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Sample records for large-scale human brain

  1. Organization and evolution of brain lipidome revealed by large-scale analysis of human, chimpanzee, macaque, and mouse tissues.

    PubMed

    Bozek, Katarzyna; Wei, Yuning; Yan, Zheng; Liu, Xiling; Xiong, Jieyi; Sugimoto, Masahiro; Tomita, Masaru; Pääbo, Svante; Sherwood, Chet C; Hof, Patrick R; Ely, John J; Li, Yan; Steinhauser, Dirk; Willmitzer, Lothar; Giavalisco, Patrick; Khaitovich, Philipp

    2015-02-18

    Lipids are prominent components of the nervous system. Here we performed a large-scale mass spectrometry-based analysis of the lipid composition of three brain regions as well as kidney and skeletal muscle of humans, chimpanzees, rhesus macaques, and mice. The human brain shows the most distinct lipid composition: 76% of 5,713 lipid compounds examined in our study are either enriched or depleted in the human brain. Concentration levels of lipids enriched in the brain evolve approximately four times faster among primates compared with lipids characteristic of non-neural tissues and show further acceleration of change in human neocortical regions but not in the cerebellum. Human-specific concentration changes are supported by human-specific expression changes for corresponding enzymes. These results provide the first insights into the role of lipids in human brain evolution. PMID:25661180

  2. Large-scale in silico modeling of metabolic interactions between cell types in the human brain.

    PubMed

    Lewis, Nathan E; Schramm, Gunnar; Bordbar, Aarash; Schellenberger, Jan; Andersen, Michael P; Cheng, Jeffrey K; Patel, Nilam; Yee, Alex; Lewis, Randall A; Eils, Roland; König, Rainer; Palsson, Bernhard Ø

    2010-12-01

    Metabolic interactions between multiple cell types are difficult to model using existing approaches. Here we present a workflow that integrates gene expression data, proteomics data and literature-based manual curation to model human metabolism within and between different types of cells. Transport reactions are used to account for the transfer of metabolites between models of different cell types via the interstitial fluid. We apply the method to create models of brain energy metabolism that recapitulate metabolic interactions between astrocytes and various neuron types relevant to Alzheimer's disease. Analysis of the models identifies genes and pathways that may explain observed experimental phenomena, including the differential effects of the disease on cell types and regions of the brain. Constraint-based modeling can thus contribute to the study and analysis of multicellular metabolic processes in the human tissue microenvironment and provide detailed mechanistic insight into high-throughput data analysis. PMID:21102456

  3. Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

    PubMed Central

    Arsiwalla, Xerxes D.; Zucca, Riccardo; Betella, Alberto; Martinez, Enrique; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F. M. J.

    2015-01-01

    BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimulations to observe reverberating network activity, simulate lesion dynamics or implement network analysis functions from a library of graph theoretic measures. BrainX3 can thus be used as a novel immersive platform for exploration and analysis of dynamical activity patterns in brain networks, both at rest or in a task-related state, for discovery of signaling pathways associated to brain function and/or dysfunction and as a tool for virtual neurosurgery. Our results demonstrate these functionalities and shed insight on the dynamics of the resting-state attractor. Specifically, we found that a noisy network seems to favor a low firing attractor state. We also found that the dynamics of a noisy network is less resilient to lesions. Our simulations on TMS perturbations show that even though TMS inhibits most of the network, it also sparsely excites a few regions. This is presumably due to anti-correlations in the dynamics and suggests that even a lesioned network can show sparsely distributed increased activity compared to healthy resting-state, over specific brain areas. PMID:25759649

  4. Knowledge-Guided Robust MRI Brain Extraction for Diverse Large-Scale Neuroimaging Studies on Humans and Non-Human Primates

    PubMed Central

    Wang, Yaping; Nie, Jingxin; Yap, Pew-Thian; Li, Gang; Shi, Feng; Geng, Xiujuan; Guo, Lei; Shen, Dinggang

    2014-01-01

    Accurate and robust brain extraction is a critical step in most neuroimaging analysis pipelines. In particular, for the large-scale multi-site neuroimaging studies involving a significant number of subjects with diverse age and diagnostic groups, accurate and robust extraction of the brain automatically and consistently is highly desirable. In this paper, we introduce population-specific probability maps to guide the brain extraction of diverse subject groups, including both healthy and diseased adult human populations, both developing and aging human populations, as well as non-human primates. Specifically, the proposed method combines an atlas-based approach, for coarse skull-stripping, with a deformable-surface-based approach that is guided by local intensity information and population-specific prior information learned from a set of real brain images for more localized refinement. Comprehensive quantitative evaluations were performed on the diverse large-scale populations of ADNI dataset with over 800 subjects (55∼90 years of age, multi-site, various diagnosis groups), OASIS dataset with over 400 subjects (18∼96 years of age, wide age range, various diagnosis groups), and NIH pediatrics dataset with 150 subjects (5∼18 years of age, multi-site, wide age range as a complementary age group to the adult dataset). The results demonstrate that our method consistently yields the best overall results across almost the entire human life span, with only a single set of parameters. To demonstrate its capability to work on non-human primates, the proposed method is further evaluated using a rhesus macaque dataset with 20 subjects. Quantitative comparisons with popularly used state-of-the-art methods, including BET, Two-pass BET, BET-B, BSE, HWA, ROBEX and AFNI, demonstrate that the proposed method performs favorably with superior performance on all testing datasets, indicating its robustness and effectiveness. PMID:24489639

  5. Development of a large-scale functional brain network during human non-rapid eye movement sleep.

    PubMed

    Spoormaker, Victor I; Schröter, Manuel S; Gleiser, Pablo M; Andrade, Katia C; Dresler, Martin; Wehrle, Renate; Sämann, Philipp G; Czisch, Michael

    2010-08-25

    Graph theoretical analysis of functional magnetic resonance imaging (fMRI) time series has revealed a small-world organization of slow-frequency blood oxygen level-dependent (BOLD) signal fluctuations during wakeful resting. In this study, we used graph theoretical measures to explore how physiological changes during sleep are reflected in functional connectivity and small-world network properties of a large-scale, low-frequency functional brain network. Twenty-five young and healthy participants fell asleep during a 26.7 min fMRI scan with simultaneous polysomnography. A maximum overlap discrete wavelet transformation was applied to fMRI time series extracted from 90 cortical and subcortical regions in normalized space after residualization of the raw signal against unspecific sources of signal fluctuations; functional connectivity analysis focused on the slow-frequency BOLD signal fluctuations between 0.03 and 0.06 Hz. We observed that in the transition from wakefulness to light sleep, thalamocortical connectivity was sharply reduced, whereas corticocortical connectivity increased; corticocortical connectivity subsequently broke down in slow-wave sleep. Local clustering values were closest to random values in light sleep, whereas slow-wave sleep was characterized by the highest clustering ratio (gamma). Our findings support the hypothesis that changes in consciousness in the descent to sleep are subserved by reduced thalamocortical connectivity at sleep onset and a breakdown of general connectivity in slow-wave sleep, with both processes limiting the capacity of the brain to integrate information across functional modules. PMID:20739559

  6. Large-scale functional connectivity networks in the rodent brain.

    PubMed

    Gozzi, Alessandro; Schwarz, Adam J

    2016-02-15

    Resting-state functional Magnetic Resonance Imaging (rsfMRI) of the human brain has revealed multiple large-scale neural networks within a hierarchical and complex structure of coordinated functional activity. These distributed neuroanatomical systems provide a sensitive window on brain function and its disruption in a variety of neuropathological conditions. The study of macroscale intrinsic connectivity networks in preclinical species, where genetic and environmental conditions can be controlled and manipulated with high specificity, offers the opportunity to elucidate the biological determinants of these alterations. While rsfMRI methods are now widely used in human connectivity research, these approaches have only relatively recently been back-translated into laboratory animals. Here we review recent progress in the study of functional connectivity in rodent species, emphasising the ability of this approach to resolve large-scale brain networks that recapitulate neuroanatomical features of known functional systems in the human brain. These include, but are not limited to, a distributed set of regions identified in rats and mice that may represent a putative evolutionary precursor of the human default mode network (DMN). The impact and control of potential experimental and methodological confounds are also critically discussed. Finally, we highlight the enormous potential and some initial application of connectivity mapping in transgenic models as a tool to investigate the neuropathological underpinnings of the large-scale connectional alterations associated with human neuropsychiatric and neurological conditions. We conclude by discussing the translational potential of these methods in basic and applied neuroscience. PMID:26706448

  7. Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

    ERIC Educational Resources Information Center

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-01-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

  8. Large-scale functional brain networks in human non-rapid eye movement sleep: insights from combined electroencephalographic/functional magnetic resonance imaging studies.

    PubMed

    Spoormaker, Victor I; Czisch, Michael; Maquet, Pierre; Jäncke, Lutz

    2011-10-13

    This paper reviews the existing body of knowledge on the neural correlates of spontaneous oscillations, functional connectivity and brain plasticity in human non-rapid eye movement (NREM) sleep. The first section reviews the evidence that specific sleep events as slow waves and spindles are associated with transient increases in regional brain activity. The second section describes the changes in functional connectivity during NREM sleep, with a particular focus on changes within a low-frequency, large-scale functional brain network. The third section will discuss the possibility that spontaneous oscillations and differential functional connectivity are related to brain plasticity and systems consolidation, with a particular focus on motor skill acquisition. Implications for the mode of information processing per sleep stage and future experimental studies are discussed. PMID:21893524

  9. Development of large-scale functional brain networks in children.

    PubMed

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-07-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

  10. Large-scale imaging in small brains

    PubMed Central

    Ahrens, Misha B.; Engert, Florian

    2016-01-01

    The dense connectivity in the brain and arrangements of cells into circuits means that one neuron’s activity can influence many others. To observe this interconnected system comprehensively, an aspiration within neuroscience is to record from as many neurons as possible at the same time. There are two useful routes toward this goal: one is to expand the spatial extent of functional imaging techniques, and the second is to use animals with small brains. Here we review recent progress toward imaging many neurons and complete populations of identified neurons in small vertebrates and invertebrates. PMID:25636154

  11. Foundational perspectives on causality in large-scale brain networks.

    PubMed

    Mannino, Michael; Bressler, Steven L

    2015-12-01

    A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical

  12. Foundational perspectives on causality in large-scale brain networks

    NASA Astrophysics Data System (ADS)

    Mannino, Michael; Bressler, Steven L.

    2015-12-01

    A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical

  13. Large-scale brain networks in cognition: emerging methods and principles.

    PubMed

    Bressler, Steven L; Menon, Vinod

    2010-06-01

    An understanding of how the human brain produces cognition ultimately depends on knowledge of large-scale brain organization. Although it has long been assumed that cognitive functions are attributable to the isolated operations of single brain areas, we demonstrate that the weight of evidence has now shifted in support of the view that cognition results from the dynamic interactions of distributed brain areas operating in large-scale networks. We review current research on structural and functional brain organization, and argue that the emerging science of large-scale brain networks provides a coherent framework for understanding of cognition. Critically, this framework allows a principled exploration of how cognitive functions emerge from, and are constrained by, core structural and functional networks of the brain. PMID:20493761

  14. Complex modular structure of large-scale brain networks

    NASA Astrophysics Data System (ADS)

    Valencia, M.; Pastor, M. A.; Fernández-Seara, M. A.; Artieda, J.; Martinerie, J.; Chavez, M.

    2009-06-01

    Modular structure is ubiquitous among real-world networks from related proteins to social groups. Here we analyze the modular organization of brain networks at a large scale (voxel level) extracted from functional magnetic resonance imaging signals. By using a random-walk-based method, we unveil the modularity of brain webs and show modules with a spatial distribution that matches anatomical structures with functional significance. The functional role of each node in the network is studied by analyzing its patterns of inter- and intramodular connections. Results suggest that the modular architecture constitutes the structural basis for the coexistence of functional integration of distant and specialized brain areas during normal brain activities at rest.

  15. Identifying Large-Scale Brain Networks in Fragile X Syndrome

    PubMed Central

    Hall, Scott S.; Jiang, Heidi; Reiss, Allan L.; Greicius, Michael D.

    2014-01-01

    IMPORTANCE Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS. OBJECTIVE To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10–23 years) included 17 males and females with FXS and 16 males and females serving as controls. MAIN OUTCOMES AND MEASURES Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression. RESULTS Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS. CONCLUSIONS AND RELEVANCE Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that

  16. Spatiotemporal dynamics of large-scale brain activity

    NASA Astrophysics Data System (ADS)

    Neuman, Jeremy

    Understanding the dynamics of large-scale brain activity is a tough challenge. One reason for this is the presence of an incredible amount of complexity arising from having roughly 100 billion neurons connected via 100 trillion synapses. Because of the extremely high number of degrees of freedom in the nervous system, the question of how the brain manages to properly function and remain stable, yet also be adaptable, must be posed. Neuroscientists have identified many ways the nervous system makes this possible, of which synaptic plasticity is possibly the most notable one. On the other hand, it is vital to understand how the nervous system also loses stability, resulting in neuropathological diseases such as epilepsy, a disease which affects 1% of the population. In the following work, we seek to answer some of these questions from two different perspectives. The first uses mean-field theory applied to neuronal populations, where the variables of interest are the percentages of active excitatory and inhibitory neurons in a network, to consider how the nervous system responds to external stimuli, self-organizes and generates epileptiform activity. The second method uses statistical field theory, in the framework of single neurons on a lattice, to study the concept of criticality, an idea borrowed from physics which posits that in some regime the brain operates in a collectively stable or marginally stable manner. This will be examined in two different neuronal networks with self-organized criticality serving as the overarching theme for the union of both perspectives. One of the biggest problems in neuroscience is the question of to what extent certain details are significant to the functioning of the brain. These details give rise to various spatiotemporal properties that at the smallest of scales explain the interaction of single neurons and synapses and at the largest of scales describe, for example, behaviors and sensations. In what follows, we will shed some

  17. Modeling dynamic functional information flows on large-scale brain networks.

    PubMed

    Lv, Peili; Guo, Lei; Hu, Xintao; Li, Xiang; Jin, Changfeng; Han, Junwei; Li, Lingjiang; Liu, Tianming

    2013-01-01

    Growing evidence from the functional neuroimaging field suggests that human brain functions are realized via dynamic functional interactions on large-scale structural networks. Even in resting state, functional brain networks exhibit remarkable temporal dynamics. However, it has been rarely explored to computationally model such dynamic functional information flows on large-scale brain networks. In this paper, we present a novel computational framework to explore this problem using multimodal resting state fMRI (R-fMRI) and diffusion tensor imaging (DTI) data. Basically, recent literature reports including our own studies have demonstrated that the resting state brain networks dynamically undergo a set of distinct brain states. Within each quasi-stable state, functional information flows from one set of structural brain nodes to other sets of nodes, which is analogous to the message package routing on the Internet from the source node to the destination. Therefore, based on the large-scale structural brain networks constructed from DTI data, we employ a dynamic programming strategy to infer functional information transition routines on structural networks, based on which hub routers that most frequently participate in these routines are identified. It is interesting that a majority of those hub routers are located within the default mode network (DMN), revealing a possible mechanism of the critical functional hub roles played by the DMN in resting state. Also, application of this framework on a post trauma stress disorder (PTSD) dataset demonstrated interesting difference in hub router distributions between PTSD patients and healthy controls. PMID:24579202

  18. Large-Scale Functional Brain Network Reorganization During Taoist Meditation.

    PubMed

    Jao, Tun; Li, Chia-Wei; Vértes, Petra E; Wu, Changwei Wesley; Achard, Sophie; Hsieh, Chao-Hsien; Liou, Chien-Hui; Chen, Jyh-Horng; Bullmore, Edward T

    2016-02-01

    Meditation induces a distinct and reversible mental state that provides insights into brain correlates of consciousness. We explored brain network changes related to meditation by graph theoretical analysis of resting-state functional magnetic resonance imaging data. Eighteen Taoist meditators with varying levels of expertise were scanned using a within-subjects counterbalanced design during resting and meditation states. State-related differences in network topology were measured globally and at the level of individual nodes and edges. Although measures of global network topology, such as small-worldness, were unchanged, meditation was characterized by an extensive and expertise-dependent reorganization of the hubs (highly connected nodes) and edges (functional connections). Areas of sensory cortex, especially the bilateral primary visual and auditory cortices, and the bilateral temporopolar areas, which had the highest degree (or connectivity) during the resting state, showed the biggest decrease during meditation. Conversely, bilateral thalamus and components of the default mode network, mainly the bilateral precuneus and posterior cingulate cortex, had low degree in the resting state but increased degree during meditation. Additionally, these changes in nodal degree were accompanied by reorganization of anatomical orientation of the edges. During meditation, long-distance longitudinal (antero-posterior) edges increased proportionally, whereas orthogonal long-distance transverse (right-left) edges connecting bilaterally homologous cortices decreased. Our findings suggest that transient changes in consciousness associated with meditation introduce convergent changes in the topological and spatial properties of brain functional networks, and the anatomical pattern of integration might be as important as the global level of integration when considering the network basis for human consciousness. PMID:26165867

  19. Dietary Omega-3 Fatty Acids Modulate Large-Scale Systems Organization in the Rhesus Macaque Brain

    PubMed Central

    Kroenke, Christopher D.; Neuringer, Martha; Fair, Damien A.

    2014-01-01

    Omega-3 fatty acids are essential for healthy brain and retinal development and have been implicated in a variety of neurodevelopmental disorders. This study used resting-state functional connectivity MRI to define the large-scale organization of the rhesus macaque brain and changes associated with differences in lifetime ω-3 fatty acid intake. Monkeys fed docosahexaenoic acid, the long-chain ω-3 fatty acid abundant in neural membranes, had cortical modular organization resembling the healthy human brain. In contrast, those with low levels of dietary ω-3 fatty acids had decreased functional connectivity within the early visual pathway and throughout higher-order associational cortex and showed impairment of distributed cortical networks. Our findings illustrate the similarity in modular cortical organization between the healthy human and macaque brain and support the notion that ω-3 fatty acids play a crucial role in developing and/or maintaining distributed, large-scale brain systems, including those essential for normal cognitive function. PMID:24501348

  20. Overlapping communities reveal rich structure in large-scale brain networks during rest and task conditions.

    PubMed

    Najafi, Mahshid; McMenamin, Brenton W; Simon, Jonathan Z; Pessoa, Luiz

    2016-07-15

    Large-scale analysis of functional MRI data has revealed that brain regions can be grouped into stable "networks" or communities. In many instances, the communities are characterized as relatively disjoint. Although recent work indicates that brain regions may participate in multiple communities (for example, hub regions), the extent of community overlap is poorly understood. To address these issues, here we investigated large-scale brain networks based on "rest" and task human functional MRI data by employing a mixed-membership Bayesian model that allows each brain region to belong to all communities simultaneously with varying membership strengths. The approach allowed us to 1) compare the structure of disjoint and overlapping communities; 2) determine the relationship between functional diversity (how diverse is a region's functional activation repertoire) and membership diversity (how diverse is a region's affiliation to communities); 3) characterize overlapping community structure; 4) characterize the degree of non-modularity in brain networks; 5) study the distribution of "bridges", including bottleneck and hub bridges. Our findings revealed the existence of dense community overlap that was not limited to "special" hubs. Furthermore, the findings revealed important differences between community organization during rest and during specific task states. Overall, we suggest that dense overlapping communities are well suited to capture the flexible and task dependent mapping between brain regions and their functions. PMID:27129758

  1. Large-scale data mining pilot project in human genome

    SciTech Connect

    Musick, R.; Fidelis, R.; Slezak, T.

    1997-05-01

    This whitepaper briefly describes a new, aggressive effort in large- scale data Livermore National Labs. The implications of `large- scale` will be clarified Section. In the short term, this effort will focus on several @ssion-critical questions of Genome project. We will adapt current data mining techniques to the Genome domain, to quantify the accuracy of inference results, and lay the groundwork for a more extensive effort in large-scale data mining. A major aspect of the approach is that we will be fully-staffed data warehousing effort in the human Genome area. The long term goal is strong applications- oriented research program in large-@e data mining. The tools, skill set gained will be directly applicable to a wide spectrum of tasks involving a for large spatial and multidimensional data. This includes applications in ensuring non-proliferation, stockpile stewardship, enabling Global Ecology (Materials Database Industrial Ecology), advancing the Biosciences (Human Genome Project), and supporting data for others (Battlefield Management, Health Care).

