstract parameters of clustering methods. GEsture explores genes showing similar, opposite and time-delay expression patterns with a gene expression curve as input from time series datasets. We presented three examples that illustrate the capacity of GEsture in gene hunting while following users' requirements. GEsture also provides visualization tools (such as expression pattern figure, heat map and correlation network) to display the searching results. The result outputs may provide useful information for researchers to understand the targets, function and biological processes of the involved genes.

Temporal Dynamics of Activation of Thematic and Functional Knowledge During Conceptual Processing of Manipulable Artifacts

PubMed Central

Kalénine, Solène; Mirman, Daniel; Middleton, Erica L.; Buxbaum, Laurel J.

2012-01-01

The current research aimed at specifying the activation time course of different types of semantic information during object conceptual processing and the effect of context on this time course. We distinguished between thematic and functional knowledge and the specificity of functional similarity. Two experiments were conducted with healthy older adults using eye tracking in a word-to-picture matching task. The time course of gaze fixations was used to assess activation of distractor objects during the identification of manipulable artifact targets (e.g., broom). Distractors were (a) thematically related (e.g., dustpan), (b) related by a specific function (e.g., vacuum cleaner), or (c) related by a general function (e.g., sponge). Growth curve analyses were used to assess competition effects when target words were presented in isolation (Experiment 1) and embedded in contextual sentences of different generality levels (Experiment 2). In the absence of context, there was earlier and shorter lasting activation of thematically related as compared to functionally related objects. The time course difference was more pronounced for general functions than specific functions. When contexts were provided, functional similarities that were congruent with context generality level increased in salience with earlier activation of those objects. Context had little impact on thematic activation time course. These data demonstrate that processing a single manipulable artifact concept implicitly activates thematic and functional knowledge with different time courses and that context speeds activation of context-congruent functional similarity. PMID:22449134

TMDD & MS/ETMCC guide : standard for functional level traffic management data dictionary (TMDD) and message sets for external traffic management center communications

DOT National Transportation Integrated Search

2000-01-01

These draft standards are intended to work together to provide a high level of interoperability among regional and local traffic control centers. They provide consistent names, definitions and concepts similar to spelling and parts of speech to world...

Abstract analogical reasoning in high-functioning children with autism spectrum disorders.

PubMed

Green, Adam E; Kenworthy, Lauren; Mosner, Maya G; Gallagher, Natalie M; Fearon, Edward W; Balhana, Carlos D; Yerys, Benjamin E

2014-12-01

Children with autism spectrum disorders (ASD) exhibit a deficit in spontaneously recognizing abstract similarities that are crucial for generalizing learning to new situations. This may contribute to deficits in the development of appropriate schemas for navigating novel situations, including social interactions. Analogical reasoning is the central cognitive mechanism that enables typically developing children to understand abstract similarities between different situations. Intriguingly, studies of high-functioning children with ASD point to a relative cognitive strength in basic, nonabstract forms of analogical reasoning. If this analogical reasoning ability extends to abstract analogical reasoning (i.e., between superficially dissimilar situations), it may provide a bridge between a cognitive capability and core ASD deficits in areas such as generalization and categorization. This study tested whether preserved analogical reasoning abilities in ASD can be extended to abstract analogical reasoning, using photographs of real-world items and situations. Abstractness of the analogies was determined via a quantitative measure of semantic distance derived from latent semantic analysis. Children with ASD performed as well as typically developing children at identifying abstract analogical similarities when explicitly instructed to apply analogical reasoning. Individual differences in abstract analogical reasoning ability predicted individual differences in a measure of social function in the ASD group. Preliminary analyses indicated that children with ASD, but not typically developing children, showed an effect of age on abstract analogical reasoning. These results provide new evidence that children with ASD are capable of identifying abstract similarities through analogical reasoning, pointing to abstract analogical reasoning as a potential lever for improving generalization skills and social function in ASD. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Qualitative similarities in the visual short-term memory of pigeons and people.

PubMed

Gibson, Brett; Wasserman, Edward; Luck, Steven J

2011-10-01

Visual short-term memory plays a key role in guiding behavior, and individual differences in visual short-term memory capacity are strongly predictive of higher cognitive abilities. To provide a broader evolutionary context for understanding this memory system, we directly compared the behavior of pigeons and humans on a change detection task. Although pigeons had a lower storage capacity and a higher lapse rate than humans, both species stored multiple items in short-term memory and conformed to the same basic performance model. Thus, despite their very different evolutionary histories and neural architectures, pigeons and humans have functionally similar visual short-term memory systems, suggesting that the functional properties of visual short-term memory are subject to similar selective pressures across these distant species.

Bed Rest Affects Ventricular and Arterial Elastances in Monkeys: Implications for Humans

DTIC Science & Technology

2004-01-01

Eart may provide insight into adaptation and compromise of cardiovascular function induced by exposure to microgravity or confinement to bed rest...control treatments in our animals in order for Ees to increase in a similar magnitude across LBNP. Although we did not measure cardiac baroreflex function ...treatments. Sunagawa and co-workers have proposed that the integrity of cardiovascular function during rest and exercise is dependent on a mechanical

Gender similarities and differences in brain activation strategies: Voxel-based meta-analysis on fMRI studies.

PubMed

AlRyalat, Saif Aldeen

2017-01-01

Gender similarities and differences have long been a matter of debate in almost all human research, especially upon reaching the discussion about brain functions. This large scale meta-analysis was performed on functional MRI studies. It included more than 700 active brain foci from more than 70 different experiments to study gender related similarities and differences in brain activation strategies for three of the main brain functions: Visual-spatial cognition, memory, and emotion. Areas that are significantly activated by both genders (i.e. core areas) for the tested brain function are mentioned, whereas those areas significantly activated exclusively in one gender are the gender specific areas. During visual-spatial cognition task, and in addition to the core areas, males significantly activated their left superior frontal gyrus, compared with left superior parietal lobule in females. For memory tasks, several different brain areas activated by each gender, but females significantly activated two areas from the limbic system during memory retrieval tasks. For emotional task, males tend to recruit their bilateral prefrontal regions, whereas females tend to recruit their bilateral amygdalae. This meta-analysis provides an overview based on functional MRI studies on how males and females use their brain.

Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

PubMed Central

Kinjo, Akira R.; Nakamura, Haruki

2012-01-01

Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

Hidden relationships between metalloproteins unveiled by structural comparison of their metal sites

NASA Astrophysics Data System (ADS)

Valasatava, Yana; Andreini, Claudia; Rosato, Antonio

2015-03-01

Metalloproteins account for a substantial fraction of all proteins. They incorporate metal atoms, which are required for their structure and/or function. Here we describe a new computational protocol to systematically compare and classify metal-binding sites on the basis of their structural similarity. These sites are extracted from the MetalPDB database of minimal functional sites (MFSs) in metal-binding biological macromolecules. Structural similarity is measured by the scoring function of the available MetalS2 program. Hierarchical clustering was used to organize MFSs into clusters, for each of which a representative MFS was identified. The comparison of all representative MFSs provided a thorough structure-based classification of the sites analyzed. As examples, the application of the proposed computational protocol to all heme-binding proteins and zinc-binding proteins of known structure highlighted the existence of structural subtypes, validated known evolutionary links and shed new light on the occurrence of similar sites in systems at different evolutionary distances. The present approach thus makes available an innovative viewpoint on metalloproteins, where the functionally crucial metal sites effectively lead the discovery of structural and functional relationships in a largely protein-independent manner.

Cerebral palsy in Victoria: motor types, topography and gross motor function.

PubMed

Howard, Jason; Soo, Brendan; Graham, H Kerr; Boyd, Roslyn N; Reid, Sue; Lanigan, Anna; Wolfe, Rory; Reddihough, Dinah S

2005-01-01

To study the relationships between motor type, topographical distribution and gross motor function in a large, population-based cohort of children with cerebral palsy (CP), from the State of Victoria, and compare this cohort to similar cohorts from other countries. An inception cohort was generated from the Victorian Cerebral Palsy Register (VCPR) for the birth years 1990-1992. Demographic information, motor types and topographical distribution were obtained from the register and supplemented by grading gross motor function according to the Gross Motor Function Classification System (GMFCS). Complete data were obtained on 323 (86%) of 374 children in the cohort. Gross motor function varied from GMFCS level I (35%) to GMFCS level V (18%) and was similar in distribution to a contemporaneous Swedish cohort. There was a fairly even distribution across the topographical distributions of hemiplegia (35%), diplegia (28%) and quadriplegia (37%) with a large majority of young people having the spastic motor type (86%). The VCPR is ideal for population-based studies of gross motor function in children with CP. Gross motor function is similar in populations of children with CP in developed countries but the comparison of motor types and topographical distribution is difficult because of lack of consensus with classification systems. Use of the GMFCS provides a valid and reproducible method for clinicians to describe gross motor function in children with CP using a universal language.

Combined invariants to similarity transformation and to blur using orthogonal Zernike moments

PubMed Central

Beijing, Chen; Shu, Huazhong; Zhang, Hui; Coatrieux, Gouenou; Luo, Limin; Coatrieux, Jean-Louis

2011-01-01

The derivation of moment invariants has been extensively investigated in the past decades. In this paper, we construct a set of invariants derived from Zernike moments which is simultaneously invariant to similarity transformation and to convolution with circularly symmetric point spread function (PSF). Two main contributions are provided: the theoretical framework for deriving the Zernike moments of a blurred image and the way to construct the combined geometric-blur invariants. The performance of the proposed descriptors is evaluated with various PSFs and similarity transformations. The comparison of the proposed method with the existing ones is also provided in terms of pattern recognition accuracy, template matching and robustness to noise. Experimental results show that the proposed descriptors perform on the overall better. PMID:20679028

Functional diversity of Csk, Chk, and Src SH2 domains due to a single residue variation.

PubMed

Ayrapetov, Marina K; Nam, Nguyen Hai; Ye, Guofeng; Kumar, Anil; Parang, Keykavous; Sun, Gongqin

2005-07-08

The C-terminal Src kinase (Csk) family of protein tyrosine kinases contains two members: Csk and Csk homologous kinase (Chk). Both phosphorylate and inactivate Src family kinases. Recent reports suggest that the Src homology (SH) 2 domains of Csk and Chk may bind to different phosphoproteins, which provides a basis for different cellular functions for Csk and Chk. To verify and characterize such a functional divergence, we compared the binding properties of the Csk, Chk, and Src SH2 domains and investigated the structural basis for the functional divergence. First, the study demonstrated striking functional differences between the Csk and Chk SH2 domains and revealed functional similarities between the Chk and Src SH2 domains. Second, structural analysis and mutagenic studies revealed that the functional differences among the three SH2 domains were largely controlled by one residue, Glu127 in Csk, Ile167 in Chk, and Lys200 in Src. Mutating these residues in the Csk or Chk SH2 domain to the Src counterpart resulted in dramatic gain of function similar to Src SH2 domain, whereas mutating Lys200 in Src SH2 domain to Glu (the Csk counterpart) resulted in loss of Src SH2 function. Third, a single point mutation of E127K rendered Csk responsive to activation by a Src SH2 domain ligand. Finally, the optimal phosphopeptide sequence for the Chk SH2 domain was determined. These results provide a compelling explanation for the functional differences between two homologous protein tyrosine kinases and reveal a new structure-function relationship for the SH2 domains.

Nature versus nurture: functional assessment of restoration effects on wetland services using Nuclear Magnetic Resonance Spectroscopy

USGS Publications Warehouse

Sundareshwar, P.V.; Richardson, C.J.; Gleason, R.A.; Pellechia, P.J.; Honomichl, S.

2009-01-01

Land-use change has altered the ability of wetlands to provide vital services such as nutrient retention. While compensatory practices attempt to restore degraded wetlands and their functions, it is difficult to evaluate the recovery of soil biogeochemical functions that are critical for restoration of ecosystem services. Using solution 31P Nuclear Magnetic Resonance Spectroscopy, we examined the chemical forms of phosphorus (P) in soils from wetlands located across a land-use gradient. We report that soil P diversity, a functional attribute, was lowest in farmland, and greatest in native wetlands. Soil P diversity increased with age of restoration, indicating restoration of biogeochemical function. The trend in soil P diversity was similar to documented trends in soil bacterial taxonomic composition but opposite that of soil bacterial diversity at our study sites. These findings provide insights into links between ecosystem structure and function and provide a tool for evaluating the success of ecosystem restoration efforts. Copyright 2009 by the American Geophysical Union.

Predicting protein-protein interactions on a proteome scale by matching evolutionary and structural similarities at interfaces using PRISM.

PubMed

Tuncbag, Nurcan; Gursoy, Attila; Nussinov, Ruth; Keskin, Ozlem

2011-08-11

Prediction of protein-protein interactions at the structural level on the proteome scale is important because it allows prediction of protein function, helps drug discovery and takes steps toward genome-wide structural systems biology. We provide a protocol (termed PRISM, protein interactions by structural matching) for large-scale prediction of protein-protein interactions and assembly of protein complex structures. The method consists of two components: rigid-body structural comparisons of target proteins to known template protein-protein interfaces and flexible refinement using a docking energy function. The PRISM rationale follows our observation that globally different protein structures can interact via similar architectural motifs. PRISM predicts binding residues by using structural similarity and evolutionary conservation of putative binding residue 'hot spots'. Ultimately, PRISM could help to construct cellular pathways and functional, proteome-scale annotation. PRISM is implemented in Python and runs in a UNIX environment. The program accepts Protein Data Bank-formatted protein structures and is available at http://prism.ccbb.ku.edu.tr/prism_protocol/.

Functional Equivalence of Spatial Images from Touch and Vision: Evidence from Spatial Updating in Blind and Sighted Individuals

PubMed Central

Giudice, Nicholas A.; Betty, Maryann R.; Loomis, Jack M.

2012-01-01

This research examines whether visual and haptic map learning yield functionally equivalent spatial images in working memory, as evidenced by similar encoding bias and updating performance. In three experiments, participants learned four-point routes either by seeing or feeling the maps. At test, blindfolded participants made spatial judgments about the maps from imagined perspectives that were either aligned or misaligned with the maps as represented in working memory. Results from Experiments 1 and 2 revealed a highly similar pattern of latencies and errors between visual and haptic conditions. These findings extend the well known alignment biases for visual map learning to haptic map learning, provide further evidence of haptic updating, and most importantly, show that learning from the two modalities yields very similar performance across all conditions. Experiment 3 found the same encoding biases and updating performance with blind individuals, demonstrating that functional equivalence cannot be due to visual recoding and is consistent with an amodal hypothesis of spatial images. PMID:21299331

Psychosocial functioning and stress-processing of children with asthma in the school context: differences and similarities with children without asthma.

PubMed

Röder, Irma; Kroonenberg, Pieter M; Boekaerts, Monique

2003-01-01

To characterize children with asthma by their stress processing at school and their psychosocial functioning. To establish similarities and differences between children with and without asthma. Participants were 79 children with asthma and 359 children without asthma (ages 8-12). Children completed questionnaires on stress processing and their well-being at school. Parents filled in a questionnaire on behavior problems, and teachers provided data on school performance and absence rate. Children with asthma had higher scores on absence rates, teacher-rated well-being, internalizing behavior problems, occurrence of "rejection by peers," and use of aggression when coping with "problems with school work." However, using discriminant analyses, the groups could not reliably be distinguished from one another by these variables. Children with asthma are similar to other children with regard to their stress processing at school and their psychosocial functioning. The value of conducting multivariate analysis over several univariate tests is underscored.

Spectral functions of strongly correlated extended systems via an exact quantum embedding

NASA Astrophysics Data System (ADS)

Booth, George H.; Chan, Garnet Kin-Lic

2015-04-01

Density matrix embedding theory (DMET) [Phys. Rev. Lett. 109, 186404 (2012), 10.1103/PhysRevLett.109.186404], introduced an approach to quantum cluster embedding methods whereby the mapping of strongly correlated bulk problems to an impurity with finite set of bath states was rigorously formulated to exactly reproduce the entanglement of the ground state. The formalism provided similar physics to dynamical mean-field theory at a tiny fraction of the cost but was inherently limited by the construction of a bath designed to reproduce ground-state, static properties. Here, we generalize the concept of quantum embedding to dynamic properties and demonstrate accurate bulk spectral functions at similarly small computational cost. The proposed spectral DMET utilizes the Schmidt decomposition of a response vector, mapping the bulk dynamic correlation functions to that of a quantum impurity cluster coupled to a set of frequency-dependent bath states. The resultant spectral functions are obtained on the real-frequency axis, without bath discretization error, and allows for the construction of arbitrary dynamic correlation functions. We demonstrate the method on the one- (1D) and two-dimensional (2D) Hubbard model, where we obtain zero temperature and thermodynamic limit spectral functions, and show the trivial extension to two-particle Green's functions. This advance therefore extends the scope and applicability of DMET in condensed-matter problems as a computationally tractable route to correlated spectral functions of extended systems and provides a competitive alternative to dynamical mean-field theory for dynamic quantities.

StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zemla, A; Lang, D; Kostova, T

2010-11-29

Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitatemore » the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected residues at a given sequence position.« less

Quality assessment of protein model-structures based on structural and functional similarities.

PubMed

Konopka, Bogumil M; Nebel, Jean-Christophe; Kotulska, Malgorzata

2012-09-21

Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology. GOBA--Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests. The validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and one of CASP9, compared to the contest participants. Consequently, GOBA offers a novel single model quality assessment program that addresses the practical needs of biologists. In conjunction with other Model Quality Assessment Programs (MQAPs), it would prove useful for the evaluation of single protein models.

Isofunctional Protein Subfamily Detection Using Data Integration and Spectral Clustering.

PubMed

Boari de Lima, Elisa; Meira, Wagner; Melo-Minardi, Raquel Cardoso de

2016-06-01

As increasingly more genomes are sequenced, the vast majority of proteins may only be annotated computationally, given experimental investigation is extremely costly. This highlights the need for computational methods to determine protein functions quickly and reliably. We believe dividing a protein family into subtypes which share specific functions uncommon to the whole family reduces the function annotation problem's complexity. Hence, this work's purpose is to detect isofunctional subfamilies inside a family of unknown function, while identifying differentiating residues. Similarity between protein pairs according to various properties is interpreted as functional similarity evidence. Data are integrated using genetic programming and provided to a spectral clustering algorithm, which creates clusters of similar proteins. The proposed framework was applied to well-known protein families and to a family of unknown function, then compared to ASMC. Results showed our fully automated technique obtained better clusters than ASMC for two families, besides equivalent results for other two, including one whose clusters were manually defined. Clusters produced by our framework showed great correspondence with the known subfamilies, besides being more contrasting than those produced by ASMC. Additionally, for the families whose specificity determining positions are known, such residues were among those our technique considered most important to differentiate a given group. When run with the crotonase and enolase SFLD superfamilies, the results showed great agreement with this gold-standard. Best results consistently involved multiple data types, thus confirming our hypothesis that similarities according to different knowledge domains may be used as functional similarity evidence. Our main contributions are the proposed strategy for selecting and integrating data types, along with the ability to work with noisy and incomplete data; domain knowledge usage for detecting subfamilies in a family with different specificities, thus reducing the complexity of the experimental function characterization problem; and the identification of residues responsible for specificity.

Isofunctional Protein Subfamily Detection Using Data Integration and Spectral Clustering

PubMed Central

Boari de Lima, Elisa; Meira, Wagner; de Melo-Minardi, Raquel Cardoso

2016-01-01

As increasingly more genomes are sequenced, the vast majority of proteins may only be annotated computationally, given experimental investigation is extremely costly. This highlights the need for computational methods to determine protein functions quickly and reliably. We believe dividing a protein family into subtypes which share specific functions uncommon to the whole family reduces the function annotation problem’s complexity. Hence, this work’s purpose is to detect isofunctional subfamilies inside a family of unknown function, while identifying differentiating residues. Similarity between protein pairs according to various properties is interpreted as functional similarity evidence. Data are integrated using genetic programming and provided to a spectral clustering algorithm, which creates clusters of similar proteins. The proposed framework was applied to well-known protein families and to a family of unknown function, then compared to ASMC. Results showed our fully automated technique obtained better clusters than ASMC for two families, besides equivalent results for other two, including one whose clusters were manually defined. Clusters produced by our framework showed great correspondence with the known subfamilies, besides being more contrasting than those produced by ASMC. Additionally, for the families whose specificity determining positions are known, such residues were among those our technique considered most important to differentiate a given group. When run with the crotonase and enolase SFLD superfamilies, the results showed great agreement with this gold-standard. Best results consistently involved multiple data types, thus confirming our hypothesis that similarities according to different knowledge domains may be used as functional similarity evidence. Our main contributions are the proposed strategy for selecting and integrating data types, along with the ability to work with noisy and incomplete data; domain knowledge usage for detecting subfamilies in a family with different specificities, thus reducing the complexity of the experimental function characterization problem; and the identification of residues responsible for specificity. PMID:27348631

Correlated gene expression and anatomical communication support synchronized brain activity in the mouse functional connectome.

PubMed

Mills, Brian D; Grayson, David S; Shunmugavel, Anandakumar; Miranda-Dominguez, Oscar; Feczko, Eric; Earl, Eric; Neve, Kim; Fair, Damien A

2018-05-22

Cognition and behavior depend on synchronized intrinsic brain activity that is organized into functional networks across the brain. Research has investigated how anatomical connectivity both shapes and is shaped by these networks, but not how anatomical connectivity interacts with intra-areal molecular properties to drive functional connectivity. Here, we present a novel linear model to explain functional connectivity by integrating systematically obtained measurements of axonal connectivity, gene expression, and resting state functional connectivity MRI in the mouse brain. The model suggests that functional connectivity arises from both anatomical links and inter-areal similarities in gene expression. By estimating these effects, we identify anatomical modules in which correlated gene expression and anatomical connectivity support functional connectivity. Along with providing evidence that not all genes equally contribute to functional connectivity, this research establishes new insights regarding the biological underpinnings of coordinated brain activity measured by BOLD fMRI. SIGNIFICANCE STATEMENT Efforts at characterizing the functional connectome with fMRI have risen exponentially over the last decade. Yet despite this rise, the biological underpinnings of these functional measurements are still largely unknown. The current report begins to fill this void by investigating the molecular underpinnings of the functional connectome through an integration of systematically obtained structural information and gene expression data throughout the rodent brain. We find that both white matter connectivity and similarity in regional gene expression relate to resting state functional connectivity. The current report furthers our understanding of the biological underpinnings of the functional connectome and provides a linear model that can be utilized to streamline preclinical animal studies of disease. Copyright © 2018 the authors.

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets

PubMed Central

2012-01-01

Background To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. Results We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. Conclusions SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery. PMID:23281852

Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets.

PubMed

Chiu, Yi-Yuan; Lin, Chun-Yu; Lin, Chih-Ta; Hsu, Kai-Cheng; Chang, Li-Zen; Yang, Jinn-Moon

2012-01-01

To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery.

The what, where, how and why of gene ontology—a primer for bioinformaticians

PubMed Central

du Plessis, Louis; Škunca, Nives

2011-01-01

With high-throughput technologies providing vast amounts of data, it has become more important to provide systematic, quality annotations. The Gene Ontology (GO) project is the largest resource for cataloguing gene function. Nonetheless, its use is not yet ubiquitous and is still fraught with pitfalls. In this review, we provide a short primer to the GO for bioinformaticians. We summarize important aspects of the structure of the ontology, describe sources and types of functional annotations, survey measures of GO annotation similarity, review typical uses of GO and discuss other important considerations pertaining to the use of GO in bioinformatics applications. PMID:21330331

Models of violently relaxed galaxies

NASA Astrophysics Data System (ADS)

Merritt, David; Tremaine, Scott; Johnstone, Doug

1989-02-01

The properties of spherical self-gravitating models derived from two distribution functions that incorporate, in a crude way, the physics of violent relaxation are investigated. The first distribution function is identical to the one discussed by Stiavelli and Bertin (1985) except for a change in the sign of the 'temperature', i.e., e exp(-aE) to e exp(+aE). It is shown that these 'negative temperature' models provide a much better description of the end-state of violent relaxation than 'positive temperature' models. The second distribution function is similar to the first except for a different dependence on angular momentum. Both distribution functions yield single-parameter families of models with surface density profiles very similar to the R exp 1/4 law. Furthermore, the central concentration of models in both families increases monotonically with the velocity anisotropy, as expected in systems that formed through cold collapse.

Effectiveness of Cognitive, Exposure, and Skills Group Manualized Treatments in OIF/OEF Female Veterans

DTIC Science & Technology

2014-04-01

compared to a normal sample showed significantly lower IQ , but still in the normal range, and poorer executive functioning, similar to male combat...68,750) was provided by the DOD to collect pre/post neuropsychological pilot data to assess for the effects of treatment on Traumatic Brain Injury...SOW). 7) Neuropsychological differences in baseline IQ and executive function were found with lower IQ and poorer functioning found in the PTSD

Functional connectivity density mapping: comparing multiband and conventional EPI protocols.

PubMed

Cohen, Alexander D; Tomasi, Dardo; Shokri-Kojori, Ehsan; Nencka, Andrew S; Wang, Yang

2018-06-01

Functional connectivity density mapping (FCDM) is a newly developed data-driven technique that quantifies the number of local and global functional connections for each voxel in the brain. In this study, we evaluated reproducibility, sensitivity, and specificity of both local functional connectivity density (lFCD) and global functional connectivity density (gFCD). We compared these metrics using the human connectome project (HCP) compatible high-resolution (2 mm isotropic, TR = 0.8 s) multiband (MB), and more typical, lower resolution (3.5 mm isotropic, TR = 2.0 s) single-band (SB) resting state functional MRI (rs-fMRI) acquisitions. Furthermore, in order to be more clinically feasible, only rs-fMRI scans that lasted seven minutes were tested. Subjects were scanned twice within a two-week span. We found sensitivity and specificity increased and reproducibility either increased or did not change for the MB compared to the SB acquisitions. The MB scans also showed improved gray matter/white matter contrast compared to the SB scans. The lFCD and gFCD patterns were similar across MB and SB scans and confined predominantly to gray matter. We also observed a strong spatial correlation of FCD between MB and SB scans indicating the two acquisitions provide similar information. These findings indicate high-resolution MB acquisitions improve the quality of FCD data, and seven minute rs-fMRI scan can provide robust FCD measurements.

FunTree: advances in a resource for exploring and contextualising protein function evolution.

PubMed

Sillitoe, Ian; Furnham, Nicholas

2016-01-04

FunTree is a resource that brings together protein sequence, structure and functional information, including overall chemical reaction and mechanistic data, for structurally defined domain superfamilies. Developed in tandem with the CATH database, the original FunTree contained just 276 superfamilies focused on enzymes. Here, we present an update of FunTree that has expanded to include 2340 superfamilies including both enzymes and proteins with non-enzymatic functions annotated by Gene Ontology (GO) terms. This allows the investigation of how novel functions have evolved within a structurally defined superfamily and provides a means to analyse trends across many superfamilies. This is done not only within the context of a protein's sequence and structure but also the relationships of their functions. New measures of functional similarity have been integrated, including for enzymes comparisons of overall reactions based on overall bond changes, reaction centres (the local environment atoms involved in the reaction) and the sub-structure similarities of the metabolites involved in the reaction and for non-enzymes semantic similarities based on the GO. To identify and highlight changes in function through evolution, ancestral character estimations are made and presented. All this is accessible through a new re-designed web interface that can be found at http://www.funtree.info. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily.

PubMed

Lakshmi, Balasubramanian; Mishra, Madhulika; Srinivasan, Narayanaswamy; Archunan, Govindaraju

2015-01-01

Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity.

K-shuff: A Novel Algorithm for Characterizing Structural and Compositional Diversity in Gene Libraries.

PubMed

Jangid, Kamlesh; Kao, Ming-Hung; Lahamge, Aishwarya; Williams, Mark A; Rathbun, Stephen L; Whitman, William B

2016-01-01

K-shuff is a new algorithm for comparing the similarity of gene sequence libraries, providing measures of the structural and compositional diversity as well as the significance of the differences between these measures. Inspired by Ripley's K-function for spatial point pattern analysis, the Intra K-function or IKF measures the structural diversity, including both the richness and overall similarity of the sequences, within a library. The Cross K-function or CKF measures the compositional diversity between gene libraries, reflecting both the number of OTUs shared as well as the overall similarity in OTUs. A Monte Carlo testing procedure then enables statistical evaluation of both the structural and compositional diversity between gene libraries. For 16S rRNA gene libraries from complex bacterial communities such as those found in seawater, salt marsh sediments, and soils, K-shuff yields reproducible estimates of structural and compositional diversity with libraries greater than 50 sequences. Similarly, for pyrosequencing libraries generated from a glacial retreat chronosequence and Illumina® libraries generated from US homes, K-shuff required >300 and 100 sequences per sample, respectively. Power analyses demonstrated that K-shuff is sensitive to small differences in Sanger or Illumina® libraries. This extra sensitivity of K-shuff enabled examination of compositional differences at much deeper taxonomic levels, such as within abundant OTUs. This is especially useful when comparing communities that are compositionally very similar but functionally different. K-shuff will therefore prove beneficial for conventional microbiome analysis as well as specific hypothesis testing.

Genomic similarity and kernel methods I: advancements by building on mathematical and statistical foundations.

PubMed

Schaid, Daniel J

2010-01-01

Measures of genomic similarity are the basis of many statistical analytic methods. We review the mathematical and statistical basis of similarity methods, particularly based on kernel methods. A kernel function converts information for a pair of subjects to a quantitative value representing either similarity (larger values meaning more similar) or distance (smaller values meaning more similar), with the requirement that it must create a positive semidefinite matrix when applied to all pairs of subjects. This review emphasizes the wide range of statistical methods and software that can be used when similarity is based on kernel methods, such as nonparametric regression, linear mixed models and generalized linear mixed models, hierarchical models, score statistics, and support vector machines. The mathematical rigor for these methods is summarized, as is the mathematical framework for making kernels. This review provides a framework to move from intuitive and heuristic approaches to define genomic similarities to more rigorous methods that can take advantage of powerful statistical modeling and existing software. A companion paper reviews novel approaches to creating kernels that might be useful for genomic analyses, providing insights with examples [1]. Copyright © 2010 S. Karger AG, Basel.

Cardiac regulation in the socially monogamous prairie vole

PubMed Central

Grippo, Angela J.; Lamb, Damon G.; Carter, C. Sue; Porges, Stephen W.

2007-01-01

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model. PMID:17107695

Pion and kaon valence-quark parton quasidistributions

NASA Astrophysics Data System (ADS)

Xu, Shu-Sheng; Chang, Lei; Roberts, Craig D.; Zong, Hong-Shi

2018-05-01

Algebraic Ansätze for the Poincaré-covariant Bethe-Salpeter wave functions of the pion and kaon are used to calculate their light-front wave functions, parton distribution amplitudes, parton quasidistribution amplitudes, valence parton distribution functions, and parton quasidistribution functions (PqDFs). The light-front wave functions are broad, concave functions, and the scale of flavor-symmetry violation in the kaon is roughly 15%, being set by the ratio of emergent masses in the s - and u -quark sectors. Parton quasidistribution amplitudes computed with longitudinal momentum Pz=1.75 GeV provide a semiquantitatively accurate representation of the objective parton distribution amplitude, but even with Pz=3 GeV , they cannot provide information about this amplitude's end point behavior. On the valence-quark domain, similar outcomes characterize PqDFs. In this connection, however, the ratio of kaon-to-pion u -quark PqDFs is found to provide a good approximation to the true parton distribution function ratio on 0.4 ≲x ≲0.8 , suggesting that with existing resources computations of ratios of parton quasidistributions can yield results that support empirical comparison.

Finding Protein and Nucleotide Similarities with FASTA

PubMed Central

Pearson, William R.

2016-01-01

The FASTA programs provide a comprehensive set of rapid similarity searching tools ( fasta36, fastx36, tfastx36, fasty36, tfasty36), similar to those provided by the BLAST package, as well as programs for slower, optimal, local and global similarity searches ( ssearch36, ggsearch36) and for searching with short peptides and oligonucleotides ( fasts36, fastm36). The FASTA programs use an empirical strategy for estimating statistical significance that accommodates a range of similarity scoring matrices and gap penalties, improving alignment boundary accuracy and search sensitivity (Unit 3.5). The FASTA programs can produce “BLAST-like” alignment and tabular output, for ease of integration into existing analysis pipelines, and can search small, representative databases, and then report results for a larger set of sequences, using links from the smaller dataset. The FASTA programs work with a wide variety of database formats, including mySQL and postgreSQL databases (Unit 9.4). The programs also provide a strategy for integrating domain and active site annotations into alignments and highlighting the mutational state of functionally critical residues. These protocols describe how to use the FASTA programs to characterize protein and DNA sequences, using protein:protein, protein:DNA, and DNA:DNA comparisons. PMID:27010337

Finding Protein and Nucleotide Similarities with FASTA.

PubMed

Pearson, William R

2016-03-24

The FASTA programs provide a comprehensive set of rapid similarity searching tools (fasta36, fastx36, tfastx36, fasty36, tfasty36), similar to those provided by the BLAST package, as well as programs for slower, optimal, local, and global similarity searches (ssearch36, ggsearch36), and for searching with short peptides and oligonucleotides (fasts36, fastm36). The FASTA programs use an empirical strategy for estimating statistical significance that accommodates a range of similarity scoring matrices and gap penalties, improving alignment boundary accuracy and search sensitivity. The FASTA programs can produce "BLAST-like" alignment and tabular output, for ease of integration into existing analysis pipelines, and can search small, representative databases, and then report results for a larger set of sequences, using links from the smaller dataset. The FASTA programs work with a wide variety of database formats, including mySQL and postgreSQL databases. The programs also provide a strategy for integrating domain and active site annotations into alignments and highlighting the mutational state of functionally critical residues. These protocols describe how to use the FASTA programs to characterize protein and DNA sequences, using protein:protein, protein:DNA, and DNA:DNA comparisons. Copyright © 2016 John Wiley & Sons, Inc.

Why are you telling me that? A conceptual model of the social function of autobiographical memory.

PubMed

Alea, Nicole; Bluck, Susan

2003-03-01

In an effort to stimulate and guide empirical work within a functional framework, this paper provides a conceptual model of the social functions of autobiographical memory (AM) across the lifespan. The model delineates the processes and variables involved when AMs are shared to serve social functions. Components of the model include: lifespan contextual influences, the qualitative characteristics of memory (emotionality and level of detail recalled), the speaker's characteristics (age, gender, and personality), the familiarity and similarity of the listener to the speaker, the level of responsiveness during the memory-sharing process, and the nature of the social relationship in which the memory sharing occurs (valence and length of the relationship). These components are shown to influence the type of social function served and/or, the extent to which social functions are served. Directions for future empirical work to substantiate the model and hypotheses derived from the model are provided.

Emerging structural insights into the function of ionotropic glutamate receptors

PubMed Central

Karakas, Erkan; Regan, Michael C.; Furukawa, Hiro

2015-01-01

Summary Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function including learning and memory formation. Recently a wealth of structural studies on iGluRs, including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available.. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, which illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. Here we review mechanistic insights into iGluR functions gained through structural studies of multiple groups. PMID:25941168

Keeping the body in mind: insula functional organization and functional connectivity integrate interoceptive, exteroceptive, and emotional awareness.

PubMed

Simmons, W Kyle; Avery, Jason A; Barcalow, Joel C; Bodurka, Jerzy; Drevets, Wayne C; Bellgowan, Patrick

2013-11-01

Relatively discrete experimental literatures have grown to support the insula's role in the domains of interoception, focal exteroceptive attention and cognitive control, and the experience of anxiety, even as theoretical accounts have asserted that the insula is a critical zone for integrating across these domains. Here we provide the first experimental demonstration that there exists a functional topography across the insula, with distinct regions in the same participants responding in a highly selective fashion for interoceptive, exteroceptive, and affective processing. Although each insular region is associated with areas of differential resting state functional connectivity relative to the other regions, overall their functional connectivity profiles are quite similar, thereby providing a map of how interoceptive, exteroceptive, and emotional awareness are integrated within the insular cortex. Copyright © 2012 Wiley Periodicals, Inc.

Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks.

PubMed

Gerlt, John A; Bouvier, Jason T; Davidson, Daniel B; Imker, Heidi J; Sadkhin, Boris; Slater, David R; Whalen, Katie L

2015-08-01

The Enzyme Function Initiative, an NIH/NIGMS-supported Large-Scale Collaborative Project (EFI; U54GM093342; http://enzymefunction.org/), is focused on devising and disseminating bioinformatics and computational tools as well as experimental strategies for the prediction and assignment of functions (in vitro activities and in vivo physiological/metabolic roles) to uncharacterized enzymes discovered in genome projects. Protein sequence similarity networks (SSNs) are visually powerful tools for analyzing sequence relationships in protein families (H.J. Atkinson, J.H. Morris, T.E. Ferrin, and P.C. Babbitt, PLoS One 2009, 4, e4345). However, the members of the biological/biomedical community have not had access to the capability to generate SSNs for their "favorite" protein families. In this article we announce the EFI-EST (Enzyme Function Initiative-Enzyme Similarity Tool) web tool (http://efi.igb.illinois.edu/efi-est/) that is available without cost for the automated generation of SSNs by the community. The tool can create SSNs for the "closest neighbors" of a user-supplied protein sequence from the UniProt database (Option A) or of members of any user-supplied Pfam and/or InterPro family (Option B). We provide an introduction to SSNs, a description of EFI-EST, and a demonstration of the use of EFI-EST to explore sequence-function space in the OMP decarboxylase superfamily (PF00215). This article is designed as a tutorial that will allow members of the community to use the EFI-EST web tool for exploring sequence/function space in protein families. Copyright © 2015 Elsevier B.V. All rights reserved.

PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs.

PubMed

Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

2015-01-01

PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Readout from iconic memory and selective spatial attention involve similar neural processes.

PubMed

Ruff, Christian C; Kristjánsson, Arni; Driver, Jon

2007-10-01

Iconic memory and spatial attention are often considered separately, but they may have functional similarities. Here we provide functional magnetic resonance imaging evidence for some common underlying neural effects. Subjects judged three visual stimuli in one hemifield of a bilateral array comprising six stimuli. The relevant hemifield for partial report was indicated by an auditory cue, administered either before the visual array (precue, spatial attention) or shortly after the array (postcue, iconic memory). Pre- and postcues led to similar activity modulations in lateral occipital cortex contralateral to the cued side. This finding indicates that readout from iconic memory can have some neural effects similar to those of spatial attention. We also found common bilateral activation of a fronto-parietal network for postcue and precue trials. These neuroimaging data suggest that some common neural mechanisms underlie selective spatial attention and readout from iconic memory. Some differences were also found; compared with precues, postcues led to higher activity in the right middle frontal gyrus.

Readout From Iconic Memory and Selective Spatial Attention Involve Similar Neural Processes

PubMed Central

Ruff, Christian C; Kristjánsson, Árni; Driver, Jon

2007-01-01

Iconic memory and spatial attention are often considered separately, but they may have functional similarities. Here we provide functional magnetic resonance imaging evidence for some common underlying neural effects. Subjects judged three visual stimuli in one hemifield of a bilateral array comprising six stimuli. The relevant hemifield for partial report was indicated by an auditory cue, administered either before the visual array (precue, spatial attention) or shortly after the array (postcue, iconic memory). Pre- and postcues led to similar activity modulations in lateral occipital cortex contralateral to the cued side. This finding indicates that readout from iconic memory can have some neural effects similar to those of spatial attention. We also found common bilateral activation of a fronto-parietal network for postcue and precue trials. These neuroimaging data suggest that some common neural mechanisms underlie selective spatial attention and readout from iconic memory. Some differences were also found; compared with precues, postcues led to higher activity in the right middle frontal gyrus. PMID:17894608

Goal striving within agentic and communal roles: separate but functionally similar pathways to enhanced well-being.

PubMed

Sheldon, Kennon M; Cooper, M Lynne

2008-06-01

Do agency and communion strivings provide functionally similar but predictively independent pathways to enhanced well-being? We tested this idea via a year-long study of 493 diverse community adults. Our process model, based on self-determination and motive disposition theories, fit the data well. First, the need for achievement predicted initial autonomous motivation for agentic (work and school) role-goals and the need for intimacy predicted felt autonomy for communal (relationship and parenting) goals. For both agentic and communal goals, autonomous motivation predicted corresponding initial expectancies that predicted later goal attainment. Finally, each type of attainment predicted improved adjustment or role-satisfaction over the year. Besides being similar across agency and communion, the model was also similar across race and gender, except that the beneficial effects of communal goal attainment were stronger for high need for intimacy women and Blacks. Implications for agency/communion theories, motivation theories, and theories of well-being are discussed.

DOSim: an R package for similarity between diseases based on Disease Ontology.

PubMed

Li, Jiang; Gong, Binsheng; Chen, Xi; Liu, Tao; Wu, Chao; Zhang, Fan; Li, Chunquan; Li, Xiang; Rao, Shaoqi; Li, Xia

2011-06-29

The construction of the Disease Ontology (DO) has helped promote the investigation of diseases and disease risk factors. DO enables researchers to analyse disease similarity by adopting semantic similarity measures, and has expanded our understanding of the relationships between different diseases and to classify them. Simultaneously, similarities between genes can also be analysed by their associations with similar diseases. As a result, disease heterogeneity is better understood and insights into the molecular pathogenesis of similar diseases have been gained. However, bioinformatics tools that provide easy and straight forward ways to use DO to study disease and gene similarity simultaneously are required. We have developed an R-based software package (DOSim) to compute the similarity between diseases and to measure the similarity between human genes in terms of diseases. DOSim incorporates a DO-based enrichment analysis function that can be used to explore the disease feature of an independent gene set. A multilayered enrichment analysis (GO and KEGG annotation) annotation function that helps users explore the biological meaning implied in a newly detected gene module is also part of the DOSim package. We used the disease similarity application to demonstrate the relationship between 128 different DO cancer terms. The hierarchical clustering of these 128 different cancers showed modular characteristics. In another case study, we used the gene similarity application on 361 obesity-related genes. The results revealed the complex pathogenesis of obesity. In addition, the gene module detection and gene module multilayered annotation functions in DOSim when applied on these 361 obesity-related genes helped extend our understanding of the complex pathogenesis of obesity risk phenotypes and the heterogeneity of obesity-related diseases. DOSim can be used to detect disease-driven gene modules, and to annotate the modules for functions and pathways. The DOSim package can also be used to visualise DO structure. DOSim can reflect the modular characteristic of disease related genes and promote our understanding of the complex pathogenesis of diseases. DOSim is available on the Comprehensive R Archive Network (CRAN) or http://bioinfo.hrbmu.edu.cn/dosim.

Management intensity at field and landscape levels affects the structure of generalist predator communities.

PubMed

Rusch, Adrien; Birkhofer, Klaus; Bommarco, Riccardo; Smith, Henrik G; Ekbom, Barbara

2014-07-01

Agricultural intensification is recognised as a major driver of biodiversity loss in human-modified landscapes. Several agro-environmental measures at different spatial scales have been suggested to mitigate the negative impact of intensification on biodiversity and ecosystem services. The effect of these measures on the functional structure of service-providing communities remains, however, largely unexplored. Using two distinct landscape designs, we examined how the management options of organic farming at the field scale and crop diversification at the landscape level affect the taxonomic and functional structure of generalist predator communities and how these effects vary along a landscape complexity gradient. Organic farming as well as landscapes with longer and more diversified crop rotations enhanced the activity-density of spiders and rove beetles, but not the species richness or evenness. Our results indicate that the two management options affected the functional composition of communities, as they primarily enhanced the activity-density of functionally similar species. The two management options increased the functional similarity between spider species in regards to hunting mode and habitat preference. Organic farming enhanced the functional similarity of rove beetles. Management options at field and landscape levels were generally more important predictors of community structure when compared to landscape complexity. Our study highlights the importance of considering the functional composition of generalist predators in order to understand how agro-environmental measures at various scales shape community assemblages and ecosystem functioning in agricultural landscapes.

Dramatic Increases of Soil Microbial Functional Gene Diversity at the Treeline Ecotone of Changbai Mountain.

PubMed

Shen, Congcong; Shi, Yu; Ni, Yingying; Deng, Ye; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong; Chu, Haiyan

2016-01-01

The elevational and latitudinal diversity patterns of microbial taxa have attracted great attention in the past decade. Recently, the distribution of functional attributes has been in the spotlight. Here, we report a study profiling soil microbial communities along an elevation gradient (500-2200 m) on Changbai Mountain. Using a comprehensive functional gene microarray (GeoChip 5.0), we found that microbial functional gene richness exhibited a dramatic increase at the treeline ecotone, but the bacterial taxonomic and phylogenetic diversity based on 16S rRNA gene sequencing did not exhibit such a similar trend. However, the β-diversity (compositional dissimilarity among sites) pattern for both bacterial taxa and functional genes was similar, showing significant elevational distance-decay patterns which presented increased dissimilarity with elevation. The bacterial taxonomic diversity/structure was strongly influenced by soil pH, while the functional gene diversity/structure was significantly correlated with soil dissolved organic carbon (DOC). This finding highlights that soil DOC may be a good predictor in determining the elevational distribution of microbial functional genes. The finding of significant shifts in functional gene diversity at the treeline ecotone could also provide valuable information for predicting the responses of microbial functions to climate change.

Using Anatomic Magnetic Resonance Image Information to Enhance Visualization and Interpretation of Functional Images: A Comparison of Methods Applied to Clinical Arterial Spin Labeling Images

PubMed Central

Dai, Weiying; Soman, Salil; Hackney, David B.; Wong, Eric T.; Robson, Philip M.; Alsop, David C.

2017-01-01

Functional imaging provides hemodynamic and metabolic information and is increasingly being incorporated into clinical diagnostic and research studies. Typically functional images have reduced signal-to-noise ratio and spatial resolution compared to other non-functional cross sectional images obtained as part of a routine clinical protocol. We hypothesized that enhancing visualization and interpretation of functional images with anatomic information could provide preferable quality and superior diagnostic value. In this work, we implemented five methods (frequency addition, frequency multiplication, wavelet transform, non-subsampled contourlet transform and intensity-hue-saturation) and a newly proposed ShArpening by Local Similarity with Anatomic images (SALSA) method to enhance the visualization of functional images, while preserving the original functional contrast and quantitative signal intensity characteristics over larger spatial scales. Arterial spin labeling blood flow MR images of the brain were visualization enhanced using anatomic images with multiple contrasts. The algorithms were validated on a numerical phantom and their performance on images of brain tumor patients were assessed by quantitative metrics and neuroradiologist subjective ratings. The frequency multiplication method had the lowest residual error for preserving the original functional image contrast at larger spatial scales (55%–98% of the other methods with simulated data and 64%–86% with experimental data). It was also significantly more highly graded by the radiologists (p<0.005 for clear brain anatomy around the tumor). Compared to other methods, the SALSA provided 11%–133% higher similarity with ground truth images in the simulation and showed just slightly lower neuroradiologist grading score. Most of these monochrome methods do not require any prior knowledge about the functional and anatomic image characteristics, except the acquired resolution. Hence, automatic implementation on clinical images should be readily feasible. PMID:27723582

The nature of inherent bactericidal activity: insights from the nanotopology of three species of dragonfly

NASA Astrophysics Data System (ADS)

Mainwaring, David E.; Nguyen, Song Ha; Webb, Hayden; Jakubov, Timur; Tobin, Mark; Lamb, Robert N.; Wu, Alex H.-F.; Marchant, Richard; Crawford, Russell J.; Ivanova, Elena P.

2016-03-01

While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces.While insect wings are widely recognised as multi-functional, recent work showed that this extends to extensive bactericidal activity brought about by cell deformation and lysis on the wing nanotopology. We now quantitatively show that subtle changes to this topography result in substantial changes in bactericidal activity that are able to span an order of magnitude. Notably, the chemical composition of the lipid nanopillars was seen by XPS and synchrotron FTIR microspectroscopy to be similar across these activity differences. Modelling the interaction between bacterial cells and the wing surface lipids of 3 species of dragonflies, that inhabit similar environments, but with distinctly different behavioural repertoires, provided the relationship between surface structure and antibacterial functionality. In doing so, these principal behavioural patterns correlated with the demands for antimicrobial efficiency dictated by differences in their foraging strategies. This work now reveals a new feature in the design elegance of natural multi-functional surfaces as well providing insights into the bactericidal mechanism underlying inherently antimicrobial materials, while suggesting that nanotopology is related to the evolutionary development of a species through the demands of its behavioural repertoire. The underlying relationship between the processes of wetting, adhesion and capillarity of the lipid nanopillars and bactericidal efficiency suggests new prospects for purely mechano-responsive antibacterial surfaces. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08542j

A topological hierarchy for functions on triangulated surfaces.

PubMed

Bremer, Peer-Timo; Edelsbrunner, Herbert; Hamann, Bernd; Pascucci, Valerio

2004-01-01

We combine topological and geometric methods to construct a multiresolution representation for a function over a two-dimensional domain. In a preprocessing stage, we create the Morse-Smale complex of the function and progressively simplify its topology by cancelling pairs of critical points. Based on a simple notion of dependency among these cancellations, we construct a hierarchical data structure supporting traversal and reconstruction operations similarly to traditional geometry-based representations. We use this data structure to extract topologically valid approximations that satisfy error bounds provided at runtime.

The next generation of similarity measures that fully explore the semantics in biomedical ontologies.

PubMed

Couto, Francisco M; Pinto, H Sofia

2013-10-01

There is a prominent trend to augment and improve the formality of biomedical ontologies. For example, this is shown by the current effort on adding description logic axioms, such as disjointness. One of the key ontology applications that can take advantage of this effort is the conceptual (functional) similarity measurement. The presence of description logic axioms in biomedical ontologies make the current structural or extensional approaches weaker and further away from providing sound semantics-based similarity measures. Although beneficial in small ontologies, the exploration of description logic axioms by semantics-based similarity measures is computational expensive. This limitation is critical for biomedical ontologies that normally contain thousands of concepts. Thus in the process of gaining their rightful place, biomedical functional similarity measures have to take the journey of finding how this rich and powerful knowledge can be fully explored while keeping feasible computational costs. This manuscript aims at promoting and guiding the development of compelling tools that deliver what the biomedical community will require in a near future: a next-generation of biomedical similarity measures that efficiently and fully explore the semantics present in biomedical ontologies.

Computational mining for hypothetical patterns of amino acid side chains in protein data bank (PDB)

NASA Astrophysics Data System (ADS)

Ghani, Nur Syatila Ab; Firdaus-Raih, Mohd

2018-04-01

The three-dimensional structure of a protein can provide insights regarding its function. Functional relationship between proteins can be inferred from fold and sequence similarities. In certain cases, sequence or fold comparison fails to conclude homology between proteins with similar mechanism. Since the structure is more conserved than the sequence, a constellation of functional residues can be similarly arranged among proteins of similar mechanism. Local structural similarity searches are able to detect such constellation of amino acids among distinct proteins, which can be useful to annotate proteins of unknown function. Detection of such patterns of amino acids on a large scale can increase the repertoire of important 3D motifs since available known 3D motifs currently, could not compensate the ever-increasing numbers of uncharacterized proteins to be annotated. Here, a computational platform for an automated detection of 3D motifs is described. A fuzzy-pattern searching algorithm derived from IMagine an Amino Acid 3D Arrangement search EnGINE (IMAAAGINE) was implemented to develop an automated method for searching of hypothetical patterns of amino acid side chains in Protein Data Bank (PDB), without the need for prior knowledge on related sequence or structure of pattern of interest. We present an example of the searches, which is the detection of a hypothetical pattern derived from known structural motif of C2H2 structural pattern from zinc fingers. The conservation of particular patterns of amino acid side chains in unrelated proteins is highlighted. This approach can act as a complementary method for available structure- and sequence-based platforms and may contribute in improving functional association between proteins.

47 CFR 32.2 - Basis of the accounts.

Code of Federal Regulations, 2014 CFR

2014-10-01

... intended to permit technological distinctions. Similarly, the primary bases of plant operations, customer... in the past, specific organizations may have performed specific functions, the future environment... technological view of the telecommunications industry. This view will provide a stable and consistent foundation...

47 CFR 32.2 - Basis of the accounts.

Code of Federal Regulations, 2013 CFR

2013-10-01

... intended to permit technological distinctions. Similarly, the primary bases of plant operations, customer... in the past, specific organizations may have performed specific functions, the future environment... technological view of the telecommunications industry. This view will provide a stable and consistent foundation...

47 CFR 32.2 - Basis of the accounts.

Code of Federal Regulations, 2012 CFR

2012-10-01

... intended to permit technological distinctions. Similarly, the primary bases of plant operations, customer... in the past, specific organizations may have performed specific functions, the future environment... technological view of the telecommunications industry. This view will provide a stable and consistent foundation...

Molecular Structures and Functional Relationships in Clostridial Neurotoxins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaminathan S.

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structuresmore » have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here.« less

Improving protein complex classification accuracy using amino acid composition profile.

PubMed

Huang, Chien-Hung; Chou, Szu-Yu; Ng, Ka-Lok

2013-09-01

Protein complex prediction approaches are based on the assumptions that complexes have dense protein-protein interactions and high functional similarity between their subunits. We investigated those assumptions by studying the subunits' interaction topology, sequence similarity and molecular function for human and yeast protein complexes. Inclusion of amino acids' physicochemical properties can provide better understanding of protein complex properties. Principal component analysis is carried out to determine the major features. Adopting amino acid composition profile information with the SVM classifier serves as an effective post-processing step for complexes classification. Improvement is based on primary sequence information only, which is easy to obtain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quenching rate for a nonlocal problem arising in the micro-electro mechanical system

NASA Astrophysics Data System (ADS)

Guo, Jong-Shenq; Hu, Bei

2018-03-01

In this paper, we study the quenching rate of the solution for a nonlocal parabolic problem which arises in the study of the micro-electro mechanical system. This question is equivalent to the stabilization of the solution to the transformed problem in self-similar variables. First, some a priori estimates are provided. In order to construct a Lyapunov function, due to the lack of time monotonicity property, we then derive some very useful and challenging estimates by a delicate analysis. Finally, with this Lyapunov function, we prove that the quenching rate is self-similar which is the same as the problem without the nonlocal term, except the constant limit depends on the solution itself.

Electrophysiological correlates of processing subject's own name.

PubMed

Li, Ran; Song, Weiqun; Du, Jubao; Huo, Su; Shan, Guixiang

2015-11-11

To understand the neurological mechanisms associated with the perception of subject's own name (SON) and provide a reference for assessing residual cognitive functions in patients with disorders of consciousness, event-related potentials were recorded in 16 healthy volunteers. Compared with event-related potentials elicited by tone stimuli, SON elicited larger MMN and P300. The amplitudes and latencies of MMN and P300 induced by subject's derived name (SDN) were similar to those induced by SON. Discriminating SON from SDN resulted in longer MMN and P300 latencies. These data showed that the SDN had similar quality as SON and might provide a useful reference for quantitatively evaluating disorders of consciousness.

Individualized Cognitive Modeling for Close-Loop Task Mitigation

NASA Technical Reports Server (NTRS)

Zhang, Guangfan; Xu, Roger; Wang, Wei; Li, Jiang; Schnell, Tom; Keller, Mike

2010-01-01

An accurate real-time operator functional state assessment makes it possible to perform task management, minimize risks, and improve mission performance. In this paper, we discuss the development of an individualized operator functional state assessment model that identifies states likely leading to operational errors. To address large individual variations, we use two different approaches to build a model for each individual using its data as well as data from subjects with similar responses. If a subject's response is similar to that of the individual of interest in a specific functional state, all the training data from this subject will be used to build the individual model. The individualization methods have been successfully verified and validated with a driving test data set provided by University of Iowa. With the individualized models, the mean squared error can be significantly decreased (by around 20%).

A path-based measurement for human miRNA functional similarities using miRNA-disease associations

NASA Astrophysics Data System (ADS)

Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

2016-09-01

Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

The language of gene ontology: a Zipf's law analysis.

PubMed

Kalankesh, Leila Ranandeh; Stevens, Robert; Brass, Andy

2012-06-07

Most major genome projects and sequence databases provide a GO annotation of their data, either automatically or through human annotators, creating a large corpus of data written in the language of GO. Texts written in natural language show a statistical power law behaviour, Zipf's law, the exponent of which can provide useful information on the nature of the language being used. We have therefore explored the hypothesis that collections of GO annotations will show similar statistical behaviours to natural language. Annotations from the Gene Ontology Annotation project were found to follow Zipf's law. Surprisingly, the measured power law exponents were consistently different between annotation captured using the three GO sub-ontologies in the corpora (function, process and component). On filtering the corpora using GO evidence codes we found that the value of the measured power law exponent responded in a predictable way as a function of the evidence codes used to support the annotation. Techniques from computational linguistics can provide new insights into the annotation process. GO annotations show similar statistical behaviours to those seen in natural language with measured exponents that provide a signal which correlates with the nature of the evidence codes used to support the annotations, suggesting that the measured exponent might provide a signal regarding the information content of the annotation.

Identification of functional candidates amongst hypothetical proteins of Mycobacterium leprae Br4923, a causative agent of leprosy.

PubMed

Naqvi, Ahmad Abu Turab; Ahmad, Faizan; Hassan, Md Imtaiyaz

2015-01-01

Mycobacterium leprae is an intracellular obligate parasite that causes leprosy in humans, and it leads to the destruction of peripheral nerves and skin deformation. Here, we report an extensive analysis of the hypothetical proteins (HPs) from M. leprae strain Br4923, assigning their functions to better understand the mechanism of pathogenesis and to search for potential therapeutic interventions. The genome of M. leprae encodes 1604 proteins, of which the functions of 632 are not known (HPs). In this paper, we predicted the probable functions of 312 HPs. First, we classified all HPs into families and subfamilies on the basis of sequence similarity, followed by domain assignment, which provides many clues for their possible function. However, the functions of 320 proteins were not predicted because of low sequence similarity with proteins of known function. Annotated HPs were categorized into enzymes, binding proteins, transporters, and proteins involved in cellular processes. We found several novel proteins whose functions were unknown for M. leprae. These proteins have a requisite association with bacterial virulence and pathogenicity. Finally, our sequence-based analysis will be helpful for further validation and the search for potential drug targets while developing effective drugs to cure leprosy.

Local-global alignment for finding 3D similarities in protein structures

DOEpatents

Zemla, Adam T [Brentwood, CA

2011-09-20

A method of finding 3D similarities in protein structures of a first molecule and a second molecule. The method comprises providing preselected information regarding the first molecule and the second molecule. Comparing the first molecule and the second molecule using Longest Continuous Segments (LCS) analysis. Comparing the first molecule and the second molecule using Global Distance Test (GDT) analysis. Comparing the first molecule and the second molecule using Local Global Alignment Scoring function (LGA_S) analysis. Verifying constructed alignment and repeating the steps to find the regions of 3D similarities in protein structures.

Functional specialisation of pelvic limb anatomy in horses (Equus caballus)

PubMed Central

Payne, RC; Hutchinson, JR; Robilliard, JJ; Smith, NC; Wilson, AM

2005-01-01

We provide quantitative anatomical data on the muscle–tendon units of the equine pelvic limb. Specifically, we recorded muscle mass, fascicle length, pennation angle, tendon mass and tendon rest length. Physiological cross sectional area was then determined and maximum isometric force estimated. There was proximal-to-distal reduction in muscle volume and fascicle length. Proximal limb tendons were few and, where present, were relatively short. By contrast, distal limb tendons were numerous and long in comparison to mean muscle fascicle length, increasing potential for elastic energy storage. When compared with published data on thoracic limb muscles, proximal pelvic limb muscles were larger in volume and had shorter fascicles. Distal limb muscle architecture was similar in thoracic and pelvic limbs with the exception of flexor digitorum lateralis (lateral head of the deep digital flexor), the architecture of which was similar to that of the pelvic and thoracic limb superficial digital flexors, suggesting a functional similarity. PMID:15960766

ontologyX: a suite of R packages for working with ontological data.

PubMed

Greene, Daniel; Richardson, Sylvia; Turro, Ernest

2017-04-01

Ontologies are widely used constructs for encoding and analyzing biomedical data, but the absence of simple and consistent tools has made exploratory and systematic analysis of such data unnecessarily difficult. Here we present three packages which aim to simplify such procedures. The ontologyIndex package enables arbitrary ontologies to be read into R, supports representation of ontological objects by native R types, and provides a parsimonius set of performant functions for querying ontologies. ontologySimilarity and ontologyPlot extend ontologyIndex with functionality for straightforward visualization and semantic similarity calculations, including statistical routines. ontologyIndex , ontologyPlot and ontologySimilarity are all available on the Comprehensive R Archive Network website under https://cran.r-project.org/web/packages/ . Daniel Greene dg333@cam.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Comparing ab initio density-functional and wave function theories: the impact of correlation on the electronic density and the role of the correlation potential.

PubMed

Grabowski, Ireneusz; Teale, Andrew M; Śmiga, Szymon; Bartlett, Rodney J

2011-09-21

The framework of ab initio density-functional theory (DFT) has been introduced as a way to provide a seamless connection between the Kohn-Sham (KS) formulation of DFT and wave-function based ab initio approaches [R. J. Bartlett, I. Grabowski, S. Hirata, and S. Ivanov, J. Chem. Phys. 122, 034104 (2005)]. Recently, an analysis of the impact of dynamical correlation effects on the density of the neon atom was presented [K. Jankowski, K. Nowakowski, I. Grabowski, and J. Wasilewski, J. Chem. Phys. 130, 164102 (2009)], contrasting the behaviour for a variety of standard density functionals with that of ab initio approaches based on second-order Møller-Plesset (MP2) and coupled cluster theories at the singles-doubles (CCSD) and singles-doubles perturbative triples [CCSD(T)] levels. In the present work, we consider ab initio density functionals based on second-order many-body perturbation theory and coupled cluster perturbation theory in a similar manner, for a range of small atomic and molecular systems. For comparison, we also consider results obtained from MP2, CCSD, and CCSD(T) calculations. In addition to this density based analysis, we determine the KS correlation potentials corresponding to these densities and compare them with those obtained for a range of ab initio density functionals via the optimized effective potential method. The correlation energies, densities, and potentials calculated using ab initio DFT display a similar systematic behaviour to those derived from electronic densities calculated using ab initio wave function theories. In contrast, typical explicit density functionals for the correlation energy, such as VWN5 and LYP, do not show behaviour consistent with this picture of dynamical correlation, although they may provide some degree of correction for already erroneous explicitly density-dependent exchange-only functionals. The results presented here using orbital dependent ab initio density functionals show that they provide a treatment of exchange and correlation contributions within the KS framework that is more consistent with traditional ab initio wave function based methods.

Hot and Spicy versus Cool and Minty as an Example of Organic Structure-Activity Relationships

NASA Astrophysics Data System (ADS)

Kimbrough, Doris R.

1997-07-01

There are two classes of substances that activate neural receptors that are involved in temperature perception. Structures of substances found in spices and food that we normally associate with "hot" (or spicy) and "cool" (or minty) flavors are presented and discussed. Functional group similarities within the two groups provide an interesting example of the relationship between molecular structure and molecular function in organic chemistry.

K-shuff: A Novel Algorithm for Characterizing Structural and Compositional Diversity in Gene Libraries

PubMed Central

Jangid, Kamlesh; Kao, Ming-Hung; Lahamge, Aishwarya; Williams, Mark A.; Rathbun, Stephen L.; Whitman, William B.

2016-01-01

K-shuff is a new algorithm for comparing the similarity of gene sequence libraries, providing measures of the structural and compositional diversity as well as the significance of the differences between these measures. Inspired by Ripley’s K-function for spatial point pattern analysis, the Intra K-function or IKF measures the structural diversity, including both the richness and overall similarity of the sequences, within a library. The Cross K-function or CKF measures the compositional diversity between gene libraries, reflecting both the number of OTUs shared as well as the overall similarity in OTUs. A Monte Carlo testing procedure then enables statistical evaluation of both the structural and compositional diversity between gene libraries. For 16S rRNA gene libraries from complex bacterial communities such as those found in seawater, salt marsh sediments, and soils, K-shuff yields reproducible estimates of structural and compositional diversity with libraries greater than 50 sequences. Similarly, for pyrosequencing libraries generated from a glacial retreat chronosequence and Illumina® libraries generated from US homes, K-shuff required >300 and 100 sequences per sample, respectively. Power analyses demonstrated that K-shuff is sensitive to small differences in Sanger or Illumina® libraries. This extra sensitivity of K-shuff enabled examination of compositional differences at much deeper taxonomic levels, such as within abundant OTUs. This is especially useful when comparing communities that are compositionally very similar but functionally different. K-shuff will therefore prove beneficial for conventional microbiome analysis as well as specific hypothesis testing. PMID:27911946

ON A GENERALIZED SELF-SIMILARITY IN THE p-ADIC FIELD

NASA Astrophysics Data System (ADS)

Mukhamedov, Farrukh; Khakimov, Otabek

2016-08-01

In the present paper, we introduce a new set which defines a generalized self-similar set for contractive functions {fi}i=1N on the unit ball ℤp of p-adic numbers. This set is called unconventional limit set. We prove that the unconventional limit set is compact, perfect and uniformly disconnected. Moreover, we provide an example of two contractions for which the corresponding unconventional limiting set is quasi-symmetrically equivalent to the symbolic Cantor set.

Emerging structural insights into the function of ionotropic glutamate receptors.

PubMed

Karakas, Erkan; Regan, Michael C; Furukawa, Hiro

2015-06-01

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission crucial for brain development and function, including learning and memory formation. Recently a wealth of structural studies on iGluRs including AMPA receptors (AMPARs), kainate receptors, and NMDA receptors (NMDARs) became available. These studies showed structures of non-NMDARs including AMPAR and kainate receptor in various functional states, thereby providing the first visual sense of how non-NMDAR iGluRs may function in the context of homotetramers. Furthermore, they provided the first view of heterotetrameric NMDAR ion channels, and this illuminated the similarities with and differences from non-NMDARs, thus raising a mechanistic distinction between the two groups of iGluRs. We review mechanistic insights into iGluR functions gained through structural studies of multiple groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular similarity measures.

PubMed

Maggiora, Gerald M; Shanmugasundaram, Veerabahu

2011-01-01

Molecular similarity is a pervasive concept in chemistry. It is essential to many aspects of chemical reasoning and analysis and is perhaps the fundamental assumption underlying medicinal chemistry. Dissimilarity, the complement of similarity, also plays a major role in a growing number of applications of molecular diversity in combinatorial chemistry, high-throughput screening, and related fields. How molecular information is represented, called the representation problem, is important to the type of molecular similarity analysis (MSA) that can be carried out in any given situation. In this work, four types of mathematical structure are used to represent molecular information: sets, graphs, vectors, and functions. Molecular similarity is a pairwise relationship that induces structure into sets of molecules, giving rise to the concept of chemical space. Although all three concepts - molecular similarity, molecular representation, and chemical space - are treated in this chapter, the emphasis is on molecular similarity measures. Similarity measures, also called similarity coefficients or indices, are functions that map pairs of compatible molecular representations that are of the same mathematical form into real numbers usually, but not always, lying on the unit interval. This chapter presents a somewhat pedagogical discussion of many types of molecular similarity measures, their strengths and limitations, and their relationship to one another. An expanded account of the material on chemical spaces presented in the first edition of this book is also provided. It includes a discussion of the topography of activity landscapes and the role that activity cliffs in these landscapes play in structure-activity studies.

Comparison and Contrast of Two General Functional Regression Modeling Frameworks

PubMed Central

Morris, Jeffrey S.

2017-01-01

In this article, Greven and Scheipl describe an impressively general framework for performing functional regression that builds upon the generalized additive modeling framework. Over the past number of years, my collaborators and I have also been developing a general framework for functional regression, functional mixed models, which shares many similarities with this framework, but has many differences as well. In this discussion, I compare and contrast these two frameworks, to hopefully illuminate characteristics of each, highlighting their respecitve strengths and weaknesses, and providing recommendations regarding the settings in which each approach might be preferable. PMID:28736502

Comparison and Contrast of Two General Functional Regression Modeling Frameworks.

PubMed

Morris, Jeffrey S

2017-02-01

In this article, Greven and Scheipl describe an impressively general framework for performing functional regression that builds upon the generalized additive modeling framework. Over the past number of years, my collaborators and I have also been developing a general framework for functional regression, functional mixed models, which shares many similarities with this framework, but has many differences as well. In this discussion, I compare and contrast these two frameworks, to hopefully illuminate characteristics of each, highlighting their respecitve strengths and weaknesses, and providing recommendations regarding the settings in which each approach might be preferable.

Thinking, Walking, Talking: Integratory Motor and Cognitive Brain Function

PubMed Central

Leisman, Gerry; Moustafa, Ahmed A.; Shafir, Tal

2016-01-01

In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID:27252937

Russian Olive Biology, Invasion, and Ecological Impacts in Western North America

DTIC Science & Technology

2016-07-01

habitat for bird species , but is not functionally equivalent to native vegetation. Leatherman (2011) lists a variety of birds that consume fruits, sap...abundance, but intermediate avian species richness and diversity, in Russian olive stands. Russian olive bird communities were somewhat similar to...provided distinctive habitat for some bird species (e.g., least flycatchers [Empidonax minimus], red-eyed vireos [Vireo olivaceous]), while providing

Quality assessment of protein model-structures based on structural and functional similarities

PubMed Central

2012-01-01

Background Experimental determination of protein 3D structures is expensive, time consuming and sometimes impossible. A gap between number of protein structures deposited in the World Wide Protein Data Bank and the number of sequenced proteins constantly broadens. Computational modeling is deemed to be one of the ways to deal with the problem. Although protein 3D structure prediction is a difficult task, many tools are available. These tools can model it from a sequence or partial structural information, e.g. contact maps. Consequently, biologists have the ability to generate automatically a putative 3D structure model of any protein. However, the main issue becomes evaluation of the model quality, which is one of the most important challenges of structural biology. Results GOBA - Gene Ontology-Based Assessment is a novel Protein Model Quality Assessment Program. It estimates the compatibility between a model-structure and its expected function. GOBA is based on the assumption that a high quality model is expected to be structurally similar to proteins functionally similar to the prediction target. Whereas DALI is used to measure structure similarity, protein functional similarity is quantified using standardized and hierarchical description of proteins provided by Gene Ontology combined with Wang's algorithm for calculating semantic similarity. Two approaches are proposed to express the quality of protein model-structures. One is a single model quality assessment method, the other is its modification, which provides a relative measure of model quality. Exhaustive evaluation is performed on data sets of model-structures submitted to the CASP8 and CASP9 contests. Conclusions The validation shows that the method is able to discriminate between good and bad model-structures. The best of tested GOBA scores achieved 0.74 and 0.8 as a mean Pearson correlation to the observed quality of models in our CASP8 and CASP9-based validation sets. GOBA also obtained the best result for two targets of CASP8, and one of CASP9, compared to the contest participants. Consequently, GOBA offers a novel single model quality assessment program that addresses the practical needs of biologists. In conjunction with other Model Quality Assessment Programs (MQAPs), it would prove useful for the evaluation of single protein models. PMID:22998498

Predicting multicellular function through multi-layer tissue networks

PubMed Central

Zitnik, Marinka; Leskovec, Jure

2017-01-01

Abstract Motivation: Understanding functions of proteins in specific human tissues is essential for insights into disease diagnostics and therapeutics, yet prediction of tissue-specific cellular function remains a critical challenge for biomedicine. Results: Here, we present OhmNet, a hierarchy-aware unsupervised node feature learning approach for multi-layer networks. We build a multi-layer network, where each layer represents molecular interactions in a different human tissue. OhmNet then automatically learns a mapping of proteins, represented as nodes, to a neural embedding-based low-dimensional space of features. OhmNet encourages sharing of similar features among proteins with similar network neighborhoods and among proteins activated in similar tissues. The algorithm generalizes prior work, which generally ignores relationships between tissues, by modeling tissue organization with a rich multiscale tissue hierarchy. We use OhmNet to study multicellular function in a multi-layer protein interaction network of 107 human tissues. In 48 tissues with known tissue-specific cellular functions, OhmNet provides more accurate predictions of cellular function than alternative approaches, and also generates more accurate hypotheses about tissue-specific protein actions. We show that taking into account the tissue hierarchy leads to improved predictive power. Remarkably, we also demonstrate that it is possible to leverage the tissue hierarchy in order to effectively transfer cellular functions to a functionally uncharacterized tissue. Overall, OhmNet moves from flat networks to multiscale models able to predict a range of phenotypes spanning cellular subsystems. Availability and implementation: Source code and datasets are available at http://snap.stanford.edu/ohmnet. Contact: jure@cs.stanford.edu PMID:28881986

The functional micro-organization of grid cells revealed by cellular-resolution imaging.

PubMed

Heys, James G; Rangarajan, Krsna V; Dombeck, Daniel A

2014-12-03

Establishing how grid cells are anatomically arranged, on a microscopic scale, in relation to their firing patterns in the environment would facilitate a greater microcircuit-level understanding of the brain's representation of space. However, all previous grid cell recordings used electrode techniques that provide limited descriptions of fine-scale organization. We therefore developed a technique for cellular-resolution functional imaging of medial entorhinal cortex (MEC) neurons in mice navigating a virtual linear track, enabling a new experimental approach to study MEC. Using these methods, we show that grid cells are physically clustered in MEC compared to nongrid cells. Additionally, we demonstrate that grid cells are functionally micro-organized: the similarity between the environment firing locations of grid cell pairs varies as a function of the distance between them according to a "Mexican hat"-shaped profile. This suggests that, on average, nearby grid cells have more similar spatial firing phases than those further apart. Copyright © 2014 Elsevier Inc. All rights reserved.

The functional micro-organization of grid cells revealed by cellular-resolution imaging

PubMed Central

Heys, James G.; Rangarajan, Krsna V.; Dombeck, Daniel A.

2015-01-01

Summary Establishing how grid cells are anatomically arranged, on a microscopic scale, in relation to their firing patterns in the environment would facilitate a greater micro-circuit level understanding of the brain’s representation of space. However, all previous grid cell recordings used electrode techniques that provide limited descriptions of fine-scale organization. We therefore developed a technique for cellular-resolution functional imaging of medial entorhinal cortex (MEC) neurons in mice navigating a virtual linear track, enabling a new experimental approach to study MEC. Using these methods, we show that grid cells are physically clustered in MEC compared to non-grid cells. Additionally, we demonstrate that grid cells are functionally micro-organized: The similarity between the environment firing locations of grid cell pairs varies as a function of the distance between them according to a “Mexican Hat” shaped profile. This suggests that, on average, nearby grid cells have more similar spatial firing phases than those further apart. PMID:25467986

Gene context analysis in the Integrated Microbial Genomes (IMG) data management system.

PubMed

Mavromatis, Konstantinos; Chu, Ken; Ivanova, Natalia; Hooper, Sean D; Markowitz, Victor M; Kyrpides, Nikos C

2009-11-24

Computational methods for determining the function of genes in newly sequenced genomes have been traditionally based on sequence similarity to genes whose function has been identified experimentally. Function prediction methods can be extended using gene context analysis approaches such as examining the conservation of chromosomal gene clusters, gene fusion events and co-occurrence profiles across genomes. Context analysis is based on the observation that functionally related genes are often having similar gene context and relies on the identification of such events across phylogenetically diverse collection of genomes. We have used the data management system of the Integrated Microbial Genomes (IMG) as the framework to implement and explore the power of gene context analysis methods because it provides one of the largest available genome integrations. Visualization and search tools to facilitate gene context analysis have been developed and applied across all publicly available archaeal and bacterial genomes in IMG. These computations are now maintained as part of IMG's regular genome content update cycle. IMG is available at: http://img.jgi.doe.gov.

Multivariate carbon and nitrogen stable isotope model for the reconstruction of prehistoric human diet.

PubMed

Froehle, A W; Kellner, C M; Schoeninger, M J

2012-03-01

Using a sample of published archaeological data, we expand on an earlier bivariate carbon model for diet reconstruction by adding bone collagen nitrogen stable isotope values (δ(15) N), which provide information on trophic level and consumption of terrestrial vs. marine protein. The bivariate carbon model (δ(13) C(apatite) vs. δ(13) C(collagen) ) provides detailed information on the isotopic signatures of whole diet and dietary protein, but is limited in its ability to distinguish between C(4) and marine protein. Here, using cluster analysis and discriminant function analysis, we generate a multivariate diet reconstruction model that incorporates δ(13) C(apatite) , δ(13) C(collagen) , and δ(15) N holistically. Inclusion of the δ(15) N data proves useful in resolving protein-related limitations of the bivariate carbon model, and splits the sample into five distinct dietary clusters. Two significant discriminant functions account for 98.8% of the sample variance, providing a multivariate model for diet reconstruction. Both carbon variables dominate the first function, while δ(15) N most strongly influences the second. Independent support for the functions' ability to accurately classify individuals according to diet comes from a small sample of experimental rats, which cluster as expected from their diets. The new model also provides a statistical basis for distinguishing between food sources with similar isotopic signatures, as in a previously analyzed archaeological population from Saipan (see Ambrose et al.: AJPA 104(1997) 343-361). Our model suggests that the Saipan islanders' (13) C-enriched signal derives mainly from sugarcane, not seaweed. Further development and application of this model can similarly improve dietary reconstructions in archaeological, paleontological, and primatological contexts. Copyright © 2011 Wiley Periodicals, Inc.

Riccati parameterized self-similar waves in two-dimensional graded-index waveguide

NASA Astrophysics Data System (ADS)

Kumar De, Kanchan; Goyal, Amit; Raju, Thokala Soloman; Kumar, C. N.; Panigrahi, Prasanta K.

2015-04-01

An analytical method based on gauge-similarity transformation technique has been employed for mapping a (2+1)- dimensional variable coefficient coupled nonlinear Schrödinger equations (vc-CNLSE) with dispersion, nonlinearity and gain to standard NLSE. Under certain functional relations we construct a large family of self-similar waves in the form of bright similaritons, Akhmediev breathers and rogue waves. We report the effect of dispersion on the intensity of the solitary waves. Further, we illustrate the procedure to amplify the intensity of self-similar waves using isospectral Hamiltonian approach. This approach provides an efficient mechanism to generate analytically a wide class of tapering profiles and widths by exploiting the Riccati parameter. Equivalently, it enables one to control efficiently the self-similar wave structures and hence their evolution.

Discovering cultural differences (and similarities) in facial expressions of emotion.

PubMed

Chen, Chaona; Jack, Rachael E

2017-10-01

Understanding the cultural commonalities and specificities of facial expressions of emotion remains a central goal of Psychology. However, recent progress has been stayed by dichotomous debates (e.g. nature versus nurture) that have created silos of empirical and theoretical knowledge. Now, an emerging interdisciplinary scientific culture is broadening the focus of research to provide a more unified and refined account of facial expressions within and across cultures. Specifically, data-driven approaches allow a wider, more objective exploration of face movement patterns that provide detailed information ontologies of their cultural commonalities and specificities. Similarly, a wider exploration of the social messages perceived from face movements diversifies knowledge of their functional roles (e.g. the 'fear' face used as a threat display). Together, these new approaches promise to diversify, deepen, and refine knowledge of facial expressions, and deliver the next major milestones for a functional theory of human social communication that is transferable to social robotics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Sequence-similar, structure-dissimilar protein pairs in the PDB.

PubMed

Kosloff, Mickey; Kolodny, Rachel

2008-05-01

It is often assumed that in the Protein Data Bank (PDB), two proteins with similar sequences will also have similar structures. Accordingly, it has proved useful to develop subsets of the PDB from which "redundant" structures have been removed, based on a sequence-based criterion for similarity. Similarly, when predicting protein structure using homology modeling, if a template structure for modeling a target sequence is selected by sequence alone, this implicitly assumes that all sequence-similar templates are equivalent. Here, we show that this assumption is often not correct and that standard approaches to create subsets of the PDB can lead to the loss of structurally and functionally important information. We have carried out sequence-based structural superpositions and geometry-based structural alignments of a large number of protein pairs to determine the extent to which sequence similarity ensures structural similarity. We find many examples where two proteins that are similar in sequence have structures that differ significantly from one another. The source of the structural differences usually has a functional basis. The number of such proteins pairs that are identified and the magnitude of the dissimilarity depend on the approach that is used to calculate the differences; in particular sequence-based structure superpositioning will identify a larger number of structurally dissimilar pairs than geometry-based structural alignments. When two sequences can be aligned in a statistically meaningful way, sequence-based structural superpositioning provides a meaningful measure of structural differences. This approach and geometry-based structure alignments reveal somewhat different information and one or the other might be preferable in a given application. Our results suggest that in some cases, notably homology modeling, the common use of nonredundant datasets, culled from the PDB based on sequence, may mask important structural and functional information. We have established a data base of sequence-similar, structurally dissimilar protein pairs that will help address this problem (http://luna.bioc.columbia.edu/rachel/seqsimstrdiff.htm).

Invited Article: Mask-modulated lensless imaging with multi-angle illuminations

NASA Astrophysics Data System (ADS)

Zhang, Zibang; Zhou, You; Jiang, Shaowei; Guo, Kaikai; Hoshino, Kazunori; Zhong, Jingang; Suo, Jinli; Dai, Qionghai; Zheng, Guoan

2018-06-01

The use of multiple diverse measurements can make lensless phase retrieval more robust. Conventional diversity functions include aperture diversity, wavelength diversity, translational diversity, and defocus diversity. Here we discuss a lensless imaging scheme that employs multiple spherical-wave illuminations from a light-emitting diode array as diversity functions. In this scheme, we place a binary mask between the sample and the detector for imposing support constraints for the phase retrieval process. This support constraint enforces the light field to be zero at certain locations and is similar to the aperture constraint in Fourier ptychographic microscopy. We use a self-calibration algorithm to correct the misalignment of the binary mask. The efficacy of the proposed scheme is first demonstrated by simulations where we evaluate the reconstruction quality using mean square error and structural similarity index. The scheme is then experimentally tested by recovering images of a resolution target and biological samples. The proposed scheme may provide new insights for developing compact and large field-of-view lensless imaging platforms. The use of the binary mask can also be combined with other diversity functions for better constraining the phase retrieval solution space. We provide the open-source implementation code for the broad research community.

Ecological structure and function in a restored versus natural salt marsh

PubMed Central

Rezek, Ryan J.; Lebreton, Benoit; Sterba-Boatwright, Blair

2017-01-01

Habitat reconstruction is commonly employed to restore degraded estuarine habitats and lost ecological functions. In this study, we use a combination of stable isotope analyses and macrofauna community analysis to compare the ecological structure and function between a recently constructed Spartina alterniflora salt marsh and a natural reference habitat over a 2-year period. The restored marsh was successful in providing habitat for economically and ecologically important macrofauna taxa; supporting similar or greater density, biomass, and species richness to the natural reference during all but one sampling period. Stable isotope analyses revealed that communities from the natural and the restored marshes relied on a similar diversity of food resources and that decapods had similar trophic levels. However, some generalist consumers (Palaemonetes spp. and Penaeus aztecus) were more 13C-enriched in the natural marsh, indicating a greater use of macrophyte derived organic matter relative to restored marsh counterparts. This difference was attributed to the higher quantities of macrophyte detritus and organic carbon in natural marsh sediments. Reduced marsh flooding frequency was associated with a reduction in macrofaunal biomass and decapod trophic levels. The restored marsh edge occurred at lower elevations than natural marsh edge, apparently due to reduced fetch and wind-wave exposure provided by the protective berm structures. The lower elevation of the restored marsh edge mitigated negative impacts in sampling periods with low tidal elevations that affected the natural marsh. The results of this study highlight the importance of considering sediment characteristics and elevation in salt marsh constructions. PMID:29261795

Disruption of Prefrontal Cortex Large Scale Neuronal Activity by Different Classes of Psychotomimetic Drugs

PubMed Central

Wood, Jesse; Kim, Yunbok; Moghaddam, Bita

2012-01-01

In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spikerate and LFP power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease. PMID:22378875

A Methodology to Assess the Accuracy with which Remote Data Characterize a Specific Surface, as a Function of Full Width at Half Maximum (FWHM): Application to Three Italian Coastal Waters

PubMed Central

Cavalli, Rosa Maria; Betti, Mattia; Campanelli, Alessandra; Di Cicco, Annalisa; Guglietta, Daniela; Penna, Pierluigi; Piermattei, Viviana

2014-01-01

This methodology assesses the accuracy with which remote data characterizes a surface, as a function of Full Width at Half Maximum (FWHM). The purpose is to identify the best remote data that improves the characterization of a surface, evaluating the number of bands in the spectral range. The first step creates an accurate dataset of remote simulated data, using in situ hyperspectral reflectances. The second step evaluates the capability of remote simulated data to characterize this surface. The spectral similarity measurements, which are obtained using classifiers, provide this capability. The third step examines the precision of this capability. The assumption is that in situ hyperspectral reflectances are considered the “real” reflectances. They are resized with the same spectral range of the remote data. The spectral similarity measurements which are obtained from “real” resized reflectances, are considered “real” measurements. Therefore, the quantity and magnitude of “errors” (i.e., differences between spectral similarity measurements obtained from “real” resized reflectances and from remote data) provide the accuracy as a function of FWHM. This methodology was applied to evaluate the accuracy with which CHRIS-mode1, CHRIS-mode2, Landsat5-TM, MIVIS and PRISMA data characterize three coastal waters. Their mean values of uncertainty are 1.59%, 3.79%, 7.75%, 3.15% and 1.18%, respectively. PMID:24434875

Ecological structure and function in a restored versus natural salt marsh.

PubMed

Rezek, Ryan J; Lebreton, Benoit; Sterba-Boatwright, Blair; Beseres Pollack, Jennifer

2017-01-01

Habitat reconstruction is commonly employed to restore degraded estuarine habitats and lost ecological functions. In this study, we use a combination of stable isotope analyses and macrofauna community analysis to compare the ecological structure and function between a recently constructed Spartina alterniflora salt marsh and a natural reference habitat over a 2-year period. The restored marsh was successful in providing habitat for economically and ecologically important macrofauna taxa; supporting similar or greater density, biomass, and species richness to the natural reference during all but one sampling period. Stable isotope analyses revealed that communities from the natural and the restored marshes relied on a similar diversity of food resources and that decapods had similar trophic levels. However, some generalist consumers (Palaemonetes spp. and Penaeus aztecus) were more 13C-enriched in the natural marsh, indicating a greater use of macrophyte derived organic matter relative to restored marsh counterparts. This difference was attributed to the higher quantities of macrophyte detritus and organic carbon in natural marsh sediments. Reduced marsh flooding frequency was associated with a reduction in macrofaunal biomass and decapod trophic levels. The restored marsh edge occurred at lower elevations than natural marsh edge, apparently due to reduced fetch and wind-wave exposure provided by the protective berm structures. The lower elevation of the restored marsh edge mitigated negative impacts in sampling periods with low tidal elevations that affected the natural marsh. The results of this study highlight the importance of considering sediment characteristics and elevation in salt marsh constructions.

Strategies and Challenges in Identifying Function for Thousands of sORF-Encoded Peptides in Meiosis.

PubMed

Hollerer, Ina; Higdon, Andrea; Brar, Gloria A

2017-09-20

Recent genomic analyses have revealed pervasive translation from formerly unrecognized short open reading frames (sORFs) during yeast meiosis. Despite their short length, which has caused these regions to be systematically overlooked by traditional gene annotation approaches, meiotic sORFs share many features with classical genes, implying the potential for similar types of cellular functions. We found that sORF expression accounts for approximately 10-20% of the cellular translation capacity in yeast during meiotic differentiation and occurs within well-defined time windows, suggesting the production of relatively abundant peptides with stage-specific meiotic roles from these regions. Here, we provide arguments supporting this hypothesis and discuss sORF similarities and differences, as a group, to traditional protein coding regions, as well as challenges in defining their specific functions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Random Partition Distribution Indexed by Pairwise Information

PubMed Central

Dahl, David B.; Day, Ryan; Tsai, Jerry W.

2017-01-01

We propose a random partition distribution indexed by pairwise similarity information such that partitions compatible with the similarities are given more probability. The use of pairwise similarities, in the form of distances, is common in some clustering algorithms (e.g., hierarchical clustering), but we show how to use this type of information to define a prior partition distribution for flexible Bayesian modeling. A defining feature of the distribution is that it allocates probability among partitions within a given number of subsets, but it does not shift probability among sets of partitions with different numbers of subsets. Our distribution places more probability on partitions that group similar items yet keeps the total probability of partitions with a given number of subsets constant. The distribution of the number of subsets (and its moments) is available in closed-form and is not a function of the similarities. Our formulation has an explicit probability mass function (with a tractable normalizing constant) so the full suite of MCMC methods may be used for posterior inference. We compare our distribution with several existing partition distributions, showing that our formulation has attractive properties. We provide three demonstrations to highlight the features and relative performance of our distribution. PMID:29276318

Assessment of protein set coherence using functional annotations

PubMed Central

Chagoyen, Monica; Carazo, Jose M; Pascual-Montano, Alberto

2008-01-01

Background Analysis of large-scale experimental datasets frequently produces one or more sets of proteins that are subsequently mined for functional interpretation and validation. To this end, a number of computational methods have been devised that rely on the analysis of functional annotations. Although current methods provide valuable information (e.g. significantly enriched annotations, pairwise functional similarities), they do not specifically measure the degree of homogeneity of a protein set. Results In this work we present a method that scores the degree of functional homogeneity, or coherence, of a set of proteins on the basis of the global similarity of their functional annotations. The method uses statistical hypothesis testing to assess the significance of the set in the context of the functional space of a reference set. As such, it can be used as a first step in the validation of sets expected to be homogeneous prior to further functional interpretation. Conclusion We evaluate our method by analysing known biologically relevant sets as well as random ones. The known relevant sets comprise macromolecular complexes, cellular components and pathways described for Saccharomyces cerevisiae, which are mostly significantly coherent. Finally, we illustrate the usefulness of our approach for validating 'functional modules' obtained from computational analysis of protein-protein interaction networks. Matlab code and supplementary data are available at PMID:18937846

Dramatic Increases of Soil Microbial Functional Gene Diversity at the Treeline Ecotone of Changbai Mountain

PubMed Central

Shen, Congcong; Shi, Yu; Ni, Yingying; Deng, Ye; Van Nostrand, Joy D.; He, Zhili; Zhou, Jizhong; Chu, Haiyan

2016-01-01

The elevational and latitudinal diversity patterns of microbial taxa have attracted great attention in the past decade. Recently, the distribution of functional attributes has been in the spotlight. Here, we report a study profiling soil microbial communities along an elevation gradient (500–2200 m) on Changbai Mountain. Using a comprehensive functional gene microarray (GeoChip 5.0), we found that microbial functional gene richness exhibited a dramatic increase at the treeline ecotone, but the bacterial taxonomic and phylogenetic diversity based on 16S rRNA gene sequencing did not exhibit such a similar trend. However, the β-diversity (compositional dissimilarity among sites) pattern for both bacterial taxa and functional genes was similar, showing significant elevational distance-decay patterns which presented increased dissimilarity with elevation. The bacterial taxonomic diversity/structure was strongly influenced by soil pH, while the functional gene diversity/structure was significantly correlated with soil dissolved organic carbon (DOC). This finding highlights that soil DOC may be a good predictor in determining the elevational distribution of microbial functional genes. The finding of significant shifts in functional gene diversity at the treeline ecotone could also provide valuable information for predicting the responses of microbial functions to climate change. PMID:27524983

Investigating the relationship among transformational leadership, interpersonal interaction and mentoring functions.

PubMed

Huang, Ching-Yuan; Weng, Rhay-Hung; Chen, Yi-Ting

2016-08-01

This study aims to ascertain the relationship between transformational leadership, interpersonal interaction and mentoring functions among new staff nurses. Mentoring functions could improve the job performance of new nurses, provide them with support and thus reduce their turnover rate. A cross-sectional study was employed. A questionnaire survey was carried out to collect data among a sample of new nurses from three hospitals in Taiwan. After gathering a total of 306 valid surveys, multiple regression analysis was applied to test the hypothesis. Inspirational motivation, idealised influence and individualised consideration had positive correlations with the overall mentoring function, but intellectual stimulation showed a positive association only with career development function. Perceived similarity and interaction frequency also had positive correlations with mentoring functions. When the shift overlap rate exceeded 80%, mentoring function showed a negative result. The transformational leadership of mentors would improve the mentoring functions among new staff nurses. Perceived similarity and interaction frequency between mentees and mentors also had positive correlations with mentoring functions. It is crucial for hospitals to redesign their leadership training and motivation programmes to enhance the transformational leadership of mentors. Furthermore, nursing managers should promote interaction between new staff nurses and their mentors; however, the shift overlap rate should not be too high. © 2016 John Wiley & Sons Ltd.

Are pathogenic bacteria just looking for food? Metabolism and microbial pathogenesis

PubMed Central

Rohmer, Laurence; Hocquet, Didier; Miller, Samuel I.

2011-01-01

It is interesting to speculate that the evolutionary drive of microbes to develop pathogenic characteristics was to access the nutrient resources that animals provided. Environments in animals that pathogens colonize have also driven the evolution of new bacterial characteristics to maximize these new nutritional opportunities. This review focuses on genomic and functional aspects of pathogen metabolism that allow efficient utilization of nutrient resources provided by animals. Similar to genes encoding specific virulence traits, some genes encoding metabolic functions have been horizontally acquired by pathogens to provide a selective advantage in host tissues. Selective advantage in host tissues can also be gained in some circumstances by loss of function due to mutations that alter metabolic capabilities. Greater understanding of bacterial metabolism within host tissues should be important for increased understanding of host-pathogen interactions and the development of future therapeutic strategies. PMID:21600774

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moody, A.

The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it can provide the absolute path to a relative directory from the current working directory.

Anatomy, function, and evolution of jaw and hyobranchial muscles in cryptobranchoid salamander larvae.

PubMed

Kleinteich, Thomas; Herzen, Julia; Beckmann, Felix; Matsui, Masafumi; Haas, Alexander

2014-02-01

Larval salamanders (Lissamphibia: Caudata) are known to be effective suction feeders in their aquatic environments, although they will eventually transform into terrestrial tongue feeding adults during metamorphosis. Early tetrapods may have had a similar biphasic life cycle and this makes larval salamanders a particularly interesting model to study the anatomy, function, development, and evolution of the feeding apparatus in terrestrial vertebrates. Here, we provide a description of the muscles that are involved in the feeding strike in salamander larvae of the Hynobiidae and compare them to larvae of the paedomorphic Cryptobranchidae. We provide a functional and evolutionary interpretation for the observed muscle characters. The cranial muscles in larvae from species of the Hynobiidae and Cryptobranchidae are generally very similar. Most notable are the differences in the presence of the m. hyomandibularis, a muscle that connects the hyobranchial apparatus with the lower jaw. We found this muscle only in Onychodactylus japonicus (Hynobiidae) but not in other hynobiid or cryptobranchid salamanders. Interestingly, the m. hyomandibularis in O. japonicus originates from the ceratobranchial I and not the ceratohyal, and thus exhibits what was previously assumed to be the derived condition. Finally, we applied a biomechanical model to simulate suction feeding in larval salamanders. We provide evidence that a flattened shape of the hyobranchial apparatus in its resting position is beneficial for a fast and successful suction feeding strike. Copyright © 2013 Wiley Periodicals, Inc.

Functionalized graphene sheets for polymer nanocomposites.

PubMed

Ramanathan, T; Abdala, A A; Stankovich, S; Dikin, D A; Herrera-Alonso, M; Piner, R D; Adamson, D H; Schniepp, H C; Chen, X; Ruoff, R S; Nguyen, S T; Aksay, I A; Prud'Homme, R K; Brinson, L C

2008-06-01

Polymer-based composites were heralded in the 1960s as a new paradigm for materials. By dispersing strong, highly stiff fibres in a polymer matrix, high-performance lightweight composites could be developed and tailored to individual applications. Today we stand at a similar threshold in the realm of polymer nanocomposites with the promise of strong, durable, multifunctional materials with low nanofiller content. However, the cost of nanoparticles, their availability and the challenges that remain to achieve good dispersion pose significant obstacles to these goals. Here, we report the creation of polymer nanocomposites with functionalized graphene sheets, which overcome these obstacles and provide superb polymer-particle interactions. An unprecedented shift in glass transition temperature of over 40 degrees C is obtained for poly(acrylonitrile) at 1 wt% functionalized graphene sheet, and with only 0.05 wt% functionalized graphene sheet in poly(methyl methacrylate) there is an improvement of nearly 30 degrees C. Modulus, ultimate strength and thermal stability follow a similar trend, with values for functionalized graphene sheet- poly(methyl methacrylate) rivaling those for single-walled carbon nanotube-poly(methyl methacrylate) composites.

Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT).

PubMed

Kaat, Aaron J; Schalet, Benjamin D; Rutsohn, Joshua; Jensen, Roxanne E; Cella, David

2018-01-01

Measuring patient-reported outcomes (PROs) is becoming an integral component of quality improvement initiatives, clinical care, and research studies in cancer, including comparative effectiveness research. However, the number of PROs limits comparability across studies. Herein, the authors attempted to link the Functional Assessment of Cancer Therapy-General Physical Well-Being (FACT-G PWB) subscale with the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) calibrated item bank. The also sought to augment a subset of the conceptually most similar FACT-G PWB items with PROMIS PF items to improve the linking. Baseline data from 5506 participants in the Measuring Your Health (MY-Health) study were used to identify the optimal items for linking FACT-G PWB with PROMIS PF. A mixed methods approach identified the optimal items for creating the 5-item FACT/PROMIS-PF5 scale. Both the linked and augmented relationships were cross-validated using the follow-up MY-Health data. A 5-item FACT-G PWB item subset was found to be optimal for linking with PROMIS PF. In addition, a 2-item subset, including only items that were conceptually very similar to the PROMIS item bank content, were augmented with 3 PROMIS PF items. This new FACT/PROMIS-PF5 provided superior score recovery. The PROMIS PF metric allows for the evaluation of the extent to which similar questionnaires can be linked and therefore expressed on the same metric. These results allow for the aggregation of existing data and provide an optimal measure for future studies wishing to use the FACT yet also report on the PROMIS PF metric. Cancer 2018;124:153-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

Molecular structures and functional relationships in clostridial neurotoxins.

PubMed

Swaminathan, Subramanyam

2011-12-01

The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here. Journal compilation © 2011 FEBS. No claim to original US government works.

Applying Pedagogical Principles to Grammar Instruction

ERIC Educational Resources Information Center

Kanda, Makiko; Beglar, David

2004-01-01

The purpose of this study was to investigate the effectiveness of two experimental methods of teaching the present progressive verb tense based on four instructional principles: teach form-function relations, compare similar grammatical forms, promote learner autonomy, and provide opportunities for generative use. Ninety-nine Japanese first-year…

Classification of high-resolution multi-swath hyperspectral data using Landsat 8 surface reflectance data as a calibration target and a novel histogram based unsupervised classification technique to determine natural classes from biophysically relevant fit parameters

NASA Astrophysics Data System (ADS)

McCann, C.; Repasky, K. S.; Morin, M.; Lawrence, R. L.; Powell, S. L.

2016-12-01

Compact, cost-effective, flight-based hyperspectral imaging systems can provide scientifically relevant data over large areas for a variety of applications such as ecosystem studies, precision agriculture, and land management. To fully realize this capability, unsupervised classification techniques based on radiometrically-calibrated data that cluster based on biophysical similarity rather than simply spectral similarity are needed. An automated technique to produce high-resolution, large-area, radiometrically-calibrated hyperspectral data sets based on the Landsat surface reflectance data product as a calibration target was developed and applied to three subsequent years of data covering approximately 1850 hectares. The radiometrically-calibrated data allows inter-comparison of the temporal series. Advantages of the radiometric calibration technique include the need for minimal site access, no ancillary instrumentation, and automated processing. Fitting the reflectance spectra of each pixel using a set of biophysically relevant basis functions reduces the data from 80 spectral bands to 9 parameters providing noise reduction and data compression. Examination of histograms of these parameters allows for determination of natural splitting into biophysical similar clusters. This method creates clusters that are similar in terms of biophysical parameters, not simply spectral proximity. Furthermore, this method can be applied to other data sets, such as urban scenes, by developing other physically meaningful basis functions. The ability to use hyperspectral imaging for a variety of important applications requires the development of data processing techniques that can be automated. The radiometric-calibration combined with the histogram based unsupervised classification technique presented here provide one potential avenue for managing big-data associated with hyperspectral imaging.

The bottom line on wound care standardization.

PubMed

McNees, Patrick; Kueven, John A

2011-03-01

North Mississippi Medical Center learned four important lessons in its effort to standardize wound care products and processes of care: Designate clinical champions. Limit the number of vendors that provide products for a specialty. Reduce the number of similar-function wound care products that are available for use, with decisions guided by clinicians. Provide transparent information related to cost, the intentions of the initiative, usage patterns, and the criteria for evaluation.

Quantifying similarity in reliability surfaces using the probability of agreement

DOE PAGES

Stevens, Nathaniel T.; Anderson-Cook, Christine Michaela

2017-03-30

When separate populations exhibit similar reliability as a function of multiple explanatory variables, combining them into a single population is tempting. This can simplify future predictions and reduce uncertainty associated with estimation. However, combining these populations may introduce bias if the underlying relationships are in fact different. The probability of agreement formally and intuitively quantifies the similarity of estimated reliability surfaces across a two-factor input space. An example from the reliability literature demonstrates the utility of the approach when deciding whether to combine two populations or to keep them as distinct. As a result, new graphical summaries provide strategies formore » visualizing the results.« less

Humpback whale (Megaptera novaeangliae) singers in Hawaii are attracted to playback of similar song (L).

PubMed

Darling, James D; Jones, Meagan E; Nicklin, Charles P

2012-11-01

The use of playback experiments to study humpback whale song was assessed. Singers clearly detected playback song while singing and with other singers in the distance. Singers approached or joined song similar to their own from as far as 800 m but did not do so for a different (foreign) song. In one compound trial, on the playback of different song, the singer moved away and continued singing; when the playback was changed to similar song, it stopped singing and joined the playback speaker. Song playback experiments on the breeding grounds are viable and may provide insight into song function.

Quantifying similarity in reliability surfaces using the probability of agreement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Nathaniel T.; Anderson-Cook, Christine Michaela

When separate populations exhibit similar reliability as a function of multiple explanatory variables, combining them into a single population is tempting. This can simplify future predictions and reduce uncertainty associated with estimation. However, combining these populations may introduce bias if the underlying relationships are in fact different. The probability of agreement formally and intuitively quantifies the similarity of estimated reliability surfaces across a two-factor input space. An example from the reliability literature demonstrates the utility of the approach when deciding whether to combine two populations or to keep them as distinct. As a result, new graphical summaries provide strategies formore » visualizing the results.« less

Identification of 15 candidate structured noncoding RNA motifs in fungi by comparative genomics.

PubMed

Li, Sanshu; Breaker, Ronald R

2017-10-13

With the development of rapid and inexpensive DNA sequencing, the genome sequences of more than 100 fungal species have been made available. This dataset provides an excellent resource for comparative genomics analyses, which can be used to discover genetic elements, including noncoding RNAs (ncRNAs). Bioinformatics tools similar to those used to uncover novel ncRNAs in bacteria, likewise, should be useful for searching fungal genomic sequences, and the relative ease of genetic experiments with some model fungal species could facilitate experimental validation studies. We have adapted a bioinformatics pipeline for discovering bacterial ncRNAs to systematically analyze many fungal genomes. This comparative genomics pipeline integrates information on conserved RNA sequence and structural features with alternative splicing information to reveal fungal RNA motifs that are candidate regulatory domains, or that might have other possible functions. A total of 15 prominent classes of structured ncRNA candidates were identified, including variant HDV self-cleaving ribozyme representatives, atypical snoRNA candidates, and possible structured antisense RNA motifs. Candidate regulatory motifs were also found associated with genes for ribosomal proteins, S-adenosylmethionine decarboxylase (SDC), amidase, and HexA protein involved in Woronin body formation. We experimentally confirm that the variant HDV ribozymes undergo rapid self-cleavage, and we demonstrate that the SDC RNA motif reduces the expression of SAM decarboxylase by translational repression. Furthermore, we provide evidence that several other motifs discovered in this study are likely to be functional ncRNA elements. Systematic screening of fungal genomes using a computational discovery pipeline has revealed the existence of a variety of novel structured ncRNAs. Genome contexts and similarities to known ncRNA motifs provide strong evidence for the biological and biochemical functions of some newly found ncRNA motifs. Although initial examinations of several motifs provide evidence for their likely functions, other motifs will require more in-depth analysis to reveal their functions.

Generalized sample entropy analysis for traffic signals based on similarity measure

NASA Astrophysics Data System (ADS)

Shang, Du; Xu, Mengjia; Shang, Pengjian

2017-05-01

Sample entropy is a prevailing method used to quantify the complexity of a time series. In this paper a modified method of generalized sample entropy and surrogate data analysis is proposed as a new measure to assess the complexity of a complex dynamical system such as traffic signals. The method based on similarity distance presents a different way of signals patterns match showing distinct behaviors of complexity. Simulations are conducted over synthetic data and traffic signals for providing the comparative study, which is provided to show the power of the new method. Compared with previous sample entropy and surrogate data analysis, the new method has two main advantages. The first one is that it overcomes the limitation about the relationship between the dimension parameter and the length of series. The second one is that the modified sample entropy functions can be used to quantitatively distinguish time series from different complex systems by the similar measure.