  2. Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain

    PubMed Central

    Kuipers, Jeroen; Kalicharan, Ruby D.; Wolters, Anouk H. G.

    2016-01-01

    Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae1-7. Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture1-5. Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)8 on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner. PMID:27285162

  3. Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain.

    PubMed

    Kuipers, Jeroen; Kalicharan, Ruby D; Wolters, Anouk H G; van Ham, Tjakko J; Giepmans, Ben N G

    2016-01-01

    Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae(1-7). Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture(1-5). Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)(8) on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner. PMID:27285162

  4. Multistability in Large Scale Models of Brain Activity.

    PubMed

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-12-01

    Noise driven exploration of a brain network's dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network's capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain's dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system's attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the "resting state" condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  5. Multistability in Large Scale Models of Brain Activity

    PubMed Central

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-01-01

    Noise driven exploration of a brain network’s dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network’s capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain’s dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system’s attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the “resting state” condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  6. Large-Scale Brain Network Coupling Predicts Total Sleep Deprivation Effects on Cognitive Capacity

    PubMed Central

    Wang, Lubin; Zhai, Tianye; Zou, Feng; Ye, Enmao; Jin, Xiao; Li, Wuju; Qi, Jianlin; Yang, Zheng

    2015-01-01

    Interactions between large-scale brain networks have received most attention in the study of cognitive dysfunction of human brain. In this paper, we aimed to test the hypothesis that the coupling strength of large-scale brain networks will reflect the pressure for sleep and will predict cognitive performance, referred to as sleep pressure index (SPI). Fourteen healthy subjects underwent this within-subject functional magnetic resonance imaging (fMRI) study during rested wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Self-reported scores of sleepiness were higher for TSD than for RW. A subsequent working memory (WM) task showed that WM performance was lower after 36 h of TSD. Moreover, SPI was developed based on the coupling strength of salience network (SN) and default mode network (DMN). Significant increase of SPI was observed after 36 h of TSD, suggesting stronger pressure for sleep. In addition, SPI was significantly correlated with both the visual analogue scale score of sleepiness and the WM performance. These results showed that alterations in SN-DMN coupling might be critical in cognitive alterations that underlie the lapse after TSD. Further studies may validate the SPI as a potential clinical biomarker to assess the impact of sleep deprivation. PMID:26218521

  7. Stability constraints on large-scale structural brain networks

    PubMed Central

    Gray, Richard T.; Robinson, Peter A.

    2013-01-01

    Stability is an important dynamical property of complex systems and underpins a broad range of coherent self-organized behavior. Based on evidence that some neurological disorders correspond to linear instabilities, we hypothesize that stability constrains the brain's electrical activity and influences its structure and physiology. Using a physiologically-based model of brain electrical activity, we investigated the stability and dispersion solutions of networks of neuronal populations with propagation time delays and dendritic time constants. We find that stability is determined by the spectrum of the network's matrix of connection strengths and is independent of the temporal damping rate of axonal propagation with stability restricting the spectrum to a region in the complex plane. Time delays and dendritic time constants modify the shape of this region but it always contains the unit disk. Instabilities resulting from changes in connection strength initially have frequencies less than a critical frequency. For physiologically plausible parameter values based on the corticothalamic system, this critical frequency is approximately 10 Hz. For excitatory networks and networks with randomly distributed excitatory and inhibitory connections, time delays and non-zero dendritic time constants have no impact on network stability but do effect dispersion frequencies. Random networks with both excitatory and inhibitory connections can have multiple marginally stable modes at low delta frequencies. PMID:23630490

  8. Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

    PubMed

    de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

    2016-09-01

    Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27133613

  9. Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain.

    PubMed

    Shah, Disha; Blockx, Ines; Keliris, Georgios A; Kara, Firat; Jonckers, Elisabeth; Verhoye, Marleen; Van der Linden, Annemie

    2016-07-01

    Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders. PMID:26195064

  10. Assessing large-scale wildlife responses to human infrastructure development.

    PubMed

    Torres, Aurora; Jaeger, Jochen A G; Alonso, Juan Carlos

    2016-07-26

    Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future. PMID:27402749

  11. Dynamic competition between large-scale functional networks differentiates fear conditioning and extinction in humans.

    PubMed

    Marstaller, Lars; Burianová, Hana; Reutens, David C

    2016-07-01

    The high evolutionary value of learning when to respond to threats or when to inhibit previously learned associations after changing threat contingencies is reflected in dedicated networks in the animal and human brain. Recent evidence further suggests that adaptive learning may be dependent on the dynamic interaction of meta-stable functional brain networks. However, it is still unclear which functional brain networks compete with each other to facilitate associative learning and how changes in threat contingencies affect this competition. The aim of this study was to assess the dynamic competition between large-scale networks related to associative learning in the human brain by combining a repeated differential conditioning and extinction paradigm with independent component analysis of functional magnetic resonance imaging data. The results (i) identify three task-related networks involved in initial and sustained conditioning as well as extinction, and demonstrate that (ii) the two main networks that underlie sustained conditioning and extinction are anti-correlated with each other and (iii) the dynamic competition between these two networks is modulated in response to changes in associative contingencies. These findings provide novel evidence for the view that dynamic competition between large-scale functional networks differentiates fear conditioning from extinction learning in the healthy brain and suggest that dysfunctional network dynamics might contribute to learning-related neuropsychiatric disorders. PMID:27079532

  12. Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

    PubMed Central

    Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

    2014-01-01

    Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

  13. Large-scale simulation of the human arterial tree.

    PubMed

    Grinberg, L; Anor, T; Madsen, J R; Yakhot, A; Karniadakis, G E

    2009-02-01

    1. Full-scale simulations of the virtual physiological human (VPH) will require significant advances in modelling, multiscale mathematics, scientific computing and further advances in medical imaging. Herein, we review some of the main issues that need to be resolved in order to make three-dimensional (3D) simulations of blood flow in the human arterial tree feasible in the near future. 2. A straightforward approach is computationally prohibitive even on the emerging petaflop supercomputers, so a three-level hierarchical approach based on vessel size is required, consisting of: (i) a macrovascular network (MaN); (ii) a mesovascular network (MeN); and (iii) a microvascular network (MiN). We present recent simulations of MaN obtained by solving the 3D Navier-Stokes equations on arterial networks with tens of arteries and bifurcations and accounting for the neglected dynamics through proper boundary conditions. 3. A multiscale simulation coupling MaN-MeN-MiN and running on hundreds of thousands of processors on petaflop computers will require no more than a few CPU hours per cardiac cycle within the next 5 years. The rapidly growing capacity of supercomputing centres opens up the possibility of simulation studies of cardiovascular diseases, drug delivery, perfusion in the brain and other pathologies. PMID:18671721

  14. Stress-induced alterations in large-scale functional networks of the rodent brain.

    PubMed

    Henckens, Marloes J A G; van der Marel, Kajo; van der Toorn, Annette; Pillai, Anup G; Fernández, Guillén; Dijkhuizen, Rick M; Joëls, Marian

    2015-01-15

    Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10 days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research. PMID:25462693

  15. Large-scale brain networks and psychopathology: a unifying triple network model.

    PubMed

    Menon, Vinod

    2011-10-01

    The science of large-scale brain networks offers a powerful paradigm for investigating cognitive and affective dysfunction in psychiatric and neurological disorders. This review examines recent conceptual and methodological developments which are contributing to a paradigm shift in the study of psychopathology. I summarize methods for characterizing aberrant brain networks and demonstrate how network analysis provides novel insights into dysfunctional brain architecture. Deficits in access, engagement and disengagement of large-scale neurocognitive networks are shown to play a prominent role in several disorders including schizophrenia, depression, anxiety, dementia and autism. Synthesizing recent research, I propose a triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology, emphasizing the surprising parallels that are beginning to emerge across psychiatric and neurological disorders. PMID:21908230

  16. PLATO: data-oriented approach to collaborative large-scale brain system modeling.

    PubMed

    Kannon, Takayuki; Inagaki, Keiichiro; Kamiji, Nilton L; Makimura, Kouji; Usui, Shiro

    2011-11-01

    The brain is a complex information processing system, which can be divided into sub-systems, such as the sensory organs, functional areas in the cortex, and motor control systems. In this sense, most of the mathematical models developed in the field of neuroscience have mainly targeted a specific sub-system. In order to understand the details of the brain as a whole, such sub-system models need to be integrated toward the development of a neurophysiologically plausible large-scale system model. In the present work, we propose a model integration library where models can be connected by means of a common data format. Here, the common data format should be portable so that models written in any programming language, computer architecture, and operating system can be connected. Moreover, the library should be simple so that models can be adapted to use the common data format without requiring any detailed knowledge on its use. Using this library, we have successfully connected existing models reproducing certain features of the visual system, toward the development of a large-scale visual system model. This library will enable users to reuse and integrate existing and newly developed models toward the development and simulation of a large-scale brain system model. The resulting model can also be executed on high performance computers using Message Passing Interface (MPI). PMID:21767932

  17. Large-Scale Proteomic Analysis of the Human Spliceosome

    PubMed Central

    Rappsilber, Juri; Ryder, Ursula; Lamond, Angus I.; Mann, Matthias

    2002-01-01

    In a previous proteomic study of the human spliceosome, we identified 42 spliceosome-associated factors, including 19 novel ones. Using enhanced mass spectrometric tools and improved databases, we now report identification of 311 proteins that copurify with splicing complexes assembled on two separate pre-mRNAs. All known essential human splicing factors were found, and 96 novel proteins were identified, of which 55 contain domains directly linking them to functions in splicing/RNA processing. We also detected 20 proteins related to transcription, which indicates a direct connection between this process and splicing. This investigation provides the most detailed inventory of human spliceosome-associated factors to date, and the data indicate a number of interesting links coordinating splicing with other steps in the gene expression pathway. PMID:12176931

  18. Collective response of human populations to large-scale emergencies.

    PubMed

    Bagrow, James P; Wang, Dashun; Barabási, Albert-László

    2011-01-01

    Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response. PMID:21479206

  19. Collective Response of Human Populations to Large-Scale Emergencies

    PubMed Central

    Barabási, Albert-László

    2011-01-01

    Despite recent advances in uncovering the quantitative features of stationary human activity patterns, many applications, from pandemic prediction to emergency response, require an understanding of how these patterns change when the population encounters unfamiliar conditions. To explore societal response to external perturbations we identified real-time changes in communication and mobility patterns in the vicinity of eight emergencies, such as bomb attacks and earthquakes, comparing these with eight non-emergencies, like concerts and sporting events. We find that communication spikes accompanying emergencies are both spatially and temporally localized, but information about emergencies spreads globally, resulting in communication avalanches that engage in a significant manner the social network of eyewitnesses. These results offer a quantitative view of behavioral changes in human activity under extreme conditions, with potential long-term impact on emergency detection and response. PMID:21479206

  20. Technologies for large-scale physical mapping of human chromosomes

    SciTech Connect

    Beugelsdijk, T.J.

    1994-12-01

    Since its inception 6 years ago, the Human Genome Project has made rapid progress towards its ultimate goal of developing the complete sequence of all human chromosomes. This progress has been made possible through the development of automated devices by laboratories throughout the world that aid the molecular biologist in various phases of the project. The initial phase involves the generation of physical and genetic maps of each chromosome. This task is nearing completion at a low resolution level with several instances of very high detailed maps being developed for isolated chromosomes. In support of the initial mapping thrust of this program, the robotics and automation effort at Los Alamos National Laboratory has developed DNA gridding technologies along with associated database and user interface systems. This paper will discuss these systems in detail and focus on the formalism developed for subsystems which allow for facile system integration.

  1. Modelling large scale human activity in San Francisco

    NASA Astrophysics Data System (ADS)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  2. Uncovering urban human mobility from large scale taxi GPS data

    NASA Astrophysics Data System (ADS)

    Tang, Jinjun; Liu, Fang; Wang, Yinhai; Wang, Hua

    2015-11-01

    Taxi GPS trajectories data contain massive spatial and temporal information of urban human activity and mobility. Taking taxi as mobile sensors, the information derived from taxi trips benefits the city and transportation planning. The original data used in study are collected from more than 1100 taxi drivers in Harbin city. We firstly divide the city area into 400 different transportation districts and analyze the origin and destination distribution in urban area on weekday and weekend. The Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is used to cluster pick-up and drop-off locations. Furthermore, four spatial interaction models are calibrated and compared based on trajectories in shopping center of Harbin city to study the pick-up location searching behavior. By extracting taxi trips from GPS data, travel distance, time and average speed in occupied and non-occupied status are then used to investigate human mobility. Finally, we use observed OD matrix of center area in Harbin city to model the traffic distribution patterns based on entropy-maximizing method, and the estimation performance verify its effectiveness in case study.

  3. Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence Effects on Craving and Cognitive Function

    PubMed Central

    Lerman, Caryn; Gu, Hong; Loughead, James; Ruparel, Kosha; Yang, Yihong; Stein, Elliot A.

    2014-01-01

    IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders. OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks–salience, executive control, and default mode–will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks. DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses. INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety. MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary). RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P = .002; right RAI, P = .04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = −0.59; P = .007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = −0.66, P = .003; posterior cingulate cortex, r = −0.65, P = .001). CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may

  4. scMRI Reveals Large-Scale Brain Network Abnormalities in Autism

    PubMed Central

    Zielinski, Brandon A.; Anderson, Jeffrey S.; Froehlich, Alyson L.; Prigge, Molly B. D.; Nielsen, Jared A.; Cooperrider, Jason R.; Cariello, Annahir N.; Fletcher, P. Thomas; Alexander, Andrew L.; Lange, Nicholas; Bigler, Erin D.; Lainhart, Janet E.

    2012-01-01

    Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI. PMID:23185305

  5. Nengo: a Python tool for building large-scale functional brain models

    PubMed Central

    Bekolay, Trevor; Bergstra, James; Hunsberger, Eric; DeWolf, Travis; Stewart, Terrence C.; Rasmussen, Daniel; Choo, Xuan; Voelker, Aaron Russell; Eliasmith, Chris

    2014-01-01

    Neuroscience currently lacks a comprehensive theory of how cognitive processes can be implemented in a biological substrate. The Neural Engineering Framework (NEF) proposes one such theory, but has not yet gathered significant empirical support, partly due to the technical challenge of building and simulating large-scale models with the NEF. Nengo is a software tool that can be used to build and simulate large-scale models based on the NEF; currently, it is the primary resource for both teaching how the NEF is used, and for doing research that generates specific NEF models to explain experimental data. Nengo 1.4, which was implemented in Java, was used to create Spaun, the world's largest functional brain model (Eliasmith et al., 2012). Simulating Spaun highlighted limitations in Nengo 1.4's ability to support model construction with simple syntax, to simulate large models quickly, and to collect large amounts of data for subsequent analysis. This paper describes Nengo 2.0, which is implemented in Python and overcomes these limitations. It uses simple and extendable syntax, simulates a benchmark model on the scale of Spaun 50 times faster than Nengo 1.4, and has a flexible mechanism for collecting simulation results. PMID:24431999

  6. Regional contraction of brain surface area involves three large-scale networks in schizophrenia.

    PubMed

    Palaniyappan, Lena; Mallikarjun, Pavan; Joseph, Verghese; White, Thomas P; Liddle, Peter F

    2011-07-01

    In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls. We observed relative areal contraction affecting Default Mode Network, Central Executive Network and Salience Network, in addition to other regions in schizophrenia. We confirmed the surface area reduction across these three large-scale brain networks by undertaking further region-of-interest analysis of surface area. We also observed a significant hemispheric asymmetry in the surface area changes, with the left hemisphere showing a greater reduction in the areal contraction maps. Our findings suggest that a fundamental disturbance in cortical expansion is likely in individuals who develop schizophrenia. PMID:21497489

  7. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease

    PubMed Central

    Annese, Jacopo

    2012-01-01

    One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI) measurements to anatomical evidence produced by histological methods. In vivo and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we have established a program that characterizes the brain of individual subjects, combining MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalog representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of non-invasive studies of brain connectivity and disease. PMID:22536182

  8. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  9. Emotional speech synchronizes brains across listeners and engages large-scale dynamic brain networks

    PubMed Central

    Nummenmaa, Lauri; Saarimäki, Heini; Glerean, Enrico; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P.; Hari, Riitta; Sams, Mikko

    2014-01-01

    Speech provides a powerful means for sharing emotions. Here we implement novel intersubject phase synchronization and whole-brain dynamic connectivity measures to show that networks of brain areas become synchronized across participants who are listening to emotional episodes in spoken narratives. Twenty participants' hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI) while they listened to 45-s narratives describing unpleasant, neutral, and pleasant events spoken in neutral voice. After scanning, participants listened to the narratives again and rated continuously their feelings of pleasantness–unpleasantness (valence) and of arousal–calmness. Instantaneous intersubject phase synchronization (ISPS) measures were computed to derive both multi-subject voxel-wise similarity measures of hemodynamic activity and inter-area functional dynamic connectivity (seed-based phase synchronization, SBPS). Valence and arousal time series were subsequently used to predict the ISPS and SBPS time series. High arousal was associated with increased ISPS in the auditory cortices and in Broca's area, and negative valence was associated with enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and orbitofrontal cortices. Negative valence affected functional connectivity of fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and positive arousal affected the connectivity of the striatum, amygdala, thalamus, cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had markedly smaller effects. We propose that high arousal synchronizes the listeners' sound-processing and speech-comprehension networks, whereas negative valence synchronizes circuitries supporting emotional and self-referential processing. PMID:25128711

  10. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    PubMed

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. PMID:26512872

  11. Ising-like dynamics in large-scale functional brain networks

    NASA Astrophysics Data System (ADS)

    Fraiman, Daniel; Balenzuela, Pablo; Foss, Jennifer; Chialvo, Dante R.

    2009-06-01

    Brain “rest” is defined—more or less unsuccessfully—as the state in which there is no explicit brain input or output. This work focuses on the question of whether such state can be comparable to any known dynamical state. For that purpose, correlation networks from human brain functional magnetic resonance imaging are contrasted with correlation networks extracted from numerical simulations of the Ising model in two dimensions at different temperatures. For the critical temperature Tc , striking similarities appear in the most relevant statistical properties, making the two networks indistinguishable from each other. These results are interpreted here as lending support to the conjecture that the dynamics of the functioning brain is near a critical point.

  12. General Relationship of Global Topology, Local Dynamics, and Directionality in Large-Scale Brain Networks

    PubMed Central

    Moon, Joon-Young; Lee, UnCheol; Blain-Moraes, Stefanie; Mashour, George A.

    2015-01-01

    The balance of global integration and functional specialization is a critical feature of efficient brain networks, but the relationship of global topology, local node dynamics and information flow across networks has yet to be identified. One critical step in elucidating this relationship is the identification of governing principles underlying the directionality of interactions between nodes. Here, we demonstrate such principles through analytical solutions based on the phase lead/lag relationships of general oscillator models in networks. We confirm analytical results with computational simulations using general model networks and anatomical brain networks, as well as high-density electroencephalography collected from humans in the conscious and anesthetized states. Analytical, computational, and empirical results demonstrate that network nodes with more connections (i.e., higher degrees) have larger amplitudes and are directional targets (phase lag) rather than sources (phase lead). The relationship of node degree and directionality therefore appears to be a fundamental property of networks, with direct applicability to brain function. These results provide a foundation for a principled understanding of information transfer across networks and also demonstrate that changes in directionality patterns across states of human consciousness are driven by alterations of brain network topology. PMID:25874700

  13. Restoring large-scale brain networks in PTSD and related disorders: a proposal for neuroscientifically-informed treatment interventions

    PubMed Central

    Lanius, Ruth A.; Frewen, Paul A.; Tursich, Mischa; Jetly, Rakesh; McKinnon, Margaret C.