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression ofmore » surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.« less

Soil functional types: surveying the biophysical dimensions of soil security

NASA Astrophysics Data System (ADS)

Cécillon, Lauric; Barré, Pierre

2015-04-01

Soil is a natural capital that can deliver key ecosystem services (ES) to humans through the realization of a series of soil processes controlling ecosystem functioning. Soil is also a diverse and endangered natural resource. A huge pedodiversity has been described at all scales, which is strongly altered by global change. The multidimensional concept soil security, encompassing biophysical, economic, social, policy and legal frameworks of soils has recently been proposed, recognizing the role of soils in global environmental sustainability challenges. The biophysical dimensions of soil security focus on the functionality of a given soil that can be viewed as the combination of its capability and its condition [1]. Indeed, all soils are not equal in term of functionality. They show different processes, provide different ES to humans and respond specifically to global change. Knowledge of soil functionality in space and time is thus a crucial step towards the achievement soil security. All soil classification systems incorporate some functional information, but soil taxonomy alone cannot fully describe the functioning, limitations, resistance and resilience of soils. Droogers and Bouma [2] introduced functional variants (phenoforms) for each soil type (genoform) so as to fit more closely to soil functionality. However, different genoforms can have the same functionality. As stated by McBratney and colleagues [1], there is a great need of an agreed methodology for defining the reference state of soil functionality. Here, we propose soil functional types (SFT) as a relevant classification system for the biophysical dimensions of soil security. Following the definition of plant functional types widely used in ecology, we define a soil functional type as "a set of soil taxons or phenoforms sharing similar processes (e.g. soil respiration), similar effects on ecosystem functioning (e.g. primary productivity) and similar responses to global change (land-use, management or climate) for a particular soil-provided ecosystem service (e.g. climate regulation)". One SFT can thus include several soil types having the same functionality for a particular soil-provided ES. Another consequence is that SFT maps for two different ES may not superimpose over the same area, since some soils may fall in the same SFT for a service and in different SFT for another one. Soil functional types could be assessed and monitored in space and time by a combination of soil functional traits that correspond to inherent and manageable properties of soils. Their metrology would involve either classic (pedological observations) or advanced (molecular ecology, spectrometry, geophysics) tools. SFT could be studied and mapped at all scales, depending on the purpose of the soil security assessment (e.g. global climate modeling, land planning and management, biodiversity conservation). Overall, research is needed to find a pathway from soil pedological maps to SFT maps which would yield important benefits towards the assessment and monitoring of soil security. Indeed, this methodology would allow (i) reducing the spatial uncertainty on the assessment of ES; (ii) identifying and mapping multifunctional soils, which may be the most important soil resource to preserve. References [1] McBratney et al., 2014. Geoderma 213:203-213. [2] Droogers P, Bouma J, 1997. SSSAJ 61:1704-1710.

Neuroimaging of Pain: Human Evidence and Clinical Relevance of Central Nervous System Processes and Modulation.

PubMed

Martucci, Katherine T; Mackey, Sean C

2018-06-01

Neuroimaging research has demonstrated definitive involvement of the central nervous system in the development, maintenance, and experience of chronic pain. Structural and functional neuroimaging has helped elucidate central nervous system contributors to chronic pain in humans. Neuroimaging of pain has provided a tool for increasing our understanding of how pharmacologic and psychologic therapies improve chronic pain. To date, findings from neuroimaging pain research have benefitted clinical practice by providing clinicians with an educational framework to discuss the biopsychosocial nature of pain with patients. Future advances in neuroimaging-based therapeutics (e.g., transcranial magnetic stimulation, real-time functional magnetic resonance imaging neurofeedback) may provide additional benefits for clinical practice. In the future, with standardization and validation, brain imaging could provide objective biomarkers of chronic pain, and guide treatment for personalized pain management. Similarly, brain-based biomarkers may provide an additional predictor of perioperative prognoses.

Protein-protein interaction network-based detection of functionally similar proteins within species.

PubMed

Song, Baoxing; Wang, Fen; Guo, Yang; Sang, Qing; Liu, Min; Li, Dengyun; Fang, Wei; Zhang, Deli

2012-07-01

Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent. Copyright © 2012 Wiley Periodicals, Inc.

"I swear it is Tourette's!": On functional coprolalia and other tic-like vocalizations.

PubMed

Ganos, Christos; Edwards, Mark J; Müller-Vahl, Kirsten

2016-12-30

Coprolalia in neuropsychiatry is typically associated with tic disorders, in particular Gilles de la Tourette syndrome. To date, there has been no report of functional coprolalia. Here, we provide the clinical characteristics of 13 adolescent and adult patients with coprolalic and other functional tic-like complex vocalizations who, on the basis of these symptoms, were misdiagnosed with a primary tic disorder, most commonly Gilles de la Tourette syndrome. We describe similarities and highlight the differences from primary tic disorders in order to provide a pragmatic list of clinical clues that will facilitate correct diagnostic labeling and thereby treatment. Finally, we emphasize that the distinction between a primary and a functional tic disorder should rely on a combination of neuropsychiatric symptoms and signs and not on the presence of single, however striking, abnormal behaviors, such as coprolalia. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Determination of modulation transfer function of a printer by measuring the autocorrelation of the transmission function of a printed Ronchi grating

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madanipour, Khosro; Tavassoly, Mohammad T

2009-02-01

We show theoretically and verify experimentally that the modulation transfer function (MTF) of a printing system can be determined by measuring the autocorrelation of a printed Ronchi grating. In practice, two similar Ronchi gratings are printed on two transparencies and the transparencies are superimposed with parallel grating lines. Then, the gratings are uniformly illuminated and the transmitted light from a large section is measured versus the displacement of one grating with respect to the other in a grating pitch interval. This measurement provides the required autocorrelation function for determination of the MTF.

Teaching Function and Practice Thinking of Psychological Movies

ERIC Educational Resources Information Center

Wu, Weidong

2010-01-01

Psychology teaching was implemented in virtue of excellent psychological movies, which not only could help to stimulate students' interest, and make the abstract theory concretion and visualization, but also provide the scenes similar to the reality for students' learning with attempts to improve their learning achievement. However, as for the…

Discretely Self-Similar Solutions to the Navier-Stokes Equations with Besov Space Data

NASA Astrophysics Data System (ADS)

Bradshaw, Zachary; Tsai, Tai-Peng

2018-07-01

We construct self-similar solutions to the three dimensional Navier-Stokes equations for divergence free, self-similar initial data that can be large in the critical Besov space \\dot{B}_{p,∞}^{3/p-1} where 3 < p < 6. We also construct discretely self-similar solutions for divergence free initial data in \\dot{B}_{p,∞}^{3/p-1} for 3 < p < 6 that is discretely self-similar for some scaling factor λ > 1. These results extend those of Bradshaw and Tsai (Ann Henri Poincaré 2016. https://doi.org/10.1007/s00023-016-0519-0) which dealt with initial data in L 3 w since {L^3_w\\subsetneq \\dot{B}_{p,∞}^{3/p-1}} for p > 3. We also provide several concrete examples of vector fields in the relevant function spaces.

Combining Density Functional Theory and Green's Function Theory: Range-Separated, Nonlocal, Dynamic, and Orbital-Dependent Hybrid Functional.

PubMed

Kananenka, Alexei A; Zgid, Dominika

2017-11-14

We present a rigorous framework which combines single-particle Green's function theory with density functional theory based on a separation of electron-electron interactions into short- and long-range components. Short-range contribution to the total energy and exchange-correlation potential is provided by a density functional approximation, while the long-range contribution is calculated using an explicit many-body Green's function method. Such a hybrid results in a nonlocal, dynamic, and orbital-dependent exchange-correlation functional of a single-particle Green's function. In particular, we present a range-separated hybrid functional called srSVWN5-lrGF2 which combines the local-density approximation and the second-order Green's function theory. We illustrate that similarly to density functional approximations, the new functional is weakly basis-set dependent. Furthermore, it offers an improved description of the short-range dynamic correlation. The many-body contribution to the functional mitigates the many-electron self-interaction error present in many density functional approximations and provides a better description of molecular properties. Additionally, we illustrate that the new functional can be used to scale down the self-energy and, therefore, introduce an additional sparsity to the self-energy matrix that in the future can be exploited in calculations for large molecules or periodic systems.

Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily

PubMed Central

2016-01-01

Naively one might have expected an early division between phosphate monoesterases and diesterases of the alkaline phosphatase (AP) superfamily. On the contrary, prior results and our structural and biochemical analyses of phosphate monoesterase PafA, from Chryseobacterium meningosepticum, indicate similarities to a superfamily phosphate diesterase [Xanthomonas citri nucleotide pyrophosphatase/phosphodiesterase (NPP)] and distinct differences from the three metal ion AP superfamily monoesterase, from Escherichia coli AP (EcAP). We carried out a series of experiments to map out and learn from the differences and similarities between these enzymes. First, we asked why there would be independent instances of monoesterases in the AP superfamily? PafA has a much weaker product inhibition and slightly higher activity relative to EcAP, suggesting that different metabolic evolutionary pressures favored distinct active-site architectures. Next, we addressed the preferential phosphate monoester and diester catalysis of PafA and NPP, respectively. We asked whether the >80% sequence differences throughout these scaffolds provide functional specialization for each enzyme’s cognate reaction. In contrast to expectations from this model, PafA and NPP mutants with the common subset of active-site groups embedded in each native scaffold had the same monoesterase:diesterase specificities; thus, the >107-fold difference in native specificities appears to arise from distinct interactions at a single phosphoryl substituent. We also uncovered striking mechanistic similarities between the PafA and EcAP monoesterases, including evidence for ground-state destabilization and functional active-site networks that involve different active-site groups but may play analogous catalytic roles. Discovering common network functions may reveal active-site architectural connections that are critical for function, and identifying regions of functional modularity may facilitate the design of new enzymes from existing promiscuous templates. More generally, comparative enzymology and analysis of catalytic promiscuity can provide mechanistic and evolutionary insights. PMID:27670607

Functional Module Search in Protein Networks based on Semantic Similarity Improves the Analysis of Proteomics Data*

PubMed Central

Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W.; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

2014-01-01

The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

Effects of river impoundment on ecosystem services of large tropical rivers: embodied energy and market value of artisanal fisheries.

PubMed

Hoeinghaus, David J; Agostinho, Angelo A; Gomes, Luiz C; Pelicice, Fernando M; Okada, Edson K; Latini, João D; Kashiwaqui, Elaine A L; Winemiller, Kirk O

2009-10-01

Applying the ecosystem services concept to conservation initiatives or in managing ecosystem services requires understanding how environmental impacts affect the ecology of key species or functional groups providing the services. We examined effects of river impoundments, one of the leading threats to freshwater biodiversity, on an important ecosystem service provided by large tropical rivers (i.e., artisanal fisheries). The societal and economic importance of this ecosystem service in developing countries may provide leverage to advance conservation agendas where future impoundments are being considered. We assessed impoundment effects on the energetic costs of fisheries production (embodied energy) and commercial market value of the artisanal fishery of the Paraná River, Brazil, before and after formation of Itaipu Reservoir. High-value migratory species that dominated the fishery before the impoundment was built constituted a minor component of the contemporary fishery that is based heavily on reservoir-adapted introduced species. Cascading effects of river impoundment resulted in a mismatch between embodied energy and market value: energetic costs of fisheries production increased, whereas market value decreased. This was partially attributable to changes in species functional composition but also strongly linked to species identities that affected market value as a result of consumer preferences even when species were functionally similar. Similar trends are expected in other large tropical rivers following impoundment. In addition to identifying consequences of a common anthropogenic impact on an important ecosystem service, our assessment provides insight into the sustainability of fisheries production in tropical rivers and priorities for regional biodiversity conservation.

Human vs. Mouse Eosinophils: “That which we call an eosinophil, by any other name would stain as red”

PubMed Central

Lee, James J.; Jacobsen, Elizabeth A.; Ochkur, Sergei I; McGarry, Michael P.; Condjella, Rachel M.; Doyle, Alfred D.; Luo, Huijun; Zellner, Katie R.; Protheroe, Cheryl A.; Willetts, Lian; LeSuer, William E.; Colbert, Dana C.; Helmers, Richard A.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.

2012-01-01

The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. PMID:22935586

Pyranopterin conformation defines the function of molybdenum and tungsten enzymes.

PubMed

Rothery, Richard A; Stein, Benjamin; Solomonson, Matthew; Kirk, Martin L; Weiner, Joel H

2012-09-11

We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.

Neurocognitive similarities between severe chronic schizophrenia and behavioural variant frontotemporal dementia.

PubMed

Chan, Hui-Minn; Stolwyk, Rene; Neath, Joanna; Kelso, Wendy; Walterfang, Mark; Mocellin, Ramon; Pantelis, Christos; Velakoulis, Dennis

2015-02-28

This study focuses on a group of patients with chronic schizophrenia who have a more severe form of the disorder, as indicated by socio-functional decline, treatment resistance, and recurrent hospitalisation. Previous research has suggested that the pattern and severity of cognitive deficits in people with severe chronic schizophrenia is similar to that observed in behavioural variant frontotemporal dementia (bvFTD). In the current study, we compared neurocognitive performance in 16 cognitive domains in 7 inpatients with severe chronic schizophrenia, 13 community-dwelling outpatients with chronic schizophrenia, 12 patients with bvFTD, and 18 healthy controls. Our findings revealed more similar cognitive profiles between the schizophrenia inpatient and bvFTD groups compared to the schizophrenia outpatient group, who outperformed the former groups. The current results provide preliminary evidence for a distinct schizophrenia subgroup, distinguishable from other chronic schizophrenia patients by poorer clinical and functional status, who have levels of cognitive impairment comparable to those seen in bvFTD patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The immune signaling pathways of Manduca sexta

PubMed Central

Cao, Xiaolong; He, Yan; Hu, Yingxia; Wang, Yang; Chen, Yun-Ru; Bryant, Bart; Clem, Rollie J.; Schwartz, Lawrence M.; Blissard, Gary; Jiang, Haobo

2015-01-01

Signal transduction pathways and their coordination are critically important for proper functioning of animal immune systems. Our knowledge of the constituents of the intracellular signaling network in insects mainly comes from genetic analyses in Drosophila melanogaster. To facilitate future studies of similar systems in the tobacco hornworm and other lepidopteran insects, we have identified and examined the homologous genes in the genome of Manduca sexta. Based on 1:1 orthologous relationships in most cases, we hypothesize that the Toll, Imd, MAPK-JNK-p38 and JAK-STAT pathways are intact and operative in this species, as are most of the regulatory mechanisms. Similarly, cellular processes such as autophagy, apoptosis and RNA interference probably function in similar ways, because their mediators and modulators are mostly conserved in this lepidopteran species. We have annotated a total of 186 genes encoding 199 proteins, studied their domain structures and evolution, and examined their mRNA levels in tissues at different life stages. Such information provides a genomic perspective of the intricate signaling system in a non-drosophiline insect. PMID:25858029

Advanced lesion symptom mapping analyses and implementation as BCBtoolkit.

PubMed

Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika; Volle, Emmanuelle; Thiebaut de Schotten, Michel

2018-03-01

Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1].

Semantics of Procedures: A Cognitive Basis for Maintenance Training Competency

DTIC Science & Technology

1988-04-01

provided by presenting these multiple, interacting views. These 0 conclusions are similar to the views of George Polya , who proposed the use of... exercises . It is also clear that at least some understanding of machine structure and function is required to interpret much of the information in the...check of the problem lists provides the names of all the usual subpects. This accessibility permits the technician to modify the sequence according to

The Sla2p/HIP1/HIP1R family: similar structure, similar function in endocytosis?

PubMed

Gottfried, Irit; Ehrlich, Marcelo; Ashery, Uri

2010-02-01

HIP1 (huntingtin interacting protein 1) has two close relatives: HIP1R (HIP1-related) and yeast Sla2p. All three members of the family have a conserved domain structure, suggesting a common function. Over the past decade, a number of studies have characterized these proteins using a combination of biochemical, imaging, structural and genetic techniques. These studies provide valuable information on binding partners, structure and dynamics of HIP1/HIP1R/Sla2p. In general, all suggest a role in CME (clathrin-mediated endocytosis) for the three proteins, though some differences have emerged. In this mini-review we summarize the current views on the roles of these proteins, while emphasizing the unique attributes of each family member.

Construction and comparison of gene co-expression networks shows complex plant immune responses

PubMed Central

López, Camilo; López-Kleine, Liliana

2014-01-01

Gene co-expression networks (GCNs) are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA). Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses. PMID:25320678

Spherical hashing: binary code embedding with hyperspheres.

PubMed

Heo, Jae-Pil; Lee, Youngwoon; He, Junfeng; Chang, Shih-Fu; Yoon, Sung-Eui

2015-11-01

Many binary code embedding schemes have been actively studied recently, since they can provide efficient similarity search, and compact data representations suitable for handling large scale image databases. Existing binary code embedding techniques encode high-dimensional data by using hyperplane-based hashing functions. In this paper we propose a novel hypersphere-based hashing function, spherical hashing, to map more spatially coherent data points into a binary code compared to hyperplane-based hashing functions. We also propose a new binary code distance function, spherical Hamming distance, tailored for our hypersphere-based binary coding scheme, and design an efficient iterative optimization process to achieve both balanced partitioning for each hash function and independence between hashing functions. Furthermore, we generalize spherical hashing to support various similarity measures defined by kernel functions. Our extensive experiments show that our spherical hashing technique significantly outperforms state-of-the-art techniques based on hyperplanes across various benchmarks with sizes ranging from one to 75 million of GIST, BoW and VLAD descriptors. The performance gains are consistent and large, up to 100 percent improvements over the second best method among tested methods. These results confirm the unique merits of using hyperspheres to encode proximity regions in high-dimensional spaces. Finally, our method is intuitive and easy to implement.

OrChem - An open source chemistry search engine for Oracle(R).

PubMed

Rijnbeek, Mark; Steinbeck, Christoph

2009-10-22

Registration, indexing and searching of chemical structures in relational databases is one of the core areas of cheminformatics. However, little detail has been published on the inner workings of search engines and their development has been mostly closed-source. We decided to develop an open source chemistry extension for Oracle, the de facto database platform in the commercial world. Here we present OrChem, an extension for the Oracle 11G database that adds registration and indexing of chemical structures to support fast substructure and similarity searching. The cheminformatics functionality is provided by the Chemistry Development Kit. OrChem provides similarity searching with response times in the order of seconds for databases with millions of compounds, depending on a given similarity cut-off. For substructure searching, it can make use of multiple processor cores on today's powerful database servers to provide fast response times in equally large data sets. OrChem is free software and can be redistributed and/or modified under the terms of the GNU Lesser General Public License as published by the Free Software Foundation. All software is available via http://orchem.sourceforge.net.

Sensor Level Functional Connectivity Topography Comparison Between Different References Based EEG and MEG.

PubMed

Huang, Yunzhi; Zhang, Junpeng; Cui, Yuan; Yang, Gang; Liu, Qi; Yin, Guangfu

2018-01-01

Sensor-level functional connectivity topography (sFCT) contributes significantly to our understanding of brain networks. sFCT can be constructed using either electroencephalography (EEG) or magnetoencephalography (MEG). Here, we compared sFCT within the EEG modality and between EEG and MEG modalities. We first used simulations to look at how different EEG references-including the Reference Electrode Standardization Technique (REST), average reference (AR), linked mastoids (LM), and left mastoid references (LR)-affect EEG-based sFCT. The results showed that REST decreased the reference effects on scalp EEG recordings, making REST-based sFCT closer to the ground truth (sFCT based on ideal recordings). For the inter-modality simulation comparisons, we compared each type of EEG-sFCT with MEG-sFCT using three metrics to quantize the differences: Relative Error (RE), Overlap Rate (OR), and Hamming Distance (HD). When two sFCTs are similar, RE and HD are low, while OR is high. Results showed that among all reference schemes, EEG-and MEG-sFCT were most similar when the EEG was REST-based and the EEG and MEG were recorded simultaneously. Next, we analyzed simultaneously recorded MEG and EEG data from publicly available face-recognition experiments using a similar procedure as in the simulations. The results showed (1) if MEG-sFCT is the standard, REST-and LM-based sFCT provided results closer to this standard in the terms of HD; (2) REST-based sFCT and MEG-sFCT had the highest similarity in terms of RE; (3) REST-based sFCT had the most overlapping edges with MEG-sFCT in terms of OR. This study thus provides new insights into the effect of different reference schemes on sFCT and the similarity between MEG and EEG in terms of sFCT.

Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.

PubMed

Forrest, Osric A; Ingersoll, Sarah A; Preininger, Marcela K; Laval, Julie; Limoli, Dominique H; Brown, Milton R; Lee, Frances E; Bedi, Brahmchetna; Sadikot, Ruxana T; Goldberg, Joanna B; Tangpricha, Vin; Gaggar, Amit; Tirouvanziam, Rabindra

2018-05-09

Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies. We used multiple platforms (flow cytometry, bacteria-killing, and metabolic assays) to characterize functional properties of blood neutrophils recruited in a transepithelial migration model using airway milieu from CF subjects as an apical chemoattractant. Similarly to neutrophils recruited to CF airways in vivo, neutrophils migrated into CF airway milieu in vitro display depressed phagocytic receptor expression and bacterial killing, but enhanced granule release, immunoregulatory function (arginase-1 activation), and metabolic activities, including high Glut1 expression, glycolysis, and oxidant production. We also identify enhanced pinocytic activity as a novel feature of these cells. In vitro treatment with the leukotriene pathway inhibitor acebilustat reduces the number of transmigrating neutrophils, while the metabolic modulator metformin decreases metabolism and oxidant production, but fails to restore bacterial killing. Interestingly, we describe similar pathological conditioning of neutrophils in other inflammatory airway diseases. We successfully tested the hypothesis that recruitment of neutrophils into airway milieu from patients with CF in vitro induces similar pathological conditioning to that observed in vivo, opening new avenues for targeted therapeutic intervention. ©2018 Society for Leukocyte Biology.

A strategy for improved computational efficiency of the method of anchored distributions

NASA Astrophysics Data System (ADS)

Over, Matthew William; Yang, Yarong; Chen, Xingyuan; Rubin, Yoram

2013-06-01

This paper proposes a strategy for improving the computational efficiency of model inversion using the method of anchored distributions (MAD) by "bundling" similar model parametrizations in the likelihood function. Inferring the likelihood function typically requires a large number of forward model (FM) simulations for each possible model parametrization; as a result, the process is quite expensive. To ease this prohibitive cost, we present an approximation for the likelihood function called bundling that relaxes the requirement for high quantities of FM simulations. This approximation redefines the conditional statement of the likelihood function as the probability of a set of similar model parametrizations "bundle" replicating field measurements, which we show is neither a model reduction nor a sampling approach to improving the computational efficiency of model inversion. To evaluate the effectiveness of these modifications, we compare the quality of predictions and computational cost of bundling relative to a baseline MAD inversion of 3-D flow and transport model parameters. Additionally, to aid understanding of the implementation we provide a tutorial for bundling in the form of a sample data set and script for the R statistical computing language. For our synthetic experiment, bundling achieved a 35% reduction in overall computational cost and had a limited negative impact on predicted probability distributions of the model parameters. Strategies for minimizing error in the bundling approximation, for enforcing similarity among the sets of model parametrizations, and for identifying convergence of the likelihood function are also presented.

Is circumferential urethral mobilisation an overdo? A prospective outcome analysis of dorsal onlay and dorso - lateral onlay BMGU for anterior urethral strictures.

PubMed

Prakash, Gaurav; Singh, Bhupendra Pal; Sinha, Rahul Janak; Jhanwar, Ankur; Sankhwar, Satyanarayan

2018-01-01

For dorsal onlay graft placement, unilateral urethral mobilization is less invasive than standard circumferential urethral mobilization. Apart from success in terms of patency of urethra, other issues like sexual function, overall quality of life and patient satisfaction remain important issues while comparing outcomes of urethroplasty. To prospectively compare the objective as well as subjective outcomes of two approaches. Between July 2011 and January 2015, 136 adult males having anterior urethral stricture with urethral lumen ≥ 6 Fr. were prospectively assigned between two groups by alternate randomization. Operative time, complications, success rate (no obstructive symptoms, no need of any postoperative intervention, Q max > 15mL/sec), sexual functions (using Brief Male Sexual Function Inventory) were compared. Baseline parameters were similar in both groups (68 in each group). Overall success rate was similar in both groups (89 % and 91 % respectively). Improvement in total LUTS scores was similar in groups. Changes in overall health status (VAS and EQ 5D) was equal in both groups. Erectile function score was significantly decreased in DO than DL group while ejaculatory function and sexual desire remained stable after urethroplasty in both groups. In anterior urethral stricture buccal mucosa graft provides satisfactory results as onlay technique. No technique whether dorsolateral and dorsal techniques is superior to other. Dorsolateral technique needs minimal urethral mobilization and should be preferred whenever feasible. Copyright® by the International Brazilian Journal of Urology.

Dehydration stress memory genes of Zea mays; comparison with Arabidopsis thaliana

PubMed Central

2014-01-01

Background Pre-exposing plants to diverse abiotic stresses may alter their physiological and transcriptional responses to a subsequent stress, suggesting a form of “stress memory”. Arabidopsis thaliana plants that have experienced multiple exposures to dehydration stress display transcriptional behavior suggesting “memory” from an earlier stress. Genes that respond to a first stress by up-regulating or down-regulating their transcription but in a subsequent stress provide a significantly different response define the ‘memory genes’ category. Genes responding similarly to each stress form the ‘non-memory’ category. It is unknown whether such memory responses exists in other Angiosperm lineages and whether memory is an evolutionarily conserved response to repeated dehydration stresses. Results Here, we determine the transcriptional responses of maize (Zea mays L.) plants that have experienced repeated exposures to dehydration stress in comparison with plants encountering the stress for the first time. Four distinct transcription memory response patterns similar to those displayed by A. thaliana were revealed. The most important contribution is the evidence that monocot and eudicot plants, two lineages that have diverged 140 to 200 M years ago, display similar abilities to ‘remember’ a dehydration stress and to modify their transcriptional responses, accordingly. The highly sensitive RNA-Seq analyses allowed to identify genes that function similarly in the two lineages, as well as genes that function in species-specific ways. Memory transcription patterns indicate that the transcriptional behavior of responding genes under repeated stresses is different from the behavior during an initial dehydration stress, suggesting that stress memory is a complex phenotype resulting from coordinated responses of multiple signaling pathways. Conclusions Structurally related genes displaying the same memory responses in the two species would suggest conservation of the genes’ memory during the evolution of plants’ dehydration stress response systems. On the other hand, divergent transcription memory responses by genes encoding similar functions would suggest occurrence of species-specific memory responses. The results provide novel insights into our current knowledge of how plants respond to multiple dehydration stresses, as compared to a single exposure, and may serve as a reference platform to study the functions of memory genes in adaptive responses to water deficit in monocot and eudicot plants. PMID:24885787

Fire modifies the phylogenetic structure of soil bacterial co-occurrence networks.

PubMed

Pérez-Valera, Eduardo; Goberna, Marta; Faust, Karoline; Raes, Jeroen; García, Carlos; Verdú, Miguel

2017-01-01

Fire alters ecosystems by changing the composition and community structure of soil microbes. The phylogenetic structure of a community provides clues about its main assembling mechanisms. While environmental filtering tends to reduce the community phylogenetic diversity by selecting for functionally (and hence phylogenetically) similar species, processes like competitive exclusion by limiting similarity tend to increase it by preventing the coexistence of functionally (and phylogenetically) similar species. We used co-occurrence networks to detect co-presence (bacteria that co-occur) or exclusion (bacteria that do not co-occur) links indicative of the ecological interactions structuring the community. We propose that inspecting the phylogenetic structure of co-presence or exclusion links allows to detect the main processes simultaneously assembling the community. We monitored a soil bacterial community after an experimental fire and found that fire altered its composition, richness and phylogenetic diversity. Both co-presence and exclusion links were more phylogenetically related than expected by chance. We interpret such a phylogenetic clustering in co-presence links as a result of environmental filtering, while that in exclusion links reflects competitive exclusion by limiting similarity. This suggests that environmental filtering and limiting similarity operate simultaneously to assemble soil bacterial communities, widening the traditional view that only environmental filtering structures bacterial communities. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

PlaNet: Combined Sequence and Expression Comparisons across Plant Networks Derived from Seven Species[W][OA

PubMed Central

Mutwil, Marek; Klie, Sebastian; Tohge, Takayuki; Giorgi, Federico M.; Wilkins, Olivia; Campbell, Malcolm M.; Fernie, Alisdair R.; Usadel, Björn; Nikoloski, Zoran; Persson, Staffan

2011-01-01

The model organism Arabidopsis thaliana is readily used in basic research due to resource availability and relative speed of data acquisition. A major goal is to transfer acquired knowledge from Arabidopsis to crop species. However, the identification of functional equivalents of well-characterized Arabidopsis genes in other plants is a nontrivial task. It is well documented that transcriptionally coordinated genes tend to be functionally related and that such relationships may be conserved across different species and even kingdoms. To exploit such relationships, we constructed whole-genome coexpression networks for Arabidopsis and six important plant crop species. The interactive networks, clustered using the HCCA algorithm, are provided under the banner PlaNet (http://aranet.mpimp-golm.mpg.de). We implemented a comparative network algorithm that estimates similarities between network structures. Thus, the platform can be used to swiftly infer similar coexpressed network vicinities within and across species and can predict the identity of functional homologs. We exemplify this using the PSA-D and chalcone synthase-related gene networks. Finally, we assessed how ontology terms are transcriptionally connected in the seven species and provide the corresponding MapMan term coexpression networks. The data support the contention that this platform will considerably improve transfer of knowledge generated in Arabidopsis to valuable crop species. PMID:21441431

Transcranial direct current stimulation associated with gait training in Parkinson's disease: A pilot randomized clinical trial.

PubMed

Costa-Ribeiro, Adriana; Maux, Ariadne; Bosford, Thamyris; Aoki, Yumi; Castro, Rebeca; Baltar, Adriana; Shirahige, Lívia; Moura Filho, Alberto; Nitsche, Michael A; Monte-Silva, Kátia

2017-04-01

The aim of this study is to investigate the effects of transcranial direct current stimulation (tDCS) combined with cueing gait training (CGT) on functional mobility in patients with Parkinson´s disease (PD). A pilot double-blind controlled, randomized clinical trial was conducted with 22 patients with PD assigned to the experimental (anodal tDCS plus CGT) and control group (sham tDCS plus CGT). The primary outcome (functional mobility) was assessed by 10-m walk test, cadence, stride length, and Timed Up and Go test. Motor impairment, bradykinesia, balance, and quality of life were analyzed as secondary outcomes. Minimal clinically important differences (MCIDs) were observed when assessing outcome data. Both groups demonstrated similar gains in all outcome measures, except for the stride length. The number of participants who showed MCID was similar between groups. The CGT provided many benefits to functional mobility, motor impairment, bradykinesia, balance, and quality of life. However, these effect magnitudes were not influenced by stimulation, but tDCS seems to prolong the effects of cueing therapy on functional mobility.

Clinical neurologic indices of toxicity in animals.

PubMed Central

O'Donoghue, J L

1996-01-01

The fundamental structures and functions of the nervous systems of animals and humans are conserved in many ways across species. These similarities provide a basis for developing common neurologic examinations for a number of species of animals and also provide a basis for developing risk assessments across species for neurologic end points. The neurologic examination requires no expensive equipment and can be conducted in the field or wherever impaired animals are identified. The proper conduct of neurologic examinations in animals assumes that the examiner has a fundamental understanding of the normal structure and function of the nervous system as well as knowledge about the spontaneous disease background of the species being studied. PMID:9182039

A Coordinate-Based Meta-Analysis of Overlaps in Regional Specialization and Functional Connectivity across Subjective Value and Default Mode Networks.

PubMed

Acikalin, M Yavuz; Gorgolewski, Krzysztof J; Poldrack, Russell A

2017-01-01

Previous research has provided qualitative evidence for overlap in a number of brain regions across the subjective value network (SVN) and the default mode network (DMN). In order to quantitatively assess this overlap, we conducted a series of coordinate-based meta-analyses (CBMA) of results from 466 functional magnetic resonance imaging experiments on task-negative or subjective value-related activations in the human brain. In these analyses, we first identified significant overlaps and dissociations across activation foci related to SVN and DMN. Second, we investigated whether these overlapping subregions also showed similar patterns of functional connectivity, suggesting a shared functional subnetwork. We find considerable overlap between SVN and DMN in subregions of central ventromedial prefrontal cortex (cVMPFC) and dorsal posterior cingulate cortex (dPCC). Further, our findings show that similar patterns of bidirectional functional connectivity between cVMPFC and dPCC are present in both networks. We discuss ways in which our understanding of how subjective value (SV) is computed and represented in the brain can be synthesized with what we know about the DMN, mind-wandering, and self-referential processing in light of our findings.

Family Functioning and Relationship Quality for Adolescents in Family-based Treatment with Severe Anorexia Nervosa Compared with Non-clinical Adolescents.

PubMed

Wallis, Andrew; Miskovic-Wheatley, Jane; Madden, Sloane; Rhodes, Paul; Crosby, Ross D; Cao, Li; Touyz, Stephen

2018-01-01

This longitudinal study explored family functioning and relationship quality for adolescents with severe anorexia nervosa (AN). An important outcome given healthy family functioning supports effective adolescent development. Fifty-four female adolescents and their parents, treated with family-based treatment after inpatient admission, and 49 non-clinical age-matched adolescents and their parents were compared at assessment and 6 months after session 20. At baseline, AN group mothers and fathers reported poorer family function. AN adolescents were notably similar to controls, reporting poorer function in only one domain. There were no changes for adolescents, an improvement for mothers in the AN group, but an increase in perceived impairment for fathers in both groups, with AN fathers more affected. The similarity in adolescent reports and the increase for fathers over time may indicate that normal adolescent family processes occur even in the midst of serious illness. There is a need to provide intervention to ameliorate the impact of treatment on parents. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Exposure to Sumas Mountain chrysotile induces similar gene expression changes as Libby Amphibole but has greater effect on long-term pathology and lung function

EPA Science Inventory

This study was designed to provide understanding of the toxicity of naturally occurring asbestos (NOA) including Libby amphibole (LA), Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED) and Ontario ferroactinolite cleavage fragments (ON). Rat-respirable fractions (aer...

A common origin for immunity and digestion.

PubMed

Broderick, Nichole A

2015-01-01

Historically, the digestive and immune systems were viewed and studied as separate entities. However, there are remarkable similarities and shared functions in both nutrient acquisition and host defense. Here, I propose a common origin for both systems. This association provides a new prism for viewing the emergence and evolution of host defense mechanisms.

Social-Emotional Functioning of Elementary-Age Deaf Children: A Profile Analysis

ERIC Educational Resources Information Center

Vogel-Walcutt, Jennifer J.; Schatschneider, Christopher; Bowers, Clint

2011-01-01

Discussion and study of the social-emotional development of deaf and hard of hearing children, though extensive, has yet to provide an accurate understanding of the differences between deaf and hearing children. Consequently, the goal of the researchers was to conduct a profile analysis to determine similarities and differences between the two…

Neurophysiology and Neuroanatomy of Reflexive and Volitional Saccades: Evidence from Studies of Humans

ERIC Educational Resources Information Center

McDowell, Jennifer E.; Dyckman, Kara A.; Austin, Benjamin P.; Clementz, Brett A.

2008-01-01

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry…

GDINA and CDM Packages in R

ERIC Educational Resources Information Center

Rupp, André A.; van Rijn, Peter W.

2018-01-01

We review the GIDNA and CDM packages in R for fitting cognitive diagnosis/diagnostic classification models. We first provide a summary of their core capabilities and then use both simulated and real data to compare their functionalities in practice. We found that the most relevant routines in the two packages appear to be more similar than…

School Choice in Spain and the United States: A Comparative Study

ERIC Educational Resources Information Center

Umpstead, Regina; Jankens, Benjamin; Ortega Gil, Pablo; Weiss, Linda; Umpstead, Bruce

2016-01-01

This article explores issues of school choice in Spain and the United States by examining the roles and functions of "centros concertados," publicly funded private schools in Spain, and public charter schools in the United States, to provide key insights into the similarities and differences between them. After making a national…

Stereotaxy, navigation and the temporal concatenation.

PubMed

Apuzzo, M L; Chen, J C

1999-01-01

Nautical and cerebral navigation share similar elements of functional need and similar developmental pathways. The need for orientation necessitates the development of appropriate concepts, and such concepts are dependent on technology for practical realization. Occasionally, a concept precedes technology in time and requires periods of delay for appropriate development. A temporal concatenation exists where time allows the additive as need, concept and technology ultimately provide an endpoint of elegant solution. Nautical navigation has proceeded through periods of dead reckoning and celestial navigation to satellite orientation with associated refinements of instrumentation and charts for guidance. Cerebral navigation has progressed from craniometric orientation and burr hole mounted guidance systems to simple rectolinear and arc-centered devices based on radiographs to guidance by complex anatomical and functional maps provided as an amalgam of modern imaging modes. These maps are now augmented by complex frame and frameless systems which allow not only precise orientation, but also point and volumetric action. These complex technical modalities required and developed in part from elements of maritime navigation that have been translated to cerebral navigation in a temporal concatenation. Copyright 2000 S. Karger AG, Basel

Superpixel Cut for Figure-Ground Image Segmentation

NASA Astrophysics Data System (ADS)

Yang, Michael Ying; Rosenhahn, Bodo

2016-06-01

Figure-ground image segmentation has been a challenging problem in computer vision. Apart from the difficulties in establishing an effective framework to divide the image pixels into meaningful groups, the notions of figure and ground often need to be properly defined by providing either user inputs or object models. In this paper, we propose a novel graph-based segmentation framework, called superpixel cut. The key idea is to formulate foreground segmentation as finding a subset of superpixels that partitions a graph over superpixels. The problem is formulated as Min-Cut. Therefore, we propose a novel cost function that simultaneously minimizes the inter-class similarity while maximizing the intra-class similarity. This cost function is optimized using parametric programming. After a small learning step, our approach is fully automatic and fully bottom-up, which requires no high-level knowledge such as shape priors and scene content. It recovers coherent components of images, providing a set of multiscale hypotheses for high-level reasoning. We evaluate our proposed framework by comparing it to other generic figure-ground segmentation approaches. Our method achieves improved performance on state-of-the-art benchmark databases.

Transmission of ˜ 10 keV electron beams through thin ceramic foils: Measurements and Monte Carlo simulations of electron energy distribution functions

NASA Astrophysics Data System (ADS)

Morozov, A.; Heindl, T.; Skrobol, C.; Wieser, J.; Krücken, R.; Ulrich, A.

2008-07-01

Electron beams with particle energy of ~10 keV were sent through 300 nm thick ceramic (Si3N4 + SiO2) foils and the resulting electron energy distribution functions were recorded using a retarding grid technique. The results are compared with Monte Carlo simulations performed with two publicly available packages, Geant4 and Casino v2.42. It is demonstrated that Geant4, unlike Casino, provides electron energy distribution functions very similar to the experimental distributions. Both simulation packages provide a quite precise average energy of transmitted electrons: we demonstrate that the maximum uncertainty of the calculated values of the average energy is 6% for Geant4 and 8% for Casino, taking into account all systematic uncertainties and the discrepancies in the experimental and simulated data.

Dynamic selection mechanism for quality of service aware web services

NASA Astrophysics Data System (ADS)

D'Mello, Demian Antony; Ananthanarayana, V. S.

2010-02-01

A web service is an interface of the software component that can be accessed by standard Internet protocols. The web service technology enables an application to application communication and interoperability. The increasing number of web service providers throughout the globe have produced numerous web services providing the same or similar functionality. This necessitates the use of tools and techniques to search the suitable services available over the Web. UDDI (universal description, discovery and integration) is the first initiative to find the suitable web services based on the requester's functional demands. However, the requester's requirements may also include non-functional aspects like quality of service (QoS). In this paper, the authors define a QoS model for QoS aware and business driven web service publishing and selection. The authors propose a QoS requirement format for the requesters, to specify their complex demands on QoS for the web service selection. The authors define a tree structure called quality constraint tree (QCT) to represent the requester's variety of requirements on QoS properties having varied preferences. The paper proposes a QoS broker based architecture for web service selection, which facilitates the requesters to specify their QoS requirements to select qualitatively optimal web service. A web service selection algorithm is presented, which ranks the functionally similar web services based on the degree of satisfaction of the requester's QoS requirements and preferences. The paper defines web service provider qualities to distinguish qualitatively competitive web services. The paper also presents the modelling and selection mechanism for the requester's alternative constraints defined on the QoS. The authors implement the QoS broker based system to prove the correctness of the proposed web service selection mechanism.

Predominant Acidilobus-Like Populations from Geothermal Environments in Yellowstone National Park Exhibit Similar Metabolic Potential in Different Hypoxic Microbial Communities

PubMed Central

Jay, Z. J.; Rusch, D. B.; Tringe, S. G.; Bailey, C.; Jennings, R. M.

2014-01-01

High-temperature (>70°C) ecosystems in Yellowstone National Park (YNP) provide an unparalleled opportunity to study chemotrophic archaea and their role in microbial community structure and function under highly constrained geochemical conditions. Acidilobus spp. (order Desulfurococcales) comprise one of the dominant phylotypes in hypoxic geothermal sulfur sediment and Fe(III)-oxide environments along with members of the Thermoproteales and Sulfolobales. Consequently, the primary goals of the current study were to analyze and compare replicate de novo sequence assemblies of Acidilobus-like populations from four different mildly acidic (pH 3.3 to 6.1) high-temperature (72°C to 82°C) environments and to identify metabolic pathways and/or protein-encoding genes that provide a detailed foundation of the potential functional role of these populations in situ. De novo assemblies of the highly similar Acidilobus-like populations (>99% 16S rRNA gene identity) represent near-complete consensus genomes based on an inventory of single-copy genes, deduced metabolic potential, and assembly statistics generated across sites. Functional analysis of coding sequences and confirmation of gene transcription by Acidilobus-like populations provide evidence that they are primarily chemoorganoheterotrophs, generating acetyl coenzyme A (acetyl-CoA) via the degradation of carbohydrates, lipids, and proteins, and auxotrophic with respect to several external vitamins, cofactors, and metabolites. No obvious pathways or protein-encoding genes responsible for the dissimilatory reduction of sulfur were identified. The presence of a formate dehydrogenase (Fdh) and other protein-encoding genes involved in mixed-acid fermentation supports the hypothesis that Acidilobus spp. function as degraders of complex organic constituents in high-temperature, mildly acidic, hypoxic geothermal systems. PMID:24162572

SGFSC: speeding the gene functional similarity calculation based on hash tables.

PubMed

Tian, Zhen; Wang, Chunyu; Guo, Maozu; Liu, Xiaoyan; Teng, Zhixia

2016-11-04

In recent years, many measures of gene functional similarity have been proposed and widely used in all kinds of essential research. These methods are mainly divided into two categories: pairwise approaches and group-wise approaches. However, a common problem with these methods is their time consumption, especially when measuring the gene functional similarities of a large number of gene pairs. The problem of computational efficiency for pairwise approaches is even more prominent because they are dependent on the combination of semantic similarity. Therefore, the efficient measurement of gene functional similarity remains a challenging problem. To speed current gene functional similarity calculation methods, a novel two-step computing strategy is proposed: (1) establish a hash table for each method to store essential information obtained from the Gene Ontology (GO) graph and (2) measure gene functional similarity based on the corresponding hash table. There is no need to traverse the GO graph repeatedly for each method with the help of the hash table. The analysis of time complexity shows that the computational efficiency of these methods is significantly improved. We also implement a novel Speeding Gene Functional Similarity Calculation tool, namely SGFSC, which is bundled with seven typical measures using our proposed strategy. Further experiments show the great advantage of SGFSC in measuring gene functional similarity on the whole genomic scale. The proposed strategy is successful in speeding current gene functional similarity calculation methods. SGFSC is an efficient tool that is freely available at http://nclab.hit.edu.cn/SGFSC . The source code of SGFSC can be downloaded from http://pan.baidu.com/s/1dFFmvpZ .

Polynomial Similarity Transformation Theory: A smooth interpolation between coupled cluster doubles and projected BCS applied to the reduced BCS Hamiltonian

DOE Office of Scientific and Technical Information (OSTI.GOV)

Degroote, M.; Henderson, T. M.; Zhao, J.

We present a similarity transformation theory based on a polynomial form of a particle-hole pair excitation operator. In the weakly correlated limit, this polynomial becomes an exponential, leading to coupled cluster doubles. In the opposite strongly correlated limit, the polynomial becomes an extended Bessel expansion and yields the projected BCS wavefunction. In between, we interpolate using a single parameter. The e ective Hamiltonian is non-hermitian and this Polynomial Similarity Transformation Theory follows the philosophy of traditional coupled cluster, left projecting the transformed Hamiltonian onto subspaces of the Hilbert space in which the wave function variance is forced to be zero.more » Similarly, the interpolation parameter is obtained through minimizing the next residual in the projective hierarchy. We rationalize and demonstrate how and why coupled cluster doubles is ill suited to the strongly correlated limit whereas the Bessel expansion remains well behaved. The model provides accurate wave functions with energy errors that in its best variant are smaller than 1% across all interaction stengths. The numerical cost is polynomial in system size and the theory can be straightforwardly applied to any realistic Hamiltonian.« less

Noncoding origins of anthropoid traits and a new null model of transposon functionalization

PubMed Central

del Rosario, Ricardo C.H.; Rayan, Nirmala Arul

2014-01-01

Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions and confirmed their robust functional signatures. Of the ASC base pairs, 99.7% were noncoding, suggesting that novel anthropoid functional elements were overwhelmingly cis-regulatory. ASCs were highly enriched in loci associated with fetal brain development, motor coordination, neurotransmission, and vision, thus providing a large set of candidate elements for exploring the molecular basis of hallmark primate traits. We validated ASC192 as a primate-specific enhancer in proliferative zones of the developing brain. Unexpectedly, transposable elements (TEs) contributed to >56% of ASCs, and almost all TE families showed functional potential similar to that of nonrepetitive DNA. Three L1PA repeat-derived ASCs displayed coherent eye-enhancer function, thus demonstrating that the “gene-battery” model of TE functionalization applies to enhancers in vivo. Our study provides fundamental insights into genome evolution and the origins of anthropoid phenotypes and supports an elegantly simple new null model of TE exaptation. PMID:25043600

Four-point functions and the permutation group S4

NASA Astrophysics Data System (ADS)

Eichmann, Gernot; Fischer, Christian S.; Heupel, Walter

2015-09-01

Four-point functions are at the heart of many interesting physical processes. A prime example is the light-by-light scattering amplitude, which plays an important role in the calculation of hadronic contributions to the anomalous magnetic moment of the muon. In the calculation of such quantities one faces the challenge of finding a suitable and well-behaved basis of tensor structures in coordinate and/or momentum space. Provided all (or many) of the external legs represent similar particle content, a powerful tool to construct and organize such bases is the permutation group S4. We introduce an efficient notation for dealing with the irreducible multiplets of S4, and we highlight the merits of this treatment by exemplifying four-point functions with gauge-boson legs such as the four-gluon vertex and the light-by-light scattering amplitude. The multiplet analysis is also useful for isolating the important kinematic regions and the dynamical singularity content of such amplitudes. Our analysis serves as a basis for future efficient calculations of these and similar objects.

Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks

DOE PAGES

Zhao, Suwen; Sakai, Ayano; Zhang, Xinshuai; ...

2014-06-30

Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins inmore » 12 families in the PRS that represent ~85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.« less

Social networks uncovered: 10 tips every plastic surgeon should know.

PubMed

Dauwe, Phillip; Heller, Justin B; Unger, Jacob G; Graham, Darrell; Rohrich, Rod J

2012-11-01

Understanding online social networks is of critical importance to the plastic surgeon. With knowledge, it becomes apparent that the numerous networks available are similar in their structure, usage, and function. The key is communication between Internet media such that one maximizes exposure to patients. This article focuses on 2 social networking platforms that we feel provide the most utility to plastic surgeons. Ten tips are provided for incorporation of Facebook and Twitter into your practice.

Sequence information signal processor for local and global string comparisons

DOEpatents

Peterson, John C.; Chow, Edward T.; Waterman, Michael S.; Hunkapillar, Timothy J.

1997-01-01

A sequence information signal processing integrated circuit chip designed to perform high speed calculation of a dynamic programming algorithm based upon the algorithm defined by Waterman and Smith. The signal processing chip of the present invention is designed to be a building block of a linear systolic array, the performance of which can be increased by connecting additional sequence information signal processing chips to the array. The chip provides a high speed, low cost linear array processor that can locate highly similar global sequences or segments thereof such as contiguous subsequences from two different DNA or protein sequences. The chip is implemented in a preferred embodiment using CMOS VLSI technology to provide the equivalent of about 400,000 transistors or 100,000 gates. Each chip provides 16 processing elements, and is designed to provide 16 bit, two's compliment operation for maximum score precision of between -32,768 and +32,767. It is designed to provide a comparison between sequences as long as 4,194,304 elements without external software and between sequences of unlimited numbers of elements with the aid of external software. Each sequence can be assigned different deletion and insertion weight functions. Each processor is provided with a similarity measure device which is independently variable. Thus, each processor can contribute to maximum value score calculation using a different similarity measure.

Geometric comparison of popular mixture-model distances.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitchell, Scott A.

2010-09-01

Statistical Latent Dirichlet Analysis produces mixture model data that are geometrically equivalent to points lying on a regular simplex in moderate to high dimensions. Numerous other statistical models and techniques also produce data in this geometric category, even though the meaning of the axes and coordinate values differs significantly. A distance function is used to further analyze these points, for example to cluster them. Several different distance functions are popular amongst statisticians; which distance function is chosen is usually driven by the historical preference of the application domain, information-theoretic considerations, or by the desirability of the clustering results. Relatively littlemore » consideration is usually given to how distance functions geometrically transform data, or the distances algebraic properties. Here we take a look at these issues, in the hope of providing complementary insight and inspiring further geometric thought. Several popular distances, {chi}{sup 2}, Jensen - Shannon divergence, and the square of the Hellinger distance, are shown to be nearly equivalent; in terms of functional forms after transformations, factorizations, and series expansions; and in terms of the shape and proximity of constant-value contours. This is somewhat surprising given that their original functional forms look quite different. Cosine similarity is the square of the Euclidean distance, and a similar geometric relationship is shown with Hellinger and another cosine. We suggest a geodesic variation of Hellinger. The square-root projection that arises in Hellinger distance is briefly compared to standard normalization for Euclidean distance. We include detailed derivations of some ratio and difference bounds for illustrative purposes. We provide some constructions that nearly achieve the worst-case ratios, relevant for contours.« less

Visual management of large scale data mining projects.

PubMed

Shah, I; Hunter, L

2000-01-01

This paper describes a unified framework for visualizing the preparations for, and results of, hundreds of machine learning experiments. These experiments were designed to improve the accuracy of enzyme functional predictions from sequence, and in many cases were successful. Our system provides graphical user interfaces for defining and exploring training datasets and various representational alternatives, for inspecting the hypotheses induced by various types of learning algorithms, for visualizing the global results, and for inspecting in detail results for specific training sets (functions) and examples (proteins). The visualization tools serve as a navigational aid through a large amount of sequence data and induced knowledge. They provided significant help in understanding both the significance and the underlying biological explanations of our successes and failures. Using these visualizations it was possible to efficiently identify weaknesses of the modular sequence representations and induction algorithms which suggest better learning strategies. The context in which our data mining visualization toolkit was developed was the problem of accurately predicting enzyme function from protein sequence data. Previous work demonstrated that approximately 6% of enzyme protein sequences are likely to be assigned incorrect functions on the basis of sequence similarity alone. In order to test the hypothesis that more detailed sequence analysis using machine learning techniques and modular domain representations could address many of these failures, we designed a series of more than 250 experiments using information-theoretic decision tree induction and naive Bayesian learning on local sequence domain representations of problematic enzyme function classes. In more than half of these cases, our methods were able to perfectly discriminate among various possible functions of similar sequences. We developed and tested our visualization techniques on this application.

Modeling mixtures of thyroid gland function disruptors in a vertebrate alternative model, the zebrafish eleutheroembryo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thienpont, Benedicte; Barata, Carlos; Raldúa, Demetrio, E-mail: drpqam@cid.csic.es

2013-06-01

Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable alternative model for screening chemicals impairing the thyroid hormone synthesis. The present study usedmore » the intrafollicular T4-content (IT4C) of zebrafish eleutheroembryos as integrative endpoint for testing the hypotheses that the effect of mixtures of TGFDs with a similar mode of action [inhibition of thyroid peroxidase (TPO)] was well predicted by a concentration addition concept (CA) model, whereas the response addition concept (RA) model predicted better the effect of dissimilarly acting binary mixtures of TGFDs [TPO-inhibitors and sodium-iodide symporter (NIS)-inhibitors]. However, CA model provided better prediction of joint effects than RA in five out of the six tested mixtures. The exception being the mixture MMI (TPO-inhibitor)-KClO{sub 4} (NIS-inhibitor) dosed at a fixed ratio of EC{sub 10} that provided similar CA and RA predictions and hence it was difficult to get any conclusive result. There results support the phenomenological similarity criterion stating that the concept of concentration addition could be extended to mixture constituents having common apical endpoints or common adverse outcomes. - Highlights: • Potential synergic or additive effect of mixtures of chemicals on thyroid function. • Zebrafish as alternative model for testing the effect of mixtures of goitrogens. • Concentration addition seems to predict better the effect of mixtures of goitrogens.« less

Rebelling for a Reason: Protein Structural “Outliers”

PubMed Central

Arumugam, Gandhimathi; Nair, Anu G.; Hariharaputran, Sridhar; Ramanathan, Sowdhamini

2013-01-01

Analysis of structural variation in domain superfamilies can reveal constraints in protein evolution which aids protein structure prediction and classification. Structure-based sequence alignment of distantly related proteins, organized in PASS2 database, provides clues about structurally conserved regions among different functional families. Some superfamily members show large structural differences which are functionally relevant. This paper analyses the impact of structural divergence on function for multi-member superfamilies, selected from the PASS2 superfamily alignment database. Functional annotations within superfamilies, with structural outliers or ‘rebels’, are discussed in the context of structural variations. Overall, these data reinforce the idea that functional similarities cannot be extrapolated from mere structural conservation. The implication for fold-function prediction is that the functional annotations can only be inherited with very careful consideration, especially at low sequence identities. PMID:24073209

Retrieving cirrus microphysical properties from stellar aureoles

NASA Astrophysics Data System (ADS)

DeVore, J. G.; Kristl, J. A.; Rappaport, S. A.