    2015-01-01

    Background Three intrinsic connectivity networks in the brain, namely the central executive, salience, and default mode networks, have been identified as crucial to the understanding of higher cognitive functioning, and the functioning of these networks has been suggested to be impaired in psychopathology, including posttraumatic stress disorder (PTSD). Objective 1) To describe three main large-scale networks of the human brain; 2) to discuss the functioning of these neural networks in PTSD and related symptoms; and 3) to offer hypotheses for neuroscientifically-informed interventions based on treating the abnormalities observed in these neural networks in PTSD and related disorders. Method Literature relevant to this commentary was reviewed. Results Increasing evidence for altered functioning of the central executive, salience, and default mode networks in PTSD has been demonstrated. We suggest that each network is associated with specific clinical symptoms observed in PTSD, including cognitive dysfunction (central executive network), increased and decreased arousal/interoception (salience network), and an altered sense of self (default mode network). Specific testable neuroscientifically-informed treatments aimed to restore each of these neural networks and related clinical dysfunction are proposed. Conclusions Neuroscientifically-informed treatment interventions will be essential to future research agendas aimed at targeting specific PTSD and related symptoms. PMID:25854674

  14. The Autism Brain Imaging Data Exchange: Towards Large-Scale Evaluation of the Intrinsic Brain Architecture in Autism

    PubMed Central

    Di Martino, Adriana; Yan, Chao-Gan; Li, Qingyang; Denio, Erin; Castellanos, Francisco X.; Alaerts, Kaat; Anderson, Jeffrey S.; Assaf, Michal; Bookheimer, Susan Y.; Dapretto, Mirella; Deen, Ben; Delmonte, Sonja; Dinstein, Ilan; Ertl-Wagner, Birgit; Fair, Damien A.; Gallagher, Louise; Kennedy, Daniel P.; Keown, Christopher L.; Keysers, Christian; Lainhart, Janet E.; Lord, Catherine; Luna, Beatriz; Menon, Vinod; Minshew, Nancy; Monk, Christopher S.; Mueller, Sophia; Müller, Ralph-Axel; Nebel, Mary Beth; Nigg, Joel T.; O’Hearn, Kirsten; Pelphrey, Kevin A.; Peltier, Scott J.; Rudie, Jeffrey D.; Sunaert, Stefan; Thioux, Marc; Tyszka, J. Michael; Uddin, Lucina Q.; Verhoeven, Judith S.; Wenderoth, Nicole; Wiggins, Jillian L.; Mostofsky, Stewart H.; Milham, Michael P.

    2014-01-01

    Autism spectrum disorders (ASD) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, life-long nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. While the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE) – a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) datasets with corresponding structural MRI and phenotypic information from 539 individuals with ASD and 573 age-matched typical controls (TC; 7–64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 males with ASD and 403 male age-matched TC. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo and hyperconnectivity in the ASD literature; both were detected, though hypoconnectivity dominated, particularly for cortico-cortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASD (mid and posterior insula, posterior cingulate cortex), and highlighted less commonly explored regions such as thalamus. The survey of the ABIDE R-fMRI datasets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international datasets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies. PMID:23774715

  15. The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism.

    PubMed

    Di Martino, A; Yan, C-G; Li, Q; Denio, E; Castellanos, F X; Alaerts, K; Anderson, J S; Assaf, M; Bookheimer, S Y; Dapretto, M; Deen, B; Delmonte, S; Dinstein, I; Ertl-Wagner, B; Fair, D A; Gallagher, L; Kennedy, D P; Keown, C L; Keysers, C; Lainhart, J E; Lord, C; Luna, B; Menon, V; Minshew, N J; Monk, C S; Mueller, S; Müller, R-A; Nebel, M B; Nigg, J T; O'Hearn, K; Pelphrey, K A; Peltier, S J; Rudie, J D; Sunaert, S; Thioux, M; Tyszka, J M; Uddin, L Q; Verhoeven, J S; Wenderoth, N; Wiggins, J L; Mostofsky, S H; Milham, M P

    2014-06-01

    Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies. PMID:23774715

  16. Measuring accurate body parameters of dressed humans with large-scale motion using a Kinect sensor.

    PubMed

    Xu, Huanghao; Yu, Yao; Zhou, Yu; Li, Yang; Du, Sidan

    2013-01-01

    Non-contact human body measurement plays an important role in surveillance, physical healthcare, on-line business and virtual fitting. Current methods for measuring the human body without physical contact usually cannot handle humans wearing clothes, which limits their applicability in public environments. In this paper, we propose an effective solution that can measure accurate parameters of the human body with large-scale motion from a Kinect sensor, assuming that the people are wearing clothes. Because motion can drive clothes attached to the human body loosely or tightly, we adopt a space-time analysis to mine the information across the posture variations. Using this information, we recover the human body, regardless of the effect of clothes, and measure the human body parameters accurately. Experimental results show that our system can perform more accurate parameter estimation on the human body than state-of-the-art methods. PMID:24064597

  17. Large-Scale Refolding and Enzyme Reaction of Human Preproinsulin for Production of Human Insulin.

    PubMed

    Kim, Chang-Kyu; Lee, Seung-Bae; Son, Young-Jin

    2015-10-28

    Human insulin is composed of 21 amino acids of an A-chain and 30 amino acids of a B-chain. This is the protein hormone that has the role of blood sugar control. When the recombinant human proinsulin is expressed in Escherichia coli, a serious problem is the formation of an inclusion body. Therefore, the inclusion body must be denatured and refolded under chaotropic agents and suitable reductants. In this study, H27R-proinsulin was refolded from the denatured form with β-mercaptoethanol and urea. The refolding reaction was completed after 15 h at 15°C, whereas the reaction at 25°C was faster than that at 15°C. The refolding yield at 15°C was 17% higher than that at 25°C. The refolding reaction could be carried out at a high protein concentration (2 g/l) using direct refolding without sulfonation. The most economical and optimal refolding condition for human preproinsulin was 1.5 g/l protein, 10 mM glycine buffer containing 0.6 M urea, pH 10.6, and 0.3 mM β-mercaptoethanol at 15°C for 16 h. The maximum refolding yield was 74.8% at 15°C with 1.5 g/l protein. Moreover, the refolded preproinsulin could be converted into normal mature insulin with two enzymes. The average amount of human insulin was 138.2 g from 200 L of fermentation broth after enzyme reaction with H27R-proinsulin. The direct refolding process for H27R-proinsulin was successfully set up without sulfonation. The step yields for refolding and enzyme reaction were comparatively high. Therefore, our refolding process for production of recombinant insulin may be beneficial to the large-scale production of other biologically active proteins. PMID:26139616

  18. Reconstructing Large-Scale Brain Resting-State Networks from High-Resolution EEG: Spatial and Temporal Comparisons with fMRI.

    PubMed

    Yuan, Han; Ding, Lei; Zhu, Min; Zotev, Vadim; Phillips, Raquel; Bodurka, Jerzy

    2016-03-01

    Functional magnetic resonance imaging (fMRI) studies utilizing measures of hemodynamic signal, such as the blood oxygenation level-dependent (BOLD) signal, have discovered that resting-state brain activities are organized into multiple large-scale functional networks, coined as resting-state networks (RSNs). However, an important limitation of the available fMRI studies is that hemodynamic signals only provide an indirect measure of the neuronal activity. In contrast, electroencephalography (EEG) directly measures electrophysiological activity of the brain. However, little is known about the brain-wide organization of such spontaneous neuronal population signals at the resting state. It is not entirely clear if or how the network structure built upon slowly fluctuating hemodynamic signals is represented in terms of fast, dynamic, and spontaneous neuronal activity. In this study, we investigated the electrophysiological representation of RSNs from simultaneously acquired EEG and fMRI data in the resting human brain. We developed a data-driven analysis approach that reconstructed multiple large-scale electrophysiological networks from high-resolution EEG data alone. The networks derived from EEG were then compared with RSNs independently derived from simultaneously acquired fMRI in their spatial structures as well as temporal dynamics. Results reveal spatially and temporally specific electrophysiological correlates for the fMRI-RSNs. Findings suggest that the spontaneous activity of various large-scale cortical networks is reflected in macroscopic EEG potentials. PMID:26414793

  19. Optimization of large-scale mouse brain connectome via joint evaluation of DTI and neuron tracing data.

    PubMed

    Chen, Hanbo; Liu, Tao; Zhao, Yu; Zhang, Tuo; Li, Yujie; Li, Meng; Zhang, Hongmiao; Kuang, Hui; Guo, Lei; Tsien, Joe Z; Liu, Tianming

    2015-07-15

    Tractography based on diffusion tensor imaging (DTI) data has been used as a tool by a large number of recent studies to investigate structural connectome. Despite its great success in offering unique 3D neuroanatomy information, DTI is an indirect observation with limited resolution and accuracy and its reliability is still unclear. Thus, it is essential to answer this fundamental question: how reliable is DTI tractography in constructing large-scale connectome? To answer this question, we employed neuron tracing data of 1772 experiments on the mouse brain released by the Allen Mouse Brain Connectivity Atlas (AMCA) as the ground-truth to assess the performance of DTI tractography in inferring white matter fiber pathways and inter-regional connections. For the first time in the neuroimaging field, the performance of whole brain DTI tractography in constructing a large-scale connectome has been evaluated by comparison with tracing data. Our results suggested that only with the optimized tractography parameters and the appropriate scale of brain parcellation scheme, can DTI produce relatively reliable fiber pathways and a large-scale connectome. Meanwhile, a considerable amount of errors were also identified in optimized DTI tractography results, which we believe could be potentially alleviated by efforts in developing better DTI tractography approaches. In this scenario, our framework could serve as a reliable and quantitative test bed to identify errors in tractography results which will facilitate the development of such novel tractography algorithms and the selection of optimal parameters. PMID:25953631

  20. How institutions shaped the last major evolutionary transition to large-scale human societies.

    PubMed

    Powers, Simon T; van Schaik, Carel P; Lehmann, Laurent

    2016-02-01

    What drove the transition from small-scale human societies centred on kinship and personal exchange, to large-scale societies comprising cooperation and division of labour among untold numbers of unrelated individuals? We propose that the unique human capacity to negotiate institutional rules that coordinate social actions was a key driver of this transition. By creating institutions, humans have been able to move from the default 'Hobbesian' rules of the 'game of life', determined by physical/environmental constraints, into self-created rules of social organization where cooperation can be individually advantageous even in large groups of unrelated individuals. Examples include rules of food sharing in hunter-gatherers, rules for the usage of irrigation systems in agriculturalists, property rights and systems for sharing reputation between mediaeval traders. Successful institutions create rules of interaction that are self-enforcing, providing direct benefits both to individuals that follow them, and to individuals that sanction rule breakers. Forming institutions requires shared intentionality, language and other cognitive abilities largely absent in other primates. We explain how cooperative breeding likely selected for these abilities early in the Homo lineage. This allowed anatomically modern humans to create institutions that transformed the self-reliance of our primate ancestors into the division of labour of large-scale human social organization. PMID:26729937

  1. Large-scale production of functional human lysozyme from marker-free transgenic cloned cows

    PubMed Central

    Lu, Dan; Liu, Shen; Ding, Fangrong; Wang, Haiping; Li, Jing; Li, Ling; Dai, Yunping; Li, Ning

    2016-01-01

    Human lysozyme is an important natural non-specific immune protein that is highly expressed in breast milk and participates in the immune response of infants against bacterial and viral infections. Considering the medicinal value and market demand for human lysozyme, an animal model for large-scale production of recombinant human lysozyme (rhLZ) is needed. In this study, we generated transgenic cloned cows with the marker-free vector pBAC-hLF-hLZ, which was shown to efficiently express rhLZ in cow milk. Seven transgenic cloned cows, identified by polymerase chain reaction, Southern blot, and western blot analyses, produced rhLZ in milk at concentrations of up to 3149.19 ± 24.80 mg/L. The purified rhLZ had a similar molecular weight and enzymatic activity as wild-type human lysozyme possessed the same C-terminal and N-terminal amino acid sequences. The preliminary results from the milk yield and milk compositions from a naturally lactating transgenic cloned cow 0906 were also tested. These results provide a solid foundation for the large-scale production of rhLZ in the future. PMID:26961596

  2. Large-scale production of functional human lysozyme from marker-free transgenic cloned cows.

    PubMed

    Lu, Dan; Liu, Shen; Ding, Fangrong; Wang, Haiping; Li, Jing; Li, Ling; Dai, Yunping; Li, Ning

    2016-01-01

    Human lysozyme is an important natural non-specific immune protein that is highly expressed in breast milk and participates in the immune response of infants against bacterial and viral infections. Considering the medicinal value and market demand for human lysozyme, an animal model for large-scale production of recombinant human lysozyme (rhLZ) is needed. In this study, we generated transgenic cloned cows with the marker-free vector pBAC-hLF-hLZ, which was shown to efficiently express rhLZ in cow milk. Seven transgenic cloned cows, identified by polymerase chain reaction, Southern blot, and western blot analyses, produced rhLZ in milk at concentrations of up to 3149.19 ± 24.80 mg/L. The purified rhLZ had a similar molecular weight and enzymatic activity as wild-type human lysozyme possessed the same C-terminal and N-terminal amino acid sequences. The preliminary results from the milk yield and milk compositions from a naturally lactating transgenic cloned cow 0906 were also tested. These results provide a solid foundation for the large-scale production of rhLZ in the future. PMID:26961596

  3. Large-scale gene expression profiling of discrete brain regions: potential, limitations, and application in genetics of aggressive behavior.

    PubMed

    Feldker, Dorine E M; de Kloet, E Ronald; Kruk, Menno R; Datson, Nicole A

    2003-09-01

    Many behavioral geneticists are interested in unraveling the molecular mechanisms underlying aggressive behavior. So far, most scientists have based their search for aggression-related genes on a preliminary functional hypothesis. Large-scale gene expression profiling techniques, such as serial analysis of gene expression (SAGE) and DNA microarrays, now enable the screening of expression levels of thousands of genes simultaneously, allowing the identification of new candidate aggression-related genes expressed in brain and thus the generation of new hypotheses. However, expression profiling in the brain is challenging, as brain is a complex heterogeneous tissue where large numbers of genes are expressed and relatively small changes in gene expression occur. In this special issue, we focus on the principles of SAGE and DNA microarrays, as well as their advantages and disadvantages and application to analysis in brain tissue in order to identify aggression-related genes. PMID:14574131

  4. The causality analysis of climate change and large-scale human crisis.

    PubMed

    Zhang, David D; Lee, Harry F; Wang, Cong; Li, Baosheng; Pei, Qing; Zhang, Jane; An, Yulun

    2011-10-18

    Recent studies have shown strong temporal correlations between past climate changes and societal crises. However, the specific causal mechanisms underlying this relation have not been addressed. We explored quantitative responses of 14 fine-grained agro-ecological, socioeconomic, and demographic variables to climate fluctuations from A.D. 1500-1800 in Europe. Results show that cooling from A.D. 1560-1660 caused successive agro-ecological, socioeconomic, and demographic catastrophes, leading to the General Crisis of the Seventeenth Century. We identified a set of causal linkages between climate change and human crisis. Using temperature data and climate-driven economic variables, we simulated the alternation of defined "golden" and "dark" ages in Europe and the Northern Hemisphere during the past millennium. Our findings indicate that climate change was the ultimate cause, and climate-driven economic downturn was the direct cause, of large-scale human crises in preindustrial Europe and the Northern Hemisphere. PMID:21969578

  5. Estimating Large-Scale Network Convergence in the Human Functional Connectome.

    PubMed

    Bell, Peter T; Shine, James M

    2015-11-01

    The study of resting-state networks provides an informative paradigm for understanding the functional architecture of the human brain. Although investigating specialized resting-state networks has led to significant advances in our understanding of brain organization, the manner in which information is integrated across these networks remains unclear. Here, we have developed and validated a data-driven methodology for describing the topography of resting-state network convergence in the human brain. Our results demonstrate the importance of an ensemble of cortical and subcortical regions in supporting the convergence of multiple resting-state networks, including the rostral anterior cingulate, precuneus, posterior cingulate cortex, posterior parietal cortex, dorsal prefrontal cortex, along with the caudate head, anterior claustrum, and posterior thalamus. In addition, we have demonstrated a significant correlation between voxel-wise network convergence and global brain connectivity, emphasizing the importance of resting-state network convergence in facilitating global brain communication. Finally, we examined the convergence of systems within each of the individual resting-state networks in the brain, revealing the heterogeneity by which individual resting-state networks balance the competing demands of specialized processing against the integration of information. Together, our results suggest that the convergence of resting-state networks represents an important organizational principle underpinning systems-level integration in the human brain. PMID:26005099

  6. Demonstration of Mobile Auto-GPS for Large Scale Human Mobility Analysis

    NASA Astrophysics Data System (ADS)

    Horanont, Teerayut; Witayangkurn, Apichon; Shibasaki, Ryosuke

    2013-04-01

    The greater affordability of digital devices and advancement of positioning and tracking capabilities have presided over today's age of geospatial Big Data. Besides, the emergences of massive mobile location data and rapidly increase in computational capabilities open up new opportunities for modeling of large-scale urban dynamics. In this research, we demonstrate the new type of mobile location data called "Auto-GPS" and its potential use cases for urban applications. More than one million Auto-GPS mobile phone users in Japan have been observed nationwide in a completely anonymous form for over an entire year from August 2010 to July 2011 for this analysis. A spate of natural disasters and other emergencies during the past few years has prompted new interest in how mobile location data can help enhance our security, especially in urban areas which are highly vulnerable to these impacts. New insights gleaned from mining the Auto-GPS data suggest a number of promising directions of modeling human movement during a large-scale crisis. We question how people react under critical situation and how their movement changes during severe disasters. Our results demonstrate a case of major earthquake and explain how people who live in Tokyo Metropolitan and vicinity area behave and return home after the Great East Japan Earthquake on March 11, 2011.

  7. Large-scale imputation of epigenomic datasets for systematic annotation of diverse human tissues.

    PubMed

    Ernst, Jason; Kellis, Manolis

    2015-04-01

    With hundreds of epigenomic maps, the opportunity arises to exploit the correlated nature of epigenetic signals, across both marks and samples, for large-scale prediction of additional datasets. Here, we undertake epigenome imputation by leveraging such correlations through an ensemble of regression trees. We impute 4,315 high-resolution signal maps, of which 26% are also experimentally observed. Imputed signal tracks show overall similarity to observed signals and surpass experimental datasets in consistency, recovery of gene annotations and enrichment for disease-associated variants. We use the imputed data to detect low-quality experimental datasets, to find genomic sites with unexpected epigenomic signals, to define high-priority marks for new experiments and to delineate chromatin states in 127 reference epigenomes spanning diverse tissues and cell types. Our imputed datasets provide the most comprehensive human regulatory region annotation to date, and our approach and the ChromImpute software constitute a useful complement to large-scale experimental mapping of epigenomic information. PMID:25690853

  8. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells.

    PubMed

    Cho, Myung Soo; Lee, Young-Eun; Kim, Ji Young; Chung, Seungsoo; Cho, Yoon Hee; Kim, Dae-Sung; Kang, Sang-Moon; Lee, Haksup; Kim, Myung-Hwa; Kim, Jeong-Hoon; Leem, Joong Woo; Oh, Sun Kyung; Choi, Young Min; Hwang, Dong-Youn; Chang, Jin Woo; Kim, Dong-Wook

    2008-03-01

    We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications. PMID:18305158

  9. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells

    PubMed Central

    Cho, Myung Soo; Lee, Young-Eun; Kim, Ji Young; Chung, Seungsoo; Cho, Yoon Hee; Kim, Dae-Sung; Kang, Sang-Moon; Lee, Haksup; Kim, Myung-Hwa; Kim, Jeong-Hoon; Leem, Joong Woo; Oh, Sun Kyung; Choi, Young Min; Hwang, Dong-Youn; Chang, Jin Woo; Kim, Dong-Wook

    2008-01-01

    We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications. PMID:18305158

  10. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

    PubMed

    Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Yao, Yin; Ho, Yvonne Y W; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

    2016-03-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  11. Spatiotemporal reconfiguration of large-scale brain functional networks during propofol-induced loss of consciousness.