2013-06-01

The aureoles around stars caused by thin cirrus limit nighttime measurement opportunities for ground-based astronomy, but can provide information on high-altitude ice crystals for climate research. In this paper we attempt to demonstrate quantitatively how this works. Aureole profiles can be followed out to ~0.2° from stars and ~0.5° from Jupiter. Interpretation of diffracted starlight is similar to that for sunlight, but emphasizes larger particles. Stellar diffraction profiles are very distinctive, typically being approximately flat out to a critical angle followed by gradually steepening power-law falloff with slope less steep than -3. Using the relationship between the phase function for diffraction and the average Fourier transform of the projected area of complex ice crystals, we show that defining particle size in terms of average projected area normal to the propagation direction of the starlight leads to a simple, analytic approximation representing large-particle diffraction that is nearly independent of crystal habit. A similar analytic approximation for the diffraction aureole allows it to be separated from the point spread function and the sky background. Multiple scattering is deconvolved using the Hankel transform leading to the diffraction phase function. Application of constrained numerical inversion to the phase function then yields a solution for the particle size distribution in the range between ~50 μm and ~400 μm. Stellar aureole measurements can provide one of the very few, as well as least expensive, methods for retrieving cirrus microphysical properties from ground-based observations.

Obesity-Induced Dysfunctions in Female Reproduction: Lessons from Birds and Mammals123

PubMed Central

Walzem, Rosemary L.; Chen, Shuen-ei

2014-01-01

Follicle wall rupture and ovum release, i.e., ovulation, has been described as a controlled inflammatory event. The process involves tissue remodeling achieved through leukocyte-mediated proteolysis. In birds, ovulation is the first step in the energy-intensive process of egg formation, yet hens that consume energy in excess of productive requirements experience impaired egg-laying ability. Broiler chickens, selected for rapid lean muscle gain, and coincidentally hyperphagia, develop adult obesity when given free access to feed. Obese broiler hens experience elevated circulating concentrations of insulin and leptin, changes in lipid and lipoprotein metabolism similar to those of human metabolic syndrome, as well as increased systemic inflammation. Overall, the manifestations in poultry are similar to those of women with polycystic ovary syndrome. It was shown recently that, in hens, as in mammals, changes in lipid synthesis and metabolism cause granulosa cell apoptosis and altered immune function and hormone production, further compromising ovarian function. To date, there is insufficient information on the means used by the ovary to direct leukocyte function toward successful ovulation. More information is needed regarding the control of proteolytic actions by leukocytes with regards to the roles of specific enzymes in both ovulation and atresia. The broiler hen has provided unique insight into the interrelations of energy intake, obesity, leukocyte function, and reproduction. Additional work with this model can serve the dual purposes of improving avian reproduction and providing novel insights into polycystic ovary syndrome in women. PMID:24618762

Important Functional Roles of Basigin in Thymocyte Development and T cell Activation

PubMed Central

Yao, Hui; Teng, Yan; Sun, Qian; Xu, Jing; Chen, Ya-Tong; Hou, Ning; Cheng, Xuan; Yang, Xiao; Chen, Zhi-Nan

2014-01-01

Basigin is a highly glycosylated transmembrane protein that is expressed in a broad range of tissues and is involved in a number of physiological and pathological processes. However, the in vivo role of basigin remains unknown. To better understand the physiological and pathological functions of basigin in vivo, we generated a conditional null allele by introducing two loxP sites flanking exons 2 and 7 of the basigin gene (Bsg). Bsgfl/fl mice were born at the expected Mendelian ratio and showed a similar growth rate compared with wildtype mice. After crossing these mice with Lck-Cre transgenic mice, basigin expression was specifically inactivated in T cells in the resulting Lck-Cre; Bsgfl/fl mice. Although the birth and growth rate of Lck-Cre; Bsgfl/fl mice were similar to control mice, thymus development was partially arrested in Lck-Cre; Bsgfl/fl mice, specifically at the CD4+CD8+ double-positive (DP) and CD4 single-positive (CD4+CD8-, CD4SP) stages. In addition, CD4+ T cell activation was enhanced upon Concanavalin A (Con A) or anti-CD3/anti-CD28 stimulation but not upon PMA/Ionomycin stimulation in the absence of basigin. Overall, this study provided the first in vivo evidence for the function of basigin in thymus development. Moreover, the successful generation of the conditional null basigin allele provides a useful tool for the study of distinct physiological or pathological functions of basigin in different tissues at different development stages. PMID:24391450

Human versus mouse eosinophils: "that which we call an eosinophil, by any other name would stain as red".

PubMed

Lee, James J; Jacobsen, Elizabeth A; Ochkur, Sergei I; McGarry, Michael P; Condjella, Rachel M; Doyle, Alfred D; Luo, Huijun; Zellner, Katie R; Protheroe, Cheryl A; Willetts, Lian; Lesuer, William E; Colbert, Dana C; Helmers, Richard A; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A

2012-09-01

The respective life histories of human subjects and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiologic pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils, their effector functions, or both. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide experimental details comparing and contrasting eosinophils and eosinophil effector functions in human subjects versus mice. In particular, our review will provide a summation and an easy-to-use reference guide to important studies demonstrating that although differences exist, more often than not, their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function but instead species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Networks of plants: how to measure similarity in vegetable species.

PubMed

Vivaldo, Gianna; Masi, Elisa; Pandolfi, Camilla; Mancuso, Stefano; Caldarelli, Guido

2016-06-07

Despite the common misconception of nearly static organisms, plants do interact continuously with the environment and with each other. It is fair to assume that during their evolution they developed particular features to overcome similar problems and to exploit possibilities from environment. In this paper we introduce various quantitative measures based on recent advancements in complex network theory that allow to measure the effective similarities of various species. By using this approach on the similarity in fruit-typology ecological traits we obtain a clear plant classification in a way similar to traditional taxonomic classification. This result is not trivial, since a similar analysis done on the basis of diaspore morphological properties do not provide any clear parameter to classify plants species. Complex network theory can then be used in order to determine which feature amongst many can be used to distinguish scope and possibly evolution of plants. Future uses of this approach range from functional classification to quantitative determination of plant communities in nature.

Current challenges in genome annotation through structural biology and bioinformatics.

PubMed

Furnham, Nicholas; de Beer, Tjaart A P; Thornton, Janet M

2012-10-01

With the huge volume in genomic sequences being generated from high-throughout sequencing projects the requirement for providing accurate and detailed annotations of gene products has never been greater. It is proving to be a huge challenge for computational biologists to use as much information as possible from experimental data to provide annotations for genome data of unknown function. A central component to this process is to use experimentally determined structures, which provide a means to detect homology that is not discernable from just the sequence and permit the consequences of genomic variation to be realized at the molecular level. In particular, structures also form the basis of many bioinformatics methods for improving the detailed functional annotations of enzymes in combination with similarities in sequence and chemistry. Copyright © 2012. Published by Elsevier Ltd.

Space Physiology Studies

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Ballard, R. E.; Boda, W. L.; Ertl, A. C.; Schneider, S. M.; Hutchinson, K. J.; Lee, S. M.; Murthy, G.; Putcha, L.; Watenpaugh, D. E.

1999-01-01

Calculations suggest that exercise in space to date has lacked sufficient loads to maintain musculoskeletal mass. Lower body negative pressure (LBNP) produces a force at the feet equal to the product of the LBNP and body cross-sectional area at the waist. Supine exercise within 50-60 mm Hg LBNP improves tolerance to LBNP and produces forces similar to those occurring during upright posture on Earth. Thus, exercise within LBNP may help prevent deconditioning of astronauts by stressing tissues of the lower body in a manner similar to gravity and also, may provide a safe and effective alternative to centrifugation in terms of cost, mass, volume, and power usage. We hypothesize that supine treadmill exercise during LBNP at one body weight (50-60 mm Hg LBNP) will provide cardiovascular and musculoskeletal loads similar to those experienced while upright in lg. Also, daily supine treadmill running in a LBNP chamber will maintain aerobic fitness, orthostatic tolerance, and musculoskeletal structure and function during bed rest (simulated microgravity).

The HMMER Web Server for Protein Sequence Similarity Search.

PubMed

Prakash, Ananth; Jeffryes, Matt; Bateman, Alex; Finn, Robert D

2017-12-08

Protein sequence similarity search is one of the most commonly used bioinformatics methods for identifying evolutionarily related proteins. In general, sequences that are evolutionarily related share some degree of similarity, and sequence-search algorithms use this principle to identify homologs. The requirement for a fast and sensitive sequence search method led to the development of the HMMER software, which in the latest version (v3.1) uses a combination of sophisticated acceleration heuristics and mathematical and computational optimizations to enable the use of profile hidden Markov models (HMMs) for sequence analysis. The HMMER Web server provides a common platform by linking the HMMER algorithms to databases, thereby enabling the search for homologs, as well as providing sequence and functional annotation by linking external databases. This unit describes three basic protocols and two alternate protocols that explain how to use the HMMER Web server using various input formats and user defined parameters. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Perceived Similarity With Gay Men Mediates the Effect of Antifemininity on Heterosexual Men's Antigay Prejudice.

PubMed

Martínez, Carmen; Vázquez, Carolina; Falomir-Pichastor, Juan Manuel

2015-01-01

This research examined the hypothesis that heterosexual men's motivation to differentiate themselves from gay men mediates the relationship between the antifemininity norm of masculinity and antigay prejudice. We assessed masculinity through three concepts: status, thoughness, and antifemininity. Participants then reported their perceived similarity with gay men and their antigay prejudice. The results showed that antifemininity was the best predictor of both perceived similarity and antigay prejudice: The more people endorsed the antifemininity norm, the more they perceived themselves as dissimilar from gay men and showed antigay prejudice. More important, perceived similarity mediated the effect of antifemininity on antigay prejudice. These findings provide direct evidence for the link between masculinity and the motivation to differentiate oneself from gay men, and they suggest that antigay prejudice accomplishes the identity function of maintaining unambiguous gender boundaries.

COGcollator: a web server for analysis of distant relationships between homologous protein families.

PubMed

Dibrova, Daria V; Konovalov, Kirill A; Perekhvatov, Vadim V; Skulachev, Konstantin V; Mulkidjanian, Armen Y

2017-11-29

The Clusters of Orthologous Groups (COGs) of proteins systematize evolutionary related proteins into specific groups with similar functions. However, the available databases do not provide means to assess the extent of similarity between the COGs. We intended to provide a method for identification and visualization of evolutionary relationships between the COGs, as well as a respective web server. Here we introduce the COGcollator, a web tool for identification of evolutionarily related COGs and their further analysis. We demonstrate the utility of this tool by identifying the COGs that contain distant homologs of (i) the catalytic subunit of bacterial rotary membrane ATP synthases and (ii) the DNA/RNA helicases of the superfamily 1. This article was reviewed by Drs. Igor N. Berezovsky, Igor Zhulin and Yuri Wolf.

The crystal structure of P450-TT heme-domain provides the first structural insights into the versatile class VII P450s.

PubMed

Tavanti, Michele; Porter, Joanne L; Levy, Colin W; Gómez Castellanos, J Rubén; Flitsch, Sabine L; Turner, Nicholas J

2018-07-02

The first crystal structure of a class VII P450, CYP116B46 from Tepidiphilus thermophilus, has been solved at 1.9 Å resolution. The structure reveals overall conservation of the P450-fold and a water conduit around the I-helix. Active site residues have been identified and sequence comparisons have been made with other class VII enzymes. A structure similarity search demonstrated that the P450-TT structure is similar to enzymes capable of oxy-functionalization of fatty acids, terpenes, macrolides, steroids and statins. The insight gained from solving this structure will provide a guideline for future engineering and modelling studies on this catalytically promiscuous class of enzymes. Copyright © 2018 Elsevier Inc. All rights reserved.

On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report

PubMed Central

Thomas, Paul D.; Wood, Valerie; Mungall, Christopher J.; Lewis, Suzanna E.; Blake, Judith A.

2012-01-01

A recent paper (Nehrt et al., PLoS Comput. Biol. 7:e1002073, 2011) has proposed a metric for the “functional similarity” between two genes that uses only the Gene Ontology (GO) annotations directly derived from published experimental results. Applying this metric, the authors concluded that paralogous genes within the mouse genome or the human genome are more functionally similar on average than orthologous genes between these genomes, an unexpected result with broad implications if true. We suggest, based on both theoretical and empirical considerations, that this proposed metric should not be interpreted as a functional similarity, and therefore cannot be used to support any conclusions about the “ortholog conjecture” (or, more properly, the “ortholog functional conservation hypothesis”). First, we reexamine the case studies presented by Nehrt et al. as examples of orthologs with divergent functions, and come to a very different conclusion: they actually exemplify how GO annotations for orthologous genes provide complementary information about conserved biological functions. We then show that there is a global ascertainment bias in the experiment-based GO annotations for human and mouse genes: particular types of experiments tend to be performed in different model organisms. We conclude that the reported statistical differences in annotations between pairs of orthologous genes do not reflect differences in biological function, but rather complementarity in experimental approaches. Our results underscore two general considerations for researchers proposing novel types of analysis based on the GO: 1) that GO annotations are often incomplete, potentially in a biased manner, and subject to an “open world assumption” (absence of an annotation does not imply absence of a function), and 2) that conclusions drawn from a novel, large-scale GO analysis should whenever possible be supported by careful, in-depth examination of examples, to help ensure the conclusions have a justifiable biological basis. PMID:22359495

Advanced lesion symptom mapping analyses and implementation as BCBtoolkit

PubMed Central

Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika

2018-01-01

Abstract Background Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Findings Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. Conclusions The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1]. PMID:29432527

The functional cancer map: a systems-level synopsis of genetic deregulation in cancer.

PubMed

Krupp, Markus; Maass, Thorsten; Marquardt, Jens U; Staib, Frank; Bauer, Tobias; König, Rainer; Biesterfeld, Stefan; Galle, Peter R; Tresch, Achim; Teufel, Andreas

2011-06-30

Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies. Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors. We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'. The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.

12 CFR 561.4 - Affiliate.

Code of Federal Regulations, 2010 CFR

2010-01-01

... other persons exercising similar functions at the preceding election, or controls in any manner the election of a majority of its directors, trustees, or other persons exercising similar functions; or (b) Of... exercising similar functions are directors of any one savings association. ...

[Architecture of receptor-operated ionic channels of biological membranes].

PubMed

Bregestovski, P D

2011-01-01

Ion channels of biological membranes are the key proteins, which provide bioelectric functioning of living systems. These proteins are homo- or heterooligomers assembled from several identical or different subunits. Understanding the architectural organization and functioning of ion channels has been significantly extended due to resolving the crystal structure of several types of voltage-gated and receptor-operated channels. This review summarizes the information obtained from crystal structures of potassium, nicotinic acetylcholine receptor, P2X, and other ligand-gated ion channels. Despite the differences in the function, topology, ionic selectivity, and the subunit stoichiometry, a high similarity in the principles of organization of these macromolecular complexes has been revealed.

The fractal geometry of life.

PubMed

Losa, Gabriele A

2009-01-01

The extension of the concepts of Fractal Geometry (Mandelbrot [1983]) toward the life sciences has led to significant progress in understanding complex functional properties and architectural / morphological / structural features characterising cells and tissues during ontogenesis and both normal and pathological development processes. It has even been argued that fractal geometry could provide a coherent description of the design principles underlying living organisms (Weibel [1991]). Fractals fulfil a certain number of theoretical and methodological criteria including a high level of organization, shape irregularity, functional and morphological self-similarity, scale invariance, iterative pathways and a peculiar non-integer fractal dimension [FD]. Whereas mathematical objects are deterministic invariant or self-similar over an unlimited range of scales, biological components are statistically self-similar only within a fractal domain defined by upper and lower limits, called scaling window, in which the relationship between the scale of observation and the measured size or length of the object can be established (Losa and Nonnenmacher [1996]). Selected examples will contribute to depict complex biological shapes and structures as fractal entities, and also to show why the application of the fractal principle is valuable for measuring dimensional, geometrical and functional parameters of cells, tissues and organs occurring within the vegetal and animal realms. If the criteria for a strict description of natural fractals are met, then it follows that a Fractal Geometry of Life may be envisaged and all natural objects and biological systems exhibiting self-similar patterns and scaling properties may be considered as belonging to the new subdiscipline of "fractalomics".

Degree Audit Systems: Are They Worth It?

ERIC Educational Resources Information Center

Johns, Virginia

2006-01-01

A lot of various degree audit systems are available on the market and most often they have similar features such as the functionality they each provide, the technical platforms upon which they operate, their requirements for interfacing with the local SIS, the ease of use, and the level of effort required to implement and operate. However, the…

In Situ Grafting of Hyperbranched Poly(Etherketone)s onto Multiwalled Carbon Nanotubes Via A3 + B2 Approach (Preprint)

DTIC Science & Technology

2007-04-01

MWNTs.20 These defects would provide sites for the electrophilic substitution reaction. In our previous work, FT-IR had been used to characterize the...various surface functionalities.22 In this study, MWNTs containing polar surface groups such as amino-, hydroxyl-, and fluorine groups displayed similar

Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

PubMed Central

Stark, Alexander; Lin, Michael F.; Kheradpour, Pouya; Pedersen, Jakob S.; Parts, Leopold; Carlson, Joseph W.; Crosby, Madeline A.; Rasmussen, Matthew D.; Roy, Sushmita; Deoras, Ameya N.; Ruby, J. Graham; Brennecke, Julius; Hodges, Emily; Hinrichs, Angie S.; Caspi, Anat; Paten, Benedict; Park, Seung-Won; Han, Mira V.; Maeder, Morgan L.; Polansky, Benjamin J.; Robson, Bryanne E.; Aerts, Stein; van Helden, Jacques; Hassan, Bassem; Gilbert, Donald G.; Eastman, Deborah A.; Rice, Michael; Weir, Michael; Hahn, Matthew W.; Park, Yongkyu; Dewey, Colin N.; Pachter, Lior; Kent, W. James; Haussler, David; Lai, Eric C.; Bartel, David P.; Hannon, Gregory J.; Kaufman, Thomas C.; Eisen, Michael B.; Clark, Andrew G.; Smith, Douglas; Celniker, Susan E.; Gelbart, William M.; Kellis, Manolis

2008-01-01

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or ‘evolutionary signatures’, dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies. PMID:17994088

Framework for robot skill learning using reinforcement learning

NASA Astrophysics Data System (ADS)

Wei, Yingzi; Zhao, Mingyang

2003-09-01

Robot acquiring skill is a process similar to human skill learning. Reinforcement learning (RL) is an on-line actor critic method for a robot to develop its skill. The reinforcement function has become the critical component for its effect of evaluating the action and guiding the learning process. We present an augmented reward function that provides a new way for RL controller to incorporate prior knowledge and experience into the RL controller. Also, the difference form of augmented reward function is considered carefully. The additional reward beyond conventional reward will provide more heuristic information for RL. In this paper, we present a strategy for the task of complex skill learning. Automatic robot shaping policy is to dissolve the complex skill into a hierarchical learning process. The new form of value function is introduced to attain smooth motion switching swiftly. We present a formal, but practical, framework for robot skill learning and also illustrate with an example the utility of method for learning skilled robot control on line.

Functional variability of habitats within the Sacramento-San Joaquin Delta: Restoration implications

USGS Publications Warehouse

Lucas, L.V.; Cloern, J.E.; Thompson, J.K.; Monsen, N.E.

2002-01-01

We have now entered an era of large-scale attempts to restore ecological functions and biological communities in impaired ecosystems. Our knowledge base of complex ecosystems and interrelated functions is limited, so the outcomes of specific restoration actions are highly uncertain. One approach for exploring that uncertainty and anticipating the range of possible restoration outcomes is comparative study of existing habitats similar to future habitats slated for construction. Here we compare two examples of one habitat type targeted for restoration in the Sacramento-San Joaquin River Delta. We compare one critical ecological function provided by these shallow tidal habitats - production and distribution of phytoplankton biomass as the food supply to pelagic consumers. We measured spatial and short-term temporal variability of phytoplankton biomass and growth rate and quantified the hydrodynamic and biological processes governing that variability. Results show that the production and distribution of phytoplankton biomass can be highly variable within and between nearby habitats of the same type, due to variations in phytoplankton sources, sinks, and transport. Therefore, superficially similar, geographically proximate habitats can function very differently, and that functional variability introduces large uncertainties into the restoration process. Comparative study of existing habitats is one way ecosystem science can elucidate and potentially minimize restoration uncertainties, by identifying processes shaping habitat functionality, including those that can be controlled in the restoration design.

The Orphan Nuclear Receptors at Their 25th Year Reunion

PubMed Central

Mullican, Shannon E.; DiSpirito, Joanna R.; Lazar, Mitchell A.

2013-01-01

The Nuclear Receptor superfamily includes many receptors identified based on their similarity to steroid hormone receptors but without a known ligand. The study of how these receptors are diversely regulated to interact with genomic regions to control a plethora of biological processes has provided critical insight into development, physiology and the molecular pathology of disease. Here we provide a compendium of these so-called Orphan Receptors, and focus on what has been learned about their modes of action, physiological functions, and therapeutic promise. PMID:24096517

[Principles of management in biological infections].

PubMed

Płusa, Tadeusz

2012-11-01

The effectiveness of the management in respiratory infection is depending on the nature of the biological pathogen and the immune status of the patient. For this reason, providing assistance to victims the organ function support, similarly as defining the pathogen and targeted antibiotic therapy should be applied. Available diagnostic tests provide rapid ability to identify the pathogen and antibiotics are able to control infection. Lack of efficacy of treatment may indicate the diversity of the pathogen than previously known and raises suspicion of biological warfare pathogen.

Determination of Flower Structure in Elaeis guineensis: Do Palms use the Same Homeotic Genes as Other Species?

PubMed Central

Adam, Helene; Jouannic, Stefan; Morcillo, Fabienne; Verdeil, Jean-Luc; Duval, Yves; Tregear, James W.

2007-01-01

Aims In this article a review is made of data recently obtained on the structural diversity and possible functions of MADS box genes in the determination of flower structure in the African oil palm (Elaeis guineensis). MADS box genes play a dominant role in the ABC model established to explain how floral organ identity is determined in model dicotyledon species such as Arabidopsis thaliana and Antirrhinum majus. In the monocotyledons, although there appears to be a broad general conservation of ABC gene functions, the model itself needs to be adapted in some cases, notably for certain species which produce flowers with sepals and petals of similar appearance. For the moment, ABC genes remain unstudied in a number of key monocot clades, so only a partial picture is available for the Liliopsida as a whole. The aim of this article is to summarize data recently obtained for the African oil palm Elaeis guineensis, a member of the family Arecaceae (Arecales), and to discuss their significance with respect to knowledge gained from other Angiosperm groups, particularly within the monocotyledons. Scope The essential details of reproductive development in oil palm are discussed and an overview is provided of the structural and functional characterization of MADS box genes likely to play a homeotic role in flower development in this species. Conclusions The structural and functional data provide evidence for a general conservation of the generic ‘ABC’ model in oil palm, rather than the ‘modified ABC model’ proposed for some other monocot species which produce homochlamydeous flowers (i.e. with morphologically similar organs in both perianth whorls), such as members of the Liliales. Our oil palm data therefore follow a similar pattern to those obtained for other Commelinid species in the orders Commelinales and Poales. The significance of these findings is discussed. PMID:17355996

Fast and accurate non-sequential protein structure alignment using a new asymmetric linear sum assignment heuristic.

PubMed

Brown, Peter; Pullan, Wayne; Yang, Yuedong; Zhou, Yaoqi

2016-02-01

The three dimensional tertiary structure of a protein at near atomic level resolution provides insight alluding to its function and evolution. As protein structure decides its functionality, similarity in structure usually implies similarity in function. As such, structure alignment techniques are often useful in the classifications of protein function. Given the rapidly growing rate of new, experimentally determined structures being made available from repositories such as the Protein Data Bank, fast and accurate computational structure comparison tools are required. This paper presents SPalignNS, a non-sequential protein structure alignment tool using a novel asymmetrical greedy search technique. The performance of SPalignNS was evaluated against existing sequential and non-sequential structure alignment methods by performing trials with commonly used datasets. These benchmark datasets used to gauge alignment accuracy include (i) 9538 pairwise alignments implied by the HOMSTRAD database of homologous proteins; (ii) a subset of 64 difficult alignments from set (i) that have low structure similarity; (iii) 199 pairwise alignments of proteins with similar structure but different topology; and (iv) a subset of 20 pairwise alignments from the RIPC set. SPalignNS is shown to achieve greater alignment accuracy (lower or comparable root-mean squared distance with increased structure overlap coverage) for all datasets, and the highest agreement with reference alignments from the challenging dataset (iv) above, when compared with both sequentially constrained alignments and other non-sequential alignments. SPalignNS was implemented in C++. The source code, binary executable, and a web server version is freely available at: http://sparks-lab.org yaoqi.zhou@griffith.edu.au. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Functional connectivity experiments reflect routine movement behavior of a tropical hummingbird species.

PubMed

Volpe, Noelia L; Hadley, Adam S; Robinson, W Douglas; Betts, Matthew G

Translocation experiments, in which researchers displace animals and then monitor their movements to return home, are commonly used as tools to assess functional connectivity of fragmented landscapes. Such experiments are purported to have important advantages of being time efficient and of standardizing “motivation” to move across individuals. Yet, we lack tests of whether movement behavior of translocated birds reflects natural behavior of unmanipulated birds. We compared the routine movement behavior of a tropical hummingbird, the Green Hermit (Phaethornis guy), to that of experimentally translocated individuals. We tested for differences in site selection patterns during movement at two spatial scales (point and path levels). We also compared movement rates between treatments. Behaviors documented during translocation experiments reflected those observed during routine movements. At the point level, both translocated and non-translocated birds showed similar levels of preference for mature tropical forest. At the path level, step selection functions showed both translocated and non-translocated hummingbirds avoiding movement across non-forested matrix and selecting streams as movement corridors. Movement rates were generally higher during translocation experiments. However, the negative influence of forest cover on movement rates was proportionately similar in translocation and routine movement treatments. We report the first evidence showing that movement behavior of birds during translocation experiments is similar to their natural movement behavior. Therefore, translocation experiments may be reliable tools to address effects of landscape structure on animal movement. We observed consistent selection of landscape elements between translocated and non-translocated birds, indicating that both routine and translocation movement studies lead to similar conclusions regarding the effect of landscape structure and forest composition on functional connectivity. Our observation that hummingbirds avoid non-forest matrix and select riparian corridors also provides a potential mechanism for pollen limitation in fragmented tropical forest.

The time course of spoken word learning and recognition: studies with artificial lexicons.

PubMed

Magnuson, James S; Tanenhaus, Michael K; Aslin, Richard N; Dahan, Delphine

2003-06-01

The time course of spoken word recognition depends largely on the frequencies of a word and its competitors, or neighbors (similar-sounding words). However, variability in natural lexicons makes systematic analysis of frequency and neighbor similarity difficult. Artificial lexicons were used to achieve precise control over word frequency and phonological similarity. Eye tracking provided time course measures of lexical activation and competition (during spoken instructions to perform visually guided tasks) both during and after word learning, as a function of word frequency, neighbor type, and neighbor frequency. Apparent shifts from holistic to incremental competitor effects were observed in adults and neural network simulations, suggesting such shifts reflect general properties of learning rather than changes in the nature of lexical representations.

Metabolic Rate Regulation by the Renin-Angiotensin System: Brain vs. Body

PubMed Central

Grobe, Justin L.; Rahmouni, Kamal; Liu, Xuebo; Sigmund, Curt D.

2013-01-01

Substantial evidence supports a role for the renin-angiotensin system (RAS) in the regulation of metabolic function, but an apparent paradox exists where genetic or pharmacological inhibition of the RAS occasionally have similar physiological effects as chronic angiotensin infusion. Similarly, while RAS targeting in animal models has robust metabolic consequences, effects in humans are more subtle. Here we review the data supporting a role for the RAS in metabolic rate regulation and propose a model where the local brain RAS works in opposition to the peripheral RAS, thus helping to explain the paradoxically similar effects of RAS supplementation and inhibition. Selectively modulating the peripheral RAS or brain RAS may thus provide a more effective treatment paradigm for obesity and obesity-related disorders. PMID:22491893

Comparable polyfunctionality of ectromelia virus- and vaccinia virus-specific murine T cells despite markedly different in vivo replication and pathogenicity.

PubMed

Hersperger, Adam R; Siciliano, Nicholas A; Eisenlohr, Laurence C

2012-07-01

Vaccinia virus (VACV) stimulates long-term immunity against highly pathogenic orthopoxvirus infection of humans (smallpox) and mice (mousepox [ectromelia virus {ECTV}]) despite the lack of a natural host-pathogen relationship with either of these species. Previous research revealed that VACV is able to induce polyfunctional CD8(+) T-cell responses after immunization of humans. However, the degree to which the functional profile of T cells induced by VACV is similar to that generated during natural poxvirus infection remains unknown. In this study, we monitored virus-specific T-cell responses following the dermal infection of C57BL/6 mice with ECTV or VACV. Using polychromatic flow cytometry, we measured levels of degranulation, cytokine expression (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]), and the cytolytic mediator granzyme B. We observed that the functional capacities of T cells induced by VACV and ECTV were of a similar quality in spite of the markedly different replication abilities and pathogenic outcomes of these viruses. In general, a significant fraction (≥50%) of all T-cell responses were positive for at least three functions both during acute infection and into the memory phase. In vivo killing assays revealed that CD8(+) T cells specific for both viruses were equally cytolytic (∼80% target cell lysis after 4 h), consistent with the similar levels of granzyme B and degranulation detected among these cells. Collectively, these data provide a mechanism to explain the ability of VACV to induce protective T-cell responses against pathogenic poxviruses in their natural hosts and provide further support for the use of VACV as a vaccine platform able to induce polyfunctional T cells.

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

PubMed Central

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-01-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method. PMID:24887553

Improving the Glucose Meter Error Grid With the Taguchi Loss Function.

PubMed

Krouwer, Jan S

2016-07-01

Glucose meters often have similar performance when compared by error grid analysis. This is one reason that other statistics such as mean absolute relative deviation (MARD) are used to further differentiate performance. The problem with MARD is that too much information is lost. But additional information is available within the A zone of an error grid by using the Taguchi loss function. Applying the Taguchi loss function gives each glucose meter difference from reference a value ranging from 0 (no error) to 1 (error reaches the A zone limit). Values are averaged over all data which provides an indication of risk of an incorrect medical decision. This allows one to differentiate glucose meter performance for the common case where meters have a high percentage of values in the A zone and no values beyond the B zone. Examples are provided using simulated data. © 2015 Diabetes Technology Society.

Postfragmentation density function for bacterial aggregates in laminar flow

PubMed Central

Byrne, Erin; Dzul, Steve; Solomon, Michael; Younger, John

2014-01-01

The postfragmentation probability density of daughter flocs is one of the least well-understood aspects of modeling flocculation. We use three-dimensional positional data of Klebsiella pneumoniae bacterial flocs in suspension and the knowledge of hydrodynamic properties of a laminar flow field to construct a probability density function of floc volumes after a fragmentation event. We provide computational results which predict that the primary fragmentation mechanism for large flocs is erosion. The postfragmentation probability density function has a strong dependence on the size of the original floc and indicates that most fragmentation events result in clumps of one to three bacteria eroding from the original floc. We also provide numerical evidence that exhaustive fragmentation yields a limiting density inconsistent with the log-normal density predicted in the literature, most likely due to the heterogeneous nature of K. pneumoniae flocs. To support our conclusions, artificial flocs were generated and display similar postfragmentation density and exhaustive fragmentation. PMID:21599205

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

NASA Astrophysics Data System (ADS)

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-06-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.

Awareness of Age-Related Change: Examination of a (Mostly) Unexplored Concept

PubMed Central

Wahl, Hans-Werner

2010-01-01

This theoretical article discusses the emerging concept of awareness of age-related change (AARC). We propose that a focus on AARC extends the research traditions on subjective age experiences and age identity and that examination of this concept can serve a stimulating role in social gerontology. After defining and contrasting AARC against similar concepts, several reasons for the relevance of this mostly unexplored construct are provided. The sample domains of health and physical functioning, cognitive functioning, and interpersonal relations are used to illustrate the relevance of AARC. Based on this review, we then provide a heuristic framework that describes antecedents, processes, and outcomes related to AARC. Overall, we argue that research on AARC should become an integral part of social gerontological research. PMID:20008026

An evaluation of Skylab habitability hardware

NASA Technical Reports Server (NTRS)

Stokes, J.

1974-01-01

For effective mission performance, participants in space missions lasting 30-60 days or longer must be provided with hardware to accommodate their personal needs. Such habitability hardware was provided on Skylab. Equipment defined as habitability hardware was that equipment composing the food system, water system, sleep system, waste management system, personal hygiene system, trash management system, and entertainment equipment. Equipment not specifically defined as habitability hardware but which served that function were the Wardroom window, the exercise equipment, and the intercom system, which was occasionally used for private communications. All Skylab habitability hardware generally functioned as intended for the three missions, and most items could be considered as adequate concepts for future flights of similar duration. Specific components were criticized for their shortcomings.

CIPK9 is involved in seed oil regulation in Brassica napus L. and Arabidopsis thaliana (L.) Heynh.

PubMed

Guo, Yanli; Huang, Yi; Gao, Jie; Pu, Yuanyuan; Wang, Nan; Shen, Wenyun; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Zou, Jitao; Shen, Jinxiong

2018-01-01

Accumulation of storage compounds during seed development plays an important role in the life cycle of oilseed plants; these compounds provide carbon and energy resources to support the establishment of seedlings. In this study, we show that BnCIPK9 has a broad expression pattern in Brassica napus L. tissues and that wounding stress strongly induces its expression. The overexpression of BnCIPK9 during seed development reduced oil synthesis in transgenic B. napus compared to that observed in wild-type (WT) plants. Functional analysis revealed that seed oil content (OC) of complementation lines was similar to that of WT plants, whereas OC in Arabidopsis thaliana (L.) Heynh. Atcipk9 knockout mutants ( cipk9 ) was higher than that of WT plants. Seedling of cipk9 mutants failed to establish roots on a sugar-free medium, but root establishment could be rescued by supplementation of sucrose or glucose. The phenotype of complementation transgenic lines was similar to that of WT plants when grown on sugar-free medium. Mutants, cipk9 , cbl2 , and cbl3 presented similar phenotypes, suggesting that CIPK9, CBL2, and CBL3 might work together and play similar roles in root establishment under sugar-free condition. This study showed that BnCIPK9 and AtCIPK9 encode a protein kinase that is involved in sugar-related response and plays important roles in the regulation of energy reserves. Our results suggest that AtCIPK9 negatively regulates lipid accumulation and has a significant effect on early seedling establishment in A. thaliana . The functional characterization of CIPK9 provides insights into the regulation of OC, and might be used for improving OC in B. napus . We believe that our study makes a significant contribution to the literature because it provides information on how CIPKs coordinate stress regulation and energy signaling.

African Americans with LVH demonstrate depressed sensitivity of the coronary microcirculation to stimulated relaxation.

PubMed

Houghton, Jan Laws; Strogatz, David S; Torosoff, Mikhail T; Smith, Vivienne E; Fein, Steven A; Kuhner, Patricia A; Philbin, Edward F; Carr, Albert A

2003-09-01

Excess coronary heart disease morbidity and mortality among African Americans remains an important yet unexplained public health problem. We hypothesized that adverse outcome is in part due to intrinsic or acquired abnormalities in coronary endothelial function and vasoreactivity. We compared dose-response curves relating changes in coronary blood flow and epicardial diameter to graded infusions of acetylcholine in 50 African American and 65 white subjects with hypertensive left ventricular hypertrophy (LVH) and normal coronary arteries. These groups were similar for age, body mass index, mean arterial pressure, and indexed left ventricular mass. The same protocol was conducted in 24 normotensive African American and 56 similar white subjects. We found significant depression in the coronary blood flow dose-response curve relation among African Americans when compared with white subjects with similar LVH (P<0.03). Racial differences were observed at all doses of acetylcholine but were less precisely estimated at the highest dose. The same testing among normotensive subjects revealed similar dose-response curves with no significant effect of race. Qualitatively similar results were found with respect to coronary diameter. Adenosine responses, a measure of endothelium-independent function, were similar after partitioning by LVH. Our study demonstrates that there are racial differences in sensitivity of coronary arteries to acetylcholine-stimulated relaxation among those with LVH. These results provide a mechanism whereby racial differences in coronary vasoreactivity might contribute to adverse coronary heart disease outcome among African Americans, a group in whom LVH is prevalent.

Cryptic diversity in a fig wasp community-morphologically differentiated species are sympatric but cryptic species are parapatric.

PubMed

Darwell, C T; Cook, J M

2017-02-01

A key debate in ecology centres on the relative importance of niche and neutral processes in determining patterns of community assembly with particular focus on whether ecologically similar species with similar functional traits are able to coexist. Meanwhile, molecular studies are increasingly revealing morphologically indistinguishable cryptic species with presumably similar ecological roles. Determining the geographic distribution of such cryptic species provides opportunities to contrast predictions of niche vs. neutral models. Discovery of sympatric cryptic species increases alpha diversity and supports neutral models, while documentation of allopatric/parapatric cryptic species increases beta diversity and supports niche models. We tested these predictions using morphological and molecular data, coupled with environmental niche modelling analyses, of a fig wasp community along its 2700-km latitudinal range. Molecular methods increased previous species diversity estimates from eight to eleven species, revealing morphologically cryptic species in each of the four wasp genera studied. Congeneric species pairs that were differentiated by a key morphological functional trait (ovipositor length) coexisted sympatrically over large areas. In contrast, morphologically similar species, with similar ovipositor lengths, typically showed parapatric ranges with very little overlap. Despite parapatric ranges, environmental niche models of cryptic congeneric pairs indicate large regions of potential sympatry, suggesting that competitive processes are important in determining the distributions of ecologically similar species. Niche processes appear to structure this insect community, and cryptic diversity may typically contribute mostly to beta rather than alpha diversity. © 2016 John Wiley & Sons Ltd.

Step-by-step integration for fractional operators

NASA Astrophysics Data System (ADS)

Colinas-Armijo, Natalia; Di Paola, Mario

2018-06-01

In this paper, an approach based on the definition of the Riemann-Liouville fractional operators is proposed in order to provide a different discretisation technique as alternative to the Grünwald-Letnikov operators. The proposed Riemann-Liouville discretisation consists of performing step-by-step integration based upon the discretisation of the function f(t). It has been shown that, as f(t) is discretised as stepwise or piecewise function, the Riemann-Liouville fractional integral and derivative are governing by operators very similar to the Grünwald-Letnikov operators. In order to show the accuracy and capabilities of the proposed Riemann-Liouville discretisation technique and the Grünwald-Letnikov discrete operators, both techniques have been applied to: unit step functions, exponential functions and sample functions of white noise.

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

PubMed

Masi, Stefano; Georgiopoulos, Georgios; Khan, Tauseef; Johnson, William; Wong, Andrew; Charakida, Marietta; Whincup, Peter; Hughes, Alun D; Richards, Marcus; Hardy, Rebecca; Deanfield, John

2018-05-28

The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships.

Network-based function prediction and interactomics: the case for metabolic enzymes.

PubMed

Janga, S C; Díaz-Mejía, J Javier; Moreno-Hagelsieb, G

2011-01-01

As sequencing technologies increase in power, determining the functions of unknown proteins encoded by the DNA sequences so produced becomes a major challenge. Functional annotation is commonly done on the basis of amino-acid sequence similarity alone. Long after sequence similarity becomes undetectable by pair-wise comparison, profile-based identification of homologs can often succeed due to the conservation of position-specific patterns, important for a protein's three dimensional folding and function. Nevertheless, prediction of protein function from homology-driven approaches is not without problems. Homologous proteins might evolve different functions and the power of homology detection has already started to reach its maximum. Computational methods for inferring protein function, which exploit the context of a protein in cellular networks, have come to be built on top of homology-based approaches. These network-based functional inference techniques provide both a first hand hint into a proteins' functional role and offer complementary insights to traditional methods for understanding the function of uncharacterized proteins. Most recent network-based approaches aim to integrate diverse kinds of functional interactions to boost both coverage and confidence level. These techniques not only promise to solve the moonlighting aspect of proteins by annotating proteins with multiple functions, but also increase our understanding on the interplay between different functional classes in a cell. In this article we review the state of the art in network-based function prediction and describe some of the underlying difficulties and successes. Given the volume of high-throughput data that is being reported the time is ripe to employ these network-based approaches, which can be used to unravel the functions of the uncharacterized proteins accumulating in the genomic databases. © 2010 Elsevier Inc. All rights reserved.

Drug addiction and sexual dysfunction.

PubMed

Zaazaa, Adham; Bella, Anthony J; Shamloul, Rany

2013-09-01

This article attempts to review the most current and the well-established facts concerning drug addiction and sexual dysfunction. Surprisingly, even though alcohol is prevalent in many societies with many myths surrounding its sexual-enhancing effects, current scientific research cannot provide a solid conclusion on its effect on sexual function. Unfortunately, the same concept applies to tobacco smoking; however, most of the current knowledge tends to support the notion that it, indeed, can negatively affect sexual function. Similar ambiguities also prevail with substances of abuse. Copyright © 2013 Elsevier Inc. All rights reserved.

A common neural code for similar conscious experiences in different individuals

PubMed Central

Naci, Lorina; Cusack, Rhodri; Anello, Mimma; Owen, Adrian M.

2014-01-01

The interpretation of human consciousness from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. We asked whether there is a common neural code that underpins similar conscious experiences, which could be used to decode these experiences in the absence of behavior. To this end, we used richly evocative stimulation (an engaging movie) portraying real-world events to elicit a similar conscious experience in different people. Common neural correlates of conscious experience were quantified and related to measurable, quantitative and qualitative, executive components of the movie through two additional behavioral investigations. The movie’s executive demands drove synchronized brain activity across healthy participants’ frontal and parietal cortices in regions known to support executive function. Moreover, the timing of activity in these regions was predicted by participants’ highly similar qualitative experience of the movie’s moment-to-moment executive demands, suggesting that synchronization of activity across participants underpinned their similar experience. Thus we demonstrate, for the first time to our knowledge, that a neural index based on executive function reliably predicted every healthy individual’s similar conscious experience in response to real-world events unfolding over time. This approach provided strong evidence for the conscious experience of a brain-injured patient, who had remained entirely behaviorally nonresponsive for 16 y. The patient’s executive engagement and moment-to-moment perception of the movie content were highly similar to that of every healthy participant. These findings shed light on the common basis of human consciousness and enable the interpretation of conscious experience in the absence of behavior. PMID:25225384

Comparing adaptive procedures for estimating the psychometric function for an auditory gap detection task.

PubMed

Shen, Yi

2013-05-01

A subject's sensitivity to a stimulus variation can be studied by estimating the psychometric function. Generally speaking, three parameters of the psychometric function are of interest: the performance threshold, the slope of the function, and the rate at which attention lapses occur. In the present study, three psychophysical procedures were used to estimate the three-parameter psychometric function for an auditory gap detection task. These were an up-down staircase (up-down) procedure, an entropy-based Bayesian (entropy) procedure, and an updated maximum-likelihood (UML) procedure. Data collected from four young, normal-hearing listeners showed that while all three procedures provided similar estimates of the threshold parameter, the up-down procedure performed slightly better in estimating the slope and lapse rate for 200 trials of data collection. When the lapse rate was increased by mixing in random responses for the three adaptive procedures, the larger lapse rate was especially detrimental to the efficiency of the up-down procedure, and the UML procedure provided better estimates of the threshold and slope than did the other two procedures.

Intraluminal valves: development, function and disease

PubMed Central

Geng, Xin; Cha, Boksik; Mahamud, Md. Riaj

2017-01-01

ABSTRACT The circulatory system consists of the heart, blood vessels and lymphatic vessels, which function in parallel to provide nutrients and remove waste from the body. Vascular function depends on valves, which regulate unidirectional fluid flow against gravitational and pressure gradients. Severe valve disorders can cause mortality and some are associated with severe morbidity. Although cardiac valve defects can be treated by valve replacement surgery, no treatment is currently available for valve disorders of the veins and lymphatics. Thus, a better understanding of valves, their development and the progression of valve disease is warranted. In the past decade, molecules that are important for vascular function in humans have been identified, with mouse studies also providing new insights into valve formation and function. Intriguing similarities have recently emerged between the different types of valves concerning their molecular identity, architecture and development. Shear stress generated by fluid flow has also been shown to regulate endothelial cell identity in valves. Here, we review our current understanding of valve development with an emphasis on its mechanobiology and significance to human health, and highlight unanswered questions and translational opportunities. PMID:29125824

An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

PubMed

Bhagavat, Raghu; Sankar, Santhosh; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2018-03-06

Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships. To bridge this gap, we detect pockets in proteins of known 3D structures, using computational techniques. This augmented pocketome (PocketDB) consists of 249,096 pockets, which is about seven times larger than what is currently known. We deduce possible ligand associations for about 46% of the newly identified pockets. The augmented pocketome, when subjected to clustering based on similarities among pockets, yielded 2,161 site types, which are associated with 1,037 ligand types, together providing fold-site-type-ligand-type associations. The PocketDB resource facilitates a structure-based function annotation, delineation of the structural basis of ligand recognition, and provides functional clues for domains of unknown functions, allosteric proteins, and druggable pockets. Copyright © 2018 Elsevier Ltd. All rights reserved.

Phase function of a spherical particle when scattering an inhomogeneous electromagnetic plane wave.

PubMed

Frisvad, Jeppe Revall

2018-04-01

In absorbing media, electromagnetic plane waves are most often inhomogeneous. Existing solutions for the scattering of an inhomogeneous plane wave by a spherical particle provide no explicit expressions for the scattering components. In addition, current analytical solutions require evaluation of the complex hypergeometric function F 1 2 for every term of a series expansion. In this work, I develop a simpler solution based on associated Legendre functions with argument zero. It is similar to the solution for homogeneous plane waves but with new explicit expressions for the angular dependency of the far-field scattering components, that is, the phase function. I include recurrence formulas for practical evaluation and provide numerical examples to evaluate how well the new expressions match previous work in some limiting cases. The predicted difference in the scattering phase function due to inhomogeneity is not negligible for light entering an absorbing medium at an oblique angle. The presented theory could thus be useful for predicting scattering behavior in dye-based random lasing and in solar cell absorption enhancement.

Efficient conformational space exploration in ab initio protein folding simulation.

PubMed

Ullah, Ahammed; Ahmed, Nasif; Pappu, Subrata Dey; Shatabda, Swakkhar; Ullah, A Z M Dayem; Rahman, M Sohel

2015-08-01

Ab initio protein folding simulation largely depends on knowledge-based energy functions that are derived from known protein structures using statistical methods. These knowledge-based energy functions provide us with a good approximation of real protein energetics. However, these energy functions are not very informative for search algorithms and fail to distinguish the types of amino acid interactions that contribute largely to the energy function from those that do not. As a result, search algorithms frequently get trapped into the local minima. On the other hand, the hydrophobic-polar (HP) model considers hydrophobic interactions only. The simplified nature of HP energy function makes it limited only to a low-resolution model. In this paper, we present a strategy to derive a non-uniform scaled version of the real 20×20 pairwise energy function. The non-uniform scaling helps tackle the difficulty faced by a real energy function, whereas the integration of 20×20 pairwise information overcomes the limitations faced by the HP energy function. Here, we have applied a derived energy function with a genetic algorithm on discrete lattices. On a standard set of benchmark protein sequences, our approach significantly outperforms the state-of-the-art methods for similar models. Our approach has been able to explore regions of the conformational space which all the previous methods have failed to explore. Effectiveness of the derived energy function is presented by showing qualitative differences and similarities of the sampled structures to the native structures. Number of objective function evaluation in a single run of the algorithm is used as a comparison metric to demonstrate efficiency.

OrChem - An open source chemistry search engine for Oracle®

PubMed Central

2009-01-01

Background Registration, indexing and searching of chemical structures in relational databases is one of the core areas of cheminformatics. However, little detail has been published on the inner workings of search engines and their development has been mostly closed-source. We decided to develop an open source chemistry extension for Oracle, the de facto database platform in the commercial world. Results Here we present OrChem, an extension for the Oracle 11G database that adds registration and indexing of chemical structures to support fast substructure and similarity searching. The cheminformatics functionality is provided by the Chemistry Development Kit. OrChem provides similarity searching with response times in the order of seconds for databases with millions of compounds, depending on a given similarity cut-off. For substructure searching, it can make use of multiple processor cores on today's powerful database servers to provide fast response times in equally large data sets. Availability OrChem is free software and can be redistributed and/or modified under the terms of the GNU Lesser General Public License as published by the Free Software Foundation. All software is available via http://orchem.sourceforge.net. PMID:20298521

[Morphology of basement membrane and associated matrix proteins in normal and pathological tissues].

PubMed

Nerlich, A

1995-01-01

Basement membranes (BM) are specialized structures of the extracellular matrix. Their composition is of particular importance for the maintenance of normal morphological and functional properties of a multitude of organs and tissue systems and it is thus required for regular homeostasis of body function. Generally, they possess three main functions, i.e. participation in the maintenance of tissue structure, control of fluid and substrate exchange, and regulation of cell growth and differentiation. BMs are made up by various components which are in part specifically localized within the BM zone, or which represent ubiquitous matrix constituents with specific quantitative and/or qualitative differences in their localization. On the basis of a thorough immunohistochemical analysis of normal and diseased tissues, we provide here a concept of "functional morphology/pathomorphology" of the different BM components analyzed: 1.) The ubiquitous BM-constituent collagen IV primarily stabilizes the BM-zone and thus represents the "backbone" of the BM providing mechanical strength. Its loss leads to cystic tissue transformation as it is evidenced from the analysis of polycystic nephropathies. Thus, in other cystic tissue transformations a similar formal pathogenesis may be present. 2.) The specific localization of collagen VII as the main structural component of anchoring fibrils underlines the mechanical anchoring function of this collagenous protein. Defects in this protein lead to hereditary epidermolysis. The rapid re-occurrence of epidermal collagen VII during normal human wound healing indicates a quick reconstitution of the mechanical tensile strength of healing wounds. 3.) The BM-specific heparan sulfate proteoglycan (HSPG, Perlecan) with its highly negative anionic charge can be assumed to exert filter control. This assumption is corroborated by the localizatory findings of a preferential deposition of HSPG in endothelial and particularly in glomerular BM. Similarly, the lack of HSPG in the BM of lymph capillaries can be regarded as the correlate for a free fluid influx into lymphatic capillaries. The relative reduction in HSPG-staining in the developing glomerular BM also explains the still immature filter function. Furthermore, the low content of HSPG in placental chorionic capillaries can be regarded as morphological correlate for the required free fluid exchange between maternal and fetal blood systems. In diabetic glomerulopathy, the loss of HSPG coincides with a reduced filter function providing further support for the function of the HSPG. In further analyses of diabetic glomerulopathy, we provide evidence for an extensive matrix dysregulation resulting in either the overexpression of certain BM-components (diffuse glomerulosclerosis) or microfibrillar collagen VI (nodular glomerulosclerosis) indicating changes in cell function and possibly also cellular "differentiation". The analysis of congenital nephropathies additionally indicates that also the HSPG side chains with their negative charges may be involved in certain diseases with filter impairment. 4.) Furthermore, HSPG serves as a binding site for growth factors, particularly for the basic fibroblast growth factor (bFGF). It is of particular interest that the localization of HSPG and bFGF is not completely identical indicating some tissue specific differences in the receptor-ligand interaction. The functional importance of the bFGF-HSPG-interaction is exemplified by arteriosclerotic intima lesions where in highly cellular lesions high amounts of bFGF and HSPG coincide and low levels of both appear in poorly cellular lesions. Similarly, the granulation tissue in wound healing contains large amounts of bFGF-positive mesenchymal cells. 5.) The role of individual matrix components can be deduced from the normal human wound healing process, where epithelial cells migrate on a fibronectin matrix without complete BM.

Multimodal description of whole brain connectivity: A comparison of resting state MEG, fMRI, and DWI.

PubMed

Garcés, Pilar; Pereda, Ernesto; Hernández-Tamames, Juan A; Del-Pozo, Francisco; Maestú, Fernando; Pineda-Pardo, José Ángel

2016-01-01

Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion-weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood-oxygenation level-dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI-FC, and MEG-FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI-FC, and MEG-FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI-FC; SC and MEG-FC at theta, alpha, beta and gamma bands; and fMRI-FC and MEG-FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance. © 2015 Wiley Periodicals, Inc.

The Gestalt Principle of Similarity Benefits Visual Working Memory

PubMed Central

Peterson, Dwight J.; Berryhill, Marian E.

2013-01-01

Visual working memory (VWM) is essential for many cognitive processes yet it is notably limited in capacity. Visual perception processing is facilitated by Gestalt principles of grouping, such as connectedness, similarity, and proximity. This introduces the question: do these perceptual benefits extend to VWM? If so, can this be an approach to enhance VWM function by optimizing the processing of information? Previous findings demonstrate that several Gestalt principles (connectedness, common region, and spatial proximity) do facilitate VWM performance in change detection tasks (Woodman, Vecera, & Luck, 2003; Xu, 2002a, 2006; Xu & Chun, 2007; Jiang, Olson & Chun, 2000). One prevalent Gestalt principle, similarity, has not been examined with regard to facilitating VWM. Here, we investigated whether grouping by similarity benefits VWM. Experiment 1 established the basic finding that VWM performance could benefit from grouping. Experiment 2 replicated and extended this finding by showing that similarity was only effective when the similar stimuli were proximal. In short, the VWM performance benefit derived from similarity was constrained by spatial proximity such that similar items need to be near each other. Thus, the Gestalt principle of similarity benefits visual perception, but it can provide benefits to VWM as well. PMID:23702981

The Gestalt principle of similarity benefits visual working memory.

PubMed

Peterson, Dwight J; Berryhill, Marian E

2013-12-01

Visual working memory (VWM) is essential for many cognitive processes, yet it is notably limited in capacity. Visual perception processing is facilitated by Gestalt principles of grouping, such as connectedness, similarity, and proximity. This introduces the question, do these perceptual benefits extend to VWM? If so, can this be an approach to enhance VWM function by optimizing the processing of information? Previous findings have demonstrated that several Gestalt principles (connectedness, common region, and spatial proximity) do facilitate VWM performance in change detection tasks (Jiang, Olson, & Chun, 2000; Woodman, Vecera, & Luck, 2003; Xu, 2002, 2006; Xu & Chun, 2007). However, one prevalent Gestalt principle, similarity, has not been examined with regard to facilitating VWM. Here, we investigated whether grouping by similarity benefits VWM. Experiment 1 established the basic finding that VWM performance could benefit from grouping. Experiment 2 replicated and extended this finding by showing that similarity was only effective when the similar stimuli were proximal. In short, the VWM performance benefit derived from similarity was constrained by spatial proximity, such that similar items need to be near each other. Thus, the Gestalt principle of similarity benefits visual perception, but it can provide benefits to VWM as well.

Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

NASA Technical Reports Server (NTRS)

Sastry, Jagannadha K.

1998-01-01

We conducted a series of experiments using mouse immune-precursor cells, and observed that bioreactor culturing results in the loss of antigen-specific cytotoxic T lymphocyte (CTL) function. The reason for the abrogation of CTL function is microgravity conditions in the bioreactor, but not the antigen per se or its MHC restriction. Similarly, we observed that allostimulation of human PBMC in the bioreactor, but not in the T flask, resulted in the blunting of both allo-CTL function and the NK activity, indicating that the microgravity-associated functional defects are not unique to the mouse system. These results provide further confirmation to the microgravity-associated immune dysfunction, and constitute ground-based confirmatory data for those related to space-travel.

Hidden addiction: Television

PubMed Central

Sussman, Steve; Moran, Meghan B.

2013-01-01

Background and aims: The most popular recreational pastime in the U.S. is television viewing. Some researchers have claimed that television may be addictive. We provide a review of the definition, etiology, prevention and treatment of the apparent phenomenon of television addiction. Methods: Selective review. Results: We provide a description of television (TV) addiction, including its negative consequences, assessment and potential etiology, considering neurobiological, cognitive and social/cultural factors. Next, we provide information on its prevention and treatment. Discussion and conclusions: We suggest that television addiction may function similarly to substance abuse disorders but a great deal more research is needed. PMID:25083294

RNA-TVcurve: a Web server for RNA secondary structure comparison based on a multi-scale similarity of its triple vector curve representation.

PubMed

Li, Ying; Shi, Xiaohu; Liang, Yanchun; Xie, Juan; Zhang, Yu; Ma, Qin

2017-01-21

RNAs have been found to carry diverse functionalities in nature. Inferring the similarity between two given RNAs is a fundamental step to understand and interpret their functional relationship. The majority of functional RNAs show conserved secondary structures, rather than sequence conservation. Those algorithms relying on sequence-based features usually have limitations in their prediction performance. Hence, integrating RNA structure features is very critical for RNA analysis. Existing algorithms mainly fall into two categories: alignment-based and alignment-free. The alignment-free algorithms of RNA comparison usually have lower time complexity than alignment-based algorithms. An alignment-free RNA comparison algorithm was proposed, in which novel numerical representations RNA-TVcurve (triple vector curve representation) of RNA sequence and corresponding secondary structure features are provided. Then a multi-scale similarity score of two given RNAs was designed based on wavelet decomposition of their numerical representation. In support of RNA mutation and phylogenetic analysis, a web server (RNA-TVcurve) was designed based on this alignment-free RNA comparison algorithm. It provides three functional modules: 1) visualization of numerical representation of RNA secondary structure; 2) detection of single-point mutation based on secondary structure; and 3) comparison of pairwise and multiple RNA secondary structures. The inputs of the web server require RNA primary sequences, while corresponding secondary structures are optional. For the primary sequences alone, the web server can compute the secondary structures using free energy minimization algorithm in terms of RNAfold tool from Vienna RNA package. RNA-TVcurve is the first integrated web server, based on an alignment-free method, to deliver a suite of RNA analysis functions, including visualization, mutation analysis and multiple RNAs structure comparison. The comparison results with two popular RNA comparison tools, RNApdist and RNAdistance, showcased that RNA-TVcurve can efficiently capture subtle relationships among RNAs for mutation detection and non-coding RNA classification. All the relevant results were shown in an intuitive graphical manner, and can be freely downloaded from this server. RNA-TVcurve, along with test examples and detailed documents, are available at: http://ml.jlu.edu.cn/tvcurve/ .

Computational Functional Analysis of Lipid Metabolic Enzymes.

PubMed

Bagnato, Carolina; Have, Arjen Ten; Prados, María B; Beligni, María V

2017-01-01

The computational analysis of enzymes that participate in lipid metabolism has both common and unique challenges when compared to the whole protein universe. Some of the hurdles that interfere with the functional annotation of lipid metabolic enzymes that are common to other pathways include the definition of proper starting datasets, the construction of reliable multiple sequence alignments, the definition of appropriate evolutionary models, and the reconstruction of phylogenetic trees with high statistical support, particularly for large datasets. Most enzymes that take part in lipid metabolism belong to complex superfamilies with many members that are not involved in lipid metabolism. In addition, some enzymes that do not have sequence similarity catalyze similar or even identical reactions. Some of the challenges that, albeit not unique, are more specific to lipid metabolism refer to the high compartmentalization of the routes, the catalysis in hydrophobic environments and, related to this, the function near or in biological membranes.In this work, we provide guidelines intended to assist in the proper functional annotation of lipid metabolic enzymes, based on previous experiences related to the phospholipase D superfamily and the annotation of the triglyceride synthesis pathway in algae. We describe a pipeline that starts with the definition of an initial set of sequences to be used in similarity-based searches and ends in the reconstruction of phylogenies. We also mention the main issues that have to be taken into consideration when using tools to analyze subcellular localization, hydrophobicity patterns, or presence of transmembrane domains in lipid metabolic enzymes.

Analagous Population Structures for Two Alphabaculoviruses Highlight a Functional Role for Deletion Mutants

PubMed Central

Serrano, Amaya; Williams, Trevor; Simón, Oihane; López-Ferber, Miguel; Caballero, Primitivo

2013-01-01

A natural Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) isolate from Florida shares a strikingly similar genotypic composition to that of a natural Spodoptera frugiperda MNPV (SfMNPV) isolate from Nicaragua. Both isolates comprise a high proportion of large-deletion genotypes that lack genes that are essential for viral replication or transmission. To determine the likely origins of such genotypically similar population structures, we performed genomic and functional analyses of these genotypes. The homology of nucleotides in the deleted regions was as high as 79%, similar to those of other colinear genomic regions, although some SfMNPV genes were not present in SeMNPV. In addition, no potential consensus sequences were shared between the deletion flanking sequences. These results indicate an evolutionary mechanism that independently generates and sustains deletion mutants within each virus population. Functional analyses using different proportions of complete and deletion genotypes were performed with the two viruses in mixtures of occlusion bodies (OBs) or co-occluded virions. Ratios greater than 3:1 of complete/deletion genotypes resulted in reduced pathogenicity (expressed as median lethal dose), but there were no significant changes in the speed of kill. In contrast, OB yields increased only in the 1:1 mixture. The three phenotypic traits analyzed provide a broader picture of the functional significance of the most extensively deleted SeMNPV genotype and contribute toward the elucidation of the role of such mutants in baculovirus populations. PMID:23204420

An improved method for functional similarity analysis of genes based on Gene Ontology.

PubMed

Tian, Zhen; Wang, Chunyu; Guo, Maozu; Liu, Xiaoyan; Teng, Zhixia

2016-12-23

Measures of gene functional similarity are essential tools for gene clustering, gene function prediction, evaluation of protein-protein interaction, disease gene prioritization and other applications. In recent years, many gene functional similarity methods have been proposed based on the semantic similarity of GO terms. However, these leading approaches may make errorprone judgments especially when they measure the specificity of GO terms as well as the IC of a term set. Therefore, how to estimate the gene functional similarity reliably is still a challenging problem. We propose WIS, an effective method to measure the gene functional similarity. First of all, WIS computes the IC of a term by employing its depth, the number of its ancestors as well as the topology of its descendants in the GO graph. Secondly, WIS calculates the IC of a term set by means of considering the weighted inherited semantics of terms. Finally, WIS estimates the gene functional similarity based on the IC overlap ratio of term sets. WIS is superior to some other representative measures on the experiments of functional classification of genes in a biological pathway, collaborative evaluation of GO-based semantic similarity measures, protein-protein interaction prediction and correlation with gene expression. Further analysis suggests that WIS takes fully into account the specificity of terms and the weighted inherited semantics of terms between GO terms. The proposed WIS method is an effective and reliable way to compare gene function. The web service of WIS is freely available at http://nclab.hit.edu.cn/WIS/ .

Spin properties of supermassive black holes with powerful outflows

NASA Astrophysics Data System (ADS)

Daly, Ruth. A.

2016-05-01

Relationships between beam power and accretion disc luminosity are studied for a sample of 55 high excitation radio galaxies (HERG), 13 low excitation radio galaxies (LERG), and 29 radio loud quasars (RLQ) with powerful outflows. The ratio of beam power to disc luminosity tends to be high for LERG, low for RLQ, and spans the full range of values for HERG. Writing general expressions for the disc luminosity and beam power and applying the empirically determined relationships allows a function that parametrizes the spins of the holes to be estimated. Interestingly, one of the solutions that is consistent with the data has a functional form that is remarkably similar to that expected in the generalized Blandford-Znajek model with a magnetic field that is similar in form to that expected in magnetically arrested disk (MAD) and advection-dominated accretion flow (ADAF) models. Values of the spin function, obtained independent of specific outflow models, suggest that spin and active galactic nucleus type are not related for these types of sources. The spin function can be used to solve for black hole spin in the context of particular outflow models, and one example is provided.

Pattern, growth, and aging in aggregation kinetics of a Vicsek-like active matter model

NASA Astrophysics Data System (ADS)

Das, Subir K.

2017-01-01

Via molecular dynamics simulations, we study kinetics in a Vicsek-like phase-separating active matter model. Quantitative results, for isotropic bicontinuous pattern, are presented on the structure, growth, and aging. These are obtained via the two-point equal-time density-density correlation function, the average domain length, and the two-time density autocorrelation function. Both the correlation functions exhibit basic scaling properties, implying self-similarity in the pattern dynamics, for which the average domain size exhibits a power-law growth in time. The equal-time correlation has a short distance behavior that provides reasonable agreement between the corresponding structure factor tail and the Porod law. The autocorrelation decay is a power-law in the average domain size. Apart from these basic similarities, the overall quantitative behavior of the above-mentioned observables is found to be vastly different from those of the corresponding passive limit of the model which also undergoes phase separation. The functional forms of these have been quantified. An exceptionally rapid growth in the active system occurs due to fast coherent motion of the particles, mean-squared-displacements of which exhibit multiple scaling regimes, including a long time ballistic one.

Electrospun microcrimped fibers with nonlinear mechanical properties enhance ligament fibroblast phenotype.

PubMed

Grace Chao, Pen-hsiu; Hsu, Hsiang-Yi; Tseng, Hsiao-Yun

2014-09-01

Fiber structure and order greatly impact the mechanical behavior of fibrous materials. In biological tissues, the nonlinear mechanics of fibrous scaffolds contribute to the functionality of the material. The nonlinear mechanical properties of the wavy structure (crimp) in collagen allow tissue flexibility while preventing over-extension. A number of approaches have tried to recreate this complex mechanical functionality. We generated microcrimped fibers by briefly heating electrospun parallel fibers over the glass transition temperature or by ethanol treatment. The crimp structure is similar to those of collagen fibers found in native aorta, intestines, or ligaments. Using poly-L-lactic acid fibers, we demonstrated that the bulk materials exhibit changed stress-strain behaviors with a significant increase in the toe region in correlation to the degree of crimp, similar to those observed in collagenous tissues. In addition to mimicking the stress-strain behavior of biological tissues, the microcrimped fibers are instructive in cell morphology and promote ligament phenotypic gene expression. This effect can be further enhanced by dynamic tensile loading, a physiological perturbation in vivo. This rapid and economical approach for microcrimped fiber production provides an accessible platform to study structure-function relationships and a novel functional scaffold for tissue engineering and cell mechanobiology studies.

High-speed spectral calibration by complex FIR filter in phase-sensitive optical coherence tomography.

PubMed

Kim, Sangmin; Raphael, Patrick D; Oghalai, John S; Applegate, Brian E

2016-04-01

Swept-laser sources offer a number of advantages for Phase-sensitive Optical Coherence Tomography (PhOCT). However, inter- and intra-sweep variability leads to calibration errors that adversely affect phase sensitivity. While there are several approaches to overcoming this problem, our preferred method is to simply calibrate every sweep of the laser. This approach offers high accuracy and phase stability at the expense of a substantial processing burden. In this approach, the Hilbert phase of the interferogram from a reference interferometer provides the instantaneous wavenumber of the laser, but is computationally expensive. Fortunately, the Hilbert transform may be approximated by a Finite Impulse-Response (FIR) filter. Here we explore the use of several FIR filter based Hilbert transforms for calibration, explicitly considering the impact of filter choice on phase sensitivity and OCT image quality. Our results indicate that the complex FIR filter approach is the most robust and accurate among those considered. It provides similar image quality and slightly better phase sensitivity than the traditional FFT-IFFT based Hilbert transform while consuming fewer resources in an FPGA implementation. We also explored utilizing the Hilbert magnitude of the reference interferogram to calculate an ideal window function for spectral amplitude calibration. The ideal window function is designed to carefully control sidelobes on the axial point spread function. We found that after a simple chromatic correction, calculating the window function using the complex FIR filter and the reference interferometer gave similar results to window functions calculated using a mirror sample and the FFT-IFFT Hilbert transform. Hence, the complex FIR filter can enable accurate and high-speed calibration of the magnitude and phase of spectral interferograms.

High-speed spectral calibration by complex FIR filter in phase-sensitive optical coherence tomography

PubMed Central

Kim, Sangmin; Raphael, Patrick D.; Oghalai, John S.; Applegate, Brian E.

2016-01-01

Swept-laser sources offer a number of advantages for Phase-sensitive Optical Coherence Tomography (PhOCT). However, inter- and intra-sweep variability leads to calibration errors that adversely affect phase sensitivity. While there are several approaches to overcoming this problem, our preferred method is to simply calibrate every sweep of the laser. This approach offers high accuracy and phase stability at the expense of a substantial processing burden. In this approach, the Hilbert phase of the interferogram from a reference interferometer provides the instantaneous wavenumber of the laser, but is computationally expensive. Fortunately, the Hilbert transform may be approximated by a Finite Impulse-Response (FIR) filter. Here we explore the use of several FIR filter based Hilbert transforms for calibration, explicitly considering the impact of filter choice on phase sensitivity and OCT image quality. Our results indicate that the complex FIR filter approach is the most robust and accurate among those considered. It provides similar image quality and slightly better phase sensitivity than the traditional FFT-IFFT based Hilbert transform while consuming fewer resources in an FPGA implementation. We also explored utilizing the Hilbert magnitude of the reference interferogram to calculate an ideal window function for spectral amplitude calibration. The ideal window function is designed to carefully control sidelobes on the axial point spread function. We found that after a simple chromatic correction, calculating the window function using the complex FIR filter and the reference interferometer gave similar results to window functions calculated using a mirror sample and the FFT-IFFT Hilbert transform. Hence, the complex FIR filter can enable accurate and high-speed calibration of the magnitude and phase of spectral interferograms. PMID:27446666

Chorusing, synchrony, and the evolutionary functions of rhythm.

PubMed

Ravignani, Andrea; Bowling, Daniel L; Fitch, W Tecumseh

2014-01-01

A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc.) with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony), we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, arguing that group behavior is key to understanding the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates). Finally, we propose an "Evolving Signal Timing" hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s) of rhythmic behavior in our "proto-musical" primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and language.

Chorusing, synchrony, and the evolutionary functions of rhythm

PubMed Central

Ravignani, Andrea; Bowling, Daniel L.; Fitch, W. Tecumseh

2014-01-01

A central goal of biomusicology is to understand the biological basis of human musicality. One approach to this problem has been to compare core components of human musicality (relative pitch perception, entrainment, etc.) with similar capacities in other animal species. Here we extend and clarify this comparative approach with respect to rhythm. First, whereas most comparisons between human music and animal acoustic behavior have focused on spectral properties (melody and harmony), we argue for the central importance of temporal properties, and propose that this domain is ripe for further comparative research. Second, whereas most rhythm research in non-human animals has examined animal timing in isolation, we consider how chorusing dynamics can shape individual timing, as in human music and dance, arguing that group behavior is key to understanding the adaptive functions of rhythm. To illustrate the interdependence between individual and chorusing dynamics, we present a computational model of chorusing agents relating individual call timing with synchronous group behavior. Third, we distinguish and clarify mechanistic and functional explanations of rhythmic phenomena, often conflated in the literature, arguing that this distinction is key for understanding the evolution of musicality. Fourth, we expand biomusicological discussions beyond the species typically considered, providing an overview of chorusing and rhythmic behavior across a broad range of taxa (orthopterans, fireflies, frogs, birds, and primates). Finally, we propose an “Evolving Signal Timing” hypothesis, suggesting that similarities between timing abilities in biological species will be based on comparable chorusing behaviors. We conclude that the comparative study of chorusing species can provide important insights into the adaptive function(s) of rhythmic behavior in our “proto-musical” primate ancestors, and thus inform our understanding of the biology and evolution of rhythm in human music and language. PMID:25346705

Do Behavioral Foraging Responses of Prey to Predators Function Similarly in Restored and Pristine Foodwebs?

PubMed Central

Madin, Elizabeth M. P.; Gaines, Steven D.; Madin, Joshua S.; Link, Anne-Katrin; Lubchenco, Peggy J.; Selden, Rebecca L.; Warner, Robert R.

2012-01-01

Efforts to restore top predators in human-altered systems raise the question of whether rebounds in predator populations are sufficient to restore pristine foodweb dynamics. Ocean ecosystems provide an ideal system to test this question. Removal of fishing in marine reserves often reverses declines in predator densities and size. However, whether this leads to restoration of key functional characteristics of foodwebs, especially prey foraging behavior, is unclear. The question of whether restored and pristine foodwebs function similarly is nonetheless critically important for management and restoration efforts. We explored this question in light of one important determinant of ecosystem function and structure – herbivorous prey foraging behavior. We compared these responses for two functionally distinct herbivorous prey fishes (the damselfish Plectroglyphidodon dickii and the parrotfish Chlorurus sordidus) within pairs of coral reefs in pristine and restored ecosystems in two regions of these species' biogeographic ranges, allowing us to quantify the magnitude and temporal scale of this key ecosystem variable's recovery. We demonstrate that restoration of top predator abundances also restored prey foraging excursion behaviors to a condition closely resembling those of a pristine ecosystem. Increased understanding of behavioral aspects of ecosystem change will greatly improve our ability to predict the cascading consequences of conservation tools aimed at ecological restoration, such as marine reserves. PMID:22403650

Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors: An Investigation of Design Flexibility.

PubMed

Kumar, E K Pramod; Jølck, Rasmus I; Andresen, Thomas L

2015-09-01

The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors. Both approaches provide stable nanosensors with similar pKa profiles and thereby nanosensors with similar pH sensitivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ab Initio Study of Polarizabilities of Oligothiophene, Oligocyclopentadiene and Oligofulvene and their Cyano Substituted Oligomers

NASA Astrophysics Data System (ADS)

Lagowski, Jolanta; Ferdous, Sultana

2005-03-01

Ab Initio polarizabilities of thiophene, fulvene and cyclopentadiene based conducting oligomers and polymers and their cyano derivatives have been calculated using the Hartree-Fock (HF), configuration interaction (singles) (CIS ) and density functional (DF) theories with 3-21G* basis using Gaussian software. The main motivation of this investigation is to determine the correlation between the excitation energies and polarizabilities for the conjugated systems studied. It has been found that HF and DF approaches give similar magnitudes for polarizabilities whereas CIS theory provides results that are considerably different. All three methods predict similar trends in polarizabilities as a function of oligomer length and bond alternation along the backbone of the oligomers. It has also been observed that the end groups and the number of `double' bonds have a significant effect on the magnitude of polarizability per C-C bond. Comparison with experimental results will be made where possible.

The protective function of noncoding DNA in genome defense of eukaryotic male germ cells.

PubMed

Qiu, Guo-Hua; Huang, Cuiqin; Zheng, Xintian; Yang, Xiaoyan

2018-04-01

Peripheral and abundant noncoding DNA has been hypothesized to protect the genome and the central protein-coding sequences against DNA damage in somatic genome. In the cytosol, invading exogenous nucleic acids may first be deactivated by small RNAs encoded by noncoding DNA via mechanisms similar to the prokaryotic CRISPR-Cas system. In the nucleus, the radicals generated by radiation in the cytosol, radiation energy and invading exogenous nucleic acids are absorbed, blocked and/or reduced by peripheral heterochromatin, and damaged DNA in heterochromatin is removed and excluded from the nucleus to the cytoplasm through nuclear pore complexes. To further strengthen the hypothesis, this review summarizes the experimental evidence supporting the protective function of noncoding DNA in the genome of male germ cells. Based on these data, this review provides evidence supporting the protective role of noncoding DNA in the genome defense of sperm genome through similar mechanisms to those of the somatic genome.

A novel perivascular cell population in the zebrafish brain.

PubMed

Venero Galanternik, Marina; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-04-11

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or 'Mato Cells' in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium.

Extending the accuracy of the SNAP interatomic potential form

NASA Astrophysics Data System (ADS)

Wood, Mitchell A.; Thompson, Aidan P.

2018-06-01

The Spectral Neighbor Analysis Potential (SNAP) is a classical interatomic potential that expresses the energy of each atom as a linear function of selected bispectrum components of the neighbor atoms. An extension of the SNAP form is proposed that includes quadratic terms in the bispectrum components. The extension is shown to provide a large increase in accuracy relative to the linear form, while incurring only a modest increase in computational cost. The mathematical structure of the quadratic SNAP form is similar to the embedded atom method (EAM), with the SNAP bispectrum components serving as counterparts to the two-body density functions in EAM. The effectiveness of the new form is demonstrated using an extensive set of training data for tantalum structures. Similar to artificial neural network potentials, the quadratic SNAP form requires substantially more training data in order to prevent overfitting. The quality of this new potential form is measured through a robust cross-validation analysis.

Canonical Structure and Orthogonality of Forces and Currents in Irreversible Markov Chains

NASA Astrophysics Data System (ADS)

Kaiser, Marcus; Jack, Robert L.; Zimmer, Johannes

2018-03-01

We discuss a canonical structure that provides a unifying description of dynamical large deviations for irreversible finite state Markov chains (continuous time), Onsager theory, and Macroscopic Fluctuation Theory (MFT). For Markov chains, this theory involves a non-linear relation between probability currents and their conjugate forces. Within this framework, we show how the forces can be split into two components, which are orthogonal to each other, in a generalised sense. This splitting allows a decomposition of the pathwise rate function into three terms, which have physical interpretations in terms of dissipation and convergence to equilibrium. Similar decompositions hold for rate functions at level 2 and level 2.5. These results clarify how bounds on entropy production and fluctuation theorems emerge from the underlying dynamical rules. We discuss how these results for Markov chains are related to similar structures within MFT, which describes hydrodynamic limits of such microscopic models.

North Dakota

USGS Publications Warehouse

,

1999-01-01

North Dakota prairies contain numerous wetlands. The complex functions of these prairie wetlands have been of interest for decades. The hydrology, water chemistry, and biological characteristics of these wetlands are highly variable because of extreme warm/cold and wet/dry conditions. The U.S. Geological Survey (USGS) has been conducting studies (fig. 1) to gain insight into the functions of the prairie wetlands. The USGS Northern Prairie Wildlife Research Center in Jamestown has maintained an active wetland research program since the mid-1960’s. Current work in North Dakota began in 1978, and focuses on the response of biological communities to climate-induced variations in hydrology and chemistry, and on evaluating the success of previously drained wetlands restored under the Conservation Reserve Program (CRP) and on similar lands. The information provided from this long-term study has provided the bulk of our knowledge about prairie wetlands, and has provided land managers with valuable information to manage the Nation’s prairie wetland resource.

Optimal policy for value-based decision-making.

PubMed

Tajima, Satohiro; Drugowitsch, Jan; Pouget, Alexandre

2016-08-18

For decades now, normative theories of perceptual decisions, and their implementation as drift diffusion models, have driven and significantly improved our understanding of human and animal behaviour and the underlying neural processes. While similar processes seem to govern value-based decisions, we still lack the theoretical understanding of why this ought to be the case. Here, we show that, similar to perceptual decisions, drift diffusion models implement the optimal strategy for value-based decisions. Such optimal decisions require the models' decision boundaries to collapse over time, and to depend on the a priori knowledge about reward contingencies. Diffusion models only implement the optimal strategy under specific task assumptions, and cease to be optimal once we start relaxing these assumptions, by, for example, using non-linear utility functions. Our findings thus provide the much-needed theory for value-based decisions, explain the apparent similarity to perceptual decisions, and predict conditions under which this similarity should break down.

Optimal policy for value-based decision-making

PubMed Central

Tajima, Satohiro; Drugowitsch, Jan; Pouget, Alexandre

2016-01-01

For decades now, normative theories of perceptual decisions, and their implementation as drift diffusion models, have driven and significantly improved our understanding of human and animal behaviour and the underlying neural processes. While similar processes seem to govern value-based decisions, we still lack the theoretical understanding of why this ought to be the case. Here, we show that, similar to perceptual decisions, drift diffusion models implement the optimal strategy for value-based decisions. Such optimal decisions require the models' decision boundaries to collapse over time, and to depend on the a priori knowledge about reward contingencies. Diffusion models only implement the optimal strategy under specific task assumptions, and cease to be optimal once we start relaxing these assumptions, by, for example, using non-linear utility functions. Our findings thus provide the much-needed theory for value-based decisions, explain the apparent similarity to perceptual decisions, and predict conditions under which this similarity should break down. PMID:27535638

Neural Correlates of Consumer Buying Motivations: A 7T functional Magnetic Resonance Imaging (fMRI) Study

PubMed Central

Goodman, Adam M.; Wang, Yun; Kwon, Wi-Suk; Byun, Sang-Eun; Katz, Jeffrey S.; Deshpande, Gopikrishna

2017-01-01

Consumer buying motivations can be distinguished into three categories: functional, experiential, or symbolic motivations (Keller, 1993). Although prior neuroimaging studies have examined the neural substrates which enable these motivations, direct comparisons between these three types of consumer motivations have yet to be made. In the current study, we used 7 Tesla (7T) functional magnetic resonance imaging (fMRI) to assess the neural correlates of each motivation by instructing participants to view common consumer goods while emphasizing either functional, experiential, or symbolic values of these products. The results demonstrated mostly consistent activations between symbolic and experiential motivations. Although, these motivations differed in that symbolic motivation was associated with medial frontal gyrus (MFG) activation, whereas experiential motivation was associated with posterior cingulate cortex (PCC) activation. Functional motivation was associated with dorsolateral prefrontal cortex (DLPFC) activation, as compared to other motivations. These findings provide a neural basis for how symbolic and experiential motivations may be similar, yet different in subtle ways. Furthermore, the dissociation of functional motivation within the DLPFC supports the notion that this motivation relies on executive function processes relatively more than hedonic motivation. These findings provide a better understanding of the underlying neural functioning which may contribute to poor self-control choices. PMID:28959182

Noncoding origins of anthropoid traits and a new null model of transposon functionalization.

PubMed

del Rosario, Ricardo C H; Rayan, Nirmala Arul; Prabhakar, Shyam

2014-09-01

Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions and confirmed their robust functional signatures. Of the ASC base pairs, 99.7% were noncoding, suggesting that novel anthropoid functional elements were overwhelmingly cis-regulatory. ASCs were highly enriched in loci associated with fetal brain development, motor coordination, neurotransmission, and vision, thus providing a large set of candidate elements for exploring the molecular basis of hallmark primate traits. We validated ASC192 as a primate-specific enhancer in proliferative zones of the developing brain. Unexpectedly, transposable elements (TEs) contributed to >56% of ASCs, and almost all TE families showed functional potential similar to that of nonrepetitive DNA. Three L1PA repeat-derived ASCs displayed coherent eye-enhancer function, thus demonstrating that the "gene-battery" model of TE functionalization applies to enhancers in vivo. Our study provides fundamental insights into genome evolution and the origins of anthropoid phenotypes and supports an elegantly simple new null model of TE exaptation. © 2014 del Rosario et al.; Published by Cold Spring Harbor Laboratory Press.

The Role of the Tutor from a Community Perspective. TTnet Dossier No. 2.

ERIC Educational Resources Information Center

de Blignieres-Legeraud, Anne; Gerard, Francoise; Selka, Reinhard; Voskamp, Heinz-Dieter; Laermanns, Mathias

This publication highlights the role of the tutor (a person providing on-the-job training to new hires and persons moving into new jobs while still functioning in the same or a similar job, rather than being a full-time trainer) in industry through a comparative study of these four European countries: Austria, France, Germany, and Spain. Following…

Trophic groups and modules: two levels of group detection in food webs

PubMed Central

Gauzens, Benoit; Thébault, Elisa; Lacroix, Gérard; Legendre, Stéphane

2015-01-01

Within food webs, species can be partitioned into groups according to various criteria. Two notions have received particular attention: trophic groups (TGs), which have been used for decades in the ecological literature, and more recently, modules. The relationship between these two group concepts remains unknown in empirical food webs. While recent developments in network theory have led to efficient methods for detecting modules in food webs, the determination of TGs (groups of species that are functionally similar) is largely based on subjective expert knowledge. We develop a novel algorithm for TG detection. We apply this method to empirical food webs and show that aggregation into TGs allows for the simplification of food webs while preserving their information content. Furthermore, we reveal a two-level hierarchical structure where modules partition food webs into large bottom–top trophic pathways, whereas TGs further partition these pathways into groups of species with similar trophic connections. This provides new perspectives for the study of dynamical and functional consequences of food-web structure, bridging topological and dynamical analysis. TGs have a clear ecological meaning and are found to provide a trade-off between network complexity and information loss. PMID:25878127

STIM and Orai proteins and the non-capacitative ARC channels

PubMed Central

Shuttleworth, Trevor J.

2012-01-01

The ARC channel is a small conductance, highly Ca2+-selective ion channel whose activation is specifically dependent on low concentrations of arachidonic acid acting at an intracellular site. They are widely distributed in diverse cell types where they provide an alternative, store-independent pathway for agonist-activated Ca2+ entry. Although biophysically similar to the store-operated CRAC channels, these two conductances function under distinct conditions of agonist stimulation, with the ARC channels providing the predominant route of Ca2+ entry during the oscillatory signals generated at low agonist concentrations. Despite these differences in function, like the CRAC channel, activation of the ARC channels is dependent on STIM1, but it is the pool of STIM1 that constitutively resides in the plasma membrane that is responsible. Similarly, both channels are formed by Orai proteins but, whilst the CRAC channel pore is a tetrameric assembly of Orai1 subunits, the ARC channel pore is formed by a heteropentameric assembly of three Orai1 subunits and two Orai3 subunits. There is increasing evidence that the activity of these channels plays a critical role a variety of different cellular activities. PMID:22201777

Proximity Navigation of Highly Constrained Spacecraft

NASA Technical Reports Server (NTRS)

Scarritt, S.; Swartwout, M.

2007-01-01

Bandit is a 3-kg automated spacecraft in development at Washington University in St. Louis. Bandit's primary mission is to demonstrate proximity navigation, including docking, around a 25-kg student-built host spacecraft. However, because of extreme constraints in mass, power and volume, traditional sensing and actuation methods are not available. In particular, Bandit carries only 8 fixed-magnitude cold-gas thrusters to control its 6 DOF motion. Bandit lacks true inertial sensing, and the ability to sense position relative to the host has error bounds that approach the size of the Bandit itself. Some of the navigation problems are addressed through an extremely robust, error-tolerant soft dock. In addition, we have identified a control methodology that performs well in this constrained environment: behavior-based velocity potential functions, which use a minimum-seeking method similar to Lyapunov functions. We have also adapted the discrete Kalman filter for use on Bandit for position estimation and have developed a similar measurement vs. propagation weighting algorithm for attitude estimation. This paper provides an overview of Bandit and describes the control and estimation approach. Results using our 6DOF flight simulator are provided, demonstrating that these methods show promise for flight use.

Study for fabrication, evaluation, and testing of monolayer woven type materials for space suit insulation

NASA Technical Reports Server (NTRS)

Merrick, E. B.

1979-01-01

An alternative space suit insulation concept using a monolayer woven pile material is discussed. The material reduces cost and improves the durability of the overgarment, while providing protection similar to that provided by multilayer insulation (MLI). Twelve samples of different configurations were fabricated and tested for compressibility and thermal conductivity as a function of compression loading. Two samples which showed good results in the initial tests were further tested for thermal conductivity with respect to ambient pressure and temperature. Results of these tests were similar to results of the MLI tests, indicating the potential of the monolayer fabric to replace the present MLI. A seaming study illustrated that the fabric can be sewn in a structurally sound seam with minimal heat loss. It is recommended that a prototype thermal meteroid garment be fabricated.

Query3d: a new method for high-throughput analysis of functional residues in protein structures.

PubMed

Ausiello, Gabriele; Via, Allegra; Helmer-Citterich, Manuela

2005-12-01

The identification of local similarities between two protein structures can provide clues of a common function. Many different methods exist for searching for similar subsets of residues in proteins of known structure. However, the lack of functional and structural information on single residues, together with the low level of integration of this information in comparison methods, is a limitation that prevents these methods from being fully exploited in high-throughput analyses. Here we describe Query3d, a program that is both a structural DBMS (Database Management System) and a local comparison method. The method conserves a copy of all the residues of the Protein Data Bank annotated with a variety of functional and structural information. New annotations can be easily added from a variety of methods and known databases. The algorithm makes it possible to create complex queries based on the residues' function and then to compare only subsets of the selected residues. Functional information is also essential to speed up the comparison and the analysis of the results. With Query3d, users can easily obtain statistics on how many and which residues share certain properties in all proteins of known structure. At the same time, the method also finds their structural neighbours in the whole PDB. Programs and data can be accessed through the PdbFun web interface.

Query3d: a new method for high-throughput analysis of functional residues in protein structures

PubMed Central

Ausiello, Gabriele; Via, Allegra; Helmer-Citterich, Manuela

2005-01-01

Background The identification of local similarities between two protein structures can provide clues of a common function. Many different methods exist for searching for similar subsets of residues in proteins of known structure. However, the lack of functional and structural information on single residues, together with the low level of integration of this information in comparison methods, is a limitation that prevents these methods from being fully exploited in high-throughput analyses. Results Here we describe Query3d, a program that is both a structural DBMS (Database Management System) and a local comparison method. The method conserves a copy of all the residues of the Protein Data Bank annotated with a variety of functional and structural information. New annotations can be easily added from a variety of methods and known databases. The algorithm makes it possible to create complex queries based on the residues' function and then to compare only subsets of the selected residues. Functional information is also essential to speed up the comparison and the analysis of the results. Conclusion With Query3d, users can easily obtain statistics on how many and which residues share certain properties in all proteins of known structure. At the same time, the method also finds their structural neighbours in the whole PDB. Programs and data can be accessed through the PdbFun web interface. PMID:16351754

Azaborines: Unique Isosteres of Aromatic and Heteroaromatic Systems

NASA Astrophysics Data System (ADS)

Davies, Geraint H. M.

The azaborine motif provides a unique opportunity to develop core isosteres by inserting B-N units in place of C=C bonds within aromatic scaffolds. These boron/nitrogen-containing heteroaromatic systems provide molecular frameworks that have similar, but not identical, geometrical shapes and electronic distributions to the analogous all carbon systems. Synthetic routes to the 1,3,2-benzodiazaborole core have been developed utilizing entirely bench-stable starting materials, including organotrifluoroborates, enabling a wider array of substrate analogues under facile reaction conditions. The physical, structural, and electronic properties of these compounds were explored computationally to understand the influence of the B-N replacement on structure, aromaticity, and the isosteric viability of these analogues. The class of azaborininones could similarly be accessed from both organotrifluoroborates and boronic acids. An inexpensive, common reagent, SiO2, was found to serve as both a fluorophile and desiccant to facilitate the annulation process across three different azaborininone platforms. Computationally-derived pK a values, NICS aromaticity calculations, and electrostatic potential surfaces revealed a unique isoelectronic/isostructural relationship between these azaborines and their carbon isosteres that changed based on boron connectivity. The 2,1-borazaronaphthalene motif can be accessed through robust methods of synthesis and subsequent functionalization strategies, affording an ideal platform to use for a variety of applications. However, the initial scope of substructures for this archetype has been limited by the lack of nitrogen-containing heteroaryls that can be incorporated within them. Modified reaction conditions enabled greater tolerance to provide access to a wider range of substructures. Additionally, computational and experimental studies of solvent decomposition demonstrate that substitution off boron is important to stability. Post-annulation derivitization of the azaborine cores can allow access to higher order functionalized structures. A method for functionalizing the 2,1-borazaronaphthalene scaffold using ammonium alkylbis(catecholato)silicates via photoredox/nickel dual catalysis was found to be highly effective. By forging Csp3-C sp2 bonds via this approach, alkyl fragments with various functional groups can be introduced to the azaborine core, affording previously inaccessible heterocyclic isosteres in good to excellent yields. These conditions provide sensitive functional group tolerance, even permitting the cross-coupling of unprotected primary and secondary amines. Regioselective C-H borylation and subsequent cross-coupling of the 2,1-borazaronaphthalene core could also be achieved. Although 2,1-borazaronaphthalene is closely related to naphthalene in terms of structure, the argument is made that the former has electronic similarities to indole. Based on that premise, iridium-mediated C-H activation has enabled facile installation of a versatile, nucleophilic coupling handle at a previously inaccessible site of 2,1-borazaronaphthalenes. A variety of substituted 2,1-borazaronaphthalene cores can be successfully borylated and further cross-coupled in a facile manner to yield diverse C(8)-substituted 2,1-borazaronaphthalenes.

Application of the 4D Fingerprint Method with a Robust Scoring Function for Scaffold-Hopping and Drug Repurposing Strategies

PubMed Central

2015-01-01

Two factors contribute to the inefficiency associated with screening pharmaceutical library collections as a means of identifying new drugs: [1] the limited success of virtual screening (VS) methods in identifying new scaffolds; [2] the limited accuracy of computational methods in predicting off-target effects. We recently introduced a 3D shape-based similarity algorithm of the SABRE program, which encodes a consensus molecular shape pattern of a set of active ligands into a 4D fingerprint descriptor. Here, we report a mathematical model for shape similarity comparisons and ligand database filtering using this 4D fingerprint method and benchmarked the scoring function HWK (Hamza–Wei–Korotkov), using the 81 targets of the DEKOIS database. Subsequently, we applied our combined 4D fingerprint and HWK scoring function VS approach in scaffold-hopping and drug repurposing using the National Cancer Institute (NCI) and Food and Drug Administration (FDA) databases, and we identified new inhibitors with different scaffolds of MycP1 protease from the mycobacterial ESX-1 secretion system. Experimental evaluation of nine compounds from the NCI database and three from the FDA database displayed IC50 values ranging from 70 to 100 μM against MycP1 and possessed high structural diversity, which provides departure points for further structure–activity relationship (SAR) optimization. In addition, this study demonstrates that the combination of our 4D fingerprint algorithm and the HWK scoring function may provide a means for identifying repurposed drugs for the treatment of infectious diseases and may be used in the drug-target profile strategy. PMID:25229183

Application of the 4D fingerprint method with a robust scoring function for scaffold-hopping and drug repurposing strategies.

PubMed

Hamza, Adel; Wagner, Jonathan M; Wei, Ning-Ning; Kwiatkowski, Stefan; Zhan, Chang-Guo; Watt, David S; Korotkov, Konstantin V

2014-10-27

Two factors contribute to the inefficiency associated with screening pharmaceutical library collections as a means of identifying new drugs: [1] the limited success of virtual screening (VS) methods in identifying new scaffolds; [2] the limited accuracy of computational methods in predicting off-target effects. We recently introduced a 3D shape-based similarity algorithm of the SABRE program, which encodes a consensus molecular shape pattern of a set of active ligands into a 4D fingerprint descriptor. Here, we report a mathematical model for shape similarity comparisons and ligand database filtering using this 4D fingerprint method and benchmarked the scoring function HWK (Hamza-Wei-Korotkov), using the 81 targets of the DEKOIS database. Subsequently, we applied our combined 4D fingerprint and HWK scoring function VS approach in scaffold-hopping and drug repurposing using the National Cancer Institute (NCI) and Food and Drug Administration (FDA) databases, and we identified new inhibitors with different scaffolds of MycP1 protease from the mycobacterial ESX-1 secretion system. Experimental evaluation of nine compounds from the NCI database and three from the FDA database displayed IC50 values ranging from 70 to 100 μM against MycP1 and possessed high structural diversity, which provides departure points for further structure-activity relationship (SAR) optimization. In addition, this study demonstrates that the combination of our 4D fingerprint algorithm and the HWK scoring function may provide a means for identifying repurposed drugs for the treatment of infectious diseases and may be used in the drug-target profile strategy.

GeneRIF indexing: sentence selection based on machine learning.

PubMed

Jimeno-Yepes, Antonio J; Sticco, J Caitlin; Mork, James G; Aronson, Alan R

2013-05-31

A Gene Reference Into Function (GeneRIF) describes novel functionality of genes. GeneRIFs are available from the National Center for Biotechnology Information (NCBI) Gene database. GeneRIF indexing is performed manually, and the intention of our work is to provide methods to support creating the GeneRIF entries. The creation of GeneRIF entries involves the identification of the genes mentioned in MEDLINE®; citations and the sentences describing a novel function. We have compared several learning algorithms and several features extracted or derived from MEDLINE sentences to determine if a sentence should be selected for GeneRIF indexing. Features are derived from the sentences or using mechanisms to augment the information provided by them: assigning a discourse label using a previously trained model, for example. We show that machine learning approaches with specific feature combinations achieve results close to one of the annotators. We have evaluated different feature sets and learning algorithms. In particular, Naïve Bayes achieves better performance with a selection of features similar to one used in related work, which considers the location of the sentence, the discourse of the sentence and the functional terminology in it. The current performance is at a level similar to human annotation and it shows that machine learning can be used to automate the task of sentence selection for GeneRIF annotation. The current experiments are limited to the human species. We would like to see how the methodology can be extended to other species, specifically the normalization of gene mentions in other species.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold.

PubMed

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel; Ten Have, Arjen

2018-01-01

Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER.

HMMER Cut-off Threshold Tool (HMMERCTTER): Supervised classification of superfamily protein sequences with a reliable cut-off threshold

PubMed Central

Pagnuco, Inti Anabela; Revuelta, María Victoria; Bondino, Hernán Gabriel; Brun, Marcel

2018-01-01

Background Protein superfamilies can be divided into subfamilies of proteins with different functional characteristics. Their sequences can be classified hierarchically, which is part of sequence function assignation. Typically, there are no clear subfamily hallmarks that would allow pattern-based function assignation by which this task is mostly achieved based on the similarity principle. This is hampered by the lack of a score cut-off that is both sensitive and specific. Results HMMER Cut-off Threshold Tool (HMMERCTTER) adds a reliable cut-off threshold to the popular HMMER. Using a high quality superfamily phylogeny, it clusters a set of training sequences such that the cluster-specific HMMER profiles show cluster or subfamily member detection with 100% precision and recall (P&R), thereby generating a specific threshold as inclusion cut-off. Profiles and thresholds are then used as classifiers to screen a target dataset. Iterative inclusion of novel sequences to groups and the corresponding HMMER profiles results in high sensitivity while specificity is maintained by imposing 100% P&R self detection. In three presented case studies of protein superfamilies, classification of large datasets with 100% precision was achieved with over 95% recall. Limits and caveats are presented and explained. Conclusions HMMERCTTER is a promising protein superfamily sequence classifier provided high quality training datasets are used. It provides a decision support system that aids in the difficult task of sequence function assignation in the twilight zone of sequence similarity. All relevant data and source codes are available from the Github repository at the following URL: https://github.com/BBCMdP/HMMERCTTER. PMID:29579071

A new modification in the exponential rational function method for nonlinear fractional differential equations

NASA Astrophysics Data System (ADS)

Ahmed, Naveed; Bibi, Sadaf; Khan, Umar; Mohyud-Din, Syed Tauseef

2018-02-01

We have modified the traditional exponential rational function method (ERFM) and have used it to find the exact solutions of two different fractional partial differential equations, one is the time fractional Boussinesq equation and the other is the (2+1)-dimensional time fractional Zoomeron equation. In both the cases it is observed that the modified scheme provides more types of solutions than the traditional one. Moreover, a comparison of the recent solutions is made with some already existing solutions. We can confidently conclude that the modified scheme works better and provides more types of solutions with almost similar computational cost. Our generalized solutions include periodic, soliton-like, singular soliton and kink solutions. A graphical simulation of all types of solutions is provided and the correctness of the solution is verified by direct substitution. The extended version of the solutions is expected to provide more flexibility to scientists working in the relevant field to test their simulation data.

Logistic Model to Support Service Modularity for the Promotion of Reusability in a Web Objects-Enabled IoT Environment.

PubMed

Kibria, Muhammad Golam; Ali, Sajjad; Jarwar, Muhammad Aslam; Kumar, Sunil; Chong, Ilyoung

2017-09-22

Due to a very large number of connected virtual objects in the surrounding environment, intelligent service features in the Internet of Things requires the reuse of existing virtual objects and composite virtual objects. If a new virtual object is created for each new service request, then the number of virtual object would increase exponentially. The Web of Objects applies the principle of service modularity in terms of virtual objects and composite virtual objects. Service modularity is a key concept in the Web Objects-Enabled Internet of Things (IoT) environment which allows for the reuse of existing virtual objects and composite virtual objects in heterogeneous ontologies. In the case of similar service requests occurring at the same, or different locations, the already-instantiated virtual objects and their composites that exist in the same, or different ontologies can be reused. In this case, similar types of virtual objects and composite virtual objects are searched and matched. Their reuse avoids duplication under similar circumstances, and reduces the time it takes to search and instantiate them from their repositories, where similar functionalities are provided by similar types of virtual objects and their composites. Controlling and maintaining a virtual object means controlling and maintaining a real-world object in the real world. Even though the functional costs of virtual objects are just a fraction of those for deploying and maintaining real-world objects, this article focuses on reusing virtual objects and composite virtual objects, as well as discusses similarity matching of virtual objects and composite virtual objects. This article proposes a logistic model that supports service modularity for the promotion of reusability in the Web Objects-enabled IoT environment. Necessary functional components and a flowchart of an algorithm for reusing composite virtual objects are discussed. Also, to realize the service modularity, a use case scenario is studied and implemented.

Logistic Model to Support Service Modularity for the Promotion of Reusability in a Web Objects-Enabled IoT Environment

PubMed Central

Chong, Ilyoung

2017-01-01

Due to a very large number of connected virtual objects in the surrounding environment, intelligent service features in the Internet of Things requires the reuse of existing virtual objects and composite virtual objects. If a new virtual object is created for each new service request, then the number of virtual object would increase exponentially. The Web of Objects applies the principle of service modularity in terms of virtual objects and composite virtual objects. Service modularity is a key concept in the Web Objects-Enabled Internet of Things (IoT) environment which allows for the reuse of existing virtual objects and composite virtual objects in heterogeneous ontologies. In the case of similar service requests occurring at the same, or different locations, the already-instantiated virtual objects and their composites that exist in the same, or different ontologies can be reused. In this case, similar types of virtual objects and composite virtual objects are searched and matched. Their reuse avoids duplication under similar circumstances, and reduces the time it takes to search and instantiate them from their repositories, where similar functionalities are provided by similar types of virtual objects and their composites. Controlling and maintaining a virtual object means controlling and maintaining a real-world object in the real world. Even though the functional costs of virtual objects are just a fraction of those for deploying and maintaining real-world objects, this article focuses on reusing virtual objects and composite virtual objects, as well as discusses similarity matching of virtual objects and composite virtual objects. This article proposes a logistic model that supports service modularity for the promotion of reusability in the Web Objects-enabled IoT environment. Necessary functional components and a flowchart of an algorithm for reusing composite virtual objects are discussed. Also, to realize the service modularity, a use case scenario is studied and implemented. PMID:28937590

Coexpression landscape in ATTED-II: usage of gene list and gene network for various types of pathways.

PubMed

Obayashi, Takeshi; Kinoshita, Kengo

2010-05-01

Gene coexpression analyses are a powerful method to predict the function of genes and/or to identify genes that are functionally related to query genes. The basic idea of gene coexpression analyses is that genes with similar functions should have similar expression patterns under many different conditions. This approach is now widely used by many experimental researchers, especially in the field of plant biology. In this review, we will summarize recent successful examples obtained by using our gene coexpression database, ATTED-II. Specifically, the examples will describe the identification of new genes, such as the subunits of a complex protein, the enzymes in a metabolic pathway and transporters. In addition, we will discuss the discovery of a new intercellular signaling factor and new regulatory relationships between transcription factors and their target genes. In ATTED-II, we provide two basic views of gene coexpression, a gene list view and a gene network view, which can be used as guide gene approach and narrow-down approach, respectively. In addition, we will discuss the coexpression effectiveness for various types of gene sets.

On Integral Invariants for Effective 3-D Motion Trajectory Matching and Recognition.

PubMed

Shao, Zhanpeng; Li, Youfu

2016-02-01

Motion trajectories tracked from the motions of human, robots, and moving objects can provide an important clue for motion analysis, classification, and recognition. This paper defines some new integral invariants for a 3-D motion trajectory. Based on two typical kernel functions, we design two integral invariants, the distance and area integral invariants. The area integral invariants are estimated based on the blurred segment of noisy discrete curve to avoid the computation of high-order derivatives. Such integral invariants for a motion trajectory enjoy some desirable properties, such as computational locality, uniqueness of representation, and noise insensitivity. Moreover, our formulation allows the analysis of motion trajectories at a range of scales by varying the scale of kernel function. The features of motion trajectories can thus be perceived at multiscale levels in a coarse-to-fine manner. Finally, we define a distance function to measure the trajectory similarity to find similar trajectories. Through the experiments, we examine the robustness and effectiveness of the proposed integral invariants and find that they can capture the motion cues in trajectory matching and sign recognition satisfactorily.

Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI

PubMed Central

Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo

2014-01-01

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441

Near-field observations of microearthquake source physics using dense array

NASA Astrophysics Data System (ADS)

Chen, X.; Nakata, N.; Abercrombie, R. E.

2017-12-01

The recorded waveform includes contributions from earthquake source properties and propagation effects, leading to long-standing trade-off problems between site/path effects and source effects. This problem is especially significant for small earthquakes where the corner frequencies are within similar ranges of near-site attenuation effects. Fortunately, this problem can be remedied by dense near-field recordings at high frequency, and large databases with wide magnitude range. The 2016 IRIS wavefield experiment provides high-quality recordings of earthquake sequences in north-central Oklahoma with about 400 sensors in 15 km area. Preliminary processing of the IRIS wavefield array resulted with about 20,000 microearthquakes ranging from M-1 to M2, while only 2 earthquakes are listed in the catalog during the same time period. A preliminary examination of the catalog reveals three similar magnitude earthquakes (M 2) occurred at similar locations within 9 seconds of each other. Utilizing this catalog, we will combine individual empirical Green's function (EGF) analysis and stacking over multiple EGFs to examine if there are any systematic variations of source time functions and spectral ratios across the array, which will provide constrains of rupture complexity, directivity and earthquake interactions. For example, this would help us to understand if these three earthquakes rupture overlapping fault patches from cascading failure, or from repeated rupture at the same slip patch due to external stress loading. Deciphering the interaction at smaller scales with near-field observations is important for a controlled earthquake experiment.

Bacterial avirulence genes.

PubMed

Leach, J E; White, F F

1996-01-01

Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance.

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.

PubMed

Gabardi, Steven; Asipenko, Natalya; Fleming, James; Lor, Kevin; McDevitt-Potter, Lisa; Mohammed, Anisa; Rogers, Christin; Tichy, Eric M; Weng, Renee; Lee, Ruth-Ann

2015-07-01

Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.