    PubMed

    Schröter, Manuel S; Spoormaker, Victor I; Schorer, Anna; Wohlschläger, Afra; Czisch, Michael; Kochs, Eberhard F; Zimmer, Claus; Hemmer, Bernhard; Schneider, Gerhard; Jordan, Denis; Ilg, Rüdiger

    2012-09-12

    Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging (fMRI), we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness (PI-LOC). After extraction of regional fMRI time series from 110 cortical and subcortical regions, we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain's intrinsic spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico-cortical and corticocortical connectivity. Decrease of connectivity was pronounced in thalamocortical connections, whereas no changes were found for connectivity within primary sensory cortices. Graph theoretical analyses revealed significant changes in the degree distribution and local organization metrics of brain functional networks during PI-LOC: compared with a random network, normalized clustering was significantly increased, as was small-worldness. Furthermore we observed a profound decline in long-range connections and a reduction in whole-brain spatiotemporal integration, supporting a topological reconfiguration during PI-LOC. Our findings shed light on the functional significance of intrinsic brain activity as measured by spontaneous BOLD signal fluctuations and help to understand propofol-induced loss of consciousness. PMID:22973006

  12. BrainModes: a principled approach to modeling and measuring large-scale neuronal activity.

    PubMed

    Breakspear, Michael J; Daffertshofer, Andreas; Ritter, Petra

    2009-09-30

    Complex systems, such as the brain, exhibit multiple levels of organization due to processes which support the separation of scales across time and/or space. That is, cooperative phenomena--or "modes" of activity--occurring at one scale give rise to coherent spatiotemporal structures at a coarser scale. In turn, structures at the coarser scale constrain--and hence influence--emerging activity at a finer scale. BrainModes is an annual scientific summit which seeks to bring together experimental, computational and theoretical neuroscientists engaged at different levels of organization, with the goal of advancing a principled approach to understanding brain function based on the concept of cooperative phenomena in complex systems. Phenomena of particular interest include synchronization, stochastic influences, and spatiotemporal processes in both healthy and pathological states such as seizures. This Special Issue reports the 2008 BrainModes Workshop, held in Amsterdam (December 2008) which focused on the application of this framework to the analysis of brain oscillations and synchronization phenomena across time scales. PMID:19607859

  13. Large-Scale Recombinant Expression and Purification of Human Tyrosinase Suitable for Structural Studies.

    PubMed

    Lai, Xuelei; Soler-Lopez, Montserrat; Wichers, Harry J; Dijkstra, Bauke W

    2016-01-01

    Human tyrosinase (TYR) is a glycoprotein that initiates the first two reactions in the melanin biosynthesis pathway. Mutations in its encoding gene cause Oculocutaneous Albinism type I (OCA1), the most severe form of albinism, which is a group of autosomal recessive disorders characterized by reduced or absent production of melanin in skin, hair and eyes. Despite extensive structural and characterization studies of its homologues in lower eukaryotic organisms, the catalytic mechanism of human TYR and the molecular basis of OCA1 are largely unknown. In this work, we have carried out a large-scale recombinant expression of TYR that has enabled us to obtain high yields of pure and active protein, required for crystallization trials and screening of skin whitening agents, which is highly demanded in the cosmetic industry. Addition of an N-terminal honeybee melittin signal peptide for secretion of the produced protein into the (protein-free) medium, as well as a cleavable His-tag at the C-terminus, was crucial for increasing the yield of pure protein. We have successfully crystallized two TYR variants, in both glycosylated and deglycosylated forms, showing preliminary X-ray diffraction patterns at 3.5 Å resolution. Hence, we have established an expression and purification protocol suitable for the crystal structure determination of human TYR, which will give unique atomic insight into the nature and conformation of the residues that shape the substrate binding pocket that will ultimately lead to efficient compound design. PMID:27551823

  14. Large-Scale Recombinant Expression and Purification of Human Tyrosinase Suitable for Structural Studies

    PubMed Central

    Lai, Xuelei; Soler-Lopez, Montserrat; Wichers, Harry J.

    2016-01-01

    Human tyrosinase (TYR) is a glycoprotein that initiates the first two reactions in the melanin biosynthesis pathway. Mutations in its encoding gene cause Oculocutaneous Albinism type I (OCA1), the most severe form of albinism, which is a group of autosomal recessive disorders characterized by reduced or absent production of melanin in skin, hair and eyes. Despite extensive structural and characterization studies of its homologues in lower eukaryotic organisms, the catalytic mechanism of human TYR and the molecular basis of OCA1 are largely unknown. In this work, we have carried out a large-scale recombinant expression of TYR that has enabled us to obtain high yields of pure and active protein, required for crystallization trials and screening of skin whitening agents, which is highly demanded in the cosmetic industry. Addition of an N-terminal honeybee melittin signal peptide for secretion of the produced protein into the (protein-free) medium, as well as a cleavable His-tag at the C-terminus, was crucial for increasing the yield of pure protein. We have successfully crystallized two TYR variants, in both glycosylated and deglycosylated forms, showing preliminary X-ray diffraction patterns at 3.5 Å resolution. Hence, we have established an expression and purification protocol suitable for the crystal structure determination of human TYR, which will give unique atomic insight into the nature and conformation of the residues that shape the substrate binding pocket that will ultimately lead to efficient compound design. PMID:27551823

  15. An Efficient and Reliable Statistical Method for Estimating Functional Connectivity in Large Scale Brain Networks Using Partial Correlation

    PubMed Central

    Wang, Yikai; Kang, Jian; Kemmer, Phebe B.; Guo, Ying

    2016-01-01

    Currently, network-oriented analysis of fMRI data has become an important tool for understanding brain organization and brain networks. Among the range of network modeling methods, partial correlation has shown great promises in accurately detecting true brain network connections. However, the application of partial correlation in investigating brain connectivity, especially in large-scale brain networks, has been limited so far due to the technical challenges in its estimation. In this paper, we propose an efficient and reliable statistical method for estimating partial correlation in large-scale brain network modeling. Our method derives partial correlation based on the precision matrix estimated via Constrained L1-minimization Approach (CLIME), which is a recently developed statistical method that is more efficient and demonstrates better performance than the existing methods. To help select an appropriate tuning parameter for sparsity control in the network estimation, we propose a new Dens-based selection method that provides a more informative and flexible tool to allow the users to select the tuning parameter based on the desired sparsity level. Another appealing feature of the Dens-based method is that it is much faster than the existing methods, which provides an important advantage in neuroimaging applications. Simulation studies show that the Dens-based method demonstrates comparable or better performance with respect to the existing methods in network estimation. We applied the proposed partial correlation method to investigate resting state functional connectivity using rs-fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) study. Our results show that partial correlation analysis removed considerable between-module marginal connections identified by full correlation analysis, suggesting these connections were likely caused by global effects or common connection to other nodes. Based on partial correlation, we find that the most significant

  16. Construction and analyses of human large-scale tissue specific networks.

    PubMed

    Liu, Wei; Wang, Jianying; Wang, Tengjiao; Xie, Hongwei

    2014-01-01

    Construction and analyses of tissue specific networks is crucial to unveil the function and organizational structure of biological systems. As a direct method to detect protein dynamics, human proteome-wide expression data provide an valuable resource to investigate the tissue specificity of proteins and interactions. By integrating protein expression data with large-scale interaction network, we constructed 30 tissue/cell specific networks in human and analyzed their properties and functions. Rather than the tissue specificity of proteins, we mainly focused on the tissue specificity of interactions to distill tissue specific networks. Through comparing our tissue specific networks with those inferred from gene expression data, we found our networks have larger scales and higher reliability. Furthermore, we investigated the similar extent of multiple tissue specific networks, which proved that tissues with similar functions tend to contain more common interactions. Finally, we found that the tissue specific networks differed from the static network in multiple topological properties. The proteins in tissue specific networks are interacting looser and the hubs play more important roles than those in the static network. PMID:25513809

  17. An Integrative Approach for the Large-scale Identification of Human Genome Kinases Regulating Cancer Metastasis

    PubMed Central

    Zhang, Hanshuo; Wu, Pu-Yen; Ma, Ming; Ye, Yanzheng; Hao, Yang; Yang, Junyu; Yin, Shenyi; Sun, Changhong; Phan, John H.; Wang, May D.; Xi, Jianzhong Jeff

    2016-01-01

    Kinases regulate the majority of biological processes and become one of important groups of drug targets. To identify more kinases being potential for cancer therapy, we developed an integrative approach for the large-scale screen of functional genes capable of regulating the main traits of cancer metastasis, including cell migration as well as invasion. We first employed self-assembled cell microarray (SAMcell) to screen functional genes that regulate cancer cell migration using a siRNA library targeting 710 human genome kinase genes. We identified 81 genes capable of significantly regulating cancer cell migration. Following with invasion assays and bio-informatics analysis, we discovered that 16 genes with differentially expression in cancer samples can regulate both cell migration and invasion, among which 10 genes have been well known to play critical roles in the cancer development. The remaining 6 genes were experimentally validated to have the capacities of regulating the metastasis-related traits, including cell proliferation, apoptosis and anoikis activities besides cell motility. Together, these findings provide a new insight into the therapeutic use of human kinases. PMID:23751374

  18. The causality analysis of climate change and large-scale human crisis

    PubMed Central

    Zhang, David D.; Lee, Harry F.; Wang, Cong; Li, Baosheng; Pei, Qing; Zhang, Jane; An, Yulun

    2011-01-01

    Recent studies have shown strong temporal correlations between past climate changes and societal crises. However, the specific causal mechanisms underlying this relation have not been addressed. We explored quantitative responses of 14 fine-grained agro-ecological, socioeconomic, and demographic variables to climate fluctuations from A.D. 1500–1800 in Europe. Results show that cooling from A.D. 1560–1660 caused successive agro-ecological, socioeconomic, and demographic catastrophes, leading to the General Crisis of the Seventeenth Century. We identified a set of causal linkages between climate change and human crisis. Using temperature data and climate-driven economic variables, we simulated the alternation of defined “golden” and “dark” ages in Europe and the Northern Hemisphere during the past millennium. Our findings indicate that climate change was the ultimate cause, and climate-driven economic downturn was the direct cause, of large-scale human crises in preindustrial Europe and the Northern Hemisphere. PMID:21969578

  19. Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins

    PubMed Central

    Kennedy, Jacob J.; Abbatiello, Susan E.; Kim, Kyunggon; Yan, Ping; Whiteaker, Jeffrey R.; Lin, Chenwei; Kim, Jun Seok; Zhang, Yuzheng; Wang, Xianlong; Ivey, Richard G.; Zhao, Lei; Min, Hophil; Lee, Youngju; Yu, Myeong-Hee; Yang, Eun Gyeong; Lee, Cheolju; Wang, Pei; Rodriguez, Henry; Kim, Youngsoo; Carr, Steven A.; Paulovich, Amanda G.

    2014-01-01

    The successful application of MRM in biological specimens raises the exciting possibility that assays can be configured to measure all human proteins, resulting in an assay resource that would promote advances in biomedical research. We report the results of a pilot study designed to test the feasibility of a large-scale, international effort in MRM assay generation. We have configured, validated across three laboratories, and made publicly available as a resource to the community 645 novel MRM assays representing 319 proteins expressed in human breast cancer. Assays were multiplexed in groups of >150 peptides and deployed to quantify endogenous analyte in a panel of breast cancer-related cell lines. Median assay precision was 5.4%, with high inter-laboratory correlation (R2 >0.96). Peptide measurements in breast cancer cell lines were able to discriminate amongst molecular subtypes and identify genome-driven changes in the cancer proteome. These results establish the feasibility of a scaled, international effort. PMID:24317253

  20. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    PubMed

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. PMID:26453902

  1. A Large-Scale Behavioral Screen to Identify Neurons Controlling Motor Programs in the Drosophila Brain

    PubMed Central

    Flood, Thomas F.; Gorczyca, Michael; White, Benjamin H.; Ito, Kei; Yoshihara, Motojiro

    2013-01-01

    Drosophila is increasingly used for understanding the neural basis of behavior through genetically targeted manipulation of specific neurons. The primary approach in this regard has relied on the suppression of neuronal activity. Here, we report the results of a novel approach to find and characterize neural circuits by expressing neuronal activators to stimulate subsets of neurons to induce behavior. Classical electrophysiological studies demonstrated that stimulation of command neurons could activate neural circuits to trigger fixed action patterns. Our method was designed to find such command neurons for diverse behaviors by screening flies in which random subsets of brain cells were activated. We took advantage of the large collection of Gal4 lines from the NP project and crossed 835 Gal4 strains with relatively limited Gal4 expression in the brain to flies carrying a UAS transgene encoding TRPM8, a cold-sensitive ion channel. Low temperatures opened the TRPM8 channel in Gal4-expressing cells, leading to their excitation, and in many cases induced overt behavioral changes in adult flies. Paralysis was reproducibly observed in the progeny of crosses with 84 lines, whereas more specific behaviors were induced with 24 other lines. Stimulation performed using the heat-activated channel, TrpA1, resulted in clearer and more robust behaviors, including flight, feeding, and egg-laying. Through follow-up studies starting from this screen, we expect to find key components of the neural circuits underlying specific behaviors, thus providing a new avenue for their functional analysis. PMID:23934998

  2. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

    PubMed

    Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

    2016-01-01

    The production of megakaryocytes (MKs)-the precursors of blood platelets-from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology. PMID:27052461

  3. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

    PubMed Central

    Moreau, Thomas; Evans, Amanda L.; Vasquez, Louella; Tijssen, Marloes R.; Yan, Ying; Trotter, Matthew W.; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M.; Pask, Dean C.; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H.; Pedersen, Roger A.; Ghevaert, Cedric

    2016-01-01

    The production of megakaryocytes (MKs)—the precursors of blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology. PMID:27052461

  4. Analysis of a large-scale weighted network of one-to-one human communication

    NASA Astrophysics Data System (ADS)

    Onnela, Jukka-Pekka; Saramäki, Jari; Hyvönen, Jörkki; Szabó, Gábor; Argollo de Menezes, M.; Kaski, Kimmo; Barabási, Albert-László; Kertész, János

    2007-06-01

    We construct a connected network of 3.9 million nodes from mobile phone call records, which can be regarded as a proxy for the underlying human communication network at the societal level. We assign two weights on each edge to reflect the strength of social interaction, which are the aggregate call duration and the cumulative number of calls placed between the individuals over a period of 18 weeks. We present a detailed analysis of this weighted network by examining its degree, strength, and weight distributions, as well as its topological assortativity and weighted assortativity, clustering and weighted clustering, together with correlations between these quantities. We give an account of motif intensity and coherence distributions and compare them to a randomized reference system. We also use the concept of link overlap to measure the number of common neighbours any two adjacent nodes have, which serves as a useful local measure for identifying the interconnectedness of communities. We report a positive correlation between the overlap and weight of a link, thus providing strong quantitative evidence for the weak ties hypothesis, a central concept in social network analysis. The percolation properties of the network are found to depend on the type and order of removed links, and they can help understand how the local structure of the network manifests itself at the global level. We hope that our results will contribute to modelling weighted large-scale social networks, and believe that the systematic approach followed here can be adopted to study other weighted networks.

  5. Large-scale gene discovery in human airway epithelia reveals novel transcripts.

    PubMed

    Scheetz, Todd E; Zabner, Joseph; Welsh, Michael J; Coco, Justin; Eyestone, Mari de Fatima; Bonaldo, Maria; Kucaba, Tamara; Casavant, Thomas L; Soares, M Bento; McCray, Paul B

    2004-03-12

    The airway epithelium represents an important barrier between the host and the environment. It is a first site of contact with pathogens, particulates, and other stimuli, and has evolved the means to dynamically respond to these challenges. In an effort to define the transcript profile of airway epithelia, we created and sequenced cDNA libraries from cystic fibrosis (CF) and non-CF epithelia and from human lung tissue. Sequencing of these libraries produced approximately 53,000 3'-expressed sequence tags (3'-ESTs). From these, a nonredundant UniGene set of more than 19,000 sequences was generated. Despite the relatively small contribution of airway epithelia to the total mass of the lung, focused gene discovery in this tissue yielded novel results. The ESTs included several thousand transcripts (6,416) not previously identified from cDNA sequences as expressed in the lung. Among the abundant transcripts were several genes involved in host defense. Most importantly, the set also included 879 3'-ESTs that appear to be novel sequences not previously represented in the National Center for Biotechnology Information UniGene collection. This UniGene set should be useful for studies of pulmonary diseases involving the airway epithelium including cystic fibrosis, respiratory infections and asthma. It also provides a reagent for large-scale expression profiling. PMID:14701920

  6. Diversity and relationships of cocirculating modern human rotaviruses revealed using large-scale comparative genomics.

    PubMed

    McDonald, Sarah M; McKell, Allison O; Rippinger, Christine M; McAllen, John K; Akopov, Asmik; Kirkness, Ewen F; Payne, Daniel C; Edwards, Kathryn M; Chappell, James D; Patton, John T

    2012-09-01

    Group A rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses and are primary causes of gastroenteritis in young children. Despite their medical relevance, the genetic diversity of modern human RVs is poorly understood, and the impact of vaccine use on circulating strains remains unknown. In this study, we report the complete genome sequence analysis of 58 RVs isolated from children with severe diarrhea and/or vomiting at Vanderbilt University Medical Center (VUMC) in Nashville, TN, during the years spanning community vaccine implementation (2005 to 2009). The RVs analyzed include 36 G1P[8], 18 G3P[8], and 4 G12P[8] Wa-like genogroup 1 strains with VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genotype constellations of I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees, we identified 2 to 5 subgenotype alleles for each gene. The results show evidence of intragenogroup gene reassortment among the cocirculating strains. However, several isolates from different seasons maintained identical allele constellations, consistent with the notion that certain RV clades persisted in the community. By comparing the genes of VUMC RVs to those of other archival and contemporary RV strains for which sequences are available, we defined phylogenetic lineages and verified that the diversity of the strains analyzed in this study reflects that seen in other regions of the world. Importantly, the VP4 and VP7 proteins encoded by VUMC RVs and other contemporary strains show amino acid changes in or near neutralization domains, which might reflect antigenic drift of the virus. Thus, this large-scale, comparative genomic study of modern human RVs provides significant insight into how this pathogen evolves during its spread in the community. PMID:22696651

  7. Diversity and Relationships of Cocirculating Modern Human Rotaviruses Revealed Using Large-Scale Comparative Genomics

    PubMed Central

    McKell, Allison O.; Rippinger, Christine M.; McAllen, John K.; Akopov, Asmik; Kirkness, Ewen F.; Payne, Daniel C.; Edwards, Kathryn M.; Chappell, James D.; Patton, John T.

    2012-01-01

    Group A rotaviruses (RVs) are 11-segmented, double-stranded RNA viruses and are primary causes of gastroenteritis in young children. Despite their medical relevance, the genetic diversity of modern human RVs is poorly understood, and the impact of vaccine use on circulating strains remains unknown. In this study, we report the complete genome sequence analysis of 58 RVs isolated from children with severe diarrhea and/or vomiting at Vanderbilt University Medical Center (VUMC) in Nashville, TN, during the years spanning community vaccine implementation (2005 to 2009). The RVs analyzed include 36 G1P[8], 18 G3P[8], and 4 G12P[8] Wa-like genogroup 1 strains with VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 genotype constellations of I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees, we identified 2 to 5 subgenotype alleles for each gene. The results show evidence of intragenogroup gene reassortment among the cocirculating strains. However, several isolates from different seasons maintained identical allele constellations, consistent with the notion that certain RV clades persisted in the community. By comparing the genes of VUMC RVs to those of other archival and contemporary RV strains for which sequences are available, we defined phylogenetic lineages and verified that the diversity of the strains analyzed in this study reflects that seen in other regions of the world. Importantly, the VP4 and VP7 proteins encoded by VUMC RVs and other contemporary strains show amino acid changes in or near neutralization domains, which might reflect antigenic drift of the virus. Thus, this large-scale, comparative genomic study of modern human RVs provides significant insight into how this pathogen evolves during its spread in the community. PMID:22696651

  8. Clinical prediction from structural brain MRI scans: a large-scale empirical study.

    PubMed

    Sabuncu, Mert R; Konukoglu, Ender

    2015-01-01

    Multivariate pattern analysis (MVPA) methods have become an important tool in neuroimaging, revealing complex associations and yielding powerful prediction models. Despite methodological developments and novel application domains, there has been little effort to compile benchmark results that researchers can reference and compare against. This study takes a significant step in this direction. We employed three classes of state-of-the-art MVPA algorithms and common types of structural measurements from brain Magnetic Resonance Imaging (MRI) scans to predict an array of clinically relevant variables (diagnosis of Alzheimer's, schizophrenia, autism, and attention deficit and hyperactivity disorder; age, cerebrospinal fluid derived amyloid-β levels and mini-mental state exam score). We analyzed data from over 2,800 subjects, compiled from six publicly available datasets. The employed data and computational tools are freely distributed ( https://www.nmr.mgh.harvard.edu/lab/mripredict), making this the largest, most comprehensive, reproducible benchmark image-based prediction experiment to date in structural neuroimaging. Finally, we make several observations regarding the factors that influence prediction performance and point to future research directions. Unsurprisingly, our results suggest that the biological footprint (effect size) has a dramatic influence on prediction performance. Though the choice of image measurement and MVPA algorithm can impact the result, there was no universally optimal selection. Intriguingly, the choice of algorithm seemed to be less critical than the choice of measurement type. Finally, our results showed that cross-validation estimates of performance, while generally optimistic, correlate well with generalization accuracy on a new dataset. PMID:25048627

  9. Towards human-computer synergetic analysis of large-scale biological data

    PubMed Central

    2013-01-01

    Background Advances in technology have led to the generation of massive amounts of complex and multifarious biological data in areas ranging from genomics to structural biology. The volume and complexity of such data leads to significant challenges in terms of its analysis, especially when one seeks to generate hypotheses or explore the underlying biological processes. At the state-of-the-art, the application of automated algorithms followed by perusal and analysis of the results by an expert continues to be the predominant paradigm for analyzing biological data. This paradigm works well in many problem domains. However, it also is limiting, since domain experts are forced to apply their instincts and expertise such as contextual reasoning, hypothesis formulation, and exploratory analysis after the algorithm has produced its results. In many areas where the organization and interaction of the biological processes is poorly understood and exploratory analysis is crucial, what is needed is to integrate domain expertise during the data analysis process and use it to drive the analysis itself. Results In context of the aforementioned background, the results presented in this paper describe advancements along two methodological directions. First, given the context of biological data, we utilize and extend a design approach called experiential computing from multimedia information system design. This paradigm combines information visualization and human-computer interaction with algorithms for exploratory analysis of large-scale and complex data. In the proposed approach, emphasis is laid on: (1) allowing users to directly visualize, interact, experience, and explore the data through interoperable visualization-based and algorithmic components, (2) supporting unified query and presentation spaces to facilitate experimentation and exploration, (3) providing external contextual information by assimilating relevant supplementary data, and (4) encouraging user

  10. Improvement of methods for large scale sequencing; application to human Xq28

    SciTech Connect

    Gibbs, R.A.; Andersson, B.; Wentland, M.A.

    1994-09-01

    Sequencing of a one-metabase region of Xq28, spanning the FRAXA and IDS loci has been undertaken in order to investigate the practicality of the shotgun approach for large scale sequencing and as a platform to develop improved methods. The efficiency of several steps in the shotgun sequencing strategy has been increased using PCR-based approaches. An improved method for preparation of M13 libraries has been developed. This protocol combines a previously described adaptor-based protocol with the uracil DNA glycosylase (UDG)-cloning procedure. The efficiency of this procedure has been found to be up to 100-fold higher than that of previously used protocols. In addition the novel protocol is more reliable and thus easy to establish in a laboratory. The method has also been adapted for the simultaneous shotgun sequencing of multiple short fragments by concentrating them before library construction is presented. This protocol is suitable for rapid characterization of cDNA clones. A library was constructed from 15 PCR-amplified and concentrated human cDNA inserts, and the insert sequences could easily be identified as separate contigs during the assembly process and the sequence coverage was even along each fragment. Using this strategy, the fine structures of the FraxA and IDS loci have been revealed and several EST homologies indicating novel expressed sequences have been identified. Use of PCR to close repetitive regions that are difficult to clone was tested by determination of the sequence of a cosmid mapping DXS455 in Xq28, containing a polymorphic VNTR. The region containing the VNTR was not represented in the shotgun library, but by designing PCR primers in the sequences flanking the gap and by cloning and sequencing the PCR product, the fine structure of the VNTR has been determined. It was found to be an AT-rich VNTR with a repeated 25-mer at the center.

  11. Human-Machine Cooperation in Large-Scale Multimedia Retrieval: A Survey

    ERIC Educational Resources Information Center

    Shirahama, Kimiaki; Grzegorzek, Marcin; Indurkhya, Bipin

    2015-01-01

    "Large-Scale Multimedia Retrieval" (LSMR) is the task to fast analyze a large amount of multimedia data like images or videos and accurately find the ones relevant to a certain semantic meaning. Although LSMR has been investigated for more than two decades in the fields of multimedia processing and computer vision, a more…

  12. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python.

    PubMed

    Rey-Villamizar, Nicolas; Somasundar, Vinay; Megjhani, Murad; Xu, Yan; Lu, Yanbin; Padmanabhan, Raghav; Trett, Kristen; Shain, William; Roysam, Badri

    2014-01-01

    In this article, we describe the use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes, including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis tasks, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral images of brain tissue surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels. Each channel consists of 6000 × 10,000 × 500 voxels with 16 bits/voxel, implying image sizes exceeding 250 GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analysis for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN) capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment. Our Python script enables efficient data storage and movement between computers and storage servers, logs all the processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries. PMID:24808857

  13. Large-scale remapping of visual cortex is absent in adult humans with macular degeneration.

    PubMed

    Baseler, Heidi A; Gouws, André; Haak, Koen V; Racey, Christopher; Crossland, Michael D; Tufail, Adnan; Rubin, Gary S; Cornelissen, Frans W; Morland, Antony B

    2011-05-01

    The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively. PMID:21441924

  14. Climate, Water, and Human Health: Large Scale Hydroclimatic Controls in Forecasting Cholera Epidemics

    NASA Astrophysics Data System (ADS)

    Akanda, A. S.; Jutla, A. S.; Islam, S.

    2009-12-01

    Despite ravaging the continents through seven global pandemics in past centuries, the seasonal and interannual variability of cholera outbreaks remain a mystery. Previous studies have focused on the role of various environmental and climatic factors, but provided little or no predictive capability. Recent findings suggest a more prominent role of large scale hydroclimatic extremes - droughts and floods - and attempt to explain the seasonality and the unique dual cholera peaks in the Bengal Delta region of South Asia. We investigate the seasonal and interannual nature of cholera epidemiology in three geographically distinct locations within the region to identify the larger scale hydroclimatic controls that can set the ecological and environmental ‘stage’ for outbreaks and have significant memory on a seasonal scale. Here we show that two distinctly different, pre and post monsoon, cholera transmission mechanisms related to large scale climatic controls prevail in the region. An implication of our findings is that extreme climatic events such as prolonged droughts, record floods, and major cyclones may cause major disruption in the ecosystem and trigger large epidemics. We postulate that a quantitative understanding of the large-scale hydroclimatic controls and dominant processes with significant system memory will form the basis for forecasting such epidemic outbreaks. A multivariate regression method using these predictor variables to develop probabilistic forecasts of cholera outbreaks will be explored. Forecasts from such a system with a seasonal lead-time are likely to have measurable impact on early cholera detection and prevention efforts in endemic regions.

  15. Sediment transport dynamics in response to large-scale human intervention

    NASA Astrophysics Data System (ADS)

    Eelkema, Menno; Wang, Zheng Bing

    2010-05-01

    SEDIMENT TRANSPORT DYNAMICS IN RESPONSE TO LARGE-SCALE HUMAN INTERVENTION M. Eelkema and Z.B. Wang The Eastern Scheldt basin in the southwestern part of the Netherlands is an elongated tidal basin of approximately 50 km in length with an average tidal range of roughly 3 meters at the inlet. Before 1969 A.D., this basin was also connected to two more tidal basins to the north through several narrow, yet deep channels. These connections were closed off with dams in the nineteen sixties in response to the catastrophic flooding in 1953. In the inlet of the Eastern Scheldt a storm-surge barrier was built in order to safeguard against flooding during storms while retaining a part of the tidal influence inside the basin during normal conditions. This barrier was finalized in 1986. The construction of the back-barrier dams in 1965 and 1969 had a significant impact on the tidal hydrodynamics and sediment transport (Van den Berg, 1986). The effects of these interventions were still ongoing when the hydrodynamic regime was altered again by the construction of the storm-surge barrier between 1983 and 1986. This research aims to describe the hydrodynamic and morphodynamic evolution of the Eastern Scheldt between 1953 and 1983, before construction of the storm-surge barrier had started. An analysis is made of the manner in which the back-barrier dams changed the tidal flow through the basin, and how these altered hydrodynamics influenced the sediment transport and morphology. This analysis consists first of all of a description of the observed hydrodynamical and bathymetrical changes. Second, these observations are used as input for a process-based hydrodynamic model (Delft3D), which is applied in order to gain more insight into the changes in sediment transport patterns. The model is used to simulate the situations before and after the closures of the connections between the Eastern Scheldt and the basins north of it In the decades before 1965, the Eastern Scheldt exported

  16. Investigating Coastal Processes Responsible for Large-Scale Shoreline Responses to Human Shoreline Stabilization

    NASA Astrophysics Data System (ADS)

    Slott, J. M.; Murray, A. B.; Ashton, A. D.

    2006-12-01

    Human shoreline stabilization practices, such as beach nourishment (i.e. placing sand on an eroding beach), have become more prevalent as erosion threatens coastal communities. On sandy shorelines, recent experiments with a numerical model of shoreline change (Slott, et al., in press) indicate that moderate shifts in storminess patterns, one possible outcome of global warming, may accelerate the rate at which shorelines erode or accrete, by altering the angular distribution of approaching waves (the `wave climate'). Accelerated erosion would undoubtedly place greater demands on stabilization. Scientists and coastal engineers have typically only considered the site-specific consequences of shoreline stabilization; here we explore the coastal processes responsible for large-scale (10's kms) and long-term (decades) effects using a numerical model developed by Ashton, et al. (2001). In this numerical model, waves breaking at oblique angles drive a flux of sediment along the shoreline, where gradients in this flux can shape the coastline into surprisingly complex forms (e.g. cuspate-capes found on the Carolina coast). Wave "shadowing" plays a major role in shoreline evolution, whereby coastline features may block incoming waves from reaching distant parts. In this work, we include beach nourishment in the Ashton, et al. (2001) model. Using a cuspate-cape shoreline as our initial model condition, we conducted pairs of experiments and varied the wave-climate forcing across each pair, each representing different storminess scenarios. Here we report on one scenario featuring increased extra-tropical storm influence. For each experiment-pair we ran a control experiment with no shoreline stabilization and a second where a beach nourishment project stabilized a cape tip. By comparing the results of these two parallel runs, we isolate the tendency of the shoreline to migrate landward or seaward along the domain due solely to beach nourishment. Significant effects from beach

  17. Facile large-scale synthesis of brain-like mesoporous silica nanocomposites via a selective etching process.

    PubMed

    Chen, Yu; Wang, Qihua; Wang, Tingmei

    2015-10-21

    The core-shell structured mesoporous silica nanomaterials (MSNs) are experiencing rapid development in many applications such as heterogeneous catalysis, bio-imaging and drug delivery wherein a large pore volume is desirable. We develop a one-pot method for large-scale synthesis of brain-like mesoporous silica nanocomposites based on the reasonable change of the intrinsic nature of the -Si-O-Si- framework of silica nanoparticles together with a selective etching strategy. The as-synthesized products show good monodispersion and a large pore volume of 1.0 cm(3) g(-1). The novelty of this approach lies in the use of an inorganic-organic hybrid layer to assist the creation of large-pore morphology on the outermost shell thereby promoting efficient mass transfer or storage. Importantly, the method is reliable and grams of products can be easily prepared. The morphology on the outermost silica shell can be controlled by simply adjusting the VTES-to-TEOS molar ratio (VTES: triethoxyvinylsilane, TEOS: tetraethyl orthosilicate) as well as the etching time. The as-synthesized products exhibit fluorescence performance by incorporating rhodamine B isothiocyanate (RITC) covalently into the inner silica walls, which provide potential application in bioimaging. We also demonstrate the applications of as-synthesized large-pore structured nanocomposites in drug delivery systems and stimuli-responsive nanoreactors for heterogeneous catalysis. PMID:26394819

  18. Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface

    PubMed Central

    Acqualagna, Laura; Botrel, Loic; Vidaurre, Carmen; Kübler, Andrea; Blankertz, Benjamin

    2016-01-01

    In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods. PMID:26891350

  19. Systematic large-scale study of the inheritance mode of Mendelian disorders provides new insight into human diseasome

    PubMed Central

    Hao, Dapeng; Wang, Guangyu; Yin, Zuojing; Li, Chuanxing; Cui, Yan; Zhou, Meng

    2014-01-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity. PMID:24448549

  20. Small-Scale Screening to Large-Scale Over-Expression of Human Membrane Proteins for Structural Studies.

    PubMed

    Chaudhary, Sarika; Saha, Sukanya; Thamminana, Sobrahani; Stroud, Robert M

    2016-01-01

    Membrane protein structural studies are frequently hampered by poor expression. The low natural abundance of these proteins implies a need for utilizing different heterologous expression systems. E. coli and yeast are commonly used expression systems due to rapid cell growth at high cell density, economical production, and ease of manipulation. Here we report a simplified, systematically developed robust strategy from small-scale screening to large-scale over-expression of human integral membrane proteins in the mammalian expression system for structural studies. This methodology streamlines small-scale screening of several different constructs utilizing fluorescence size-exclusion chromatography (FSEC) towards optimization of buffer, additives, and detergents for achieving stability and homogeneity. This is followed by the generation of stable clonal cell lines expressing desired constructs, and lastly large-scale expression for crystallization. These techniques are designed to rapidly advance the structural studies of eukaryotic integral membrane proteins including that of human membrane proteins. PMID:27485338

  1. Differences in human cortical gene expression match the temporal properties of large-scale functional networks.

    PubMed

    Cioli, Claudia; Abdi, Hervé; Beaton, Derek; Burnod, Yves; Mesmoudi, Salma

    2014-01-01

    We explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings. The first ring--Visual-Sensorimotor-Auditory (VSA)--comprises visual, auditory, somatosensory, and motor cortices that process real time world interactions. The second ring--Parieto-Temporo-Frontal (PTF)--comprises parietal, temporal, and frontal regions with networks dedicated to cognitive functions, emotions, biological needs, and internally driven rhythms. We found--with correspondence analysis--that the patterns of expression of the 938 genes most differentially expressed across the cortex organized the cortex into two sets of regions that match the two rings. We confirmed this result using discriminant correspondence analysis by showing that the genetic profiles of cortical regions can reliably predict to what ring these regions belong. We found that several of the proteins--coded by genes that most differentiate the rings--were involved in neuronal information processing such as ionic channels and neurotransmitter release. The systematic study of families of genes revealed specific proteins within families preferentially expressed in each ring. The results showed strong congruence between the preferential expression of subsets of genes, temporal properties of the proteins they code, and the preferred processing modes of the rings. Ionic channels and release-related proteins more expressed in the VSA ring favor temporal precision of fast evoked neural transmission (Sodium channels SCNA1, SCNB1 potassium channel KCNA1, calcium channel CACNA2D2, Synaptotagmin SYT2, Complexin CPLX1, Synaptobrevin VAMP1). Conversely, genes expressed in the PTF ring favor slower, sustained, or rhythmic activation (Sodium channels SCNA3

  2. Differences in Human Cortical Gene Expression Match the Temporal Properties of Large-Scale Functional Networks

    PubMed Central

    Cioli, Claudia; Abdi, Hervé; Beaton, Derek; Burnod, Yves; Mesmoudi, Salma

    2014-01-01

    We explore the relationships between the cortex functional organization and genetic expression (as provided by the Allen Human Brain Atlas). Previous work suggests that functional cortical networks (resting state and task based) are organized as two large networks (differentiated by their preferred information processing mode) shaped like two rings. The first ring–Visual-Sensorimotor-Auditory (VSA)–comprises visual, auditory, somatosensory, and motor cortices that process real time world interactions. The second ring–Parieto-Temporo-Frontal (PTF)–comprises parietal, temporal, and frontal regions with networks dedicated to cognitive functions, emotions, biological needs, and internally driven rhythms. We found–with correspondence analysis–that the patterns of expression of the 938 genes most differentially expressed across the cortex organized the cortex into two sets of regions that match the two rings. We confirmed this result using discriminant correspondence analysis by showing that the genetic profiles of cortical regions can reliably predict to what ring these regions belong. We found that several of the proteins–coded by genes that most differentiate the rings–were involved in neuronal information processing such as ionic channels and neurotransmitter release. The systematic study of families of genes revealed specific proteins within families preferentially expressed in each ring. The results showed strong congruence between the preferential expression of subsets of genes, temporal properties of the proteins they code, and the preferred processing modes of the rings. Ionic channels and release-related proteins more expressed in the VSA ring favor temporal precision of fast evoked neural transmission (Sodium channels SCNA1, SCNB1 potassium channel KCNA1, calcium channel CACNA2D2, Synaptotagmin SYT2, Complexin CPLX1, Synaptobrevin VAMP1). Conversely, genes expressed in the PTF ring favor slower, sustained, or rhythmic activation (Sodium

  3. Large-scale sequencing and the natural history of model human RNA viruses

    PubMed Central

    Dugan, Vivien G; Saira, Kazima; Ghedin, Elodie

    2012-01-01

    RNA virus exploration within the field of medical virology has greatly benefited from technological developments in genomics, deepening our understanding of viral dynamics and emergence. Large-scale first-generation technology sequencing projects have expedited molecular epidemiology studies at an unprecedented scale for two pathogenic RNA viruses chosen as models: influenza A virus and dengue. Next-generation sequencing approaches are now leading to a more in-depth analysis of virus genetic diversity, which is greater for RNA than DNA viruses because of high replication rates and the absence of proofreading activity of the RNA-dependent RNA polymerase. In the field of virus discovery, technological advancements and metagenomic approaches are expanding the catalogs of novel viruses by facilitating our probing into the RNA virus world. PMID:23682295

  4. Facile large-scale synthesis of brain-like mesoporous silica nanocomposites via a selective etching process

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Wang, Qihua; Wang, Tingmei

    2015-10-01

    The core-shell structured mesoporous silica nanomaterials (MSNs) are experiencing rapid development in many applications such as heterogeneous catalysis, bio-imaging and drug delivery wherein a large pore volume is desirable. We develop a one-pot method for large-scale synthesis of brain-like mesoporous silica nanocomposites based on the reasonable change of the intrinsic nature of the -Si-O-Si- framework of silica nanoparticles together with a selective etching strategy. The as-synthesized products show good monodispersion and a large pore volume of 1.0 cm3 g-1. The novelty of this approach lies in the use of an inorganic-organic hybrid layer to assist the creation of large-pore morphology on the outermost shell thereby promoting efficient mass transfer or storage. Importantly, the method is reliable and grams of products can be easily prepared. The morphology on the outermost silica shell can be controlled by simply adjusting the VTES-to-TEOS molar ratio (VTES: triethoxyvinylsilane, TEOS: tetraethyl orthosilicate) as well as the etching time. The as-synthesized products exhibit fluorescence performance by incorporating rhodamine B isothiocyanate (RITC) covalently into the inner silica walls, which provide potential application in bioimaging. We also demonstrate the applications of as-synthesized large-pore structured nanocomposites in drug delivery systems and stimuli-responsive nanoreactors for heterogeneous catalysis.The core-shell structured mesoporous silica nanomaterials (MSNs) are experiencing rapid development in many applications such as heterogeneous catalysis, bio-imaging and drug delivery wherein a large pore volume is desirable. We develop a one-pot method for large-scale synthesis of brain-like mesoporous silica nanocomposites based on the reasonable change of the intrinsic nature of the -Si-O-Si- framework of silica nanoparticles together with a selective etching strategy. The as-synthesized products show good monodispersion and a large pore volume