Sensor Level Functional Connectivity Topography Comparison Between Different References Based EEG and MEG

PubMed Central

Huang, Yunzhi; Zhang, Junpeng; Cui, Yuan; Yang, Gang; Liu, Qi; Yin, Guangfu

2018-01-01

Sensor-level functional connectivity topography (sFCT) contributes significantly to our understanding of brain networks. sFCT can be constructed using either electroencephalography (EEG) or magnetoencephalography (MEG). Here, we compared sFCT within the EEG modality and between EEG and MEG modalities. We first used simulations to look at how different EEG references—including the Reference Electrode Standardization Technique (REST), average reference (AR), linked mastoids (LM), and left mastoid references (LR)—affect EEG-based sFCT. The results showed that REST decreased the reference effects on scalp EEG recordings, making REST-based sFCT closer to the ground truth (sFCT based on ideal recordings). For the inter-modality simulation comparisons, we compared each type of EEG-sFCT with MEG-sFCT using three metrics to quantize the differences: Relative Error (RE), Overlap Rate (OR), and Hamming Distance (HD). When two sFCTs are similar, RE and HD are low, while OR is high. Results showed that among all reference schemes, EEG-and MEG-sFCT were most similar when the EEG was REST-based and the EEG and MEG were recorded simultaneously. Next, we analyzed simultaneously recorded MEG and EEG data from publicly available face-recognition experiments using a similar procedure as in the simulations. The results showed (1) if MEG-sFCT is the standard, REST—and LM-based sFCT provided results closer to this standard in the terms of HD; (2) REST-based sFCT and MEG-sFCT had the highest similarity in terms of RE; (3) REST-based sFCT had the most overlapping edges with MEG-sFCT in terms of OR. This study thus provides new insights into the effect of different reference schemes on sFCT and the similarity between MEG and EEG in terms of sFCT. PMID:29867395

Neurophysiological evidence for transfer appropriate processing of memory: processing versus feature similarity.

PubMed

Schendan, Haune E; Kutas, Malra

2007-08-01

Transfer appropriate processing (TAP) accounts propose that memory is a function of the degree to which the same neural processes transfer appropriately from the study experience to the memory test. However, in prior research, study and test stimuli were often similar physically. In two experiments, event-related brain potentials (ERPs) were recorded to fragmented objects during an indirect memory test to isolate transfer of a specific perceptual process from overlap of physical features between experiences. An occipitotemporoparietal P2(00) at 200 msec showed implicit memory effects only when similar perceptual grouping processes of good continuation were repeatedly engaged-despite physical feature differences--as TAP accounts hypothesize. This result provides direct neurophysiological evidence for the critical role of process transfer across experiences for memory.

Understand protein functions by comparing the similarity of local structural environments.

PubMed

Chen, Jiawen; Xie, Zhong-Ru; Wu, Yinghao

2017-02-01

The three-dimensional structures of proteins play an essential role in regulating binding between proteins and their partners, offering a direct relationship between structures and functions of proteins. It is widely accepted that the function of a protein can be determined if its structure is similar to other proteins whose functions are known. However, it is also observed that proteins with similar global structures do not necessarily correspond to the same function, while proteins with very different folds can share similar functions. This indicates that function similarity is originated from the local structural information of proteins instead of their global shapes. We assume that proteins with similar local environments prefer binding to similar types of molecular targets. In order to testify this assumption, we designed a new structural indicator to define the similarity of local environment between residues in different proteins. This indicator was further used to calculate the probability that a given residue binds to a specific type of structural neighbors, including DNA, RNA, small molecules and proteins. After applying the method to a large-scale non-redundant database of proteins, we show that the positive signal of binding probability calculated from the local structural indicator is statistically meaningful. In summary, our studies suggested that the local environment of residues in a protein is a good indicator to recognize specific binding partners of the protein. The new method could be a potential addition to a suite of existing template-based approaches for protein function prediction. Copyright © 2016 Elsevier B.V. All rights reserved.

Does the Body Survive Death? Cultural Variation in Beliefs About Life Everlasting.

PubMed

Watson-Jones, Rachel E; Busch, Justin T A; Harris, Paul L; Legare, Cristine H

2017-04-01

Mounting evidence suggests that endorsement of psychological continuity and the afterlife increases with age. This developmental change raises questions about the cognitive biases, social representations, and cultural input that may support afterlife beliefs. To what extent is there similarity versus diversity across cultures in how people reason about what happens after death? The objective of this study was to compare beliefs about the continuation of biological and psychological functions after death in Tanna, Vanuatu (a Melanesian archipelago), and the United States (Austin, Texas). Children, adolescents, and adults were primed with a story that contained either natural (non-theistic) or supernatural (theistic) cues. Participants were then asked whether or not different biological and psychological processes continue to function after death. We predicted that across cultures individuals would be more likely to endorse the continuation of psychological processes over biological processes (dualism) and that a theistic prime would increase continuation responses regarding both types of process. Results largely supported predictions; U.S. participants provided more continuation responses for psychological than biological processes following both the theistic and non-theistic primes. Participants in Vanuatu, however, provided more continuation responses for biological than psychological processes following the theistic prime. The data provide evidence for both cultural similarity and variability in afterlife beliefs and demonstrate that individuals use both natural and supernatural explanations to interpret the same events. Copyright © 2016 Cognitive Science Society, Inc.

Shuttle user analysis (study 2.2). Volume 4: Standardized subsystem modules analysis

NASA Technical Reports Server (NTRS)

1974-01-01

The capability to analyze payloads constructed of standardized modules was provided for the planning of future mission models. An inventory of standardized module designs previously obtained was used as a starting point. Some of the conclusions and recommendations are: (1) the two growth factor synthesis methods provide logical configurations for satellite type selection; (2) the recommended method is the one that determines the growth factor as a function of the baseline subsystem weight, since it provides a larger growth factor for small subsystem weights and results in a greater overkill due to standardization; (3) the method that is not recommended is the one that depends upon a subsystem similarity selection, since care must be used in the subsystem similarity selection; (4) it is recommended that the application of standardized subsystem factors be limited to satellites with baseline dry weights between about 700 and 6,500 lbs; and (5) the standardized satellite design approach applies to satellites maintainable in orbit or retrieved for ground maintenance.

On the distribution of a product of N Gaussian random variables

NASA Astrophysics Data System (ADS)

Stojanac, Željka; Suess, Daniel; Kliesch, Martin

2017-08-01

The product of Gaussian random variables appears naturally in many applications in probability theory and statistics. It has been known that the distribution of a product of N such variables can be expressed in terms of a Meijer G-function. Here, we compute a similar representation for the corresponding cumulative distribution function (CDF) and provide a power-log series expansion of the CDF based on the theory of the more general Fox H-functions. Numerical computations show that for small values of the argument the CDF of products of Gaussians is well approximated by the lowest orders of this expansion. Analogous results are also shown for the absolute value as well as the square of such products of N Gaussian random variables. For the latter two settings, we also compute the moment generating functions in terms of Meijer G-functions.

Variable-range-hopping magnetoresistance

NASA Astrophysics Data System (ADS)

Azbel, Mark Ya

1991-03-01

The hopping magnetoresistance R of a two-dimensional insulator with metallic impurities is considered. In sufficiently weak magnetic fields it increases or decreases depending on the impurity density n: It decreases if n is low and increases if n is high. In high magnetic fields B, it always exponentially increases with √B . Such fields yield a one-dimensional temperature dependence: lnR~1/ √T . The calculation provides an accurate leading approximation for small impurities with one eigenstate in their potential well. In the limit of infinitesimally small impurities, an impurity potential is described by a generalized function. This function, similar to a δ function, is localized at a point, but, contrary to a δ function in the dimensionality above 1, it has finite eigenenergies. Such functions may be helpful in the study of scattering and localization of any waves.

Acyl-Lipid Metabolism

PubMed Central

Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

2013-01-01

Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

Acyl-Lipid Metabolism

PubMed Central

Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

2010-01-01

Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:22303259

An efficient method for hybrid density functional calculation with spin-orbit coupling

NASA Astrophysics Data System (ADS)

Wang, Maoyuan; Liu, Gui-Bin; Guo, Hong; Yao, Yugui

2018-03-01

In first-principles calculations, hybrid functional is often used to improve accuracy from local exchange correlation functionals. A drawback is that evaluating the hybrid functional needs significantly more computing effort. When spin-orbit coupling (SOC) is taken into account, the non-collinear spin structure increases computing effort by at least eight times. As a result, hybrid functional calculations with SOC are intractable in most cases. In this paper, we present an approximate solution to this problem by developing an efficient method based on a mixed linear combination of atomic orbital (LCAO) scheme. We demonstrate the power of this method using several examples and we show that the results compare very well with those of direct hybrid functional calculations with SOC, yet the method only requires a computing effort similar to that without SOC. The presented technique provides a good balance between computing efficiency and accuracy, and it can be extended to magnetic materials.

Detection of functionally important regions in "hypothetical proteins" of known structure.

PubMed

Nimrod, Guy; Schushan, Maya; Steinberg, David M; Ben-Tal, Nir

2008-12-10

Structural genomics initiatives provide ample structures of "hypothetical proteins" (i.e., proteins of unknown function) at an ever increasing rate. However, without function annotation, this structural goldmine is of little use to biologists who are interested in particular molecular systems. To this end, we used (an improved version of) the PatchFinder algorithm for the detection of functional regions on the protein surface, which could mediate its interactions with, e.g., substrates, ligands, and other proteins. Examination, using a data set of annotated proteins, showed that PatchFinder outperforms similar methods. We collected 757 structures of hypothetical proteins and their predicted functional regions in the N-Func database. Inspection of several of these regions demonstrated that they are useful for function prediction. For example, we suggested an interprotein interface and a putative nucleotide-binding site. A web-server implementation of PatchFinder and the N-Func database are available at http://patchfinder.tau.ac.il/.

Specialisation of extracellular matrix for function in tendons and ligaments

PubMed Central

Birch, Helen L.; Thorpe, Chavaunne T.; Rumian, Adam P.

2013-01-01

Summary Tendons and ligaments are similar structures in terms of their composition, organisation and mechanical properties. The distinction between them stems from their anatomical location; tendons form a link between muscle and bone while ligaments link bones to bones. A range of overlapping functions can be assigned to tendon and ligaments and each structure has specific mechanical properties which appear to be suited for particular in vivo function. The extracellular matrix in tendon and ligament varies in accordance with function, providing appropriate mechanical properties. The most useful framework in which to consider extracellular matrix differences therefore is that of function rather than anatomical location. In this review we discuss what is known about the relationship between functional requirements, structural properties from molecular to gross level, cellular gene expression and matrix turnover. The relevance of this information is considered by reviewing clinical aspects of tendon and ligament repair and reconstructive procedures. PMID:23885341

12 CFR 48.14 - Supervision.

Code of Federal Regulations, 2014 CFR

2014-01-01

....14 Supervision. (a) Supervision by the national bank. A national bank engaging in retail forex... occupying a similar status or performing a similar function) of all retail forex accounts carried, operated... persons occupying a similar status or performing a similar function) relating to its retail forex business...

12 CFR 48.14 - Supervision.

Code of Federal Regulations, 2012 CFR

2012-01-01

....14 Supervision. (a) Supervision by the national bank. A national bank engaging in retail forex... occupying a similar status or performing a similar function) of all retail forex accounts carried, operated... persons occupying a similar status or performing a similar function) relating to its retail forex business...

12 CFR 48.14 - Supervision.

Code of Federal Regulations, 2013 CFR

2013-01-01

....14 Supervision. (a) Supervision by the national bank. A national bank engaging in retail forex... occupying a similar status or performing a similar function) of all retail forex accounts carried, operated... persons occupying a similar status or performing a similar function) relating to its retail forex business...

Custom controls

NASA Astrophysics Data System (ADS)

Butell, Bart

1996-02-01

Microsoft's Visual Basic (VB) and Borland's Delphi provide an extremely robust programming environment for delivering multimedia solutions for interactive kiosks, games and titles. Their object oriented use of standard and custom controls enable a user to build extremely powerful applications. A multipurpose, database enabled programming environment that can provide an event driven interface functions as a multimedia kernel. This kernel can provide a variety of authoring solutions (e.g. a timeline based model similar to Macromedia Director or a node authoring model similar to Icon Author). At the heart of the kernel is a set of low level multimedia components providing object oriented interfaces for graphics, audio, video and imaging. Data preparation tools (e.g., layout, palette and Sprite Editors) could be built to manage the media database. The flexible interface for VB allows the construction of an infinite number of user models. The proliferation of these models within a popular, easy to use environment will allow the vast developer segment of 'producer' types to bring their ideas to the market. This is the key to building exciting, content rich multimedia solutions. Microsoft's VB and Borland's Delphi environments combined with multimedia components enable these possibilities.

Lower Emittance Lattice for the Advanced Photon Source Upgrade Using Reverse Bending Magnets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borland, M.; Berenc, T.; Sun, Y.

The Advanced Photon Source (APS) is pursuing an upgrade to the storage ring to a hybrid seven-bend-achromat design [1]. The nominal design provides a natural emittance of 67 pm [2]. By adding reverse dipole fields to several quadrupoles [3, 4] we can reduce the natural emittance to 41 pm while simultaneously providing more optimal beta functions in the insertion devices and increasing the dispersion function at the chromaticity sextupole magnets. The improved emittance results from a combination of increased energy loss per turn and a change in the damping partition. At the same time, the nonlinear dynamics performance is verymore » similar, thanks in part to increased dispersion in the sextupoles. This paper describes the properties, optimization, and performance of the new lattice.« less

TRANSAT-- method for detecting the conserved helices of functional RNA structures, including transient, pseudo-knotted and alternative structures.

PubMed

Wiebe, Nicholas J P; Meyer, Irmtraud M

2010-06-24

The prediction of functional RNA structures has attracted increased interest, as it allows us to study the potential functional roles of many genes. RNA structure prediction methods, however, assume that there is a unique functional RNA structure and also do not predict functional features required for in vivo folding. In order to understand how functional RNA structures form in vivo, we require sophisticated experiments or reliable prediction methods. So far, there exist only a few, experimentally validated transient RNA structures. On the computational side, there exist several computer programs which aim to predict the co-transcriptional folding pathway in vivo, but these make a range of simplifying assumptions and do not capture all features known to influence RNA folding in vivo. We want to investigate if evolutionarily related RNA genes fold in a similar way in vivo. To this end, we have developed a new computational method, Transat, which detects conserved helices of high statistical significance. We introduce the method, present a comprehensive performance evaluation and show that Transat is able to predict the structural features of known reference structures including pseudo-knotted ones as well as those of known alternative structural configurations. Transat can also identify unstructured sub-sequences bound by other molecules and provides evidence for new helices which may define folding pathways, supporting the notion that homologous RNA sequence not only assume a similar reference RNA structure, but also fold similarly. Finally, we show that the structural features predicted by Transat differ from those assuming thermodynamic equilibrium. Unlike the existing methods for predicting folding pathways, our method works in a comparative way. This has the disadvantage of not being able to predict features as function of time, but has the considerable advantage of highlighting conserved features and of not requiring a detailed knowledge of the cellular environment.

Basis for substrate recognition and distinction by matrix metalloproteinases

PubMed Central

Ratnikov, Boris I.; Cieplak, Piotr; Gramatikoff, Kosi; Pierce, James; Eroshkin, Alexey; Igarashi, Yoshinobu; Kazanov, Marat; Sun, Qing; Godzik, Adam; Osterman, Andrei; Stec, Boguslaw; Strongin, Alex; Smith, Jeffrey W.

2014-01-01

Genomic sequencing and structural genomics produced a vast amount of sequence and structural data, creating an opportunity for structure–function analysis in silico [Radivojac P, et al. (2013) Nat Methods 10(3):221–227]. Unfortunately, only a few large experimental datasets exist to serve as benchmarks for function-related predictions. Furthermore, currently there are no reliable means to predict the extent of functional similarity among proteins. Here, we quantify structure–function relationships among three phylogenetic branches of the matrix metalloproteinase (MMP) family by comparing their cleavage efficiencies toward an extended set of phage peptide substrates that were selected from ∼64 million peptide sequences (i.e., a large unbiased representation of substrate space). The observed second-order rate constants [k(obs)] across the substrate space provide a distance measure of functional similarity among the MMPs. These functional distances directly correlate with MMP phylogenetic distance. There is also a remarkable and near-perfect correlation between the MMP substrate preference and sequence identity of 50–57 discontinuous residues surrounding the catalytic groove. We conclude that these residues represent the specificity-determining positions (SDPs) that allowed for the expansion of MMP proteolytic function during evolution. A transmutation of only a few selected SDPs proximal to the bound substrate peptide, and contributing the most to selectivity among the MMPs, is sufficient to enact a global change in the substrate preference of one MMP to that of another, indicating the potential for the rational and focused redesign of cleavage specificity in MMPs. PMID:25246591

Comparing the in Vivo Function of α-Carboxysomes and β-Carboxysomes in Two Model Cyanobacteria1[W][OPEN

PubMed Central

Whitehead, Lynne; Long, Benedict M.; Price, G. Dean; Badger, Murray R.

2014-01-01

The carbon dioxide (CO2)-concentrating mechanism of cyanobacteria is characterized by the occurrence of Rubisco-containing microcompartments called carboxysomes within cells. The encapsulation of Rubisco allows for high-CO2 concentrations at the site of fixation, providing an advantage in low-CO2 environments. Cyanobacteria with Form-IA Rubisco contain α-carboxysomes, and cyanobacteria with Form-IB Rubisco contain β-carboxysomes. The two carboxysome types have arisen through convergent evolution, and α-cyanobacteria and β-cyanobacteria occupy different ecological niches. Here, we present, to our knowledge, the first direct comparison of the carboxysome function from α-cyanobacteria (Cyanobium spp. PCC7001) and β-cyanobacteria (Synechococcus spp. PCC7942) with similar inorganic carbon (Ci; as CO2 and HCO3−) transporter systems. Despite evolutionary and structural differences between α-carboxysomes and β-carboxysomes, we found that the two strains are remarkably similar in many physiological parameters, particularly the response of photosynthesis to light and external Ci and their modulation of internal ribulose-1,5-bisphosphate, phosphoglycerate, and Ci pools when grown under comparable conditions. In addition, the different Rubisco forms present in each carboxysome had almost identical kinetic parameters. The conclusions indicate that the possession of different carboxysome types does not significantly influence the physiological function of these species and that similar carboxysome function may be possessed by each carboxysome type. Interestingly, both carboxysome types showed a response to cytosolic Ci, which is of higher affinity than predicted by current models, being saturated by 5 to 15 mm Ci. This finding has bearing on the viability of transplanting functional carboxysomes into the C3 chloroplast. PMID:24642960

Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

PubMed

Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2014-03-01

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

PubMed Central

Ramanathan, Arvind; Agarwal, Pratul K.

2011-01-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design. PMID:22087074

Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis.

PubMed

Ramanathan, Arvind; Agarwal, Pratul K

2011-11-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramanathan, Arvind; Agarwal, Pratul K

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function.more » Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.« less

Local functional descriptors for surface comparison based binding prediction

PubMed Central

2012-01-01

Background Molecular recognition in proteins occurs due to appropriate arrangements of physical, chemical, and geometric properties of an atomic surface. Similar surface regions should create similar binding interfaces. Effective methods for comparing surface regions can be used in identifying similar regions, and to predict interactions without regard to the underlying structural scaffold that creates the surface. Results We present a new descriptor for protein functional surfaces and algorithms for using these descriptors to compare protein surface regions to identify ligand binding interfaces. Our approach uses descriptors of local regions of the surface, and assembles collections of matches to compare larger regions. Our approach uses a variety of physical, chemical, and geometric properties, adaptively weighting these properties as appropriate for different regions of the interface. Our approach builds a classifier based on a training corpus of examples of binding sites of the target ligand. The constructed classifiers can be applied to a query protein providing a probability for each position on the protein that the position is part of a binding interface. We demonstrate the effectiveness of the approach on a number of benchmarks, demonstrating performance that is comparable to the state-of-the-art, with an approach with more generality than these prior methods. Conclusions Local functional descriptors offer a new method for protein surface comparison that is sufficiently flexible to serve in a variety of applications. PMID:23176080

ABOLISHING AND ESTABLISHING OPERATION ANALYSES OF SOCIAL ATTENTION AS POSITIVE REINFORCEMENT FOR PROBLEM BEHAVIOR

PubMed Central

McGinnis, Molly A; Houchins-Juárez, Nealetta; McDaniel, Jill L; Kennedy, Craig H

2010-01-01

Three participants whose problem behavior was maintained by contingent attention were exposed to 45-min presessions in which attention was withheld, provided on a fixed-time (FT) 15-s schedule, or provided on an FT 120-s schedule. Following each presession, participants were then tested in a 15-min session similar to the social attention condition of an analogue functional analysis. The results showed establishing operation conditions increased problem behavior during tests and that abolishing operation conditions decreased problem behavior during tests. PMID:20808502

Abolishing and establishing operation analyses of social attention as positive reinforcement for problem behavior.

PubMed

McGinnis, Molly A; Houchins-Juárez, Nealetta; McDaniel, Jill L; Kennedy, Craig H

2010-03-01

Three participants whose problem behavior was maintained by contingent attention were exposed to 45-min presessions in which attention was withheld, provided on a fixed-time (FT) 15-s schedule, or provided on an FT 120-s schedule. Following each presession, participants were then tested in a 15-min session similar to the social attention condition of an analogue functional analysis. The results showed establishing operation conditions increased problem behavior during tests and that abolishing operation conditions decreased problem behavior during tests.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

Functional interrogation of non-coding DNA through CRISPR genome editing

PubMed Central

Canver, Matthew C.; Bauer, Daniel E.; Orkin, Stuart H.

2017-01-01

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. PMID:28288828

General functioning predicts reward and punishment learning in schizophrenia.

PubMed

Somlai, Zsuzsanna; Moustafa, Ahmed A; Kéri, Szabolcs; Myers, Catherine E; Gluck, Mark A

2011-04-01

Previous studies investigating feedback-driven reinforcement learning in patients with schizophrenia have provided mixed results. In this study, we explored the clinical predictors of reward and punishment learning using a probabilistic classification learning task. Patients with schizophrenia (n=40) performed similarly to healthy controls (n=30) on the classification learning task. However, more severe negative and general symptoms were associated with lower reward-learning performance, whereas poorer general psychosocial functioning was correlated with both lower reward- and punishment-learning performances. Multiple linear regression analyses indicated that general psychosocial functioning was the only significant predictor of reinforcement learning performance when education, antipsychotic dose, and positive, negative and general symptoms were included in the analysis. These results suggest a close relationship between reinforcement learning and general psychosocial functioning in schizophrenia. Published by Elsevier B.V.

UK audit of analysis of quantitative parameters from renography data generated using a physical phantom.

PubMed

Nijran, Kuldip S; Houston, Alex S; Fleming, John S; Jarritt, Peter H; Heikkinen, Jari O; Skrypniuk, John V

2014-07-01

In this second UK audit of quantitative parameters obtained from renography, phantom simulations were used in cases in which the 'true' values could be estimated, allowing the accuracy of the parameters measured to be assessed. A renal physical phantom was used to generate a set of three phantom simulations (six kidney functions) acquired on three different gamma camera systems. A total of nine phantom simulations and three real patient studies were distributed to UK hospitals participating in the audit. Centres were asked to provide results for the following parameters: relative function and time-to-peak (whole kidney and cortical region). As with previous audits, a questionnaire collated information on methodology. Errors were assessed as the root mean square deviation from the true value. Sixty-one centres responded to the audit, with some hospitals providing multiple sets of results. Twenty-one centres provided a complete set of parameter measurements. Relative function and time-to-peak showed a reasonable degree of accuracy and precision in most UK centres. The overall average root mean squared deviation of the results for (i) the time-to-peak measurement for the whole kidney and (ii) the relative function measurement from the true value was 7.7 and 4.5%, respectively. These results showed a measure of consistency in the relative function and time-to-peak that was similar to the results reported in a previous renogram audit by our group. Analysis of audit data suggests a reasonable degree of accuracy in the quantification of renography function using relative function and time-to-peak measurements. However, it is reasonable to conclude that the objectives of the audit could not be fully realized because of the limitations of the mechanical phantom in providing true values for renal parameters.

Measuring semantic similarities by combining gene ontology annotations and gene co-function networks

DOE PAGES

Peng, Jiajie; Uygun, Sahra; Kim, Taehyong; ...

2015-02-14

Background: Gene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms. Results: We introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstratemore » that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families. Conclusions: Using NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited.« less

Statistical inference of dynamic resting-state functional connectivity using hierarchical observation modeling.

PubMed

Sojoudi, Alireza; Goodyear, Bradley G

2016-12-01

Spontaneous fluctuations of blood-oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) signals are highly synchronous between brain regions that serve similar functions. This provides a means to investigate functional networks; however, most analysis techniques assume functional connections are constant over time. This may be problematic in the case of neurological disease, where functional connections may be highly variable. Recently, several methods have been proposed to determine moment-to-moment changes in the strength of functional connections over an imaging session (so called dynamic connectivity). Here a novel analysis framework based on a hierarchical observation modeling approach was proposed, to permit statistical inference of the presence of dynamic connectivity. A two-level linear model composed of overlapping sliding windows of fMRI signals, incorporating the fact that overlapping windows are not independent was described. To test this approach, datasets were synthesized whereby functional connectivity was either constant (significant or insignificant) or modulated by an external input. The method successfully determines the statistical significance of a functional connection in phase with the modulation, and it exhibits greater sensitivity and specificity in detecting regions with variable connectivity, when compared with sliding-window correlation analysis. For real data, this technique possesses greater reproducibility and provides a more discriminative estimate of dynamic connectivity than sliding-window correlation analysis. Hum Brain Mapp 37:4566-4580, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Domain Selectivity in the Parahippocampal Gyrus Is Predicted by the Same Structural Connectivity Patterns in Blind and Sighted Individuals.

PubMed

Wang, Xiaoying; He, Chenxi; Peelen, Marius V; Zhong, Suyu; Gong, Gaolang; Caramazza, Alfonso; Bi, Yanchao

2017-05-03

Human ventral occipital temporal cortex contains clusters of neurons that show domain-preferring responses during visual perception. Recent studies have reported that some of these clusters show surprisingly similar domain selectivity in congenitally blind participants performing nonvisual tasks. An important open question is whether these functional similarities are driven by similar innate connections in blind and sighted groups. Here we addressed this question focusing on the parahippocampal gyrus (PHG), a region that is selective for large objects and scenes. Based on the assumption that patterns of long-range connectivity shape local computation, we examined whether domain selectivity in PHG is driven by similar structural connectivity patterns in the two populations. Multiple regression models were built to predict the selectivity of PHG voxels for large human-made objects from white matter (WM) connectivity patterns in both groups. These models were then tested using independent data from participants with similar visual experience (two sighted groups) and using data from participants with different visual experience (blind and sighted groups). Strikingly, the WM-based predictions between blind and sighted groups were as successful as predictions between two independent sighted groups. That is, the functional selectivity for large objects of a PHG voxel in a blind participant could be accurately predicted by its WM pattern using the connection-to-function model built from the sighted group data, and vice versa. Regions that significantly predicted PHG selectivity were located in temporal and frontal cortices in both sighted and blind populations. These results show that the large-scale network driving domain selectivity in PHG is independent of vision. SIGNIFICANCE STATEMENT Recent studies have reported intriguingly similar domain selectivity in sighted and congenitally blind individuals in regions within the ventral visual cortex. To examine whether these similarities originate from similar innate connectional roots, we investigated whether the domain selectivity in one population could be predicted by the structural connectivity pattern of the other. We found that the selectivity for large objects of a PHG voxel in a blind participant could be predicted by its structural connectivity pattern using the connection-to-function model built from the sighted group data, and vice versa. These results reveal that the structural connectivity underlying domain selectivity in the PHG is independent of visual experience, providing evidence for nonvisual representations in this region. Copyright © 2017 the authors 0270-6474/17/374706-12$15.00/0.

Dynamical potentials for nonequilibrium quantum many-body phases

NASA Astrophysics Data System (ADS)

Roy, Sthitadhi; Lazarides, Achilleas; Heyl, Markus; Moessner, Roderich

2018-05-01

Out of equilibrium phases of matter exhibiting order in individual eigenstates, such as many-body localized spin glasses and discrete time crystals, can be characterized by inherently dynamical quantities such as spatiotemporal correlation functions. In this paper, we introduce dynamical potentials which act as generating functions for such correlations and capture eigenstate phases and order. These potentials show formal similarities to their equilibrium counterparts, namely thermodynamic potentials. We provide three representative examples: a disordered XXZ chain showing many-body localization, a disordered Ising chain exhibiting spin-glass order, and its periodically-driven cousin exhibiting time-crystalline order.

Nuclear export of RNA: Different sizes, shapes and functions.

PubMed

Williams, Tobias; Ngo, Linh H; Wickramasinghe, Vihandha O

2018-03-01

Export of protein-coding and non-coding RNA molecules from the nucleus to the cytoplasm is critical for gene expression. This necessitates the continuous transport of RNA species of different size, shape and function through nuclear pore complexes via export receptors and adaptor proteins. Here, we provide an overview of the major RNA export pathways in humans, highlighting the similarities and differences between each. Its importance is underscored by the growing appreciation that deregulation of RNA export pathways is associated with human diseases like cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Toward chemical propulsion: synthesis of ROMP-propelled nanocars.

PubMed

Godoy, Jazmin; Vives, Guillaume; Tour, James M

2011-01-25

The synthesis and ring-opening metathesis polymerization (ROMP) activity of two nanocars functionalized with an olefin metathesis catalyst is reported. The nanocars were attached to a Hoveyda-Grubbs first- or second-generation metathesis catalyst via a benzylidene moiety. The catalytic activity of these nanocars toward ROMP of 1,5-cyclooctadiene was similar to that of their parent catalysts. The activity of the Hoveyda-Grubbs first-generation catalyst-functionalized nanocar was further tested with polymerization of norbornene. Hence, the prospect is heightened for a ROMP process to propel nanocars across a surface by providing the translational force.

Concepts for Life Cycle Cost Control Required to Achieve Space Transportation Affordability and Sustainability

NASA Technical Reports Server (NTRS)

Rhodes, Russel E.; Zapata, Edgar; Levack, Daniel J. H.; Robinson, John W.; Donahue, Benjamin B.

2009-01-01

Cost control must be implemented through the establishment of requirements and controlled continually by managing to these requirements. Cost control of the non-recurring side of life cycle cost has traditionally been implemented in both commercial and government programs. The government uses the budget process to implement this control. The commercial approach is to use a similar process of allocating the non-recurring cost to major elements of the program. This type of control generally manages through a work breakdown structure (WBS) by defining the major elements of the program. If the cost control is to be applied across the entire program life cycle cost (LCC), the approach must be addressed very differently. A functional breakdown structure (FBS) is defined and recommended. Use of a FBS provides the visibifity to allow the choice of an integrated solution reducing the cost of providing many different elements of like function. The different functional solutions that drive the hardware logistics, quantity of documentation, operational labor, reliability and maintainability balance, and total integration of the entire system from DDT&E through the life of the program must be fully defined, compared, and final decisions made among these competing solutions. The major drivers of recurring cost have been identified and are presented and discussed. The LCC requirements must be established and flowed down to provide control of LCC. This LCC control will require a structured rigid process similar to the one traditionally used to control weight/performance for space transportation systems throughout the entire program. It has been demonstrated over the last 30 years that without a firm requirement and methodically structured cost control, it is unlikely that affordable and sustainable space transportation system LCC will be achieved.

A plasma membrane sucrose-binding protein that mediates sucrose uptake shares structural and sequence similarity with seed storage proteins but remains functionally distinct.

PubMed

Overvoorde, P J; Chao, W S; Grimes, H D

1997-06-20

Photoaffinity labeling of a soybean cotyledon membrane fraction identified a sucrose-binding protein (SBP). Subsequent studies have shown that the SBP is a unique plasma membrane protein that mediates the linear uptake of sucrose in the presence of up to 30 mM external sucrose when ectopically expressed in yeast. Analysis of the SBP-deduced amino acid sequence indicates it lacks sequence similarity with other known transport proteins. Data presented here, however, indicate that the SBP shares significant sequence and structural homology with the vicilin-like seed storage proteins that organize into homotrimers. These similarities include a repeated sequence that forms the basis of the reiterated domain structure characteristic of the vicilin-like protein family. In addition, analytical ultracentrifugation and nonreducing SDS-polyacrylamide gel electrophoresis demonstrate that the SBP appears to be organized into oligomeric complexes with a Mr indicative of the existence of SBP homotrimers and homodimers. The structural similarity shared by the SBP and vicilin-like proteins provides a novel framework to explore the mechanistic basis of SBP-mediated sucrose uptake. Expression of the maize Glb protein (a vicilin-like protein closely related to the SBP) in yeast demonstrates that a closely related vicilin-like protein is unable to mediate sucrose uptake. Thus, despite sequence and structural similarities shared by the SBP and the vicilin-like protein family, the SBP is functionally divergent from other members of this group.

Box-Counting Dimension Revisited: Presenting an Efficient Method of Minimizing Quantization Error and an Assessment of the Self-Similarity of Structural Root Systems

PubMed Central

Bouda, Martin; Caplan, Joshua S.; Saiers, James E.

2016-01-01

Fractal dimension (FD), estimated by box-counting, is a metric used to characterize plant anatomical complexity or space-filling characteristic for a variety of purposes. The vast majority of published studies fail to evaluate the assumption of statistical self-similarity, which underpins the validity of the procedure. The box-counting procedure is also subject to error arising from arbitrary grid placement, known as quantization error (QE), which is strictly positive and varies as a function of scale, making it problematic for the procedure's slope estimation step. Previous studies either ignore QE or employ inefficient brute-force grid translations to reduce it. The goals of this study were to characterize the effect of QE due to translation and rotation on FD estimates, to provide an efficient method of reducing QE, and to evaluate the assumption of statistical self-similarity of coarse root datasets typical of those used in recent trait studies. Coarse root systems of 36 shrubs were digitized in 3D and subjected to box-counts. A pattern search algorithm was used to minimize QE by optimizing grid placement and its efficiency was compared to the brute force method. The degree of statistical self-similarity was evaluated using linear regression residuals and local slope estimates. QE, due to both grid position and orientation, was a significant source of error in FD estimates, but pattern search provided an efficient means of minimizing it. Pattern search had higher initial computational cost but converged on lower error values more efficiently than the commonly employed brute force method. Our representations of coarse root system digitizations did not exhibit details over a sufficient range of scales to be considered statistically self-similar and informatively approximated as fractals, suggesting a lack of sufficient ramification of the coarse root systems for reiteration to be thought of as a dominant force in their development. FD estimates did not characterize the scaling of our digitizations well: the scaling exponent was a function of scale. Our findings serve as a caution against applying FD under the assumption of statistical self-similarity without rigorously evaluating it first. PMID:26925073

"El lado oscuro": "the dark side" of social capital in Mexican American heroin using men.

PubMed

Flores, David V; Torres, Luis R; Torres-Vigil, Isabel; Ren, Yi; Haider, Ali; Bordnick, Patrick S

2013-01-01

This article describes social capital in a cohort of 227 Mexican American men who are long-term injection heroin users. Social capital scores for current and former users were similar, suggesting equal absolute values of capital, but associated with illicit activities in current users and with cessation efforts in former users. Stable drug-using relationships provided high negative capital, whereas conventional relationships provided positive capital. Thus, social capital functions dichotomously in positive and negative contextualized roles. This study provides an alternative understanding of the dynamic interactions between individuals, environment, and drug abuse and can inform prevention and treatment interventions for an important demographic group.

Hyperpolarized (3)He magnetic resonance imaging: comparison with four-dimensional x-ray computed tomography imaging in lung cancer.

PubMed

Mathew, Lindsay; Wheatley, Andrew; Castillo, Richard; Castillo, Edward; Rodrigues, George; Guerrero, Thomas; Parraga, Grace

2012-12-01

Pulmonary functional imaging using four-dimensional x-ray computed tomographic (4DCT) imaging and hyperpolarized (3)He magnetic resonance imaging (MRI) provides regional lung function estimates in patients with lung cancer in whom pulmonary function measurements are typically dominated by tumor burden. The aim of this study was to evaluate the quantitative spatial relationship between 4DCT and hyperpolarized (3)He MRI ventilation maps. Eleven patients with lung cancer provided written informed consent to 4DCT imaging and MRI performed within 11 ± 14 days. Hyperpolarized (3)He MRI was acquired in breath-hold after inhalation from functional residual capacity of 1 L hyperpolarized (3)He, whereas 4DCT imaging was acquired over a single tidal breath of room air. For hyperpolarized (3)He MRI, the percentage ventilated volume was generated using semiautomated segmentation; for 4DCT imaging, pulmonary function maps were generated using the correspondence between identical tissue elements at inspiratory and expiratory phases to generate percentage ventilated volume. After accounting for differences in image acquisition lung volumes ((3)He MRI: 1.9 ± 0.5 L ipsilateral, 2.3 ± 0.7 L contralateral; 4DCT imaging: 1.2 ± 0.3 L ipsilateral, 1.3 ± 0.4 L contralateral), there was no significant difference in percentage ventilated volume between hyperpolarized (3)He MRI (72 ± 11% ipsilateral, 79 ± 12% contralateral) and 4DCT imaging (74 ± 3% ipsilateral, 75 ± 4% contralateral). Spatial correspondence between 4DCT and (3)He MRI ventilation was evaluated using the Dice similarity coefficient index (ipsilateral, 86 ± 12%; contralateral, 88 ± 12%). Despite rather large differences in image acquisition breathing maneuvers, good spatial and significant quantitative agreement was observed for ventilation maps on hyperpolarized (3)He MRI and 4DCT imaging, suggesting that pulmonary regions with good lung function are similar between modalities in this small group of patients with lung cancer. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

The Academic Achievement and Functional Performance of Youth with Disabilities. A Report from the National Longitudinal Transition Study-2 (NLTS2). NCSER 2006-3000

ERIC Educational Resources Information Center

Wagner, Mary; Newman, Lynn; Cameto, Renee; Levine, Phyllis

2006-01-01

Background: To provide a national picture of the academic achievements of American students, the National Center for Education Statistics has administered the National Assessment of Educational Progress (NAEP) periodically since 1969, but there has been no similar national picture of the academic achievement of youth with disabilities. Purpose: To…

Stellar Inertial Navigation Workstation

NASA Technical Reports Server (NTRS)

Johnson, W.; Johnson, B.; Swaminathan, N.

1989-01-01

Software and hardware assembled to support specific engineering activities. Stellar Inertial Navigation Workstation (SINW) is integrated computer workstation providing systems and engineering support functions for Space Shuttle guidance and navigation-system logistics, repair, and procurement activities. Consists of personal-computer hardware, packaged software, and custom software integrated together into user-friendly, menu-driven system. Designed to operate on IBM PC XT. Applied in business and industry to develop similar workstations.

Bee communities along a prairie restoration chronosequence: similar abundance and diversity, distinct composition.

PubMed

Tonietto, Rebecca K; Ascher, John S; Larkin, Daniel J

2017-04-01

Recognition of the importance of bee conservation has grown in response to declines of managed honey bees and some wild bee species. Habitat loss has been implicated as a leading cause of declines, suggesting that ecological restoration is likely to play an increasing role in bee conservation efforts. In the midwestern United States, restoration of tallgrass prairie has traditionally targeted plant community objectives without explicit consideration for bees. However, restoration of prairie vegetation is likely to provide ancillary benefits to bees through increased foraging and nesting resources. We investigated community assembly of bees across a chronosequence of restored eastern tallgrass prairies and compared patterns to those in control and reference habitats (old fields and prairie remnants, respectively). We collected bees for 3 yr and measured diversity and abundance of in-bloom flowering plants, vegetation structure, ground cover, and surrounding land use as predictors of bee abundance and bee taxonomic and functional diversity. We found that site-level variables, but not site type or restoration age, were significant predictors of bee abundance (bloom diversity, P = 0.004; bare ground cover, P = 0.02) and bee diversity (bloom diversity, P = 0.01). There were significant correlations between overall composition of bee and blooming plant communities (Mantel test, P = 0.002), and both plant and bee assemblages in restorations were intermediate between those of old fields and remnant prairies. Restorations exhibited high bee beta diversity, i.e., restored sites' bee assemblages were taxonomically and functionally differentiated from each other. This pattern was strong in younger restorations (<20 yr old), but absent from older restorations (>20 yr), suggesting restored prairie bee communities become more similar to one another and more similar to remnant prairie bee communities over time with the arrival of more species and functional groups of bees. Our results indicate that old fields, restorations, and remnants provide habitat for diverse and abundant bee communities, but continued restoration of old fields will help support and conserve bee communities more similar to reference bee communities characteristic of remnant prairies. © 2016 by the Ecological Society of America.

Brain function assessment in different conscious states.

PubMed

Ozgoren, Murat; Bayazit, Onur; Kocaaslan, Sibel; Gokmen, Necati; Oniz, Adile

2010-06-03

The study of brain functioning is a major challenge in neuroscience fields as human brain has a dynamic and ever changing information processing. Case is worsened with conditions where brain undergoes major changes in so-called different conscious states. Even though the exact definition of consciousness is a hard one, there are certain conditions where the descriptions have reached a consensus. The sleep and the anesthesia are different conditions which are separable from each other and also from wakefulness. The aim of our group has been to tackle the issue of brain functioning with setting up similar research conditions for these three conscious states. In order to achieve this goal we have designed an auditory stimulation battery with changing conditions to be recorded during a 40 channel EEG polygraph (Nuamps) session. The stimuli (modified mismatch, auditory evoked etc.) have been administered both in the operation room and the sleep lab via Embedded Interactive Stimulus Unit which was developed in our lab. The overall study has provided some results for three domains of consciousness. In order to be able to monitor the changes we have incorporated Bispectral Index Monitoring to both sleep and anesthesia conditions. The first stage results have provided a basic understanding in these altered states such that auditory stimuli have been successfully processed in both light and deep sleep stages. The anesthesia provides a sudden change in brain responsiveness; therefore a dosage dependent anesthetic administration has proved to be useful. The auditory processing was exemplified targeting N1 wave, with a thorough analysis from spectrogram to sLORETA. The frequency components were observed to be shifting throughout the stages. The propofol administration and the deeper sleep stages both resulted in the decreasing of N1 component. The sLORETA revealed similar activity at BA7 in sleep (BIS 70) and target propofol concentration of 1.2 microg/mL. The current study utilized similar stimulation and recording system and incorporated BIS dependent values to validate a common approach to sleep and anesthesia. Accordingly the brain has a complex behavior pattern, dynamically changing its responsiveness in accordance with stimulations and states.

Improving the measurement of semantic similarity by combining gene ontology and co-functional network: a random walk based approach.

PubMed

Peng, Jiajie; Zhang, Xuanshuo; Hui, Weiwei; Lu, Junya; Li, Qianqian; Liu, Shuhui; Shang, Xuequn

2018-03-19

Gene Ontology (GO) is one of the most popular bioinformatics resources. In the past decade, Gene Ontology-based gene semantic similarity has been effectively used to model gene-to-gene interactions in multiple research areas. However, most existing semantic similarity approaches rely only on GO annotations and structure, or incorporate only local interactions in the co-functional network. This may lead to inaccurate GO-based similarity resulting from the incomplete GO topology structure and gene annotations. We present NETSIM2, a new network-based method that allows researchers to measure GO-based gene functional similarities by considering the global structure of the co-functional network with a random walk with restart (RWR)-based method, and by selecting the significant term pairs to decrease the noise information. Based on the EC number (Enzyme Commission)-based groups of yeast and Arabidopsis, evaluation test shows that NETSIM2 can enhance the accuracy of Gene Ontology-based gene functional similarity. Using NETSIM2 as an example, we found that the accuracy of semantic similarities can be significantly improved after effectively incorporating the global gene-to-gene interactions in the co-functional network, especially on the species that gene annotations in GO are far from complete.

Approximating lens power.

PubMed

Kaye, Stephen B

2009-04-01

To provide a scalar measure of refractive error, based on geometric lens power through principal, orthogonal and oblique meridians, that is not limited to the paraxial and sag height approximations. A function is derived to model sections through the principal meridian of a lens, followed by rotation of the section through orthogonal and oblique meridians. Average focal length is determined using the definition for the average of a function. Average univariate power in the principal meridian (including spherical aberration), can be computed from the average of a function over the angle of incidence as determined by the parameters of the given lens, or adequately computed from an integrated series function. Average power through orthogonal and oblique meridians, can be similarly determined using the derived formulae. The widely used computation for measuring refractive error, the spherical equivalent, introduces non-constant approximations, leading to a systematic bias. The equations proposed provide a good univariate representation of average lens power and are not subject to a systematic bias. They are particularly useful for the analysis of aggregate data, correlating with biological treatment variables and for developing analyses, which require a scalar equivalent representation of refractive power.

The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix Bundle Topped with a Hook.

PubMed

Stanger, Frédéric V; de Beer, Tjaart A P; Dranow, David M; Schirmer, Tilman; Phan, Isabelle; Dehio, Christoph

2017-01-03

The BID (Bep intracellular delivery) domain functions as secretion signal in a subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It mediates transfer of (1) relaxases and the attached DNA during bacterial conjugation, and (2) numerous Bartonella effector proteins (Beps) during protein transfer into host cells infected by pathogenic Bartonella species. Furthermore, BID domains of Beps have often evolved secondary effector functions within host cells. Here, we provide crystal structures for three representative BID domains and describe a novel conserved fold characterized by a compact, antiparallel four-helix bundle topped with a hook. The conserved hydrophobic core provides a rigid scaffold to a surface that, despite a few conserved exposed residues and similarities in charge distribution, displays significant variability. We propose that the genuine function of BID domains as T4S signal may primarily depend on their rigid structure, while the plasticity of their surface may facilitate adaptation to secondary effector functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Socioeconomic disparities affect prefrontal function in children.

PubMed

Kishiyama, Mark M; Boyce, W Thomas; Jimenez, Amy M; Perry, Lee M; Knight, Robert T

2009-06-01

Social inequalities have profound effects on the physical and mental health of children. Children from low socioeconomic status (SES) backgrounds perform below children from higher SES backgrounds on tests of intelligence and academic achievement, and recent findings indicate that low SES (LSES) children are impaired on behavioral measures of prefrontal function. However, the influence of socioeconomic disparity on direct measures of neural activity is unknown. Here, we provide electrophysiological evidence indicating that prefrontal function is altered in LSES children. We found that prefrontal-dependent electrophysiological measures of attention were reduced in LSES compared to high SES (HSES) children in a pattern similar to that observed in patients with lateral prefrontal cortex (PFC) damage. These findings provide neurophysiological evidence that social inequalities are associated with alterations in PFC function in LSES children. There are a number of factors associated with LSES rearing conditions that may have contributed to these results such as greater levels of stress and lack of access to cognitively stimulating materials and experiences. Targeting specific prefrontal processes affected by socioeconomic disparity could be helpful in developing intervention programs for LSES children.

The evolution of filamin – A protein domain repeat perspective

PubMed Central

Light, Sara; Sagit, Rauan; Ithychanda, Sujay S.; Qin, Jun; Elofsson, Arne

2013-01-01

Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. PMID:22414427

The evolution of filamin-a protein domain repeat perspective.

PubMed

Light, Sara; Sagit, Rauan; Ithychanda, Sujay S; Qin, Jun; Elofsson, Arne

2012-09-01

Particularly in higher eukaryotes, some protein domains are found in tandem repeats, performing broad functions often related to cellular organization. For instance, the eukaryotic protein filamin interacts with many proteins and is crucial for the cytoskeleton. The functional properties of long repeat domains are governed by the specific properties of each individual domain as well as by the repeat copy number. To provide better understanding of the evolutionary and functional history of repeating domains, we investigated the mode of evolution of the filamin domain in some detail. Among the domains that are common in long repeat proteins, sushi and spectrin domains evolve primarily through cassette tandem duplications while scavenger and immunoglobulin repeats appear to evolve through clustered tandem duplications. Additionally, immunoglobulin and filamin repeats exhibit a unique pattern where every other domain shows high sequence similarity. This pattern may be the result of tandem duplications, serve to avert aggregation between adjacent domains or it is the result of functional constraints. In filamin, our studies confirm the presence of interspersed integrin binding domains in vertebrates, while invertebrates exhibit more varied patterns, including more clustered integrin binding domains. The most notable case is leech filamin, which contains a 20 repeat expansion and exhibits unique dimerization topology. Clearly, invertebrate filamins are varied and contain examples of similar adjacent integrin-binding domains. Given that invertebrate integrin shows more similarity to the weaker filamin binder, integrin β3, it is possible that the distance between integrin-binding domains is not as crucial for invertebrate filamins as for vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

A Hypothesis for Examining Skeletal Muscle Biopsy-Derived Sarcolemmal nNOSμ as Surrogate for Enteric nNOSα Function

PubMed Central

Chaudhury, Arun

2015-01-01

The pathophysiology of gastrointestinal motility disorders is controversial and largely unresolved. This provokes empiric approaches to patient management of these so-called functional gastrointestinal disorders. Preliminary evidence demonstrates that defects in neuronal nitric oxide synthase (nNOS) expression and function, the enzyme that synthesizes nitric oxide (NO), the key inhibitory neurotransmitter mediating mechano-electrical smooth muscle relaxation, is the major pathophysiological basis for sluggishness of oro-aboral transit of luminal contents. This opinion is an ansatz of the potential of skeletal muscle biopsy and examining sarcolemmal nNOSμ to provide complementary insights regarding nNOSα expression, localization, and function within enteric nerve terminals, the site of stimulated de novo NO synthesis. The main basis of this thesis is twofold: (a) the molecular similarity of the structures of nNOS α and μ, similar mechanisms of localizations to “active zones” of nitrergic synthesis, and same mechanisms of electron transfers during NO synthesis and (b) pragmatic difficulty to routinely obtain full-thickness biopsies of gastrointestinal tract, even in patients presenting with the most recalcitrant manifestations of stasis and delayed transit of luminal contents. This opinion attempts to provoke dialog whether this approach is feasible as a surrogate to predict catalytic potential of nNOSα and defects in nitrergic neurotransmission. This discussion makes an assumption that similar molecular mechanisms of nNOS defects shall be operant in both the enteric nerve terminals and the skeletal muscles. These overlaps of skeletal and gastrointestinal dysfunction are largely unknown, thus meriting that the thesis be validated in future by proof-of-principle experiments. PMID:26284245

Rational Selection, Criticality Assessment, and Tiering of Quality Attributes and Test Methods for Analytical Similarity Evaluation of Biosimilars.

PubMed

Vandekerckhove, Kristof; Seidl, Andreas; Gutka, Hiten; Kumar, Manish; Gratzl, Gyöngyi; Keire, David; Coffey, Todd; Kuehne, Henriette

2018-05-10

Leading regulatory agencies recommend biosimilar assessment to proceed in a stepwise fashion, starting with a detailed analytical comparison of the structural and functional properties of the proposed biosimilar and reference product. The degree of analytical similarity determines the degree of residual uncertainty that must be addressed through downstream in vivo studies. Substantive evidence of similarity from comprehensive analytical testing may justify a targeted clinical development plan, and thus enable a shorter path to licensing. The importance of a careful design of the analytical similarity study program therefore should not be underestimated. Designing a state-of-the-art analytical similarity study meeting current regulatory requirements in regions such as the USA and EU requires a methodical approach, consisting of specific steps that far precede the work on the actual analytical study protocol. This white paper discusses scientific and methodological considerations on the process of attribute and test method selection, criticality assessment, and subsequent assignment of analytical measures to US FDA's three tiers of analytical similarity assessment. Case examples of selection of critical quality attributes and analytical methods for similarity exercises are provided to illustrate the practical implementation of the principles discussed.

Opposing assembly mechanisms in a neotropical dry forest: implications for phylogenetic and functional community ecology.

PubMed

Swenson, Nathan G; Enquist, Brian J

2009-08-01

Species diversity is promoted and maintained by ecological and evolutionary processes operating on species attributes through space and time. The degree to which variability in species function regulates distribution and promotes coexistence of species has been debated. Previous work has attempted to quantify the relative importance of species function by using phylogenetic relatedness as a proxy for functional similarity. The key assumption of this approach is that function is phylogenetically conserved. If this assumption is supported, then the phylogenetic dispersion in a community should mirror the functional dispersion. Here we quantify functional trait dispersion along several key axes of tree life-history variation and on multiple spatial scales in a Neotropical dry-forest community. We next compare these results to previously reported patterns of phylogenetic dispersion in this same forest. We find that, at small spatial scales, coexisting species are typically more functionally clustered than expected, but traits related to adult and regeneration niches are overdispersed. This outcome was repeated when the analyses were stratified by size class. Some of the trait dispersion results stand in contrast to the previously reported phylogenetic dispersion results. In order to address this inconsistency we examined the strength of phylogenetic signal in traits at different depths in the phylogeny. We argue that: (1) while phylogenetic relatedness may be a good general multivariate proxy for ecological similarity, it may have a reduced capacity to depict the functional mechanisms behind species coexistence when coexisting species simultaneously converge and diverge in function; and (2) the previously used metric of phylogenetic signal provided erroneous inferences about trait dispersion when married with patterns of phylogenetic dispersion.