  5. The optimization of large-scale density gradient isolation of human islets.

    PubMed

    Robertson, G S; Chadwick, D R; Contractor, H; James, R F; London, N J

    1993-01-01

    The use of the COBE 2991 cell processor (COBE Laboratories, Colorado) for large-scale islet purification using discontinuous density gradients has been widely adopted. It minimizes many of the problems such as wall effects, normally encountered during centrifugation, and avoids the vortexing at interfaces that occurs during acceleration and deceleration by allowing the gradient to be formed and the islet-containing interface to be collected while continuing to spin. We have produced cross-sectional profiles of the 2991 bag during spinning which allow the area of interfaces in such step gradients to be calculated. This allows the volumes of the gradient media layers loaded on the machine to be adjusted in order to maximize the area of the gradient interfaces. However, even using the maximal areas possible (144.5 cm2), clogging of tissue at such interfaces limits the volume of digest which can be separated on one gradient to 15 ml. We have shown that a linear continuous density gradient can be produced within the 2991 bag, that allows as much as 40 ml of digest to be successfully purified. Such a system combines the intrinsic advantages of the 2991 with those of continuous density gradients and provides the optimal method for density-dependent islet purification. PMID:8219265

  6. A 3D sphere culture system containing functional polymers for large-scale human pluripotent stem cell production.

    PubMed

    Otsuji, Tomomi G; Bin, Jiang; Yoshimura, Azumi; Tomura, Misayo; Tateyama, Daiki; Minami, Itsunari; Yoshikawa, Yoshihiro; Aiba, Kazuhiro; Heuser, John E; Nishino, Taito; Hasegawa, Kouichi; Nakatsuji, Norio

    2014-05-01

    Utilizing human pluripotent stem cells (hPSCs) in cell-based therapy and drug discovery requires large-scale cell production. However, scaling up conventional adherent cultures presents challenges of maintaining a uniform high quality at low cost. In this regard, suspension cultures are a viable alternative, because they are scalable and do not require adhesion surfaces. 3D culture systems such as bioreactors can be exploited for large-scale production. However, the limitations of current suspension culture methods include spontaneous fusion between cell aggregates and suboptimal passaging methods by dissociation and reaggregation. 3D culture systems that dynamically stir carrier beads or cell aggregates should be refined to reduce shearing forces that damage hPSCs. Here, we report a simple 3D sphere culture system that incorporates mechanical passaging and functional polymers. This setup resolves major problems associated with suspension culture methods and dynamic stirring systems and may be optimal for applications involving large-scale hPSC production. PMID:24936458

  7. Large-scale genomics unveil polygenic architecture of human cortical surface area.

    PubMed

    Chen, Chi-Hua; Peng, Qian; Schork, Andrew J; Lo, Min-Tzu; Fan, Chun-Chieh; Wang, Yunpeng; Desikan, Rahul S; Bettella, Francesco; Hagler, Donald J; Westlye, Lars T; Kremen, William S; Jernigan, Terry L; Le Hellard, Stephanie; Steen, Vidar M; Espeseth, Thomas; Huentelman, Matt; Håberg, Asta K; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole A; Schork, Nicholas; Dale, Anders M

    2015-01-01

    Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h(2)∼0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices. PMID:26189703

  8. Large-scale genomics unveil polygenic architecture of human cortical surface area

    PubMed Central

    Chen, Chi-Hua; Peng, Qian; Schork, Andrew J.; Lo, Min-Tzu; Fan, Chun-Chieh; Wang, Yunpeng; Desikan, Rahul S.; Bettella, Francesco; Hagler, Donald J.; McCabe, Connor; Chang, Linda; Akshoomoff, Natacha; Newman, Erik; Ernst, Thomas; Van Zijl, Peter; Kuperman, Joshua; Murray, Sarah; Bloss, Cinnamon; Appelbaum, Mark; Gamst, Anthony; Thompson, Wesley; Bartsch, Hauke; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack Jr, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Carrillo, Maria; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Mesulman, M. Marcel; Potter, William; Snyder, Peter J.; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia M.Y.; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Frank, Richard; Buckholtz, Neil; Albert, Marilyn; Hsiao, John; Westlye, Lars T.; Kremen, William S.; Jernigan, Terry L.; Hellard, Stephanie Le; Steen, Vidar M.; Espeseth, Thomas; Huentelman, Matt; Håberg, Asta K.; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole A.; Schork, Nicholas; Dale, Anders M.

    2015-01-01

    Little is known about how genetic variation contributes to neuroanatomical variability, and whether particular genomic regions comprising genes or evolutionarily conserved elements are enriched for effects that influence brain morphology. Here, we examine brain imaging and single-nucleotide polymorphisms (SNPs) data from ∼2,700 individuals. We show that a substantial proportion of variation in cortical surface area is explained by additive effects of SNPs dispersed throughout the genome, with a larger heritable effect for visual and auditory sensory and insular cortices (h2∼0.45). Genome-wide SNPs collectively account for, on average, about half of twin heritability across cortical regions (N=466 twins). We find enriched genetic effects in or near genes. We also observe that SNPs in evolutionarily more conserved regions contributed significantly to the heritability of cortical surface area, particularly, for medial and temporal cortical regions. SNPs in less conserved regions contributed more to occipital and dorsolateral prefrontal cortices. PMID:26189703

  9. Protein crystal growth in microgravity review of large scale temperature induction method: bovine insulin, human insulin and human alpha interferon

    NASA Astrophysics Data System (ADS)

    Long, Marianna M.; Bishop, John Bradford; Nagabhushan, Tattanahalli L.; Reichert, Paul; Smith, G. David; DeLucas, Lawrence J.

    1996-10-01

    The protein crystal growth facility (PCF) is space-flight hardware that accommodates large scale protein crystal growth experiments using temperature change as the inductive step. Recent modifications include specialized instrumentation for monitoring crystal nucleation with laser light scattering. This paper reviews results from the PCF's first seven flights on the Space Shuttle, the last with laser light scattering instrumentation. The PCF's objective is twofold: (1) production of high quality protein crystals for X-ray analysis and subsequent structure based drug design and (2) preparation of a large quantity of relatively contaminant free crystals for use as time-release protein pharmaceuticals. The first three Shuttle flights with bovine insulin constituted the PCF's proof of concept, demonstrating that the space-grown crystals were larger and diffracted to higher resolution than their earth-grown counterparts. The later four PCF missions were used to grow recombinant human insulin crystals for X-ray analysis and to continue productions trials aimed at the development of a processing facility for crystalline recombinant alpha interferon.

  10. The human footprint in the west: a large-scale analysis of anthropogenic impacts.

    PubMed

    Leu, Matthias; Hanser, Steven E; Knick, Steven T

    2008-07-01

    Anthropogenic features such as urbanization, roads, and power lines, are increasing in western United States landscapes in response to rapidly growing human populations. However, their spatial effects have not been evaluated. Our goal was to model the human footprint across the western United States. We first delineated the actual area occupied by anthropogenic features, the physical effect area. Next, we developed the human footprint model based on the ecological effect area, the zone influenced by features beyond their physical presence, by combining seven input models: three models quantified top-down anthropogenic influences of synanthropic predators (avian predators, domestic dog and cat presence risk), and four models quantified bottom-up anthropogenic influences on habitat (invasion of exotic plants, human-caused fires, energy extraction, and anthropogenic wildland fragmentation). Using independent bird population data, we found bird abundance of four synanthropic species to correlate positively with human footprint intensity and negatively for three of the six species influenced by habitat fragmentation. We then evaluated the extent of the human footprint in relation to terrestrial (ecoregions) and aquatic systems (major rivers and lakes), regional management and conservation status, physical environment, and temporal changes in human actions. The physical effect area of anthropogenic features covered 13% of the western United States with agricultural land (9.8%) being most dominant. High-intensity human footprint areas (class 8-10) overlapped highly productive low-elevation private landholdings and covered 7% of the western United States compared to 48% for low-intensity areas (class 1-3), which were confined to low-productivity high-elevation federal landholdings. Areas within 1 km of rivers were more affected by the human footprint compared to lakes. Percentage human population growth was higher in low-intensity human footprint areas. The disproportional

  11. Methods, caveats and the future of large-scale microelectrode recordings in the non-human primate

    PubMed Central

    Dotson, Nicholas M.; Goodell, Baldwin; Salazar, Rodrigo F.; Hoffman, Steven J.; Gray, Charles M.

    2015-01-01

    Cognitive processes play out on massive brain-wide networks, which produce widely distributed patterns of activity. Capturing these activity patterns requires tools that are able to simultaneously measure activity from many distributed sites with high spatiotemporal resolution. Unfortunately, current techniques with adequate coverage do not provide the requisite spatiotemporal resolution. Large-scale microelectrode recording devices, with dozens to hundreds of microelectrodes capable of simultaneously recording from nearly as many cortical and subcortical areas, provide a potential way to minimize these tradeoffs. However, placing hundreds of microelectrodes into a behaving animal is a highly risky and technically challenging endeavor that has only been pursued by a few groups. Recording activity from multiple electrodes simultaneously also introduces several statistical and conceptual dilemmas, such as the multiple comparisons problem and the uncontrolled stimulus response problem. In this perspective article, we discuss some of the techniques that we, and others, have developed for collecting and analyzing large-scale data sets, and address the future of this emerging field. PMID:26578906

  12. International Coordination of Large-Scale Human Induced Pluripotent Stem Cell Initiatives: Wellcome Trust and ISSCR Workshops White Paper

    PubMed Central

    Soares, Filipa A.C.; Sheldon, Michael; Rao, Mahendra; Mummery, Christine; Vallier, Ludovic

    2014-01-01

    There is growing recognition of the potential value of human induced pluripotent stem cells (hiPSC) for understanding disease and identifying drugs targets. This has been reflected in the establishment of multiple large-scale hiPSC initiatives worldwide. Representatives of these met recently at a workshop supported by the Welcome Trust in the UK and in a focus session at the 2014 ISSCR annual meeting in Vancouver. The purpose was to discuss strategies for making thousands of hiPSC lines widely available with as few restrictions as possible while retaining financial viability and donor privacy. The outcome of these discussions is described here. PMID:25496616

  13. Leveraging human oversight and intervention in large-scale parallel processing of open-source data

    NASA Astrophysics Data System (ADS)

    Casini, Enrico; Suri, Niranjan; Bradshaw, Jeffrey M.

    2015-05-01

    The popularity of cloud computing along with the increased availability of cheap storage have led to the necessity of elaboration and transformation of large volumes of open-source data, all in parallel. One way to handle such extensive volumes of information properly is to take advantage of distributed computing frameworks like Map-Reduce. Unfortunately, an entirely automated approach that excludes human intervention is often unpredictable and error prone. Highly accurate data processing and decision-making can be achieved by supporting an automatic process through human collaboration, in a variety of environments such as warfare, cyber security and threat monitoring. Although this mutual participation seems easily exploitable, human-machine collaboration in the field of data analysis presents several challenges. First, due to the asynchronous nature of human intervention, it is necessary to verify that once a correction is made, all the necessary reprocessing is done in chain. Second, it is often needed to minimize the amount of reprocessing in order to optimize the usage of resources due to limited availability. In order to improve on these strict requirements, this paper introduces improvements to an innovative approach for human-machine collaboration in the processing of large amounts of open-source data in parallel.

  14. An evolutionary theory of large-scale human warfare: Group-structured cultural selection.

    PubMed

    Zefferman, Matthew R; Mathew, Sarah

    2015-01-01

    When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group-structured cultural selection explains this phenomenon. PMID:25914359

  15. Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS.

    PubMed

    Varjosalo, Markku; Sacco, Roberto; Stukalov, Alexey; van Drogen, Audrey; Planyavsky, Melanie; Hauri, Simon; Aebersold, Ruedi; Bennett, Keiryn L; Colinge, Jacques; Gstaiger, Matthias; Superti-Furga, Giulio

    2013-04-01

    The characterization of all protein complexes of human cells under defined physiological conditions using affinity purification-mass spectrometry (AP-MS) is a highly desirable step in the quest to understand the phenotypic effects of genomic information. However, such a challenging goal has not yet been achieved, as it requires reproducibility of the experimental workflow and high data consistency across different studies and laboratories. We systematically investigated the reproducibility of a standardized AP-MS workflow by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human kinases. We show that it is possible to achieve high interlaboratory reproducibility of this standardized workflow despite differences in mass spectrometry configurations and subtle sample preparation-related variations and that combination of independent data sets improves the approach sensitivity, resulting in even more-detailed networks. Our analysis demonstrates the feasibility of obtaining a high-quality map of the human protein interactome with a multilaboratory project. PMID:23455922

  16. Culture rather than genes provides greater scope for the evolution of large-scale human prosociality

    PubMed Central

    Bell, Adrian V.; Richerson, Peter J.; McElreath, Richard

    2009-01-01

    Whether competition among large groups played an important role in human social evolution is dependent on how variation, whether cultural or genetic, is maintained between groups. Comparisons between genetic and cultural differentiation between neighboring groups show how natural selection on large groups is more plausible on cultural rather than genetic variation. PMID:19822753

  17. Variety in emotional life: within-category typicality of emotional experiences is associated with neural activity in large-scale brain networks

    PubMed Central

    Barrett, Lisa Feldman; Barsalou, Lawrence W.

    2015-01-01

    The tremendous variability within categories of human emotional experience receives little empirical attention. We hypothesized that atypical instances of emotion categories (e.g. pleasant fear of thrill-seeking) would be processed less efficiently than typical instances of emotion categories (e.g. unpleasant fear of violent threat) in large-scale brain networks. During a novel fMRI paradigm, participants immersed themselves in scenarios designed to induce atypical and typical experiences of fear, sadness or happiness (scenario immersion), and then focused on and rated the pleasant or unpleasant feeling that emerged (valence focus) in most trials. As predicted, reliably greater activity in the ‘default mode’ network (including medial prefrontal cortex and posterior cingulate) was observed for atypical (vs typical) emotional experiences during scenario immersion, suggesting atypical instances require greater conceptual processing to situate the socio-emotional experience. During valence focus, reliably greater activity was observed for atypical (vs typical) emotional experiences in the ‘salience’ network (including anterior insula and anterior cingulate), suggesting atypical instances place greater demands on integrating shifting body signals with the sensory and social context. Consistent with emerging psychological construction approaches to emotion, these findings demonstrate that is it important to study the variability within common categories of emotional experience. PMID:24563528

  18. Large-scale identification of sequence variants impacting human transcription factor occupancy in vivo

    PubMed Central

    Maurano, Matthew T.; Haugen, Eric; Sandstrom, Richard; Vierstra, Jeff; Shafer, Anthony; Kaul, Rajinder; Stamatoyannopoulos, John A.

    2015-01-01

    The function of human regulatory regions depends exquisitely on their local genomic environment and cellular context, complicating experimental analysis of the expanding pool of common disease- and trait-associated variants that localize within regulatory DNA. We leverage allelically resolved genomic DNaseI footprinting data encompassing 166 individuals and 114 cell types to identify >60,000 common variants that directly impact transcription factor occupancy and regulatory DNA accessibility in vivo. The unprecedented scale of these data enable systematic analysis of the impact of sequence variation on transcription factor occupancy in vivo. We leverage this analysis to develop accurate models of variation affecting the recognition sites for diverse transcription factors, and apply these models to discriminate nearly 500,000 common regulatory variants likely to affect transcription factor occupancy across the human genome. The approach and results provide a novel foundation for analysis and interpretation of noncoding variation in complete human genomes, and for systems-level investigation of disease-associated variants. PMID:26502339

  19. Large-scale CFD simulations of the transitional and turbulent regime for the large human airways during rapid inhalation.

    PubMed

    Calmet, Hadrien; Gambaruto, Alberto M; Bates, Alister J; Vázquez, Mariano; Houzeaux, Guillaume; Doorly, Denis J

    2016-02-01

    The dynamics of unsteady flow in the human large airways during a rapid inhalation were investigated using highly detailed large-scale computational fluid dynamics on a subject-specific geometry. The simulations were performed to resolve all the spatial and temporal scales of the flow, thanks to the use of massive computational resources. A highly parallel finite element code was used, running on two supercomputers, solving the transient incompressible Navier-Stokes equations on unstructured meshes. Given that the finest mesh contained 350 million elements, the study sets a precedent for large-scale simulations of the respiratory system, proposing an analysis strategy for mean flow, fluctuations and wall shear stresses on a rapid and short inhalation (a so-called sniff). The geometry used encompasses the exterior face and the airways from the nasal cavity, through the trachea and up to the third lung bifurcation; it was derived from a contrast-enhanced computed tomography (CT) scan of a 48-year-old male. The transient inflow produces complex flows over a wide range of Reynolds numbers (Re). Thanks to the high fidelity simulations, many features involving the flow transition were observed, with the level of turbulence clearly higher in the throat than in the nose. Spectral analysis revealed turbulent characteristics persisting downstream of the glottis, and were captured even with a medium mesh resolution. However a fine mesh resolution was found necessary in the nasal cavity to observe transitional features. This work indicates the potential of large-scale simulations to further understanding of airway physiological mechanics, which is essential to guide clinical diagnosis; better understanding of the flow also has implications for the design of interventions such as aerosol drug delivery. PMID:26773939

  20. Large-scale comparison of Liberase HI and collagenase NB1 utilized for human islet isolation.

    PubMed

    Brandhorst, H; Friberg, A; Nilsson, B; Andersson, H H; Felldin, M; Foss, A; Salmela, K; Tibell, A; Tufveson, G; Korsgren, O; Brandhorst, D

    2010-01-01

    For more than a decade Liberase HI was commonly used as the standard enzyme blend for clinical human islet isolation until enforced replacement by collagenase NB1 (NB1). This change resulted initially in a reduction in islet isolation outcome and transplant activities worldwide. This retrospective study was initiated to compare the efficiency of NB1 premium grade with Liberase in 197 human islet isolations. All pancreata were processed between January 2006 and June 2008 utilizing the same procedures for isolation and quality assessment except the administration of preselected lots of either Liberase (n = 101) or NB1 (n = 96). Utilizing Liberase, significantly more digested tissue and purified islet yield was produced compared to NB1. In contrast, the use of NB1 was associated with significantly higher purity and glucose stimulation index during dynamic perifusion. The expression of proinflammatory markers was almost identical except tissue factor expression, which was higher after utilization of Liberase. No difference was found in the percentage of pancreata fulfilling the criteria for clinical islet transplantation. The results suggest that Liberase is more efficient for pancreas dissociation than collagenase NB1 but seems to be more harmful to exocrine cells and islet tissue. PMID:19818208

  1. Large-scale analysis of tandem repeat variability in the human genome

    PubMed Central

    Duitama, Jorge; Zablotskaya, Alena; Gemayel, Rita; Jansen, An; Belet, Stefanie; Vermeesch, Joris R.; Verstrepen, Kevin J.; Froyen, Guy

    2014-01-01

    Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats can alter the function and/or expression of genes allowing organisms to swiftly adapt to novel environments. Importantly, some repeat expansions have also been linked to certain neurodegenerative diseases. Therefore, accurate sequencing of tandem repeats could contribute to our understanding of common phenotypic variability and might uncover missing genetic factors in idiopathic clinical conditions. However, despite long-standing evidence for the functional role of repeats, they are largely ignored because of technical limitations in sequencing, mapping and typing. Here, we report on a novel capture technique and data filtering protocol that allowed simultaneous sequencing of thousands of tandem repeats in the human genomes of a three generation family using GS-FLX-plus Titanium technology. Our results demonstrated that up to 7.6% of tandem repeats in this family (4% in coding sequences) differ from the reference sequence, and identified a de novo variation in the family tree. The method opens new routes to look at this underappreciated type of genetic variability, including the identification of novel disease-related repeats. PMID:24682812

  2. Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale.

    PubMed

    Cho, Myung-Soo; Hwang, Dong-Youn; Kim, Dong-Wook

    2008-01-01

    Cell-replacement therapy using human embryonic stem cells (hESCs) holds great promise in treating Parkinson's disease. We have recently reported a highly efficient method to generate functional dopaminergic (DA) neurons from hESCs. Our method includes a unique step, the formation of spherical neural masses (SNMs), and offers the highest yield of DA neurons ever achieved so far. In this report, we describe our method step by step, covering not only how to differentiate hESCs into DA neurons at a high yield, but also how to amplify, freeze and thaw the SNMs, which are the key structures that make our protocol unique and advantageous. Although the whole process of generation of DA neurons from hESCs takes about 2 months, only 14 d are needed to derive DA neurons from the SNMs. PMID:19008875

  3. Empirical distributions of F(ST) from large-scale human polymorphism data.

    PubMed

    Elhaik, Eran

    2012-01-01

    Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright's F(ST) that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F(ST) may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F(ST) analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F(ST) distribution closely follows an exponential distribution. Third, although the overall F(ST) distribution is similarly shaped (inverse J), F(ST) distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F(ST) of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F(ST) distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection

  4. A large-scale field assessment of carbon stocks in human-modified tropical forests.

    PubMed

    Berenguer, Erika; Ferreira, Joice; Gardner, Toby Alan; Aragão, Luiz Eduardo Oliveira Cruz; De Camargo, Plínio Barbosa; Cerri, Carlos Eduardo; Durigan, Mariana; Cosme De Oliveira Junior, Raimundo; Vieira, Ima Célia Guimarães; Barlow, Jos

    2014-12-01

    Tropical rainforests store enormous amounts of carbon, the protection of which represents a vital component of efforts to mitigate global climate change. Currently, tropical forest conservation, science, policies, and climate mitigation actions focus predominantly on reducing carbon emissions from deforestation alone. However, every year vast areas of the humid tropics are disturbed by selective logging, understory fires, and habitat fragmentation. There is an urgent need to understand the effect of such disturbances on carbon stocks, and how stocks in disturbed forests compare to those found in undisturbed primary forests as well as in regenerating secondary forests. Here, we present the results of the largest field study to date on the impacts of human disturbances on above and belowground carbon stocks in tropical forests. Live vegetation, the largest carbon pool, was extremely sensitive to disturbance: forests that experienced both selective logging and understory fires stored, on average, 40% less aboveground carbon than undisturbed forests and were structurally similar to secondary forests. Edge effects also played an important role in explaining variability in aboveground carbon stocks of disturbed forests. Results indicate a potential rapid recovery of the dead wood and litter carbon pools, while soil stocks (0-30 cm) appeared to be resistant to the effects of logging and fire. Carbon loss and subsequent emissions due to human disturbances remain largely unaccounted for in greenhouse gas inventories, but by comparing our estimates of depleted carbon stocks in disturbed forests with Brazilian government assessments of the total forest area annually disturbed in the Amazon, we show that these emissions could represent up to 40% of the carbon loss from deforestation in the region. We conclude that conservation programs aiming to ensure the long-term permanence of forest carbon stocks, such as REDD+, will remain limited in their success unless they effectively

  5. Large-scale identification of human genes implicated in epidermal barrier function

    PubMed Central

    Toulza, Eve; Mattiuzzo, Nicolas R; Galliano, Marie-Florence; Jonca, Nathalie; Dossat, Carole; Jacob, Daniel; de Daruvar, Antoine; Wincker, Patrick; Serre, Guy; Guerrin, Marina

    2007-01-01

    Background During epidermal differentiation, keratinocytes progressing through the suprabasal layers undergo complex and tightly regulated biochemical modifications leading to cornification and desquamation. The last living cells, the granular keratinocytes (GKs), produce almost all of the proteins and lipids required for the protective barrier function before their programmed cell death gives rise to corneocytes. We present here the first analysis of the transcriptome of human GKs, purified from healthy epidermis by an original approach. Results Using the ORESTES method, 22,585 expressed sequence tags (ESTs) were produced that matched 3,387 genes. Despite normalization provided by this method (mean 4.6 ORESTES per gene), some highly transcribed genes, including that encoding dermokine, were overrepresented. About 330 expressed genes displayed less than 100 ESTs in UniGene clusters and are most likely to be specific for GKs and potentially involved in barrier function. This hypothesis was tested by comparing the relative expression of 73 genes in the basal and granular layers of epidermis by quantitative RT-PCR. Among these, 33 were identified as new, highly specific markers of GKs, including those encoding a protease, protease inhibitors and proteins involved in lipid metabolism and transport. We identified filaggrin 2 (also called ifapsoriasin), a poorly characterized member of the epidermal differentiation complex, as well as three new lipase genes clustered with paralogous genes on chromosome 10q23.31. A new gene of unknown function, C1orf81, is specifically disrupted in the human genome by a frameshift mutation. Conclusion These data increase the present knowledge of genes responsible for the formation of the skin barrier and suggest new candidates for genodermatoses of unknown origin. PMID:17562024

  6. Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires.

    PubMed

    DeKosky, Brandon J; Lungu, Oana I; Park, Daechan; Johnson, Erik L; Charab, Wissam; Chrysostomou, Constantine; Kuroda, Daisuke; Ellington, Andrew D; Ippolito, Gregory C; Gray, Jeffrey J; Georgiou, George

    2016-05-10

    Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19(+)CD20(+)CD27(-) IgM-naive B cells, >120,000 antibody clusters from CD19(+)CD20(+)CD27(+) antigen-experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ-Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease. PMID:27114511

  7. Large-Scale Production and Structural and Biophysical Characterizations of the Human Hepatitis B Virus Polymerase

    PubMed Central

    Vörös, Judit; Urbanek, Annika; Rautureau, Gilles Jean Philippe; O'Connor, Maggie; Fisher, Henry C.; Ashcroft, Alison E.

    2014-01-01

    ABSTRACT Hepatitis B virus (HBV) is a major human pathogen that causes serious liver disease and 600,000 deaths annually. Approved therapies for treating chronic HBV infections usually target the multifunctional viral polymerase (hPOL). Unfortunately, these therapies—broad-spectrum antivirals—are not general cures, have side effects, and cause viral resistance. While hPOL remains an attractive therapeutic target, it is notoriously difficult to express and purify in a soluble form at yields appropriate for structural studies. Thus, no empirical structural data exist for hPOL, and this impedes medicinal chemistry and rational lead discovery efforts targeting HBV. Here, we present an efficient strategy to overexpress recombinant hPOL domains in Escherichia coli, purifying them at high yield and solving their known aggregation tendencies. This allowed us to perform the first structural and biophysical characterizations of hPOL domains. Apo-hPOL domains adopt mainly α-helical structures with small amounts of β-sheet structures. Our recombinant material exhibited metal-dependent, reverse transcriptase activity in vitro, with metal binding modulating the hPOL structure. Calcomine orange 2RS, a small molecule that inhibits duck HBV POL activity, also inhibited the in vitro priming activity of recombinant hPOL. Our work paves the way for structural and biophysical characterizations of hPOL and should facilitate high-throughput lead discovery for HBV. IMPORTANCE The viral polymerase from human hepatitis B virus (hPOL) is a well-validated therapeutic target. However, recombinant hPOL has a well-deserved reputation for being extremely difficult to express in a soluble, active form in yields appropriate to the structural studies that usually play an important role in drug discovery programs. This has hindered the development of much-needed new antivirals for HBV. However, we have solved this problem and report here procedures for expressing recombinant hPOL domains in

  8. Elucidating Common Structural Features of Human Pathogenic Variations Using Large-Scale Atomic-Resolution Protein Networks

    PubMed Central

    Das, Jishnu; Lee, Hao Ran; Sagar, Adithya; Fragoza, Robert; Liang, Jin; Wei, Xiaomu; Wang, Xiujuan; Mort, Matthew; Stenson, Peter D.; Cooper, David N.; Yu, Haiyuan

    2016-01-01

    With the rapid growth of structural genomics, numerous protein crystal structures have become available. However, the parallel increase in knowledge of the functional principles underlying biological processes, and more specifically the underlying molecular mechanisms of disease, has been less dramatic. This notwithstanding, the study of complex cellular networks has made possible the inference of protein functions on a large scale. Here, we combine the scale of network systems biology with the resolution of traditional structural biology to generate a large-scale atomic-resolution interactome-network comprising 3,398 interactions between 2,890 proteins with a well-defined interaction interface and interface residues for each interaction. Within the framework of this atomic-resolution network, we have explored the structural principles underlying variations causing human-inherited disease. We find that in-frame pathogenic variations are enriched at both the interface and in the interacting domain, suggesting that variations not only at interface “hot-spots,” but in the entire interacting domain can result in alterations of interactions. Further, the sites of pathogenic variations are closely related to the biophysical strength of the interactions they perturb. Finally, we show that biochemical alterations consequent to these variations are considerably more disruptive than evolutionary changes, with the most significant alterations at the protein interaction interface. PMID:24599843

  9. Large-scale discovery of insertion hotspots and preferential integration sites of human transposed elements

    PubMed Central

    Levy, Asaf; Schwartz, Schraga; Ast, Gil

    2010-01-01

    Throughout evolution, eukaryotic genomes have been invaded by transposable elements (TEs). Little is known about the factors leading to genomic proliferation of TEs, their preferred integration sites and the molecular mechanisms underlying their insertion. We analyzed hundreds of thousands nested TEs in the human genome, i.e. insertions of TEs into existing ones. We first discovered that most TEs insert within specific ‘hotspots’ along the targeted TE. In particular, retrotransposed Alu elements contain a non-canonical single nucleotide hotspot for insertion of other Alu sequences. We next devised a method for identification of integration sequence motifs of inserted TEs that are conserved within the targeted TEs. This method revealed novel sequences motifs characterizing insertions of various important TE families: Alu, hAT, ERV1 and MaLR. Finally, we performed a global assessment to determine the extent to which young TEs tend to nest within older transposed elements and identified a 4-fold higher tendency of TEs to insert into existing TEs than to insert within non-TE intergenic regions. Our analysis demonstrates that TEs are highly biased to insert within certain TEs, in specific orientations and within specific targeted TE positions. TE nesting events also reveal new characteristics of the molecular mechanisms underlying transposition. PMID:20008508

  10. Large-scale production of bioactive recombinant human acidic fibroblast growth factor in transgenic silkworm cocoons

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Wang, Riyuan; Wang, Yuancheng; Zhao, Ping; Xia, Qingyou

    2015-11-01

    With an increasing clinical demand for functional therapeutic proteins every year, there is an increasing requirement for the massive production of bioactive recombinant human acidic fibroblast growth factor (r-haFGF). In this present study, we delicately explore a strategy for the mass production of r-haFGF protein with biological activity in the transgenic silkworm cocoons. The sequence-optimized haFGF was inserted into an enhanced sericin-1 expression system to generate the original transgenic silkworm strain, which was then further crossed with a PIG jumpstarter strain to achieve the remobilization of the expression cassette to a “safe harbor” locus in the genome for the efficient expression of r-haFGF. In consequence, the expression of r-haFGF protein in the mutant line achieved a 5.6-fold increase compared to the original strain. The high content of r-haFGF facilitated its purification and large-scald yields. Furthermore, the r-haFGF protein bioactively promoted the growth, proliferation and migration of NIH/3T3 cells, suggesting the r-haFGF protein possessed native mitogenic activity and the potential for wound healing. These results show that the silk gland of silkworm could be an efficient bioreactor strategy for recombinant production of bioactive haFGF in silkworm cocoons.

  11. Large-scale production of bioactive recombinant human acidic fibroblast growth factor in transgenic silkworm cocoons

    PubMed Central

    Wang, Feng; Wang, Riyuan; Wang, Yuancheng; Zhao, Ping; Xia, Qingyou

    2015-01-01

    With an increasing clinical demand for functional therapeutic proteins every year, there is an increasing requirement for the massive production of bioactive recombinant human acidic fibroblast growth factor (r-haFGF). In this present study, we delicately explore a strategy for the mass production of r-haFGF protein with biological activity in the transgenic silkworm cocoons. The sequence-optimized haFGF was inserted into an enhanced sericin-1 expression system to generate the original transgenic silkworm strain, which was then further crossed with a PIG jumpstarter strain to achieve the remobilization of the expression cassette to a “safe harbor” locus in the genome for the efficient expression of r-haFGF. In consequence, the expression of r-haFGF protein in the mutant line achieved a 5.6-fold increase compared to the original strain. The high content of r-haFGF facilitated its purification and large-scald yields. Furthermore, the r-haFGF protein bioactively promoted the growth, proliferation and migration of NIH/3T3 cells, suggesting the r-haFGF protein possessed native mitogenic activity and the potential for wound healing. These results show that the silk gland of silkworm could be an efficient bioreactor strategy for recombinant production of bioactive haFGF in silkworm cocoons. PMID:26567460

  12. Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses

    PubMed Central

    Snijder, Berend; Samperio Ventayol, Pilar; Kühbacher, Andreas; Becker, Miriam; Day, Patricia M.; Schiller, John T.; Kann, Michael; Pelkmans, Lucas; Helenius, Ari; Schelhaas, Mario

    2014-01-01

    A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies. PMID:24874089

  13. Large-scale production of bioactive recombinant human acidic fibroblast growth factor in transgenic silkworm cocoons.

    PubMed

    Wang, Feng; Wang, Riyuan; Wang, Yuancheng; Zhao, Ping; Xia, Qingyou

    2015-01-01

    With an increasing clinical demand for functional therapeutic proteins every year, there is an increasing requirement for the massive production of bioactive recombinant human acidic fibroblast growth factor (r-haFGF). In this present study, we delicately explore a strategy for the mass production of r-haFGF protein with biological activity in the transgenic silkworm cocoons. The sequence-optimized haFGF was inserted into an enhanced sericin-1 expression system to generate the original transgenic silkworm strain, which was then further crossed with a PIG jumpstarter strain to achieve the remobilization of the expression cassette to a "safe harbor" locus in the genome for the efficient expression of r-haFGF. In consequence, the expression of r-haFGF protein in the mutant line achieved a 5.6-fold increase compared to the original strain. The high content of r-haFGF facilitated its purification and large-scald yields. Furthermore, the r-haFGF protein bioactively promoted the growth, proliferation and migration of NIH/3T3 cells, suggesting the r-haFGF protein possessed native mitogenic activity and the potential for wound healing. These results show that the silk gland of silkworm could be an efficient bioreactor strategy for recombinant production of bioactive haFGF in silkworm cocoons. PMID:26567460

  14. Large scale RNAi reveals the requirement of nuclear envelope breakdown for nuclear import of human papillomaviruses.

    PubMed

    Aydin, Inci; Weber, Susanne; Snijder, Berend; Samperio Ventayol, Pilar; Kühbacher, Andreas; Becker, Miriam; Day, Patricia M; Schiller, John T; Kann, Michael; Pelkmans, Lucas; Helenius, Ari; Schelhaas, Mario

    2014-05-01

    A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies. PMID:24874089

  15. Bioprocessing of cryopreservation for large-scale banking of human pluripotent stem cells.

    PubMed

    Li, Yan; Ma, Teng

    2012-10-01

    Human pluripotent stem cell (hPSC)-derived cell therapy requires production of therapeutic cells in large quantity, which starts from thawing the cryopreserved cells from a working cell bank or a master cell bank. An optimal cryopreservation and thaw process determines the efficiency of hPSC expansion and plays a significant role in the subsequent lineage-specific differentiation. However, cryopreservation in hPSC bioprocessing has been a challenge due to the unique growth requirements of hPSC, the sensitivity to cryoinjury, and the unscalable cryopreservation procedures commonly used in the laboratory. Tremendous progress has been made to identify the regulatory pathways regulating hPSC responses during cryopreservation and the development of small molecule interventions that effectively improves the efficiency of cryopreservation. The adaption of these methods in current good manufacturing practices (cGMP)-compliant cryopreservation processes not only improves cell survival, but also their therapeutic potency. This review summarizes the advances in these areas and discusses the technical requirements in the development of cGMP-compliant hPSC cryopreservation process. PMID:23515461

  16. Bioprocessing of Cryopreservation for Large-Scale Banking of Human Pluripotent Stem Cells

    PubMed Central

    Ma, Teng

    2012-01-01

    Abstract Human pluripotent stem cell (hPSC)-derived cell therapy requires production of therapeutic cells in large quantity, which starts from thawing the cryopreserved cells from a working cell bank or a master cell bank. An optimal cryopreservation and thaw process determines the efficiency of hPSC expansion and plays a significant role in the subsequent lineage-specific differentiation. However, cryopreservation in hPSC bioprocessing has been a challenge due to the unique growth requirements of hPSC, the sensitivity to cryoinjury, and the unscalable cryopreservation procedures commonly used in the laboratory. Tremendous progress has been made to identify the regulatory pathways regulating hPSC responses during cryopreservation and the development of small molecule interventions that effectively improves the efficiency of cryopreservation. The adaption of these methods in current good manufacturing practices (cGMP)-compliant cryopreservation processes not only improves cell survival, but also their therapeutic potency. This review summarizes the advances in these areas and discusses the technical requirements in the development of cGMP-compliant hPSC cryopreservation process. PMID:23515461

  17. A microfluidic platform for generating large-scale nearly identical human microphysiological system arrays

    PubMed Central

    Hsu, Yu-Hsiang; Moya, Monica L.; Hughes, Christopher C.W.; Georgea, Steven C.; Lee, Abraham P.

    2013-01-01

    This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance > 50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development. PMID:23723013

  18. Large-scale probabilistic 3D organization of human chromosome territories.

    PubMed

    Sehgal, Nitasha; Fritz, Andrew J; Vecerova, Jaromira; Ding, Hu; Chen, Zihe; Stojkovic, Branislav; Bhattacharya, Sambit; Xu, Jinhui; Berezney, Ronald

    2016-02-01

    There is growing evidence that chromosome territories (CT) have a probabilistic non-random arrangement within the cell nucleus of mammalian cells including radial positioning and preferred patterns of interchromosomal interactions that are cell-type specific. While it is generally assumed that the three-dimensional (3D) arrangement of genes within the CT is linked to genomic regulation, the degree of non-random organization of individual CT remains unclear. As a first step to elucidating the global 3D organization (topology) of individual CT, we performed multi-color fluorescence in situ hybridization using six probes extending across each chromosome in human WI38 lung fibroblasts. Six CT were selected ranging in size and gene density (1, 4, 12, 17, 18 and X). In-house computational geometric algorithms were applied to measure the 3D distances between every combination of probes and to elucidate data-mined structural patterns. Our findings demonstrate a high degree of non-random arrangement of individual CT that vary from chromosome to chromosome and display distinct changes during the cell cycle. Application of a classic, well-defined data mining and pattern recognition approach termed the 'k-means' generated 3D models for the best fit arrangement of each chromosome. These predicted models correlated well with the detailed distance measurements and analysis. We propose that the unique 3D topology of each CT and characteristic changes during the cell cycle provide the structural framework for the global gene expression programs of the individual chromosomes. PMID:26604142

  19. A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays.

    PubMed

    Hsu, Yu-Hsiang; Moya, Monica L; Hughes, Christopher C W; George, Steven C; Lee, Abraham P

    2013-08-01

    This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance >50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development. PMID:23723013

  20. Large-scale assembly of highly sensitive Si-based flexible strain sensors for human motion monitoring.

    PubMed

    Zhang, Bing-Chang; Wang, Hui; Zhao, Yu; Li, Fan; Ou, Xue-Mei; Sun, Bao-Quan; Zhang, Xiao-Hong

    2016-01-28

    Silicon is the dominant semiconductor in modern society, but the rigid nature of most Si structures hinders its applications in flexible electronics. In this work, Si-based flexible strain sensors are fabricated with Si fabric consisting of long Si nanowires. The as-obtained sensors demonstrate a large strain range of 50% and a gauge factor of up to 350, which are sufficient to detect human motions with superior performance over traditional sensors. The results reveal that the assembling strategy may potentially be applied to large-scale fabrication of highly sensitive, flexible strain sensors for emerging applications such as healthcare and sports monitoring. Moreover, the Si fabric would also enable broad applications of Si materials in other flexible and wearable devices such as flexible optoelectronics and displays. PMID:26725832

  1. Large-scale assembly of highly sensitive Si-based flexible strain sensors for human motion monitoring

    NASA Astrophysics Data System (ADS)