Construct validity of the PROMIS® sexual function and satisfaction measures in patients with cancer

PubMed Central

2013-01-01

Background With data from a diverse sample of patients either in treatment for cancer or post-treatment for cancer, we examine inter-domain and cross-domain correlations among the core domains of the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measures (PROMIS® SexFS) and the corresponding domains from conceptually-similar measures of sexual function, the International Index of Erectile Function and the Female Sexual Function Index. Findings Men (N=389) and women (N=430) were recruited from a tumor registry, oncology clinics, and an internet panel. The PROMIS SexFS, International Index of Erectile Function, and Female Sexual Function Index were used to collect participants’ self-reported sexual function. The domains shared among the measures include desire/interest in sexual activity, lubrication and vaginal discomfort/pain (women), erectile function (men), orgasm, and satisfaction. We examined correlations among different domains within the same instrument (discriminant validity) and correlations among similar domains measured by different instruments (convergent validity). Correlations demonstrating discriminant validity ranged from 0.38 to 0.73 for men and 0.48 to 0.74 for women, while correlations demonstrating convergent validity ranged from 0.62 to 0.83 for men and 0.71 to 0.92 for women. As expected, correlations demonstrating convergent validity were higher than correlations demonstrating discriminant validity, with one exception (orgasm for men). Conclusions Construct validity was supported by convergent and discriminant validity in a diverse sample of patients with cancer. For patients with cancer who may or may not have sexual dysfunction, the PROMIS SexFS measures provide a comprehensive assessment of key domains of sexual function and satisfaction. PMID:23497200

Functional group placement in protein binding sites: a comparison of GRID and MCSS

NASA Astrophysics Data System (ADS)

Bitetti-Putzer, Ryan; Joseph-McCarthy, Diane; Hogle, James M.; Karplus, Martin

2001-10-01

One approach to combinatorial ligand design begins by determining optimal locations (i.e., local potential energy minima) for functional groups in the binding site of a target macromolecule. MCSS and GRID are two methods, based on significantly different algorithms, which are used for this purpose. A comparison of the two methods for the same functional groups is reported. Calculations were performed for nonpolar and polar functional groups in the internal hydrophobic pocket of the poliovirus capsid protein, and on the binding surface of the src SH3 domain. The two approaches are shown to agree qualitatively; i.e., the global characteristics of the functional group maps generated by MCSS and GRID are similar. However, there are significant differences in the relative interaction energies of the two sets of minima, a consequence of the different functional form used to evaluate polar interactions (electrostatics and hydrogen bonding) in the two methods. The single sphere representation used by GRID affords only positional information, supplemented by the identification of hydrogen bonding interactions. By contrast, the multi-atom representation of most MCSS groups yields in both positional and orientational information. The two methods are most similar for small functional groups, while for larger functional groups MCSS yields results consistent with GRID but superior in detail. These results are in accord with the somewhat different purposes for which the two methods were developed. GRID has been used mainly to introduce functionalities at specific positions in lead compounds, in which case the orientation is predetermined by the structure of the latter. The orientational information provided by MCSS is important for its use in the de novo design of large, multi-functional ligands, as well as for improving lead compounds.

Ranked solutions to a class of combinatorial optimizations - with applications in mass spectrometry based peptide sequencing

NASA Astrophysics Data System (ADS)

Doerr, Timothy; Alves, Gelio; Yu, Yi-Kuo

2006-03-01

Typical combinatorial optimizations are NP-hard; however, for a particular class of cost functions the corresponding combinatorial optimizations can be solved in polynomial time. This suggests a way to efficiently find approximate solutions - - find a transformation that makes the cost function as similar as possible to that of the solvable class. After keeping many high-ranking solutions using the approximate cost function, one may then re-assess these solutions with the full cost function to find the best approximate solution. Under this approach, it is important to be able to assess the quality of the solutions obtained, e.g., by finding the true ranking of kth best approximate solution when all possible solutions are considered exhaustively. To tackle this statistical issue, we provide a systematic method starting with a scaling function generated from the fininte number of high- ranking solutions followed by a convergent iterative mapping. This method, useful in a variant of the directed paths in random media problem proposed here, can also provide a statistical significance assessment for one of the most important proteomic tasks - - peptide sequencing using tandem mass spectrometry data.

Comparative Study of Exchange-Correlation Functional and Potential for Evaluating Thermoelectric Transport Properties in d0 Perovskite Oxides

NASA Astrophysics Data System (ADS)

Ohkubo, Isao; Mori, Takao

2017-07-01

The influence of two different types of exchange-correlation functional/potential, namely, the generalized gradient approximation Perdew-Burke-Ernzerhof (GGA-PBE) functional and the modified Becke-Johnson (mBJ) potential, on the thermoelectric transport properties of d0 perovskite oxides (SrTiO3 and KTaO3) was investigated. The reduction of band dispersion induced by the mBJ scheme allows the improved prediction of band gap values by thelocal density approximation (LDA) and GGA, which increases the resolution of the increases in the density of states (DOS), carrier concentration, and effective mass near the conduction band edge. A comparison of the experimental effective mass values of d0 perovskite oxides shows that the effective mass values provided by the mBJ potential are similar to those provided by the GGA-PBE functional. Comparative analysis of the data obtained from Boltzmann theory calculations using the electronic structures determined with the GGA-PBE functional and the mBJ potential shows a difference in the transport coefficients owing to the increases in the DOS, carrier concentration, and effective mass induced by the mBJ scheme.

Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs

PubMed Central

Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

2016-01-01

The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians. PMID:27466206

Molecular developmental mechanism in polypterid fish provides insight into the origin of vertebrate lungs.

PubMed

Tatsumi, Norifumi; Kobayashi, Ritsuko; Yano, Tohru; Noda, Masatsugu; Fujimura, Koji; Okada, Norihiro; Okabe, Masataka

2016-07-28

The lung is an important organ for air breathing in tetrapods and originated well before the terrestrialization of vertebrates. Therefore, to better understand lung evolution, we investigated lung development in the extant basal actinopterygian fish Senegal bichir (Polypterus senegalus). First, we histologically confirmed that lung development in this species is very similar to that of tetrapods. We also found that the mesenchymal expression patterns of three genes that are known to play important roles in early lung development in tetrapods (Fgf10, Tbx4, and Tbx5) were quite similar to those of tetrapods. Moreover, we found a Tbx4 core lung mesenchyme-specific enhancer (C-LME) in the genomes of bichir and coelacanth (Latimeria chalumnae) and experimentally confirmed that these were functional in tetrapods. These findings provide the first molecular evidence that the developmental program for lung was already established in the common ancestor of actinopterygians and sarcopterygians.

Similarities and Differences in Neuroimaging.

PubMed

Sun, Yan-Kun; Sun, Yan; Lin, Xiao; Lu, Lin; Shi, Jie

2017-01-01

Addiction is a chronically relapsing disease characterized by drug intoxication, craving, bingeing, and withdrawal with loss of control. An increasing number of studies have indicated that non-substance addiction, like internet addiction and pathological gambling, share clinical, phenomenological, and biological features with substance addiction. With the development of imaging technology in the past three decades, neuroimaging studies have provided information on the neurobiological effects, and revealed neurochemical and functional changes in the brains of both drug-addicted and non-substance addicted subjects. Imaging techniques play a more critical role in understanding the neuronal processes of addiction and will lead the direction in future research for medication development of addiction treatment, especially for non-substance addiction, which shares an increasing percentage of addiction disorder. This article will review the similarities and differences between substance and non-substance addiction based on neuroimaging studies that may provide clues for future study on these two main kinds of addiction, especially the growing non-substance addiction.

Evaluation of free modeling targets in CASP11 and ROLL.

PubMed

Kinch, Lisa N; Li, Wenlin; Monastyrskyy, Bohdan; Kryshtafovych, Andriy; Grishin, Nick V

2016-09-01

We present an assessment of 'template-free modeling' (FM) in CASP11and ROLL. Community-wide server performance suggested the use of automated scores similar to previous CASPs would provide a good system of evaluating performance, even in the absence of comprehensive manual assessment. The CASP11 FM category included several outstanding examples, including successful prediction by the Baker group of a 256-residue target (T0806-D1) that lacked sequence similarity to any existing template. The top server model prediction by Zhang's Quark, which was apparently selected and refined by several manual groups, encompassed the entire fold of target T0837-D1. Methods from the same two groups tended to dominate overall CASP11 FM and ROLL rankings. Comparison of top FM predictions with those from the previous CASP experiment revealed progress in the category, particularly reflected in high prediction accuracy for larger protein domains. FM prediction models for two cases were sufficient to provide functional insights that were otherwise not obtainable by traditional sequence analysis methods. Importantly, CASP11 abstracts revealed that alignment-based contact prediction methods brought about much of the CASP11 progress, producing both of the functionally relevant models as well as several of the other outstanding structure predictions. These methodological advances enabled de novo modeling of much larger domain structures than was previously possible and allowed prediction of functional sites. Proteins 2016; 84(Suppl 1):51-66. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB

DOE PAGES

Kemege, Kyle E.; Hickey, John M.; Barta, Michael L.; ...

2014-11-10

Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies in this paper expand on those observations through protein structure, mutagenesis andmore » cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient Escherichia coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. Finally, MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia.« less

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB

PubMed Central

Kemege, Kyle E.; Hickey, John M.; Barta, Michael L.; Wickstrum, Jason; Balwalli, Namita; Lovell, Scott; Battaile, Kevin P.; Hefty, P. Scott

2015-01-01

Summary Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies herein expand on those observations through protein structure, mutagenesis, and cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient E. coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia. PMID:25382739

Chlamydia trachomatis protein CT009 is a structural and functional homolog to the key morphogenesis component RodZ and interacts with division septal plane localized MreB.

PubMed

Kemege, Kyle E; Hickey, John M; Barta, Michael L; Wickstrum, Jason; Balwalli, Namita; Lovell, Scott; Battaile, Kevin P; Hefty, P Scott

2015-02-01

Cell division in Chlamydiae is poorly understood as apparent homologs to most conserved bacterial cell division proteins are lacking and presence of elongation (rod shape) associated proteins indicate non-canonical mechanisms may be employed. The rod-shape determining protein MreB has been proposed as playing a unique role in chlamydial cell division. In other organisms, MreB is part of an elongation complex that requires RodZ for proper function. A recent study reported that the protein encoded by ORF CT009 interacts with MreB despite low sequence similarity to RodZ. The studies herein expand on those observations through protein structure, mutagenesis and cellular localization analyses. Structural analysis indicated that CT009 shares high level of structural similarity to RodZ, revealing the conserved orientation of two residues critical for MreB interaction. Substitutions eliminated MreB protein interaction and partial complementation provided by CT009 in RodZ deficient Escherichia coli. Cellular localization analysis of CT009 showed uniform membrane staining in Chlamydia. This was in contrast to the localization of MreB, which was restricted to predicted septal planes. MreB localization to septal planes provides direct experimental observation for the role of MreB in cell division and supports the hypothesis that it serves as a functional replacement for FtsZ in Chlamydia. © 2014 John Wiley & Sons Ltd.

Tuning Selectivity of Fluorescent Carbon Nanotube-Based Neurotransmitter Sensors.

PubMed

Mann, Florian A; Herrmann, Niklas; Meyer, Daniel; Kruss, Sebastian

2017-06-28

Detection of neurotransmitters is an analytical challenge and essential to understand neuronal networks in the brain and associated diseases. However, most methods do not provide sufficient spatial, temporal, or chemical resolution. Near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) have been used as building blocks for sensors/probes that detect catecholamine neurotransmitters, including dopamine. This approach provides a high spatial and temporal resolution, but it is not understood if these sensors are able to distinguish dopamine from similar catecholamine neurotransmitters, such as epinephrine or norepinephrine. In this work, the organic phase (DNA sequence) around SWCNTs was varied to create sensors with different selectivity and sensitivity for catecholamine neurotransmitters. Most DNA-functionalized SWCNTs responded to catecholamine neurotransmitters, but both dissociation constants ( K d ) and limits of detection were highly dependent on functionalization (sequence). K d values span a range of 2.3 nM (SWCNT-(GC) 15 + norepinephrine) to 9.4 μM (SWCNT-(AT) 15 + dopamine) and limits of detection are mostly in the single-digit nM regime. Additionally, sensors of different SWCNT chirality show different fluorescence increases. Moreover, certain sensors (e.g., SWCNT-(GT) 10 ) distinguish between different catecholamines, such as dopamine and norepinephrine at low concentrations (50 nM). These results show that SWCNTs functionalized with certain DNA sequences are able to discriminate between catecholamine neurotransmitters or to detect them in the presence of interfering substances of similar structure. Such sensors will be useful to measure and study neurotransmitter signaling in complex biological settings.

Functional Morphology of Eunicidan (Polychaeta) Jaws

NASA Astrophysics Data System (ADS)

Clemo, W. C.; Dorgan, K. M.

2016-02-01

Polychaetes exhibit diverse feeding strategies and diets, with some species possessing hardened teeth or jaws of varying complexity. Species in the order Eunicida have complex, rigidly articulated jaws consisting of multiple pairs of maxillae and a pair of mandibles. While all Eunicida possess this general jaw structure, a number of characteristics of the jaw parts vary considerably among families. These differences, described for fossilized and extant species' jaws, were used to infer evolutionary relationships, but current phylogeny shows that jaw structures that are similar among several families are convergent. Little has been done, however, to relate jaw functional morphology and feeding behavior to diet. To explore these relationships, we compared the jaw kinematics of two taxa with similar but evolutionarily convergent jaw structures: Diopatra (Onuphidae) and Lumbrineris (Lumbrineridae). Diopatra species are tube-dwelling and predominantly herbivorous, whereas Lumbrineris species are burrowing carnivores. Jaw kinematics were observed and analyzed by filming individuals biting or feeding and tracking tooth movements in videos. Differences in jaw structure and kinematics between Diopatra and Lumbrineris can be interpreted to be consistent with their differences in diet. Relating jaw morphology to diet would provide insight into early annelid communities by linking fossil teeth (scolecodonts) to the ecological roles of extant species with similar morphologies.

Exploring the Structure of Spatial Representations

PubMed Central

Madl, Tamas; Franklin, Stan; Chen, Ke; Trappl, Robert; Montaldi, Daniela

2016-01-01

It has been suggested that the map-like representations that support human spatial memory are fragmented into sub-maps with local reference frames, rather than being unitary and global. However, the principles underlying the structure of these ‘cognitive maps’ are not well understood. We propose that the structure of the representations of navigation space arises from clustering within individual psychological spaces, i.e. from a process that groups together objects that are close in these spaces. Building on the ideas of representational geometry and similarity-based representations in cognitive science, we formulate methods for learning dissimilarity functions (metrics) characterizing participants’ psychological spaces. We show that these learned metrics, together with a probabilistic model of clustering based on the Bayesian cognition paradigm, allow prediction of participants’ cognitive map structures in advance. Apart from insights into spatial representation learning in human cognition, these methods could facilitate novel computational tools capable of using human-like spatial concepts. We also compare several features influencing spatial memory structure, including spatial distance, visual similarity and functional similarity, and report strong correlations between these dimensions and the grouping probability in participants’ spatial representations, providing further support for clustering in spatial memory. PMID:27347681

Characterization of a Multiresistant Mosaic Plasmid from a Fish Farm Sediment Exiguobacterium sp. Isolate Reveals Aggregation of Functional Clinic-Associated Antibiotic Resistance Genes

PubMed Central

Yang, Jing; Wang, Chao; Wu, Jinyu; Liu, Li; Zhang, Gang

2014-01-01

The genus Exiguobacterium can adapt readily to, and survive in, diverse environments. Our study demonstrated that Exiguobacterium sp. strain S3-2, isolated from marine sediment, is resistant to five antibiotics. The plasmid pMC1 in this strain carries seven putative resistance genes. We functionally characterized these resistance genes in Escherichia coli, and genes encoding dihydrofolate reductase and macrolide phosphotransferase were considered novel resistance genes based on their low similarities to known resistance genes. The plasmid G+C content distribution was highly heterogeneous. Only the G+C content of one block, which shared significant similarity with a plasmid from Exiguobacterium arabatum, fit well with the mean G+C content of the host. The remainder of the plasmid was composed of mobile elements with a markedly lower G+C ratio than the host. Interestingly, five mobile elements located on pMC1 showed significant similarities to sequences found in pathogens. Our data provided an example of the link between resistance genes in strains from the environment and the clinic and revealed the aggregation of antibiotic resistance genes in bacteria isolated from fish farms. PMID:24362420

Poly(A) polymerase contains multiple functional domains.

PubMed Central

Raabe, T; Murthy, K G; Manley, J L

1994-01-01

Poly(A) polymerase (PAP) contains regions of similarity with several known protein domains. Through site-directed mutagenesis, we provide evidence that PAP contains a functional ribonucleoprotein-type RNA binding domain (RBD) that is responsible for primer binding, making it the only known polymerase to contain such a domain. The RBD is adjacent to, and probably overlaps with, an apparent catalytic region responsible for polymerization. Despite the presence of sequence similarities, this catalytic domain appears to be distinct from the conserved polymerase module found in a large number of RNA-dependent polymerases. PAP contains two nuclear localization signals (NLSs) in its C terminus, each by itself similar to the consensus bipartite NLS found in many nuclear proteins. Mutagenesis experiments indicate that both signals, which are separated by nearly 140 residues, play important roles in directing PAP exclusively to the nucleus. Surprisingly, basic amino acids in the N-terminal-most NLS are also essential for AAUAAA-dependent polyadenylation but not for nonspecific poly(A) synthesis, suggesting that this region of PAP is involved in interactions both with nuclear targeting proteins and with nuclear polyadenylation factors. The serine/threonine-rich C terminus is multiply phosphorylated, including at sites affected by mutations in either NLS. Images PMID:8164653

Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins.

PubMed

Ly, Hoai J; Ikegami, Tetsuro

2016-07-02

Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming.

PubMed

De Bellis, Francesco; Ferrara, Antonia; Errico, Domenico; Panico, Francesco; Sagliano, Laura; Conson, Massimiliano; Trojano, Luigi

2016-01-01

Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools' function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool-recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.

De Novo Protein Structure Prediction

NASA Astrophysics Data System (ADS)

Hung, Ling-Hong; Ngan, Shing-Chung; Samudrala, Ram

An unparalleled amount of sequence data is being made available from large-scale genome sequencing efforts. The data provide a shortcut to the determination of the function of a gene of interest, as long as there is an existing sequenced gene with similar sequence and of known function. This has spurred structural genomic initiatives with the goal of determining as many protein folds as possible (Brenner and Levitt, 2000; Burley, 2000; Brenner, 2001; Heinemann et al., 2001). The purpose of this is twofold: First, the structure of a gene product can often lead to direct inference of its function. Second, since the function of a protein is dependent on its structure, direct comparison of the structures of gene products can be more sensitive than the comparison of sequences of genes for detecting homology. Presently, structural determination by crystallography and NMR techniques is still slow and expensive in terms of manpower and resources, despite attempts to automate the processes. Computer structure prediction algorithms, while not providing the accuracy of the traditional techniques, are extremely quick and inexpensive and can provide useful low-resolution data for structure comparisons (Bonneau and Baker, 2001). Given the immense number of structures which the structural genomic projects are attempting to solve, there would be a considerable gain even if the computer structure prediction approach were applicable to a subset of proteins.

Limits of clinical tests to screen autonomic function in diabetes type 1.

PubMed

Ducher, M; Bertram, D; Sagnol, I; Cerutti, C; Thivolet, C; Fauvel, J P

2001-11-01

A precocious detection of cardiac autonomic dysfunction is of major clinical interest that could lead to a more intensive supervision of diabetic patients. However, classical clinical exploration of cardiac autonomic function is not easy to undertake in a reproducible way. Thus, respective interests of autonomic nervous parameters provided by both clinical tests and computerized analysis of resting blood pressure were checked in type 1 diabetic patients without orthostatic hypotension and microalbuminuria. Thirteen diabetic subjects matched for age and gender to thirteen healthy subjects volunteered to participate to the study. From clinical tests (standing up, deep breathing, Valsalva maneuver, handgrip test), autonomic function was scored according to Ewing's methodology. Analysis of resting beat to beat blood pressure provided autonomic indices of the cardiac function (spectral analysis or Z analysis). 5 of the 13 diabetic patients exhibited a pathological score (more than one pathological response) suggesting the presence of cardiovascular autonomic dysfunction. The most discriminative test was the deep breathing test. However, spectral indices of BP recordings and baro-reflex sensitivity (BRS) of these 5 subjects were similar to those of healthy subjects and of remaining diabetic subjects. Alteration in Ewing's score given by clinical tests may not reflect an alteration of cardiac autonomic function in asymptomatic type 1 diabetic patients, because spectral indices of sympathetic and parasympathetic (including BRS) function were within normal range. Our results strongly suggest to confront results provided by both methodologies before concluding to an autonomic cardiac impairment in asymptomatic diabetic patients.

Task-Based Neurofeedback Training: A Novel Approach Toward Training Executive Functions

PubMed Central

Hosseini, SM Hadi; Pritchard-Berman, Mika; Sosa, Natasha; Ceja, Angelica; Kesler, Shelli R.

2016-01-01

Cognitive training is an emergent approach to improve cognitive functions in various neurodevelopmental and neurodegenerative diseases. However, current training programs can be relatively lengthy, making adherence potentially difficult for patients with cognitive difficulties. Previous studies suggest that providing individuals with real-time feedback about the level of brain activity (neurofeedback) can potentially help them learn to control the activation of specific brain regions. In the present study, we developed a novel task-based neurofeedback training paradigm that benefits from the effects of neurofeedback in parallel with computerized training. We focused on executive function training given its core involvement in various developmental and neurodegenerative diseases. Near-infrared spectroscopy (NIRS) was employed for providing neurofeedback by measuring changes in oxygenated hemoglobin in the prefrontal cortex. Of the twenty healthy adult participants, ten received real neurofeedback (NFB) on prefrontal activity during cognitive training, and ten were presented with sham feedback (SHAM). Compared with SHAM, the NFB group showed significantly improved executive function performance including measures of working memory after four sessions of training (100 minutes total). The NFB group also showed significantly reduced training-related brain activity in the executive function network including right middle frontal and inferior frontal regions compared with SHAM. Our data suggest that providing neurofeedback along with cognitive training can enhance executive function after a relatively short period of training. Similar designs could potentially be used for patient populations with known neuropathology, potentially helping them to boost/recover the activity in the affected brain regions. PMID:27015711

Newer Approaches to Identify Potential Untoward Effects in Functional Foods.

PubMed

Marone, Palma Ann; Birkenbach, Victoria L; Hayes, A Wallace

2016-01-01

Globalization has greatly accelerated the numbers and variety of food and beverage products available worldwide. The exchange among greater numbers of countries, manufacturers, and products in the United States and worldwide has necessitated enhanced quality measures for nutritional products for larger populations increasingly reliant on functionality. These functional foods, those that provide benefit beyond basic nutrition, are increasingly being used for their potential to alleviate food insufficiency while enhancing quality and longevity of life. In the United States alone, a steady import increase of greater than 15% per year or 24 million shipments, over 70% products of which are food related, is regulated under the Food and Drug Administration (FDA). This unparalleled growth has resulted in the need for faster, cheaper, and better safety and efficacy screening methods in the form of harmonized guidelines and recommendations for product standardization. In an effort to meet this need, the in vitro toxicology testing market has similarly grown with an anticipatory 15% increase between 2010 and 2015 of US$1.3 to US$2.7 billion. Although traditionally occupying a small fraction of the market behind pharmaceuticals and cosmetic/household products, the scope of functional food testing, including additives/supplements, ingredients, residues, contact/processing, and contaminants, is potentially expansive. Similarly, as functional food testing has progressed, so has the need to identify potential adverse factors that threaten the safety and quality of these products. © The Author(s) 2015.

Secondary Plastids of Euglenids and Chlorarachniophytes Function with a Mix of Genes of Red and Green Algal Ancestry.

PubMed

Ponce-Toledo, Rafael I; Moreira, David; López-García, Purificación; Deschamps, Philippe

2018-06-19

Endosymbiosis has been common all along eukaryotic evolution, providing opportunities for genomic and organellar innovation. Plastids are a prominent example. After the primary endosymbiosis of the cyanobacterial plastid ancestor, photosynthesis spread in many eukaryotic lineages via secondary endosymbioses involving red or green algal endosymbionts and diverse heterotrophic hosts. However, the number of secondary endosymbioses and how they occurred remain poorly understood. In particular, contrasting patterns of endosymbiotic gene transfer (EGT) have been detected and subjected to various interpretations. In this context, accurate detection of EGTs is essential to avoid wrong evolutionary conclusions. We have assembled a strictly selected set of markers that provides robust phylogenomic evidence suggesting that nuclear genes involved in the function and maintenance of green secondary plastids in chlorarachniophytes and euglenids have unexpected mixed red and green algal origins. This mixed ancestry contrasts with the clear red algal origin of most nuclear genes carrying similar functions in secondary algae with red plastids.

Online adaptive decision trees: pattern classification and function approximation.

PubMed

Basak, Jayanta

2006-09-01

Recently we have shown that decision trees can be trained in the online adaptive (OADT) mode (Basak, 2004), leading to better generalization score. OADTs were bottlenecked by the fact that they are able to handle only two-class classification tasks with a given structure. In this article, we provide an architecture based on OADT, ExOADT, which can handle multiclass classification tasks and is able to perform function approximation. ExOADT is structurally similar to OADT extended with a regression layer. We also show that ExOADT is capable not only of adapting the local decision hyperplanes in the nonterminal nodes but also has the potential of smoothly changing the structure of the tree depending on the data samples. We provide the learning rules based on steepest gradient descent for the new model ExOADT. Experimentally we demonstrate the effectiveness of ExOADT in the pattern classification and function approximation tasks. Finally, we briefly discuss the relationship of ExOADT with other classification models.

Postfragmentation density function for bacterial aggregates in laminar flow.

PubMed

Byrne, Erin; Dzul, Steve; Solomon, Michael; Younger, John; Bortz, David M

2011-04-01

The postfragmentation probability density of daughter flocs is one of the least well-understood aspects of modeling flocculation. We use three-dimensional positional data of Klebsiella pneumoniae bacterial flocs in suspension and the knowledge of hydrodynamic properties of a laminar flow field to construct a probability density function of floc volumes after a fragmentation event. We provide computational results which predict that the primary fragmentation mechanism for large flocs is erosion. The postfragmentation probability density function has a strong dependence on the size of the original floc and indicates that most fragmentation events result in clumps of one to three bacteria eroding from the original floc. We also provide numerical evidence that exhaustive fragmentation yields a limiting density inconsistent with the log-normal density predicted in the literature, most likely due to the heterogeneous nature of K. pneumoniae flocs. To support our conclusions, artificial flocs were generated and display similar postfragmentation density and exhaustive fragmentation. ©2011 American Physical Society

A trait-based approach to community assembly: partitioning of species trait values into within- and among-community components.

PubMed

Ackerly, D D; Cornwell, W K

2007-02-01

Plant functional traits vary both along environmental gradients and among species occupying similar conditions, creating a challenge for the synthesis of functional and community ecology. We present a trait-based approach that provides an additive decomposition of species' trait values into alpha and beta components: beta values refer to a species' position along a gradient defined by community-level mean trait values; alpha values are the difference between a species' trait values and the mean of co-occurring taxa. In woody plant communities of coastal California, beta trait values for specific leaf area, leaf size, wood density and maximum height all covary strongly, reflecting species distributions across a gradient of soil moisture availability. Alpha values, on the other hand, are generally not significantly correlated, suggesting several independent axes of differentiation within communities. This trait-based framework provides a novel approach to integrate functional ecology and gradient analysis with community ecology and coexistence theory.

Neuron hemilineages provide the functional ground plan for the Drosophila ventral nervous system

PubMed Central

Harris, Robin M; Pfeiffer, Barret D; Rubin, Gerald M; Truman, James W

2015-01-01

Drosophila central neurons arise from neuroblasts that generate neurons in a pair-wise fashion, with the two daughters providing the basis for distinct A and B hemilineage groups. 33 postembryonically-born hemilineages contribute over 90% of the neurons in each thoracic hemisegment. We devised genetic approaches to define the anatomy of most of these hemilineages and to assessed their functional roles using the heat-sensitive channel dTRPA1. The simplest hemilineages contained local interneurons and their activation caused tonic or phasic leg movements lacking interlimb coordination. The next level was hemilineages of similar projection cells that drove intersegmentally coordinated behaviors such as walking. The highest level involved hemilineages whose activation elicited complex behaviors such as takeoff. These activation phenotypes indicate that the hemilineages vary in their behavioral roles with some contributing to local networks for sensorimotor processing and others having higher order functions of coordinating these local networks into complex behavior. DOI: http://dx.doi.org/10.7554/eLife.04493.001 PMID:26193122

[Effects of fundamental frequency and speech rate on impression formation].

PubMed

Uchida, Teruhisa; Nakaune, Naoko

2004-12-01

This study investigated the systematic relationship between nonverbal features of speech and personality trait ratings of the speaker. In Study 1, fundamental frequency (F0) in original speech was converted into five levels from 64% to 156.25%. Then 132 undergraduates rated each of the converted speeches in terms of personality traits. In Study 2 134 undergraduates similarly rated the speech stimuli, which had five speech rate levels as well as two F0 levels. Results showed that listener ratings along Big Five dimensions were mostly independent. Each dimension had a slightly different change profile over the five levels of F0 and speech rate. A quadratic regression equation provided a good approximation for each rating as a function of F0 or speech rate. The quadratic regression equations put together would provide us with a rough estimate of personality trait impression as a function of prosodic features. The functional relationship among F0, speech rate, and trait ratings was shown as a curved surface in the three-dimensional space.

Topology-function conservation in protein-protein interaction networks.

PubMed

Davis, Darren; Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Stojmirovic, Aleksandar; Pržulj, Nataša

2015-05-15

Proteins underlay the functioning of a cell and the wiring of proteins in protein-protein interaction network (PIN) relates to their biological functions. Proteins with similar wiring in the PIN (topology around them) have been shown to have similar functions. This property has been successfully exploited for predicting protein functions. Topological similarity is also used to guide network alignment algorithms that find similarly wired proteins between PINs of different species; these similarities are used to transfer annotation across PINs, e.g. from model organisms to human. To refine these functional predictions and annotation transfers, we need to gain insight into the variability of the topology-function relationships. For example, a function may be significantly associated with specific topologies, while another function may be weakly associated with several different topologies. Also, the topology-function relationships may differ between different species. To improve our understanding of topology-function relationships and of their conservation among species, we develop a statistical framework that is built upon canonical correlation analysis. Using the graphlet degrees to represent the wiring around proteins in PINs and gene ontology (GO) annotations to describe their functions, our framework: (i) characterizes statistically significant topology-function relationships in a given species, and (ii) uncovers the functions that have conserved topology in PINs of different species, which we term topologically orthologous functions. We apply our framework to PINs of yeast and human, identifying seven biological process and two cellular component GO terms to be topologically orthologous for the two organisms. © The Author 2015. Published by Oxford University Press.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

PubMed

Bedell, Victoria M; Person, Anthony D; Larson, Jon D; McLoon, Anna; Balciunas, Darius; Clark, Karl J; Neff, Kevin I; Nelson, Katie E; Bill, Brent R; Schimmenti, Lisa A; Beiraghi, Soraya; Ekker, Stephen C

2012-02-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Triangular Alignment (TAME). A Tensor-based Approach for Higher-order Network Alignment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohammadi, Shahin; Gleich, David F.; Kolda, Tamara G.

2015-11-01

Network alignment is an important tool with extensive applications in comparative interactomics. Traditional approaches aim to simultaneously maximize the number of conserved edges and the underlying similarity of aligned entities. We propose a novel formulation of the network alignment problem that extends topological similarity to higher-order structures and provide a new objective function that maximizes the number of aligned substructures. This objective function corresponds to an integer programming problem, which is NP-hard. Consequently, we approximate this objective function as a surrogate function whose maximization results in a tensor eigenvalue problem. Based on this formulation, we present an algorithm called Triangularmore » AlignMEnt (TAME), which attempts to maximize the number of aligned triangles across networks. We focus on alignment of triangles because of their enrichment in complex networks; however, our formulation and resulting algorithms can be applied to general motifs. Using a case study on the NAPABench dataset, we show that TAME is capable of producing alignments with up to 99% accuracy in terms of aligned nodes. We further evaluate our method by aligning yeast and human interactomes. Our results indicate that TAME outperforms the state-of-art alignment methods both in terms of biological and topological quality of the alignments.« less

A small world of weak ties provides optimal global integration of self-similar modules in functional brain networks.

PubMed

Gallos, Lazaros K; Makse, Hernán A; Sigman, Mariano

2012-02-21

The human brain is organized in functional modules. Such an organization presents a basic conundrum: Modules ought to be sufficiently independent to guarantee functional specialization and sufficiently connected to bind multiple processors for efficient information transfer. It is commonly accepted that small-world architecture of short paths and large local clustering may solve this problem. However, there is intrinsic tension between shortcuts generating small worlds and the persistence of modularity, a global property unrelated to local clustering. Here, we present a possible solution to this puzzle. We first show that a modified percolation theory can define a set of hierarchically organized modules made of strong links in functional brain networks. These modules are "large-world" self-similar structures and, therefore, are far from being small-world. However, incorporating weaker ties to the network converts it into a small world preserving an underlying backbone of well-defined modules. Remarkably, weak ties are precisely organized as predicted by theory maximizing information transfer with minimal wiring cost. This trade-off architecture is reminiscent of the "strength of weak ties" crucial concept of social networks. Such a design suggests a natural solution to the paradox of efficient information flow in the highly modular structure of the brain.

A small world of weak ties provides optimal global integration of self-similar modules in functional brain networks

PubMed Central

Gallos, Lazaros K.; Makse, Hernán A.; Sigman, Mariano

2012-01-01

The human brain is organized in functional modules. Such an organization presents a basic conundrum: Modules ought to be sufficiently independent to guarantee functional specialization and sufficiently connected to bind multiple processors for efficient information transfer. It is commonly accepted that small-world architecture of short paths and large local clustering may solve this problem. However, there is intrinsic tension between shortcuts generating small worlds and the persistence of modularity, a global property unrelated to local clustering. Here, we present a possible solution to this puzzle. We first show that a modified percolation theory can define a set of hierarchically organized modules made of strong links in functional brain networks. These modules are “large-world” self-similar structures and, therefore, are far from being small-world. However, incorporating weaker ties to the network converts it into a small world preserving an underlying backbone of well-defined modules. Remarkably, weak ties are precisely organized as predicted by theory maximizing information transfer with minimal wiring cost. This trade-off architecture is reminiscent of the “strength of weak ties” crucial concept of social networks. Such a design suggests a natural solution to the paradox of efficient information flow in the highly modular structure of the brain. PMID:22308319

Policing the intestinal epithelial barrier: Innate immune functions of intraepithelial lymphocytes.

PubMed

Hu, Madeleine D; Jia, Luo; Edelblum, Karen L

2018-03-01

This review will explore the contribution of IELs to mucosal innate immunity and highlight the similarities in IEL functional responses to bacteria, viruses and protozoan parasite invasion. IELs rapidly respond to microbial invasion by activating host defense responses, including the production of mucus and antimicrobial peptides to prevent microbes from reaching the epithelial surface. During active infection, IELs promote epithelial cytolysis, cytokine and chemokine production to limit pathogen invasion, replication and dissemination. Commensal-induced priming of IEL effector function or continuous surveillance of the epithelium may be important contributing factors to the rapidity of response. Impaired microbial recognition, dysregulated innate immune signaling or microbial dysbiosis may limit the protective function of IELs and increase susceptibility to disease. Further understanding of the mechanisms regulating IEL surveillance and sentinel function may provide insight into the development of more effective targeted therapies designed to reinforce the mucosal barrier.

New genes contribute to genetic and phenotypic novelties in human evolution

PubMed Central

Zhang, Yong E.; Long, Manyuan

2014-01-01

New genes in human genomes have been found relevant in evolution and biology of humans. It was conservatively estimated that the human genome encodes more than 300 human-specific genes and 1,000 primate-specific genes. These new arrivals appear to be implicated in brain function and male reproduction. Surprisingly, increasing evidence indicates that they may also bring negative pleiotropic effects, while assuming various possible biological functions as sources of phenotypic novelties, suggesting a non-progressive route for functional evolution. Similar to these fixed new genes, polymorphic new genes were found to contribute to functional evolution within species, e.g. with respect to digestion or disease resistance, revealing that new genes can acquire new or diverged functions in its initial stage as prototypic genes. These progresses have provided new opportunity to explore the genetic basis of human biology and human evolutionary history in a new dimension. PMID:25218862

The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity

PubMed Central

Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.

2012-01-01

The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406

A Method for the Alignment of Heterogeneous Macromolecules from Electron Microscopy

PubMed Central

Shatsky, Maxim; Hall, Richard J.; Brenner, Steven E.; Glaeser, Robert M.

2009-01-01

We propose a feature-based image alignment method for single-particle electron microscopy that is able to accommodate various similarity scoring functions while efficiently sampling the two-dimensional transformational space. We use this image alignment method to evaluate the performance of a scoring function that is based on the Mutual Information (MI) of two images rather than one that is based on the cross-correlation function. We show that alignment using MI for the scoring function has far less model-dependent bias than is found with cross-correlation based alignment. We also demonstrate that MI improves the alignment of some types of heterogeneous data, provided that the signal to noise ratio is relatively high. These results indicate, therefore, that use of MI as the scoring function is well suited for the alignment of class-averages computed from single particle images. Our method is tested on data from three model structures and one real dataset. PMID:19166941

Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

PubMed Central

Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

2009-01-01

Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments. PMID:19233611

MIPS bacterial genomes functional annotation benchmark dataset.

PubMed

Tetko, Igor V; Brauner, Barbara; Dunger-Kaltenbach, Irmtraud; Frishman, Goar; Montrone, Corinna; Fobo, Gisela; Ruepp, Andreas; Antonov, Alexey V; Surmeli, Dimitrij; Mewes, Hans-Wernen

2005-05-15

Any development of new methods for automatic functional annotation of proteins according to their sequences requires high-quality data (as benchmark) as well as tedious preparatory work to generate sequence parameters required as input data for the machine learning methods. Different program settings and incompatible protocols make a comparison of the analyzed methods difficult. The MIPS Bacterial Functional Annotation Benchmark dataset (MIPS-BFAB) is a new, high-quality resource comprising four bacterial genomes manually annotated according to the MIPS functional catalogue (FunCat). These resources include precalculated sequence parameters, such as sequence similarity scores, InterPro domain composition and other parameters that could be used to develop and benchmark methods for functional annotation of bacterial protein sequences. These data are provided in XML format and can be used by scientists who are not necessarily experts in genome annotation. BFAB is available at http://mips.gsf.de/proj/bfab

Further evidence that similar principles govern recall from episodic and semantic memory: the Canadian prime ministerial serial position function.

PubMed

Neath, Ian; Saint-Aubin, Jean

2011-06-01

The serial position function, with its characteristic primacy and recency effects, is one of the most ubiquitous findings in episodic memory tasks. In contrast, there are only two demonstrations of such functions in tasks thought to tap semantic memory. Here, we provide a third demonstration, showing that free recall of the prime ministers of Canada also results in a serial position function. Scale Independent Memory, Perception, and Learning (SIMPLE), a local distinctiveness model of memory that was designed to account for serial position effects in episodic memory, fit the data. According to SIMPLE, serial position functions observed in episodic and semantic memory all reflect the relative distinctiveness principle: items will be well remembered to the extent that they are more distinct than competing items at the time of retrieval. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape.

PubMed

Kinoshita, Kengo; Murakami, Yoichi; Nakamura, Haruki

2007-07-01

We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek).

Homologous structure-function relationships between native fibrocartilage and tissue engineered from MSC-seeded nanofibrous scaffolds.

PubMed

Nerurkar, Nandan L; Han, Woojin; Mauck, Robert L; Elliott, Dawn M

2011-01-01

Understanding the interplay of composition, organization and mechanical function in load-bearing tissues is a prerequisite in the successful engineering of tissues to replace diseased ones. Mesenchymal stem cells (MSCs) seeded on electrospun scaffolds have been successfully used to generate organized tissues that mimic fibrocartilages such as the knee meniscus and the annulus fibrosus of the intervertebral disc. While matrix deposition has been observed in parallel with improved mechanical properties, how composition, organization, and mechanical function are related is not known. Moreover, how this relationship compares to that of native fibrocartilage is unclear. Therefore, in the present work, functional fibrocartilage constructs were formed from MSC-seeded nanofibrous scaffolds, and the roles of collagen and glycosaminoglycan (GAG) in compressive and tensile properties were determined. MSCs deposited abundant collagen and GAG over 120 days of culture, and these extracellular molecules were organized in such a way that they performed similar mechanical functions to their native roles: collagen dominated the tensile response while GAG was important for compressive properties. GAG removal resulted in significant stiffening in tension. A similar stiffening response was observed when GAG was removed from native inner annulus fibrosus, suggesting an interaction between collagen fibers and their surrounding extrafibrillar matrix that is shared by both engineered and native fibrocartilages. These findings strongly support the use of electrospun scaffolds and MSCs for fibrocartilage tissue engineering, and provide insight on the structure-function relations of both engineered and native biomaterials. Copyright © 2010 Elsevier Ltd. All rights reserved.

HOMOLOGOUS STRUCTURE-FUNCTION RELATIONSHIPS BETWEEN NATIVE FIBROCARTILAGE AND TISSUE ENGINEERED FROM MSC-SEEDED NANOFIBROUS SCAFFOLDS

PubMed Central

Nerurkar, Nandan L.; Han, Woojin; Mauck, Robert L.; Elliott, Dawn M.

2010-01-01

Understanding the interplay of composition, organization and mechanical function in load-bearing tissues is a prerequisite in the successful engineering of replacement tissues for diseased ones. Mesenchymal stem cells (MSCs) seeded on electrospun scaffolds have been successfully used to generate organized tissues that mimic fibrocartilages such as the knee meniscus and the annulus fibrosus of the intervertebral disc. While matrix deposition has been observed in parallel with improved mechanical properties, how composition, organization, and mechanical function are related is not known. Moreover, how this relationship compares to that of native fibrocartilage is unclear. Therefore, in the present work, functional fibrocartilage constructs were formed from MSC-seeded nanofibrous scaffolds, and the roles of collagen and glycosaminoglycan (GAG) in compressive and tensile properties were determined. MSCs deposited abundant collagen and GAG over 120 days of culture, and these extracellular molecules were organized in such a way that they performed similar mechanical functions to their native roles: collagen dominated the tensile response while GAG was important for compressive properties. GAG removal resulted in significant stiffening in tension. A similar stiffening response was observed when GAG was removed from native inner annulus fibrosus, suggesting an interaction between collagen fibers and their surrounding extrafibrillar matrix that is shared by both engineered and native fibrocartilages. These findings strongly support the use of electrospun scaffolds and MSCs for fibrocartilage tissue engineering, and provide insight on the structure-function relations of both engineered and native biomaterials. PMID:20880577

Crustal structure of Precambrian terranes in the southern African subcontinent with implications for secular variation in crustal genesis

NASA Astrophysics Data System (ADS)

Kachingwe, Marsella; Nyblade, Andrew; Julià, Jordi

2015-07-01

New estimates of crustal thickness, Poisson's ratio and crustal shear wave velocity have been obtained for 39 stations in Angola, Botswana, the Democratic Republic of Congo, Malawi, Mozambique, Namibia, Rwanda, Tanzania and Zambia by modelling P-wave receiver functions using the H-κ stacking method and jointly inverting the receiver functions with Rayleigh-wave phase and group velocities. These estimates, combined with similar results from previous studies, have been examined for secular trends in Precambrian crustal structure within the southern African subcontinent. In both Archean and Proterozoic terranes we find similar Moho depths [38-39 ± 3 km SD (standard deviation)], crustal Poisson's ratio (0.26 ± 0.01 SD), mean crustal shear wave velocity (3.7 ± 0.1 km s-1 SD), and amounts of heterogeneity in the thickness of the mafic lower crust, as defined by shear wave velocities ≥4.0 km s-1. In addition, the amount of variability in these crustal parameters is similar within each individual age grouping as between age groupings. Thus, the results provide little evidence for secular variation in Precambrian crustal structure, including between Meso- and Neoarchean crust. This finding suggests that (1) continental crustal has been generated by similar processes since the Mesoarchean or (2) plate tectonic processes have reworked and modified the crust through time, erasing variations in structure resulting from crustal genesis.

A hierarchical model for probabilistic independent component analysis of multi-subject fMRI studies

PubMed Central

Tang, Li

2014-01-01

Summary An important goal in fMRI studies is to decompose the observed series of brain images to identify and characterize underlying brain functional networks. Independent component analysis (ICA) has been shown to be a powerful computational tool for this purpose. Classic ICA has been successfully applied to single-subject fMRI data. The extension of ICA to group inferences in neuroimaging studies, however, is challenging due to the unavailability of a pre-specified group design matrix. Existing group ICA methods generally concatenate observed fMRI data across subjects on the temporal domain and then decompose multi-subject data in a similar manner to single-subject ICA. The major limitation of existing methods is that they ignore between-subject variability in spatial distributions of brain functional networks in group ICA. In this paper, we propose a new hierarchical probabilistic group ICA method to formally model subject-specific effects in both temporal and spatial domains when decomposing multi-subject fMRI data. The proposed method provides model-based estimation of brain functional networks at both the population and subject level. An important advantage of the hierarchical model is that it provides a formal statistical framework to investigate similarities and differences in brain functional networks across subjects, e.g., subjects with mental disorders or neurodegenerative diseases such as Parkinson’s as compared to normal subjects. We develop an EM algorithm for model estimation where both the E-step and M-step have explicit forms. We compare the performance of the proposed hierarchical model with that of two popular group ICA methods via simulation studies. We illustrate our method with application to an fMRI study of Zen meditation. PMID:24033125

Large conservation gains possible for global biodiversity facets.

PubMed

Pollock, Laura J; Thuiller, Wilfried; Jetz, Walter

2017-06-01

Different facets of biodiversity other than species numbers are increasingly appreciated as critical for maintaining the function of ecosystems and their services to humans. While new international policy and assessment processes such as the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) recognize the importance of an increasingly global, quantitative and comprehensive approach to biodiversity protection, most insights are still focused on a single facet of biodiversity-species. Here we broaden the focus and provide an evaluation of how much of the world's species, functional and phylogenetic diversity of birds and mammals is currently protected and the scope for improvement. We show that the large existing gaps in the coverage for each facet of diversity could be remedied by a slight expansion of protected areas: an additional 5% of the land has the potential to more than triple the protected range of species or phylogenetic or functional units. Further, the same areas are often priorities for multiple diversity facets and for both taxa. However, we find that the choice of conservation strategy has a fundamental effect on outcomes. It is more difficult (that is, requires more land) to maximize basic representation of the global biodiversity pool than to maximize local diversity. Overall, species and phylogenetic priorities are more similar to each other than they are to functional priorities, and priorities for the different bird biodiversity facets are more similar than those of mammals. Our work shows that large gains in biodiversity protection are possible, while also highlighting the need to explicitly link desired conservation objectives and biodiversity metrics. We provide a framework and quantitative tools to advance these goals for multi-faceted biodiversity conservation.

Functional exploratory data analysis for high-resolution measurements of urban particulate matter.

PubMed

Ranalli, M Giovanna; Rocco, Giorgia; Jona Lasinio, Giovanna; Moroni, Beatrice; Castellini, Silvia; Crocchianti, Stefano; Cappelletti, David

2016-09-01

In this work we propose the use of functional data analysis (FDA) to deal with a very large dataset of atmospheric aerosol size distribution resolved in both space and time. Data come from a mobile measurement platform in the town of Perugia (Central Italy). An OPC (Optical Particle Counter) is integrated on a cabin of the Minimetrò, an urban transportation system, that moves along a monorail on a line transect of the town. The OPC takes a sample of air every six seconds and counts the number of particles of urban aerosols with a diameter between 0.28 μm and 10 μm and classifies such particles into 21 size bins according to their diameter. Here, we adopt a 2D functional data representation for each of the 21 spatiotemporal series. In fact, space is unidimensional since it is measured as the distance on the monorail from the base station of the Minimetrò. FDA allows for a reduction of the dimensionality of each dataset and accounts for the high space-time resolution of the data. Functional cluster analysis is then performed to search for similarities among the 21 size channels in terms of their spatiotemporal pattern. Results provide a good classification of the 21 size bins into a relatively small number of groups (between three and four) according to the season of the year. Groups including coarser particles have more similar patterns, while those including finer particles show a more different behavior according to the period of the year. Such features are consistent with the physics of atmospheric aerosol and the highlighted patterns provide a very useful ground for prospective model-based studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Large conservation gains possible for global biodiversity facets

NASA Astrophysics Data System (ADS)

Pollock, Laura J.; Thuiller, Wilfried; Jetz, Walter

2017-06-01

Different facets of biodiversity other than species numbers are increasingly appreciated as critical for maintaining the function of ecosystems and their services to humans. While new international policy and assessment processes such as the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) recognize the importance of an increasingly global, quantitative and comprehensive approach to biodiversity protection, most insights are still focused on a single facet of biodiversity—species. Here we broaden the focus and provide an evaluation of how much of the world’s species, functional and phylogenetic diversity of birds and mammals is currently protected and the scope for improvement. We show that the large existing gaps in the coverage for each facet of diversity could be remedied by a slight expansion of protected areas: an additional 5% of the land has the potential to more than triple the protected range of species or phylogenetic or functional units. Further, the same areas are often priorities for multiple diversity facets and for both taxa. However, we find that the choice of conservation strategy has a fundamental effect on outcomes. It is more difficult (that is, requires more land) to maximize basic representation of the global biodiversity pool than to maximize local diversity. Overall, species and phylogenetic priorities are more similar to each other than they are to functional priorities, and priorities for the different bird biodiversity facets are more similar than those of mammals. Our work shows that large gains in biodiversity protection are possible, while also highlighting the need to explicitly link desired conservation objectives and biodiversity metrics. We provide a framework and quantitative tools to advance these goals for multi-faceted biodiversity conservation.

Increasing protein production rates can decrease the rate at which functional protein is produced

NASA Astrophysics Data System (ADS)

Sharma, Ajeet; O'Brien, Edward

The rate at which soluble, functional protein is produced by the ribosome has recently been found to vary in complex and unexplained ways as various translation-associated rates are altered through synonymous codon substitutions. We combine a well-established ribosome-traffic model with a master-equation model of co-translational domain folding to explore the scenarios that are possible for the protein production rate, J, and the functional-nascent protein production rate, F, as the rates associated with translation are altered. We find that while J monotonically increases as the rates of translation-initiation, -elongation and -termination increase, F can either increase or decrease. F exhibits non-monotonic behavior because increasing these rates can cause a protein to be synthesized more rapidly but provide less time for nascent-protein domains to co-translationally fold thereby producing less functional nascent protein immediately after synthesis. We further demonstrate that these non-monotonic changes in Faffect the post-translational, steady-state levels of functional protein in a similar manner. Our results provide a possible explanation for recent experimental observations that the specific activity of enzymatic proteins can decrease with increased synthesis rates and can in principle be used to rationally-design transcripts to maximize the production of functional nascent protein.

Biomolecular Dynamics: Order-Disorder Transitions and Energy Landscapes

PubMed Central

Whitford, Paul C.; Sanbonmatsu, Karissa Y.; Onuchic, José N.

2013-01-01

While the energy landscape theory of protein folding is now a widely accepted view for understanding how relatively-weak molecular interactions lead to rapid and cooperative protein folding, such a framework must be extended to describe the large-scale functional motions observed in molecular machines. In this review, we discuss 1) the development of the energy landscape theory of biomolecular folding, 2) recent advances towards establishing a consistent understanding of folding and function, and 3) emerging themes in the functional motions of enzymes, biomolecular motors, and other biomolecular machines. Recent theoretical, computational, and experimental lines of investigation are providing a very dynamic picture of biomolecular motion. In contrast to earlier ideas, where molecular machines were thought to function similarly to macroscopic machines, with rigid components that move along a few degrees of freedom in a deterministic fashion, biomolecular complexes are only marginally stable. Since the stabilizing contribution of each atomic interaction is on the order of the thermal fluctuations in solution, the rigid body description of molecular function must be revisited. An emerging theme is that functional motions encompass order-disorder transitions and structural flexibility provide significant contributions to the free-energy. In this review, we describe the biological importance of order-disorder transitions and discuss the statistical-mechanical foundation of theoretical approaches that can characterize such transitions. PMID:22790780

A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.

PubMed

Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika; Krause, Tyler B; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A; Mireji, Paul O; Takáč, Peter; Denlinger, David L; Ribeiro, Jose M; Aksoy, Serap

2014-04-01

In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches.

HEPMath 1.4: A mathematica package for semi-automatic computations in high energy physics

NASA Astrophysics Data System (ADS)

Wiebusch, Martin

2015-10-01

This article introduces the Mathematica package HEPMath which provides a number of utilities and algorithms for High Energy Physics computations in Mathematica. Its functionality is similar to packages like FormCalc or FeynCalc, but it takes a more complete and extensible approach to implementing common High Energy Physics notations in the Mathematica language, in particular those related to tensors and index contractions. It also provides a more flexible method for the generation of numerical code which is based on new features for C code generation in Mathematica. In particular it can automatically generate Python extension modules which make the compiled functions callable from Python, thus eliminating the need to write any code in a low-level language like C or Fortran. It also contains seamless interfaces to LHAPDF, FeynArts, and LoopTools.

Inverse Thermal Analysis of Titanium GTA Welds Using Multiple Constraints

NASA Astrophysics Data System (ADS)

Lambrakos, S. G.; Shabaev, A.; Huang, L.

2015-06-01

Inverse thermal analysis of titanium gas-tungsten-arc welds using multiple constraint conditions is presented. This analysis employs a methodology that is in terms of numerical-analytical basis functions for inverse thermal analysis of steady-state energy deposition in plate structures. The results of this type of analysis provide parametric representations of weld temperature histories that can be adopted as input data to various types of computational procedures, such as those for prediction of solid-state phase transformations. In addition, these temperature histories can be used to construct parametric function representations for inverse thermal analysis of welds corresponding to other process parameters or welding processes whose process conditions are within similar regimes. The present study applies an inverse thermal analysis procedure that provides for the inclusion of constraint conditions associated with both solidification and phase transformation boundaries.

The Pathway Coexpression Network: Revealing pathway relationships

PubMed Central

Tanzi, Rudolph E.

2018-01-01

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer’s Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/. PMID:29554099

Striatal Pleiotrophin Overexpression Provides Functional and Morphological Neuroprotection in the 6-Hydroxydopamine Model

PubMed Central

Gombash, Sara E; Lipton, Jack W; Collier, Timothy J; Madhavan, Lalitha; Steece-Collier, Kathy; Cole-Strauss, Allyson; Terpstra, Brian T; Spieles-Engemann, Anne L; Daley, Brian F; Wohlgenant, Susan L; Thompson, Valerie B; Manfredsson, Fredric P; Mandel, Ronald J; Sortwell, Caryl E

2012-01-01

Neurotrophic factors are integrally involved in the development of the nigrostriatal system and in combination with gene therapy, possess great therapeutic potential for Parkinson's disease (PD). Pleiotrophin (PTN) is involved in the development, maintenance, and repair of the nigrostriatal dopamine (DA) system. The present study examined the ability of striatal PTN overexpression, delivered via psueudotyped recombinant adeno-associated virus type 2/1 (rAAV2/1), to provide neuroprotection and functional restoration from 6-hydroxydopamine (6-OHDA). Striatal PTN overexpression led to significant neuroprotection of tyrosine hydroxylase immunoreactive (THir) neurons in the substantia nigra pars compacta (SNpc) and THir neurite density in the striatum, with long-term PTN overexpression producing recovery from 6-OHDA-induced deficits in contralateral forelimb use. Transduced striatal PTN levels were increased threefold compared to adult striatal PTN expression and approximated peak endogenous developmental levels (P1). rAAV2/1 vector exclusively transduced neurons within the striatum and SNpc with approximately half the total striatal volume routinely transduced using our injection parameters. Our results indicate that striatal PTN overexpression can provide neuroprotection for the 6-OHDA lesioned nigrostriatal system based upon morphological and functional measures and that striatal PTN levels similar in magnitude to those expressed in the striatum during development are sufficient to provide neuroprotection from Parkinsonian insult. PMID:22008908

Functional interrogation of non-coding DNA through CRISPR genome editing.

PubMed

Canver, Matthew C; Bauer, Daniel E; Orkin, Stuart H

2017-05-15

Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic Connectivity Patterns in Conscious and Unconscious Brain

PubMed Central

Ma, Yuncong; Hamilton, Christina

2017-01-01

Abstract Brain functional connectivity undergoes dynamic changes from the awake to unconscious states. However, how the dynamics of functional connectivity patterns are linked to consciousness at the behavioral level remains elusive. In this study, we acquired resting-state functional magnetic resonance imaging data during wakefulness and graded levels of consciousness in rats. Data were analyzed using a dynamic approach combining the sliding window method and k-means clustering. Our results demonstrate that whole-brain networks contained several quasi-stable patterns that dynamically recurred from the awake state into anesthetized states. Remarkably, two brain connectivity states with distinct spatial similarity to the structure of anatomical connectivity were strongly biased toward high and low consciousness levels, respectively. These results provide compelling neuroimaging evidence linking the dynamics of whole-brain functional connectivity patterns and states of consciousness at the behavioral level. PMID:27846731

Thermal cloak-concentrator

NASA Astrophysics Data System (ADS)

Shen, Xiangying; Li, Ying; Jiang, Chaoran; Ni, Yushan; Huang, Jiping

2016-07-01

For macroscopically manipulating heat flow at will, thermal metamaterials have opened a practical way, which possesses a single function, such as either cloaking or concentrating the flow of heat even though environmental temperature varies. By developing a theory of transformation heat transfer for multiple functions, here we introduce the concept of intelligent thermal metamaterials with a dual function, which is in contrast to the existing thermal metamaterials with single functions. By assembling homogeneous isotropic materials and shape-memory alloys, we experimentally fabricate a kind of intelligent thermal metamaterials, which can automatically change from a cloak (or concentrator) to a concentrator (or cloak) when the environmental temperature changes. This work paves an efficient way for a controllable gradient of heat, and also provides guidance both for arbitrarily manipulating the flow of heat and for efficiently designing similar intelligent metamaterials in other fields.

Challenges in the Development and Evolution of Secure Open Architecture Command and Control Systems (Briefing Charts)

DTIC Science & Technology

2013-06-01

widgets for an OA system Design-time architecture: Browser, email, widget, DB, OS Go ogle Instance architecture: Chrome, Gmail, Google...provides functionally similar components or applications compatible with an OA system design Firefox Browser, WP, calendar Opera Instance...architecture: Firefox , AbiWord, Evolution, Fedora GPL Ab1Word Google Docs Instance ardlitecture: Fire fox, OR Google cal., Google Docs, Fedora

High Frontier: The Journal for Space and Cyberspace Professionals. Volume 6, Number 4, August 2010

DTIC Science & Technology

2010-08-01

information that warfighters rely on is likely to be useless (a three-way disaster is, anyway, logically impossible; if the global information grid...processing, exploitation, and dissemination (TCPED) of information . Space and cyber systems collectively provide the core functionality of the TCPED...rather than crisis management procedures. Space and cyber operations have several similarities dur- ing and can be extremely useful for informing Phase

Cognitive Functioning of Children with Severe Intellectual Disabilities and Children with Deafblindness: A Study of the Perceptions of Teachers and Parents in the USA and India

ERIC Educational Resources Information Center

Narayan, Jayanthi; Bruce, Susan M.; Bhandari, Reena; Kolli, Padmavathi

2010-01-01

Background: Teachers and parents play a very important role in providing valuable information for the assessment of children with severe disabilities. The needs of children, educational goals, and parental aspirations are similar irrespective of the part of the globe they live in. This study focused on the perceptions of teachers and parents of…

Generation and Analysis of Expressed Sequence Tags (ESTs) from Halophyte Atriplex canescens to Explore Salt-Responsive Related Genes

PubMed Central

Li, Jingtao; Sun, Xinhua; Yu, Gang; Jia, Chengguo; Liu, Jinliang; Pan, Hongyu

2014-01-01

Little information is available on gene expression profiling of halophyte A. canescens. To elucidate the molecular mechanism for stress tolerance in A. canescens, a full-length complementary DNA library was generated from A. canescens exposed to 400 mM NaCl, and provided 343 high-quality ESTs. In an evaluation of 343 valid EST sequences in the cDNA library, 197 unigenes were assembled, among which 190 unigenes (83.1% ESTs) were identified according to their significant similarities with proteins of known functions. All the 343 EST sequences have been deposited in the dbEST GenBank under accession numbers JZ535802 to JZ536144. According to Arabidopsis MIPS functional category and GO classifications, we identified 193 unigenes of the 311 annotations EST, representing 72 non-redundant unigenes sharing similarities with genes related to the defense response. The sets of ESTs obtained provide a rich genetic resource and 17 up-regulated genes related to salt stress resistance were identified by qRT-PCR. Six of these genes may contribute crucially to earlier and later stage salt stress resistance. Additionally, among the 343 unigenes sequences, 22 simple sequence repeats (SSRs) were also identified contributing to the study of A. canescens resources. PMID:24960361

Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease.

PubMed

Lyu, Zhe; Whitman, William B

2017-01-01

Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems.

De novo assembly and characterization of the garlic (Allium sativum) bud transcriptome by Illumina sequencing.

PubMed

Sun, Xiudong; Zhou, Shumei; Meng, Fanlu; Liu, Shiqi

2012-10-01

Garlic is widely used as a spice throughout the world for the culinary value of its flavor and aroma, which are created by the chemical transformation of a series of organic sulfur compounds. To analyze the transcriptome of Allium sativum and discover the genes involved in sulfur metabolism, cDNAs derived from the total RNA of Allium sativum buds were analyzed by Illumina sequencing. Approximately 26.67 million 90 bp paired-end clean reads were achieved in two libraries. A total of 127,933 unigenes were generated by de novo assembly and were compared with the sequences in public databases. Of these, 45,286 unigenes had significant hits to the sequences in the Nr database, 29,514 showed significant similarity to known proteins in the Swiss-Prot database and, 20,706 and 21,952 unigenes had significant similarity to existing sequences in the KEGG and COG databases, respectively. Moreover, genes involved in organic sulfur biosynthesis were identified. These unigenes data will provide the foundation for research on gene expression, genomics and functional genomics in Allium sativum. Key message The obtained unigenes will provide the foundation for research on functional genomics in Allium sativum and its closely related species, and fill the gap of the existing plant EST database.

In silico identification of molecular mimics involved in the pathogenesis of Clostridium botulinum ATCC 3502 strain.

PubMed

Bhardwaj, Tulika; Haque, Shafiul; Somvanshi, Pallavi

2018-05-12

Bacterial pathogens invade and disrupt the host defense system by means of protein sequences structurally similar at global and local level both. The sharing of homologous sequences between the host and the pathogenic bacteria mediates the infection and defines the concept of molecular mimicry. In this study, various computational approaches were employed to elucidate the pathogenicity of Clostridium botulinum ATCC 3502 at genome-wide level. Genome-wide study revealed that the pathogen mimics the host (Homo sapiens) and unraveled the complex pathogenic pathway of causing infection. The comparative 'omics' approaches helped in selective screening of 'molecular mimicry' candidates followed by the qualitative assessment of the virulence potential and functional enrichment. Overall, this study provides a deep insight into the emergence and surveillance of multidrug resistant C. botulinum ATCC 3502 caused infections. This is the very first report identifying C. botulinum ATCC 3502 proteome enriched similarities to the human host proteins and resulted in the identification of 20 potential mimicry candidates, which were further characterized qualitatively by sub-cellular organization prediction and functional annotation. This study will provide a variety of avenues for future studies related to infectious agents, host-pathogen interactions and the evolution of pathogenesis process. Copyright © 2018. Published by Elsevier Ltd.

What Do They Have in Common? Physical Drivers of Streamflow Spatial Correlation and Prediction of Flow Regimes at Ungauged Locations in the Contiguous United States

NASA Astrophysics Data System (ADS)

Betterle, A.; Schirmer, M.; Botter, G.

2017-12-01

Streamflow dynamics strongly influence anthropogenic activities and the ecological functions of riverine and riparian habitats. However, the widespread lack of direct discharge measurements often challenges the set-up of conscious and effective decision-making processes, including droughts and floods protection, water resources management and river restoration practices. By characterizing the spatial correlation of daily streamflow timeseries at two arbitrary locations, this study provides a method to evaluate how spatially variable catchment-scale hydrological process affects the resulting streamflow dynamics along and across river systems. In particular, streamflow spatial correlation is described analytically as a function of morphological, climatic and vegetation properties in the contributing catchments, building on a joint probabilistic description of flow dynamics at pairs of outlets. The approach enables an explicit linkage between similarities of flow dynamics and spatial patterns of hydrologically relevant features of climate and landscape. Therefore, the method is suited to explore spatial patterns of streamflow dynamics across geomorphoclimatic gradients. In particular, we show how the streamflow correlation can be used at the continental scale to individuate catchment pairs with similar hydrological dynamics, thereby providing a useful tool for the estimate of flow duration curves in poorly gauged areas.

A New Look at Rainfall Fluctuations and Scaling Properties of Spatial Rainfall Using Orthogonal Wavelets.

NASA Astrophysics Data System (ADS)

Kumar, Praveen; Foufoula-Georgiou, Efi

1993-02-01

It has been observed that the finite-dimensional distribution functions of rainfall cannot obey simple scaling laws due to rainfall intermittency (mixed distribution with an atom at zero) and the probability of rainfall being an increasing function of area. Although rainfall fluctuations do not suffer these limitations, it is interesting to note that very few attempts have been made to study them in terms of their self-similarity characteristics. This is due to the lack of unambiguous definition of fluctuations in multidimensions. This paper shows that wavelet transforms offer a convenient and consistent method for the decomposition of inhomogeneous and anisotropic rainfall fields in two dimensions and that the components of this decomposition can be looked at as fluctuations of the rainfall field. It is also shown that under some mild assumptions, the component fields can be treated as homogeneous and thus are amenable to second-order analysis, which can provide useful insight into the nature of the process. The fact that wavelet transforms are a space-scale method also provides a convenient tool to study scaling characteristics of the process. Orthogonal wavelets are used, and these properties are investigated for a squall-line storm to study the presence of self-similarity.

Trophic groups and modules: two levels of group detection in food webs.

PubMed

Gauzens, Benoit; Thébault, Elisa; Lacroix, Gérard; Legendre, Stéphane

2015-05-06

Within food webs, species can be partitioned into groups according to various criteria. Two notions have received particular attention: trophic groups (TGs), which have been used for decades in the ecological literature, and more recently, modules. The relationship between these two group concepts remains unknown in empirical food webs. While recent developments in network theory have led to efficient methods for detecting modules in food webs, the determination of TGs (groups of species that are functionally similar) is largely based on subjective expert knowledge. We develop a novel algorithm for TG detection. We apply this method to empirical food webs and show that aggregation into TGs allows for the simplification of food webs while preserving their information content. Furthermore, we reveal a two-level hierarchical structure where modules partition food webs into large bottom-top trophic pathways, whereas TGs further partition these pathways into groups of species with similar trophic connections. This provides new perspectives for the study of dynamical and functional consequences of food-web structure, bridging topological and dynamical analysis. TGs have a clear ecological meaning and are found to provide a trade-off between network complexity and information loss. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

In defense of abstract conceptual representations.

PubMed

Binder, Jeffrey R

2016-08-01

An extensive program of research in the past 2 decades has focused on the role of modal sensory, motor, and affective brain systems in storing and retrieving concept knowledge. This focus has led in some circles to an underestimation of the need for more abstract, supramodal conceptual representations in semantic cognition. Evidence for supramodal processing comes from neuroimaging work documenting a large, well-defined cortical network that responds to meaningful stimuli regardless of modal content. The nodes in this network correspond to high-level "convergence zones" that receive broadly crossmodal input and presumably process crossmodal conjunctions. It is proposed that highly conjunctive representations are needed for several critical functions, including capturing conceptual similarity structure, enabling thematic associative relationships independent of conceptual similarity, and providing efficient "chunking" of concept representations for a range of higher order tasks that require concepts to be configured as situations. These hypothesized functions account for a wide range of neuroimaging results showing modulation of the supramodal convergence zone network by associative strength, lexicality, familiarity, imageability, frequency, and semantic compositionality. The evidence supports a hierarchical model of knowledge representation in which modal systems provide a mechanism for concept acquisition and serve to ground individual concepts in external reality, whereas broadly conjunctive, supramodal representations play an equally important role in concept association and situation knowledge.

Frequency maps as a probe of secular evolution in the Milky Way

NASA Astrophysics Data System (ADS)

Valluri, Monica

2015-03-01

The frequency analysis of the orbits of halo stars and dark matter particles from a cosmological hydrodynamical simulation of a disk galaxy from the MUGS collaboration (Stinson et al. 2010) shows that even if the shape of the dark matter halo is nearly oblate, only about 50% of its orbits are on short-axis tubes, confirming a previous result: under baryonic condensation all orbit families can deform their shapes without changing orbital type (Valluri et al. 2010). Orbits of dark matter particles and halo stars are very similar reflecting their common accretion origin and the influence of baryons. Frequency maps provide a compact representation of the 6-D phase space distribution that also reveals the history of the halo (Valluri et al. 2012). The 6-D phase space coordinates for a large population of halo stars in the Milky Way that will be obtained from future surveys can be used to reconstruct the phase-space distribution function of the stellar halo. The similarity between the frequency maps of halo stars and dark matter particles (Fig. 1) implies that reconstruction of the stellar halo distribution function can reveal the phase space distribution of the unseen dark matter particles and provide evidence for secular evolution. MV is supported by NSF grant AST-0908346 and the Elizabeth Crosby grant.

Anisotropy in electromagnetic field variations and its implication for lateral inhomogeneity of the electrical conductivity structure

NASA Astrophysics Data System (ADS)

Honkura, Y.; Watanabe, N.; Kaneko, Y.; Oshima, S.

1989-03-01

Two-dimensional analyses of magnetotelluric data provide information on anisotropic response for two different polarization cases; the so-called B-polarization and E-polarization cases. Similar anisotropy should also be observed in the horizontal components of magnetic field variations. On the assumption that a reference station provides the normal magnetic field, transfer functions for the horizontal magnetic fields can be derived in a fashion similar to the impedance analysis for magnetotelluric data. We applied this method to magnetic data obtained at some observation sites in a geothermal area in Japan. Transfer functions for the horizontal magnetic fields exhibit a strong anisotropy with the preferred direction nearly perpendicular to that for the electric field. This result implies the existence of strong electric currents flowing in the direction perpendicular to the above preferred direction for the magnetic field. The present method was also applied to the horizontal components of magnetic field variations observed at the seafloor. In this case, a magnetic observatory on land was taken as the reference station, and attenuation of the amplitude of horizontal magnetic field variation was examined. Anisotropy in attenuation was then found with the preferred direction perpendicular to the axis of the Okinawa trough where the seafloor measurement was undertaken.

A new look at rainfall fluctuations and scaling properties of spatial rainfall using orthogonal wavelets

NASA Technical Reports Server (NTRS)

Kumar, Praveen; Foufoula-Georgiou, Efi

1993-01-01

It has been observed that the finite-dimensional distribution functions of rainfall cannot obey simple scaling laws due to rainfall intermittency (mixed distribution with an atom at zero) and the probability of rainfall being an increasing function of area. Although rainfall fluctuations do not suffer these limitations, it is interesting to note that very few attempts have been made to study them in terms of their self-similarity characteristics. This is due to the lack of unambiguous definition of fluctuations in multidimensions. This paper shows that wavelet transforms offer a convenient and consistent method for the decomposition of inhomogeneous and anisotropic rainfall fields in two dimensions and that the components of this decomposition can be looked at as fluctuations of the rainfall field. It is also shown that under some mild assumptions, the component fields can be treated as homogeneous and thus are amenable to second-order analysis, which can provide useful insight into the nature of the process. The fact that wavelet transforms are a space-scale method also provides a convenient tool to study scaling characteristics of the process. Orthogonal wavelets are used, and these properties are investigated for a squall-line storm to study the presence of self-similarity.

Protein architecture and core residues in unwound α-helices provide insights to the transport function of plant AtCHX17

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czerny, Daniel D.; Padmanaban, Senthilkumar; Anishkin, Andriy

Using Arabidopsis thaliana AtCHX17 as an example, we combine structural modeling and mutagenesis to provide insights on its protein architecture and transport function which is poorly characterized. This approach is based on the observation that protein structures are significantly more conserved in evolution than linear sequences, and mechanistic similarities among diverse transporters are emerging. Two homology models of AtCHX17 were obtained that show a protein fold similar to known structures of bacterial Na +/H + antiporters, EcNhaA and TtNapA. The distinct secondary and tertiary structure models highlighted residues at positions potentially important for CHX17 activity. Mutagenesis showed that asparagine-N200 andmore » aspartate-D201 inside transmembrane5 (TM5), and lysine-K355 inside TM10 are critical for AtCHX17 activity. We reveal previously unrecognized threonine-T170 and lysine-K383 as key residues at unwound regions in the middle of TM4 and TM11 α-helices, respectively. Mutation of glutamate-E111 located near the membrane surface inhibited AtCHX17 activity, suggesting a role in pH sensing. The long carboxylic tail of unknown purpose has an alternating β-sheet and α-helix secondary structure that is conserved in prokaryote universal stress proteins. Here, these results support the overall architecture of AtCHX17 and identify D201, N200 and novel residues T170 and K383 at the functional core which likely participates in ion recognition, coordination and/or translocation, similar to characterized cation/H + exchangers. The core of AtCHX17 models according to EcNhaA and TtNapA templates faces inward and outward, respectively, which may reflect two conformational states of the alternating access transport mode for proteins belonging to the plant CHX family.« less

Protein architecture and core residues in unwound α-helices provide insights to the transport function of plant AtCHX17

DOE PAGES

Czerny, Daniel D.; Padmanaban, Senthilkumar; Anishkin, Andriy; ...

2016-05-11

Using Arabidopsis thaliana AtCHX17 as an example, we combine structural modeling and mutagenesis to provide insights on its protein architecture and transport function which is poorly characterized. This approach is based on the observation that protein structures are significantly more conserved in evolution than linear sequences, and mechanistic similarities among diverse transporters are emerging. Two homology models of AtCHX17 were obtained that show a protein fold similar to known structures of bacterial Na +/H + antiporters, EcNhaA and TtNapA. The distinct secondary and tertiary structure models highlighted residues at positions potentially important for CHX17 activity. Mutagenesis showed that asparagine-N200 andmore » aspartate-D201 inside transmembrane5 (TM5), and lysine-K355 inside TM10 are critical for AtCHX17 activity. We reveal previously unrecognized threonine-T170 and lysine-K383 as key residues at unwound regions in the middle of TM4 and TM11 α-helices, respectively. Mutation of glutamate-E111 located near the membrane surface inhibited AtCHX17 activity, suggesting a role in pH sensing. The long carboxylic tail of unknown purpose has an alternating β-sheet and α-helix secondary structure that is conserved in prokaryote universal stress proteins. Here, these results support the overall architecture of AtCHX17 and identify D201, N200 and novel residues T170 and K383 at the functional core which likely participates in ion recognition, coordination and/or translocation, similar to characterized cation/H + exchangers. The core of AtCHX17 models according to EcNhaA and TtNapA templates faces inward and outward, respectively, which may reflect two conformational states of the alternating access transport mode for proteins belonging to the plant CHX family.« less

Visual circuits of the avian telencephalon: evolutionary implications

NASA Technical Reports Server (NTRS)

Shimizu, T.; Bowers, A. N.

1999-01-01

Birds and primates are vertebrates that possess the most advanced, efficient visual systems. Although lineages leading to these two classes were separated about 300 million years ago, there are striking similarities in their underlying neural mechanisms for visual processing. This paper discusses such similarities with special emphasis on the visual circuits in the avian telencephalon. These similarities include: (1) the existence of two parallel visual pathways and their distinct telencephalic targets, (2) anatomical and functional segregation within the visual pathways, (3) laminar organization of the telencephalic targets of the pathways (e.g. striate cortex in primates), and (4) possible interactions between multiple visual areas. Additional extensive analyses are necessary to determine whether these similarities are due to inheritance from a common ancestral stock or the consequences of convergent evolution based on adaptive response to similar selective pressures. Nevertheless, such a comparison is important to identify the general and specific principles of visual processing in amniotes (reptiles, birds, and mammals). Furthermore, these principles in turn will provide a critical foundation for understanding the evolution of the brain in amniotes.

Developing a 3D Gestural Interface for Anesthesia-Related Human-Computer Interaction Tasks Using Both Experts and Novices.

PubMed

Jurewicz, Katherina A; Neyens, David M; Catchpole, Ken; Reeves, Scott T

2018-06-01

The purpose of this research was to compare gesture-function mappings for experts and novices using a 3D, vision-based, gestural input system when exposed to the same context of anesthesia tasks in the operating room (OR). 3D, vision-based, gestural input systems can serve as a natural way to interact with computers and are potentially useful in sterile environments (e.g., ORs) to limit the spread of bacteria. Anesthesia providers' hands have been linked to bacterial transfer in the OR, but a gestural input system for anesthetic tasks has not been investigated. A repeated-measures study was conducted with two cohorts: anesthesia providers (i.e., experts) ( N = 16) and students (i.e., novices) ( N = 30). Participants chose gestures for 10 anesthetic functions across three blocks to determine intuitive gesture-function mappings. Reaction time was collected as a complementary measure for understanding the mappings. The two gesture-function mapping sets showed some similarities and differences. The gesture mappings of the anesthesia providers showed a relationship to physical components in the anesthesia environment that were not seen in the students' gestures. The students also exhibited evidence related to longer reaction times compared to the anesthesia providers. Domain expertise is influential when creating gesture-function mappings. However, both experts and novices should be able to use a gesture system intuitively, so development methods need to be refined for considering the needs of different user groups. The development of a touchless interface for perioperative anesthesia may reduce bacterial contamination and eventually offer a reduced risk of infection to patients.

Scaling of Topologically Similar Functional Modules Defines Mouse Primary Auditory and Somatosensory Microcircuitry

PubMed Central

Sadovsky, Alexander J.

2013-01-01

Mapping the flow of activity through neocortical microcircuits provides key insights into the underlying circuit architecture. Using a comparative analysis we determined the extent to which the dynamics of microcircuits in mouse primary somatosensory barrel field (S1BF) and auditory (A1) neocortex generalize. We imaged the simultaneous dynamics of up to 1126 neurons spanning multiple columns and layers using high-speed multiphoton imaging. The temporal progression and reliability of reactivation of circuit events in both regions suggested common underlying cortical design features. We used circuit activity flow to generate functional connectivity maps, or graphs, to test the microcircuit hypothesis within a functional framework. S1BF and A1 present a useful test of the postulate as both regions map sensory input anatomically, but each area appears organized according to different design principles. We projected the functional topologies into anatomical space and found benchmarks of organization that had been previously described using physiology and anatomical methods, consistent with a close mapping between anatomy and functional dynamics. By comparing graphs representing activity flow we found that each region is similarly organized as highlighted by hallmarks of small world, scale free, and hierarchical modular topologies. Models of prototypical functional circuits from each area of cortex were sufficient to recapitulate experimentally observed circuit activity. Convergence to common behavior by these models was accomplished using preferential attachment to scale from an auditory up to a somatosensory circuit. These functional data imply that the microcircuit hypothesis be framed as scalable principles of neocortical circuit design. PMID:23986241

Fixed-Node Diffusion Quantum Monte Carlo Method on Dissociation Energies and Their Trends for R-X Bonds (R = Me, Et, i-Pr, t-Bu).

PubMed

Hou, Aiqiang; Zhou, Xiaojun; Wang, Ting; Wang, Fan

2018-05-15

Achieving both bond dissociation energies (BDEs) and their trends for the R-X bonds with R = Me, Et, i-Pr, and t-Bu reliably is nontrivial. Density functional theory (DFT) methods with traditional exchange-correlation functionals usually have large error on both the BDEs and their trends. The M06-2X functional gives rise to reliable BDEs, but the relative BDEs are determined not as accurately. More demanding approaches such as some double-hybrid functionals, for example, G4 and CCSD(T), are generally required to achieve the BDEs and their trends reliably. The fixed-node diffusion quantum Monte Carlo method (FN-DMC) is employed to calculated BDEs of these R-X bonds with X = H, CH 3 , OCH 3 , OH, and F in this work. The single Slater-Jastrow wave function is adopted as trial wave function, and pseudopotentials (PPs) developed for quantum Monte Carlo calculations are chosen. Error of these PPs is modest in wave function methods, while it is more pronounced in DFT calculations. Our results show that accuracy of BDEs with FN-DMC is similar to that of M06-2X and G4, and trends in BDEs are calculated more reliably than M06-2X. Both BDEs and trends in BDEs of these bonds are reproduced reasonably with FN-DMC. FN-DMC using PPs can thus be applied to BDEs and their trends of similar chemical bonds in larger molecules reliably and provide valuable information on properties of these molecules.

Graded-threshold parametric response maps: towards a strategy for adaptive dose painting

NASA Astrophysics Data System (ADS)

Lausch, A.; Jensen, N.; Chen, J.; Lee, T. Y.; Lock, M.; Wong, E.

2014-03-01

Purpose: To modify the single-threshold parametric response map (ST-PRM) method for predicting treatment outcomes in order to facilitate its use for guidance of adaptive dose painting in intensity-modulated radiotherapy. Methods: Multiple graded thresholds were used to extend the ST-PRM method (Nat. Med. 2009;15(5):572-576) such that the full functional change distribution within tumours could be represented with respect to multiple confidence interval estimates for functional changes in similar healthy tissue. The ST-PRM and graded-threshold PRM (GT-PRM) methods were applied to functional imaging scans of 5 patients treated for hepatocellular carcinoma. Pre and post-radiotherapy arterial blood flow maps (ABF) were generated from CT-perfusion scans of each patient. ABF maps were rigidly registered based on aligning tumour centres of mass. ST-PRM and GT-PRM analyses were then performed on overlapping tumour regions within the registered ABF maps. Main findings: The ST-PRMs contained many disconnected clusters of voxels classified as having a significant change in function. While this may be useful to predict treatment response, it may pose challenges for identifying boost volumes or for informing dose-painting by numbers strategies. The GT-PRMs included all of the same information as ST-PRMs but also visualized the full tumour functional change distribution. Heterogeneous clusters in the ST-PRMs often became more connected in the GT-PRMs by voxels with similar functional changes. Conclusions: GT-PRMs provided additional information which helped to visualize relationships between significant functional changes identified by ST-PRMs. This may enhance ST-PRM utility for guiding adaptive dose painting.

Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence-Function Space and Genome Context to Discover Novel Functions.

PubMed

Gerlt, John A

2017-08-22

The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of "genomic enzymology" web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence-function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems.

Genomic Enzymology: Web Tools for Leveraging Protein Family Sequence–Function Space and Genome Context to Discover Novel Functions

PubMed Central

2017-01-01

The exponentially increasing number of protein and nucleic acid sequences provides opportunities to discover novel enzymes, metabolic pathways, and metabolites/natural products, thereby adding to our knowledge of biochemistry and biology. The challenge has evolved from generating sequence information to mining the databases to integrating and leveraging the available information, i.e., the availability of “genomic enzymology” web tools. Web tools that allow identification of biosynthetic gene clusters are widely used by the natural products/synthetic biology community, thereby facilitating the discovery of novel natural products and the enzymes responsible for their biosynthesis. However, many novel enzymes with interesting mechanisms participate in uncharacterized small-molecule metabolic pathways; their discovery and functional characterization also can be accomplished by leveraging information in protein and nucleic acid databases. This Perspective focuses on two genomic enzymology web tools that assist the discovery novel metabolic pathways: (1) Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST) for generating sequence similarity networks to visualize and analyze sequence–function space in protein families and (2) Enzyme Function Initiative-Genome Neighborhood Tool (EFI-GNT) for generating genome neighborhood networks to visualize and analyze the genome context in microbial and fungal genomes. Both tools have been adapted to other applications to facilitate target selection for enzyme discovery and functional characterization. As the natural products community has demonstrated, the enzymology community needs to embrace the essential role of web tools that allow the protein and genome sequence databases to be leveraged for novel insights into enzymological problems. PMID:28826221

Conceptual influences on category-based induction

PubMed Central

Gelman, Susan A.; Davidson, Natalie S.

2013-01-01

One important function of categories is to permit rich inductive inferences. Prior work shows that children use category labels to guide their inductive inferences. However, there are competing theories to explain this phenomenon, differing in the roles attributed to conceptual information versus perceptual similarity. Seven experiments with 4- to 5-year-old children and adults (N = 344) test these theories by teaching categories for which category membership and perceptual similarity are in conflict, and varying the conceptual basis of the novel categories. Results indicate that for non-natural kind categories that have little conceptual coherence, children make inferences based on perceptual similarity, whereas adults make inferences based on category membership. In contrast, for basic- and ontological-level categories that have a principled conceptual basis, children and adults alike make use of category membership more than perceptual similarity as the basis of their inferences. These findings provide evidence in favor of the role of conceptual information in preschoolers’ inferences, and further demonstrate that labeled categories are not all equivalent; they differ in their inductive potential. PMID:23517863

In-use product stocks link manufactured capital to natural capital.

PubMed

Chen, Wei-Qiang; Graedel, T E

2015-05-19

In-use stock of a product is the amount of the product in active use. In-use product stocks provide various functions or services on which we rely in our daily work and lives, and the concept of in-use product stock for industrial ecologists is similar to the concept of net manufactured capital stock for economists. This study estimates historical physical in-use stocks of 91 products and 9 product groups and uses monetary data on net capital stocks of 56 products to either approximate or compare with in-use stocks of the corresponding products in the United States. Findings include the following: (i) The development of new products and the buildup of their in-use stocks result in the increase in variety of in-use product stocks and of manufactured capital; (ii) substitution among products providing similar or identical functions reflects the improvement in quality of in-use product stocks and of manufactured capital; and (iii) the historical evolution of stocks of the 156 products or product groups in absolute, per capita, or per-household terms shows that stocks of most products have reached or are approaching an upper limit. Because the buildup, renewal, renovation, maintenance, and operation of in-use product stocks drive the anthropogenic cycles of materials that are used to produce products and that originate from natural capital, the determination of in-use product stocks together with modeling of anthropogenic material cycles provides an analytic perspective on the material linkage between manufactured capital and natural capital.

In-use product stocks link manufactured capital to natural capital

PubMed Central

Chen, Wei-Qiang; Graedel, T. E.

2015-01-01

In-use stock of a product is the amount of the product in active use. In-use product stocks provide various functions or services on which we rely in our daily work and lives, and the concept of in-use product stock for industrial ecologists is similar to the concept of net manufactured capital stock for economists. This study estimates historical physical in-use stocks of 91 products and 9 product groups and uses monetary data on net capital stocks of 56 products to either approximate or compare with in-use stocks of the corresponding products in the United States. Findings include the following: (i) The development of new products and the buildup of their in-use stocks result in the increase in variety of in-use product stocks and of manufactured capital; (ii) substitution among products providing similar or identical functions reflects the improvement in quality of in-use product stocks and of manufactured capital; and (iii) the historical evolution of stocks of the 156 products or product groups in absolute, per capita, or per-household terms shows that stocks of most products have reached or are approaching an upper limit. Because the buildup, renewal, renovation, maintenance, and operation of in-use product stocks drive the anthropogenic cycles of materials that are used to produce products and that originate from natural capital, the determination of in-use product stocks together with modeling of anthropogenic material cycles provides an analytic perspective on the material linkage between manufactured capital and natural capital. PMID:25733904

Murine Leukemia Virus Reverse Transcriptase: Structural Comparison with HIV-1 Reverse Transcriptase

PubMed Central

Coté, Marie L.; Roth, Monica J.

2008-01-01

Recent X-ray crystal structure determinations of Moloney murine leukemia virus reverse transcriptase (MoMLV RT) have allowed for more accurate structure/function comparisons to HIV-1 RT than were formerly possible. Previous biochemical studies of MoMLV RT in conjunction with knowledge of sequence homologies to HIV-1 RT and overall fold similarities to RTs in general, provided a foundation upon which to build. In addition, numerous crystal structures of the MoMLV RT fingers/palm subdomain had also shed light on one of the critical functions of the enzyme, specifically polymerization. Now in the advent of new structural information, more intricate examination of MoMLV RT in its entirety can be realized, and thus the comparisons with HIV-1 RT may be more critically elucidated. Here, we will review the similarities and differences between MoMLV RT and HIV-1 RT via structural analysis, and propose working models for the MoMLV RT based upon that information. PMID:18294720

Scaling relations for a needle-like electron beam plasma from the self-similar behavior in beam propagation

NASA Astrophysics Data System (ADS)

Bai, Xiaoyan; Chen, Chen; Li, Hong; Liu, Wandong; Chen, Wei

2017-10-01

Scaling relations of the main parameters of a needle-like electron beam plasma (EBP) to the initial beam energy, beam current, and discharge pressures are presented. The relations characterize the main features of the plasma in three parameter space and can provide great convenience in plasma design with electron beams. First, starting from the self-similar behavior of electron beam propagation, energy and charge depositions in beam propagation were expressed analytically as functions of the three parameters. Second, according to the complete coupled theoretical model of an EBP and appropriate assumptions, independent equations controlling the density and space charges were derived. Analytical expressions for the density and charges versus functions of energy and charge depositions were obtained. Finally, with the combination of the expressions derived in the above two steps, scaling relations of the density and potential to the three parameters were constructed. Meanwhile, numerical simulations were used to test part of the scaling relations.

Eye movements during object recognition in visual agnosia.

PubMed

Charles Leek, E; Patterson, Candy; Paul, Matthew A; Rafal, Robert; Cristino, Filipe

2012-07-01

This paper reports the first ever detailed study about eye movement patterns during single object recognition in visual agnosia. Eye movements were recorded in a patient with an integrative agnosic deficit during two recognition tasks: common object naming and novel object recognition memory. The patient showed normal directional biases in saccades and fixation dwell times in both tasks and was as likely as controls to fixate within object bounding contour regardless of recognition accuracy. In contrast, following initial saccades of similar amplitude to controls, the patient showed a bias for short saccades. In object naming, but not in recognition memory, the similarity of the spatial distributions of patient and control fixations was modulated by recognition accuracy. The study provides new evidence about how eye movements can be used to elucidate the functional impairments underlying object recognition deficits. We argue that the results reflect a breakdown in normal functional processes involved in the integration of shape information across object structure during the visual perception of shape. Copyright © 2012 Elsevier Ltd. All rights reserved.

Continuous vs. blocks of physiotherapy for motor development in children with cerebral palsy and similar syndromes: A prospective randomized study.

PubMed

Brunner, Anne-Louise; Rutz, Erich; Juenemann, Stephanie; Brunner, Reinald

2014-12-01

To determine whether physiotherapy is more effective when applied in blocks or continuously in children with cerebral palsy (CP). A prospective randomized cross-over design study compared the effect of regular physiotherapy (baseline) with blocks of physiotherapy alternating with no physiotherapy over one year. Thirty-nine institutionalized children with CP and clinically similar syndromes (6-16 years old, Gross Motor Function Classification Scale II-IV) were included. During the first scholastic year, group A received regular physiotherapy, group B blocks of physiotherapy and vice versa in the second year. The Gross Motor Function Measure 66 (GMFM-66) was the outcome measure. Thirteen children in each group completed the study. GMFM-66 improved (p < 0.05) over the study period in both groups in total; changes (p < 0.05) were seen only in dimension D (group B) and E (both groups) during regular therapy. Physiotherapy may be more effective when provided regularly rather than in blocks.

A novel perivascular cell population in the zebrafish brain

PubMed Central

Galanternik, Marina Venero; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-01-01

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or ‘Mato Cells’ in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium. DOI: http://dx.doi.org/10.7554/eLife.24369.001 PMID:28395729

The effect of induced sadness and moderate depression on attention networks.

PubMed

Bellaera, Lauren; von Mühlenen, Adrian

2017-09-01

This study investigates how sadness and minor/moderate depression influences the three functions of attention: alerting, orienting, and executive control using the Attention Network Test. The aim of the study is to investigate whether minor-to-moderate depression is more similar to sadness or clinical depression with regard to attentional processing. It was predicted that both induced sadness and minor-to-moderate depression will influence executive control by narrowing spatial attention and in turn this will lead to less interference from the flanker items (i.e. less effects of congruency) due to a focused attentional state. No differences were predicted for alerting or orienting functions. The results from the two experiments, the first inducing sadness (Experiment 1) and the second measuring subclinical depression (Experiment 2), show that, as expected, participants who are sad or minor to moderately depressed showed less flanker interference compared to participants who were neither sad nor depressed. This study provides strong evidence, that irrespective of its aetiology, sadness and minor/moderate depression have similar effects on spatial attention.

Structural Determination of Functional Domains in Early B-cell Factor (EBF) Family of Transcription Factors Reveals Similarities to Rel DNA-binding Proteins and a Novel Dimerization Motif*

PubMed Central

Siponen, Marina I.; Wisniewska, Magdalena; Lehtiö, Lari; Johansson, Ida; Svensson, Linda; Raszewski, Grzegorz; Nilsson, Lennart; Sigvardsson, Mikael; Berglund, Helena

2010-01-01

The early B-cell factor (EBF) transcription factors are central regulators of development in several organs and tissues. This protein family shows low sequence similarity to other protein families, which is why structural information for the functional domains of these proteins is crucial to understand their biochemical features. We have used a modular approach to determine the crystal structures of the structured domains in the EBF family. The DNA binding domain reveals a striking resemblance to the DNA binding domains of the Rel homology superfamily of transcription factors but contains a unique zinc binding structure, termed zinc knuckle. Further the EBF proteins contain an IPT/TIG domain and an atypical helix-loop-helix domain with a novel type of dimerization motif. The data presented here provide insights into unique structural features of the EBF proteins and open possibilities for detailed molecular investigations of this important transcription factor family. PMID:20592035

Uncertainty in Measurement: A Review of Monte Carlo Simulation Using Microsoft Excel for the Calculation of Uncertainties Through Functional Relationships, Including Uncertainties in Empirically Derived Constants

PubMed Central

Farrance, Ian; Frenkel, Robert

2014-01-01

The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more ‘constants’, each of which has an empirically derived numerical value. Such empirically derived ‘constants’ must also have associated uncertainties which propagate through the functional relationship and contribute to the combined standard uncertainty of the measurand. PMID:24659835

Uncertainty in measurement: a review of monte carlo simulation using microsoft excel for the calculation of uncertainties through functional relationships, including uncertainties in empirically derived constants.

PubMed

Farrance, Ian; Frenkel, Robert

2014-02-01

The Guide to the Expression of Uncertainty in Measurement (usually referred to as the GUM) provides the basic framework for evaluating uncertainty in measurement. The GUM however does not always provide clearly identifiable procedures suitable for medical laboratory applications, particularly when internal quality control (IQC) is used to derive most of the uncertainty estimates. The GUM modelling approach requires advanced mathematical skills for many of its procedures, but Monte Carlo simulation (MCS) can be used as an alternative for many medical laboratory applications. In particular, calculations for determining how uncertainties in the input quantities to a functional relationship propagate through to the output can be accomplished using a readily available spreadsheet such as Microsoft Excel. The MCS procedure uses algorithmically generated pseudo-random numbers which are then forced to follow a prescribed probability distribution. When IQC data provide the uncertainty estimates the normal (Gaussian) distribution is generally considered appropriate, but MCS is by no means restricted to this particular case. With input variations simulated by random numbers, the functional relationship then provides the corresponding variations in the output in a manner which also provides its probability distribution. The MCS procedure thus provides output uncertainty estimates without the need for the differential equations associated with GUM modelling. The aim of this article is to demonstrate the ease with which Microsoft Excel (or a similar spreadsheet) can be used to provide an uncertainty estimate for measurands derived through a functional relationship. In addition, we also consider the relatively common situation where an empirically derived formula includes one or more 'constants', each of which has an empirically derived numerical value. Such empirically derived 'constants' must also have associated uncertainties which propagate through the functional relationship and contribute to the combined standard uncertainty of the measurand.

Generation of transgenic mouse model using PTTG as an oncogene.

PubMed

Kakar, Sham S; Kakar, Cohin

2015-01-01

The close physiological similarity between the mouse and human has provided tools to understanding the biological function of particular genes in vivo by introduction or deletion of a gene of interest. Using a mouse as a model has provided a wealth of resources, knowledge, and technology, helping scientists to understand the biological functions, translocation, trafficking, and interaction of a candidate gene with other intracellular molecules, transcriptional regulation, posttranslational modification, and discovery of novel signaling pathways for a particular gene. Most importantly, the generation of the mouse model for a specific human disease has provided a powerful tool to understand the etiology of a disease and discovery of novel therapeutics. This chapter describes in detail the step-by-step generation of the transgenic mouse model, which can be helpful in guiding new investigators in developing successful models. For practical purposes, we will describe the generation of a mouse model using pituitary tumor transforming gene (PTTG) as the candidate gene of interest.

Schedule-induced drinking: rate of food delivery and Herrnstein's equation.

PubMed Central

Wetherington, C L

1979-01-01

Schedule-induced drinking was measured in four rats exposed to fixed-time schedules of food ranging from 30 to 480 seconds. Herrnstein's (1970, 1974) equation relating rate of a single response as a hyperbolic function of reinforcement rate provided a good fit to three measures of drinking: lick rate, ingestion rate, and relative time spent drinking. The functions relating the three measures of drinking to reinforcement rate were of similar form. Herrnstein's equation also provided a good description of some already published data on schedule-induced drinking. The fit both to the present data and to the already published data was improved somewhat by computing the measures by subtracting from the time base a latency constant representing the minimal time required to consume the food pellet and travel to the water source. The data from this study provide two correspondences between operant behavior and schedule-induced behavior: (a) conformity to Herrnstein's equation and (b) equivalence of rate and relative time measures. PMID:512568

Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology

PubMed Central

Barthmes, Maria; Liao, Jun; Jiang, Youxing; Brüggemann, Andrea

2016-01-01

Sodium–calcium exchangers (NCXs) are membrane transporters that play an important role in Ca2+ homeostasis and Ca2+ signaling. The recent crystal structure of NCX_Mj, a member of the NCX family from the archaebacterium Methanococcus jannaschii, provided insight into the atomistic details of sodium–calcium exchange. Here, we extend these findings by providing detailed functional data on purified NCX_Mj using solid supported membrane (SSM)–based electrophysiology, a powerful but unexploited tool for functional studies of electrogenic transporter proteins. We show that NCX_Mj is highly selective for Na+, whereas Ca2+ can be replaced by Mg2+ and Sr2+ and that NCX_Mj can be inhibited by divalent ions, particularly Cd2+. By directly comparing the apparent affinities of Na+ and Ca2+ for NCX_Mj with those for human NCX1, we show excellent agreement, indicating a strong functional similarity between NCX_Mj and its eukaryotic isoforms. We also provide detailed instructions to facilitate the adaption of this method to other electrogenic transporter proteins. Our findings demonstrate that NCX_Mj can serve as a model for the NCX family and highlight several possible applications for SSM-based electrophysiology. PMID:27241699

Chemical space visualization: transforming multidimensional chemical spaces into similarity-based molecular networks.

PubMed

de la Vega de León, Antonio; Bajorath, Jürgen

2016-09-01

The concept of chemical space is of fundamental relevance for medicinal chemistry and chemical informatics. Multidimensional chemical space representations are coordinate-based. Chemical space networks (CSNs) have been introduced as a coordinate-free representation. A computational approach is presented for the transformation of multidimensional chemical space into CSNs. The design of transformation CSNs (TRANS-CSNs) is based upon a similarity function that directly reflects distance relationships in original multidimensional space. TRANS-CSNs provide an immediate visualization of coordinate-based chemical space and do not require the use of dimensionality reduction techniques. At low network density, TRANS-CSNs are readily interpretable and make it possible to evaluate structure-activity relationship information originating from multidimensional chemical space.

Geological characterization and statistical comparison of outcrop and subsurface facies: Shannon Shelf sand ridges

NASA Astrophysics Data System (ADS)

Jackson, S.; Szpaklewicz, M.; Tomutsa, L.

1987-09-01

The primary objective of this research is to develop a methodology for constructing accurate quantitative models of reservoir heterogeneities. The resulting models are expected to improve predictions of flow patterns, spatial distribution of residual oil after secondary and tertiary recovery operations, and ultimate oil recovery. The purpose of this study is to provide preliminary evaluation of the usefulness of outcrop information in characterizing analogous reservoirs and to develop research techniques necessary for model development. The Shannon Sandstone, a shelf sand ridge deposit in the Powder River Basin, Wyoming, was studied. Sedimentologic and petrophysical features of an outcrop exposure of the High-Energy Ridge-Margin facies (HERM) within the Shannon were compared with those from a Shannon sandstone reservoir in Teapot Dome field. Comparisons of outcrop and subsurface permeability and porosity histograms, cumulative distribution functions, correlation lengths and natural logarithm of permeability versus porosity plots indicate a strong similarity between Shannon outcrop and Teapot Dome HERM facies petrophysical properties. Permeability classes found in outcrop samples can be related to crossbedded zones and shaley, rippled, and bioturbated zones. Similar permeability classes related to similar sedimentologic features were found in Teapot Dome field. The similarities of outcrop and Teapot Dome petrophysical properties, which are from the same geologic facies but from different depositional episodes, suggest that rocks deposited under similar depositional processes within a given deposystem have similar reservoir properties. The results of the study indicate that the use of quantitative outcrop information in characterizing reservoirs may provide a significant improvement in reservoir characterization.

Mirror therapy in chronic stroke survivors with severely impaired upper limb function: a randomized controlled trial.

PubMed

Colomer, Carolina; NOé, Enrique; Llorens, Roberto

2016-06-01

Mirror therapy (MT) has been proposed to improve the motor function of chronic individuals with stroke with mild to moderate impairment. With regards to severe upper limb paresis, MT has shown to provide limited motor improvement in the acute or sub-acute phase. However, no previous research has described the effects of MT in chronic individuals with stroke with severely impaired upper limb function. The aim of this study was to determine the effectiveness of MT on chronic stroke survivors with severe upper-limb impairment in comparison with passive mobilization. A randomized controlled trial. Rehabilitative outpatient unit. A total of 31 chronic subjects poststroke with severely impaired upper limb function were randomly assigned to either an experimental group (N.=15), or a control group (N.=16). Twenty-four intervention sessions were performed for both groups. Each session included 45-minute period of MT (experimental group) or passive mobilization (control group), administered three days a week. Participants were assessed before and after the intervention with the Wolf Motor Function Test, the Fugl-Meyer Assessment, and the Nottingham Sensory Assessment. Improvement in motor function was observed in both groups on the time (P=0.002) and ability (P=0.001) subscales of the Wolf Motor Function Test. No differences were detected in kinesthesis or stereognosis. However, the experimental group showed a significant improvement in tactile sensation that was mainly observed as an increased sensitivity to light touches. In comparison with passive mobilization, MT in chronic stroke survivors with severely impaired upper-limb function may provide a limited but positive effect on light touch sensitivity while providing similar motor improvement. MT is a therapeutic approach that can be used in the rehabilitation of severely impaired upper limb in chronic stroke survivors, specifically to address light touch sensitivity deficits.

DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia

PubMed Central

Rampal, Raajit; Alkalin, Altuna; Madzo, Jozef; Vasanthakumar, Aparna; Pronier, Elodie; Patel, Jay; Li, Yushan; Ahn, Jihae; Abdel-Wahab, Omar; Shih, Alan; Lu, Chao; Ward, Patrick S.; Tsai, Jennifer J.; Hricik, Todd; Tosello, Valeria; Tallman, Jacob E.; Zhao, Xinyang; Daniels, Danette; Dai, Qing; Ciminio, Luisa; Aifantis, Iannis; He, Chuan; Fuks, Francois; Tallman, Martin S.; Ferrando, Adolfo; Nimer, Stephen; Paietta, Elisabeth; Thompson, Craig B.; Licht, Jonathan D.; Mason, Chris; Godley, Lucy A.; Melnick, Ari; Figueroa, Maria E.; Levine, Ross L.

2014-01-01

Summary Somatic mutations in IDH1/2 and TET2 result in impaired TET2 mediated conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). The observation that WT1 inactivating mutations anti-correlate with TET2/IDH1/2 mutations in AML led us to hypothesize that WT1 mutations may impact TET2 function. WT1 mutant acute myeloid leukemia (AML) patients have reduced 5-hmC levels similar to TET2/IDH1/2-mutant AML. These mutations are characterized by convergent, site-specific alterations in DNA hydroxymethylation, which drive differential gene expression more than alterations in DNA promoter methylation. WT1 overexpression increases global levels of 5-hmC, and WT1 silencing reduced 5-hmC levels. WT1 physically interacts with TET2 and TET3, and WT1 loss of function results in a similar hematopoietic differentiation phenotype as observed with TET2 deficiency. These data provide a novel role for WT1 in regulating DNA hydroxymethylation and suggest that TET2 IDH1/2, and WT1 mutations define a novel AML subtype defined by dysregulated DNA hydroxymethylation. PMID:25482556

Coral identity underpins architectural complexity on Caribbean reefs.

PubMed

Alvarez-Filip, Lorenzo; Dulvy, Nicholas K; Côte, Isabelle M; Watkinson, Andrew R; Gill, Jennifer A

2011-09-01

The architectural complexity of ecosystems can greatly influence their capacity to support biodiversity and deliver ecosystem services. Understanding the components underlying this complexity can aid the development of effective strategies for ecosystem conservation. Caribbean coral reefs support and protect millions of livelihoods, but recent anthropogenic change is shifting communities toward reefs dominated by stress-resistant coral species, which are often less architecturally complex. With the regionwide decline in reef fish abundance, it is becoming increasingly important to understand changes in coral reef community structure and function. We quantify the influence of coral composition, diversity, and morpho-functional traits on the architectural complexity of reefs across 91 sites at Cozumel, Mexico. Although reef architectural complexity increases with coral cover and species richness, it is highest on sites that are low in taxonomic evenness and dominated by morpho-functionally important, reef-building coral genera, particularly Montastraea. Sites with similar coral community composition also tend to occur on reefs with very similar architectural complexity, suggesting that reef structure tends to be determined by the same key species across sites. Our findings provide support for prioritizing and protecting particular reef types, especially those dominated by key reef-building corals, in order to enhance reef complexity.