    Zhang, Bing-Chang; Wang, Hui; Zhao, Yu; Li, Fan; Ou, Xue-Mei; Sun, Bao-Quan; Zhang, Xiao-Hong

    2016-01-01

    Silicon is the dominant semiconductor in modern society, but the rigid nature of most Si structures hinders its applications in flexible electronics. In this work, Si-based flexible strain sensors are fabricated with Si fabric consisting of long Si nanowires. The as-obtained sensors demonstrate a large strain range of 50% and a gauge factor of up to 350, which are sufficient to detect human motions with superior performance over traditional sensors. The results reveal that the assembling strategy may potentially be applied to large-scale fabrication of highly sensitive, flexible strain sensors for emerging applications such as healthcare and sports monitoring. Moreover, the Si fabric would also enable broad applications of Si materials in other flexible and wearable devices such as flexible optoelectronics and displays.Silicon is the dominant semiconductor in modern society, but the rigid nature of most Si structures hinders its applications in flexible electronics. In this work, Si-based flexible strain sensors are fabricated with Si fabric consisting of long Si nanowires. The as-obtained sensors demonstrate a large strain range of 50% and a gauge factor of up to 350, which are sufficient to detect human motions with superior performance over traditional sensors. The results reveal that the assembling strategy may potentially be applied to large-scale fabrication of highly sensitive, flexible strain sensors for emerging applications such as healthcare and sports monitoring. Moreover, the Si fabric would also enable broad applications of Si materials in other flexible and wearable devices such as flexible optoelectronics and displays. Electronic supplementary information (ESI) available: The morphological and structural characterization of the silicon nanowires, the plot of the relative resistance change versus cubic strain, and the relationship between the width of the gap and the exerted strain. See DOI: 10.1039/c5nr07546g

  2. Large scale cultivation of an anti-D (IgM) antibody producing human/mouse heterohybridoma.

    PubMed

    Fizil, A; Hencsey, Z; Veszely, G; Inzelt-Kovács, M; Bánkúti, L

    1996-01-01

    A human/mouse heterohybridoma cell line secreting anti-Rh(D) antibody was established by the fusion of Epstein-Barr Virus (EBV) transformed human B lymphocytes and human/mouse heteromyelomas. During scaling-up the cell line was adapted to suspension culture, then medium composition was gradually altered into a more economical one. The adapted cell line has kept its multiplication and antibody secreting characteristics in the new medium. Parameters of large scale batch cultivation in bioreactors were optimized in working volume of 3.6 litre and production was carried out under these parameters in working volume of 24 litre. Optimized parameters were the follows: (i) the cell line is highly sensitive to dissolved oxygen (DO) level, its optimal DO is 10%; (ii) optimal inoculum cell count is 3 x 10(5) cell/ml; (iii) Marine-blade impeller was chosen for supporting the requested oxygen transfer. Using the optimized parameters HUMAN Co. Ltd. produces the Monoclonal Anti-D (IgM) reagent, which has been registered in 1995 in Hungary and now it is on the market. PMID:9147726

  3. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

    PubMed Central

    Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  4. Complex-system causality in large-scale brain networks. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Pessoa, Luiz; Najafi, Mahshid

    2015-12-01

    Mannino and Bressler [1] discuss foundational issues related to understating causality in a complex system such as the brain. We largely agree with their main point that standard versions of causality, such as those espoused in classical physics, provide an inadequate basis to support the understanding of complex systems. In a nutshell, instead of thinking that one event causes another, it is more fruitful to think that the occurrence of one event changes the probability of occurrence of other events. Such probabilistic notion of causation is, we believe, an important step in attempting to unravel the workings of the brain.

  5. XLID-Causing Mutations and Associated Genes Challenged in Light of Data From Large-Scale Human Exome Sequencing

    PubMed Central

    Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

    2013-01-01

    Because of the unbalanced sex ratio (1.3–1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. PMID:23871722

  6. Managing and analysing data from a large-scale study on Framingham Offspring relating brain structure to cognitive function.

    PubMed

    Massaro, Joseph M; D'Agostino, Ralph B; Sullivan, Lisa M; Beiser, Alexa; DeCarli, Charles; Au, Rhoda; Elias, Merrill F; Wolf, Philip A

    2004-01-30

    At the Framingham Heart Study under separate research grant funding from the National Institute of Aging, NIH, we are gathering brain structure and cognitive information on the Framingham Offspring, creating one of the largest known data sets to assess changes in brain structure associated with normative ageing and cognitive decline. Subject recruitment, data collection, data management and statistical analysis require a collaborative integrated effort on the part of the Framingham project team. Here we describe this effort, as well as the various brain structure and cognitive function parameters we are now collecting. We are currently performing analyses of data collected through 2002, and we discuss the statistical issues arising relating brain structure parameters to cognitive function. PMID:14716734

  7. Stochastic causality, criticality, and non-locality in brain networks. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Kozma, Robert; Hu, Sanqing

    2015-12-01

    For millennia, causality served as a powerful guiding principle to our understanding of natural processes, including the functioning of our body, mind, and brain. The target paper presents an impressive vista of the field of causality in brain networks, starting from philosophical issues, expanding on neuroscience effects, and addressing broad engineering and societal aspects as well. The authors conclude that the concept of stochastic causality is more suited to characterize the experimentally observed complex dynamical processes in large-scale brain networks, rather than the more traditional view of deterministic causality. We strongly support this conclusion and provide two additional examples that may enhance and complement this review: (i) a generalization of the Wiener-Granger Causality (WGC) to fit better the complexity of brain networks; (ii) employment of criticality as a key concept highly relevant to interpreting causality and non-locality in large-scale brain networks.

  8. Large-scale functional brain network changes in taxi drivers: evidence from resting-state fMRI.

    PubMed

    Wang, Lubin; Liu, Qiang; Shen, Hui; Li, Hong; Hu, Dewen

    2015-03-01

    Driving a car in the environment is a complex behavior that involves cognitive processing of visual information to generate the proper motor outputs and action controls. Previous neuroimaging studies have used virtual simulation to identify the brain areas that are associated with various driving-related tasks. Few studies, however, have focused on the specific patterns of functional organization in the driver's brain. The aim of this study was to assess differences in the resting-state networks (RSNs) of the brains of drivers and nondrivers. Forty healthy subjects (20 licensed taxi drivers, 20 nondrivers) underwent an 8-min resting-state functional MRI acquisition. Using independent component analysis, three sensory (primary and extrastriate visual, sensorimotor) RSNs and four cognitive (anterior and posterior default mode, left and right frontoparietal) RSNs were retrieved from the data. We then examined the group differences in the intrinsic brain activity of each RSN and in the functional network connectivity (FNC) between the RSNs. We found that the drivers had reduced intrinsic brain activity in the visual RSNs and reduced FNC between the sensory RSNs compared with the nondrivers. The major finding of this study, however, was that the FNC between the cognitive and sensory RSNs became more positively or less negatively correlated in the drivers relative to that in the nondrivers. Notably, the strength of the FNC between the left frontoparietal and primary visual RSNs was positively correlated with the number of taxi-driving years. Our findings may provide new insight into how the brain supports driving behavior. PMID:25338709

  9. Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI

    PubMed Central

    Peña-Gómez, Cleofé; Sala-Lonch, Roser; Junqué, Carme; Clemente, Immaculada C.; Vidal, Dídac; Bargalló, Núria; Falcón, Carles; Valls-Solé, Josep; Pascual-Leone, Álvaro; Bartrés-Faz, David

    2013-01-01

    Background Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. Objective We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. Methods Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). Results After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. Conclusions Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands. PMID:21962981

  10. The integration of large-scale neural network modeling and functional brain imaging in speech motor control

    PubMed Central

    Golfinopoulos, E.; Tourville, J.A.; Guenther, F.H.

    2009-01-01

    Speech production demands a number of integrated processing stages. The system must encode the speech motor programs that command movement trajectories of the articulators and monitor transient spatiotemporal variations in auditory and somatosensory feedback. Early models of this system proposed that independent neural regions perform specialized speech processes. As technology advanced, neuroimaging data revealed that the dynamic sensorimotor processes of speech require a distributed set of interacting neural regions. The DIVA (Directions into Velocities of Articulators) neurocomputational model elaborates on early theories, integrating existing data and contemporary ideologies, to provide a mechanistic account of acoustic, kinematic, and functional magnetic resonance imaging (fMRI) data on speech acquisition and production. This large-scale neural network model is composed of several interconnected components whose cell activities and synaptic weight strengths are governed by differential equations. Cells in the model are associated with neuroanatomical substrates and have been mapped to locations in Montreal Neurological Institute stereotactic space, providing a means to compare simulated and empirical fMRI data. The DIVA model also provides a computational and neurophysiological framework within which to interpret and organize research on speech acquisition and production in fluent and dysfluent child and adult speakers. The purpose of this review article is to demonstrate how the DIVA model is used to motivate and guide functional imaging studies. We describe how model predictions are evaluated using voxel-based, region-of-interest-based parametric analyses and inter-regional effective connectivity modeling of fMRI data. PMID:19837177

  11. Large-Scale Absence of Sharks on Reefs in the Greater-Caribbean: A Footprint of Human Pressures

    PubMed Central

    Ward-Paige, Christine A.; Mora, Camilo; Lotze, Heike K.; Pattengill-Semmens, Christy; McClenachan, Loren; Arias-Castro, Ery

    2010-01-01

    Background In recent decades, large pelagic and coastal shark populations have declined dramatically with increased fishing; however, the status of sharks in other systems such as coral reefs remains largely unassessed despite a long history of exploitation. Here we explore the contemporary distribution and sighting frequency of sharks on reefs in the greater-Caribbean and assess the possible role of human pressures on observed patterns. Methodology/Principal Findings We analyzed 76,340 underwater surveys carried out by trained volunteer divers between 1993 and 2008. Surveys were grouped within one km2 cells, which allowed us to determine the contemporary geographical distribution and sighting frequency of sharks. Sighting frequency was calculated as the ratio of surveys with sharks to the total number of surveys in each cell. We compared sighting frequency to the number of people in the cell vicinity and used population viability analyses to assess the effects of exploitation on population trends. Sharks, with the exception of nurse sharks occurred mainly in areas with very low human population or strong fishing regulations and marine conservation. Population viability analysis suggests that exploitation alone could explain the large-scale absence; however, this pattern is likely to be exacerbated by additional anthropogenic stressors, such as pollution and habitat degradation, that also correlate with human population. Conclusions/Significance Human pressures in coastal zones have lead to the broad-scale absence of sharks on reefs in the greater-Caribbean. Preventing further loss of sharks requires urgent management measures to curb fishing mortality and to mitigate other anthropogenic stressors to protect sites where sharks still exist. The fact that sharks still occur in some densely populated areas where strong fishing regulations are in place indicates the possibility of success and encourages the implementation of conservation measures. PMID:20700530

  12. Stable, continuous large-scale production of human monoclonal HIV-1 antibody using a computer-controlled pilot plant.

    PubMed

    Unterluggauer, F; Doblhoff-Dier, O; Tauer, C; Jungbauer, A; Gaida, T; Reiter, M; Schmatz, C; Zach, N; Katinger, H

    1994-01-01

    A completely automated pilot plant used for fermentation has been employed with direct digital control (DDC) technology for monitoring and regulating growth of human cells. A human hybridoma cell line (3D6) producing anti-human immunodeficiency virus (HIV)-1 antibodies was used as a model for large-scale production (300-liter airlift fermentor) in continuous culture. Parameters controlled were pH, dissolved oxygen, temperature and the flow rate of four gases used in the process. A control strategy was implemented to achieve constant fluid velocity and mixing by maintaining the rate of gas flow at a constant level. Another advantage of this approach was that the total gas flow required for optimal fluid circulation was reduced from 1 volume gas/volume fermenter/hour (vvh) to 0.3 vvh. Use of a low flow rate eliminated the serious problems of foaming, which contributed significantly to cell destruction, shorter filter-life and other considerations. Dilution rate was optimized at laboratory scale for maximum productivity, which results in relatively low viability. At a dilution rate of 0.0076 h-1, a total cell density of 6-7 x 10(5) cells/ml with a viability of approximately 75% was maintained during long-term continuous cultivation. These growth conditions resulted in a product titer stabilized in the range of 35 micrograms IgG/ml. Batchwise purification was achieved with a recovery of more than 50% and a final purification of active monoclonal antibody representing about 99% product. Results from isoelectric focusing and Western blotting demonstrated batch-to-batch consistency of the purified human monoclonal antibody to HIV-1 during the continuous growth process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8136128

  13. In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses

    PubMed Central

    Bonifazi, Paolo; Difato, Francesco; Massobrio, Paolo; Breschi, Gian L.; Pasquale, Valentina; Levi, Timothée; Goldin, Miri; Bornat, Yannick; Tedesco, Mariateresa; Bisio, Marta; Kanner, Sivan; Galron, Ronit; Tessadori, Jacopo; Taverna, Stefano; Chiappalone, Michela

    2013-01-01

    Brain-machine interfaces (BMI) were born to control “actions from thoughts” in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI—a neuromorphic chip for brain repair—to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary “bottom-up” approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of “finite size networks” which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented. PMID:23503997

  14. Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties

    PubMed Central

    Hosseini, S.M. Hadi; Black, Jessica M.; Soriano, Teresa; Bugescu, Nicolle; Martinez, Rociel; Raman, Mira M.; Kesler, Shelli R.; Hoeft, Fumiko

    2013-01-01

    Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graphtheoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH−) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome. PMID:23333415

  15. Large-Scale Hematopoietic Differentiation of Human Induced Pluripotent Stem Cells Provides Granulocytes or Macrophages for Cell Replacement Therapies

    PubMed Central

    Lachmann, Nico; Ackermann, Mania; Frenzel, Eileen; Liebhaber, Steffi; Brennig, Sebastian; Happle, Christine; Hoffmann, Dirk; Klimenkova, Olga; Lüttge, Doreen; Buchegger, Theresa; Kühnel, Mark Philipp; Schambach, Axel; Janciauskiene, Sabina; Figueiredo, Constanca; Hansen, Gesine; Skokowa, Julia; Moritz, Thomas

    2015-01-01

    Summary Interleukin-3 (IL-3) is capable of supporting the proliferation of a broad range of hematopoietic cell types, whereas granulocyte colony-stimulating factor (G-CSF) and macrophage CSF (M-CSF) represent critical cytokines in myeloid differentiation. When this was investigated in a pluripotent-stem-cell-based hematopoietic differentiation model, IL-3/G-CSF or IL-3/M-CSF exposure resulted in the continuous generation of myeloid cells from an intermediate myeloid-cell-forming complex containing CD34+ clonogenic progenitor cells for more than 2 months. Whereas IL-3/G-CSF directed differentiation toward CD45+CD11b+CD15+CD16+CD66b+ granulocytic cells of various differentiation stages up to a segmented morphology displaying the capacity of cytokine-directed migration, respiratory burst response, and neutrophil-extracellular-trap formation, exposure to IL-3/M-CSF resulted in CD45+CD11b+CD14+CD163+CD68+ monocyte/macrophage-type cells capable of phagocytosis and cytokine secretion. Hence, we show here that myeloid specification of human pluripotent stem cells by IL-3/G-CSF or IL-3/M-CSF allows for prolonged and large-scale production of myeloid cells, and thus is suited for cell-fate and disease-modeling studies as well as gene- and cell-therapy applications. PMID:25680479

  16. Spatial Fingerprints of Community Structure in Human Interaction Network for an Extensive Set of Large-Scale Regions

    PubMed Central

    Kallus, Zsófia; Barankai, Norbert; Szüle, János; Vattay, Gábor

    2015-01-01

    Human interaction networks inferred from country-wide telephone activity recordings were recently used to redraw political maps by projecting their topological partitions into geographical space. The results showed remarkable spatial cohesiveness of the network communities and a significant overlap between the redrawn and the administrative borders. Here we present a similar analysis based on one of the most popular online social networks represented by the ties between more than 5.8 million of its geo-located users. The worldwide coverage of their measured activity allowed us to analyze the large-scale regional subgraphs of entire continents and an extensive set of examples for single countries. We present results for North and South America, Europe and Asia. In our analysis we used the well-established method of modularity clustering after an aggregation of the individual links into a weighted graph connecting equal-area geographical pixels. Our results show fingerprints of both of the opposing forces of dividing local conflicts and of uniting cross-cultural trends of globalization. PMID:25993329

  17. Spatial fingerprints of community structure in human interaction network for an extensive set of large-scale regions.

    PubMed

    Kallus, Zsófia; Barankai, Norbert; Szüle, János; Vattay, Gábor

    2015-01-01

    Human interaction networks inferred from country-wide telephone activity recordings were recently used to redraw political maps by projecting their topological partitions into geographical space. The results showed remarkable spatial cohesiveness of the network communities and a significant overlap between the redrawn and the administrative borders. Here we present a similar analysis based on one of the most popular online social networks represented by the ties between more than 5.8 million of its geo-located users. The worldwide coverage of their measured activity allowed us to analyze the large-scale regional subgraphs of entire continents and an extensive set of examples for single countries. We present results for North and South America, Europe and Asia. In our analysis we used the well-established method of modularity clustering after an aggregation of the individual links into a weighted graph connecting equal-area geographical pixels. Our results show fingerprints of both of the opposing forces of dividing local conflicts and of uniting cross-cultural trends of globalization. PMID:25993329

  18. Decoding the Role of the Insula in Human Cognition: Functional Parcellation and Large-Scale Reverse Inference

    PubMed Central

    Yarkoni, Tal; Khaw, Mel Win; Sanfey, Alan G.

    2013-01-01

    Recent work has indicated that the insula may be involved in goal-directed cognition, switching between networks, and the conscious awareness of affect and somatosensation. However, these findings have been limited by the insula’s remarkably high base rate of activation and considerable functional heterogeneity. The present study used a relatively unbiased data-driven approach combining resting-state connectivity-based parcellation of the insula with large-scale meta-analysis to understand how the insula is anatomically organized based on functional connectivity patterns as well as the consistency and specificity of the associated cognitive functions. Our findings support a tripartite subdivision of the insula and reveal that the patterns of functional connectivity in the resting-state analysis appear to be relatively conserved across tasks in the meta-analytic coactivation analysis. The function of the networks was meta-analytically “decoded” using the Neurosynth framework and revealed that while the dorsoanterior insula is more consistently involved in human cognition than ventroanterior and posterior networks, each parcellated network is specifically associated with a distinct function. Collectively, this work suggests that the insula is instrumental in integrating disparate functional systems involved in processing affect, sensory-motor processing, and general cognition and is well suited to provide an interface between feelings, cognition, and action. PMID:22437053

  19. Identification of post-generation effect of 3,4-methylenedioxymethamphetamine on the mouse brain by large-scale gene expression analysis.

    PubMed

    Eun, Jung Woo; Kwack, Seung Jun; Noh, Ji Heon; Jung, Kwang Hwa; Kim, Jeong Kyu; Bae, Hyun Jin; Xie, Hongjian; Ryu, Jae Chun; Ahn, Young Min; Park, Won Sang; Lee, Jung Young; Rhee, Gyu Seek; Nam, Suk Woo

    2010-05-19

    The compound 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic, psychoactive drug chemically similar to the stimulant methamphetamine and the hallucinogen mescaline. Accumulated data has revealed potential toxic effects associated with MDMA on brain serotonin and dopamine neurons in animal models. However, the relevance of these adverse effects on prenatal exposure to this drug remains unknown. In this study, we demonstrated that prenatal (F0) exposure to MDMA caused permanent large-scale transcriptional changes in the brains of the offspring (F1), especially in the cerebral cortex, by gene expression profiling analysis. The expression analysis of the brain of F1 pups, after maternal ingestion of MDMA (20 mg/kg MDMA), revealed significant transcriptional changes in both male and female pups. Supervised analysis resulted in the identification of 804 outlier genes in males and 1784 outlier genes in females as MDMA-associated genes in the F1 generation. Most of the functional categories of genes, among the outlier genes, were intracellular signaling pathways, including the MAPK signaling pathway, Wnt signaling pathway, and neuroactive ligand-receptor interaction pathway. Although these genes were affected by MDMA exposure in utero, their association with brain dysfunction requires further investigation. The results of this study suggest that prenatal MDMA exposure may affect the developing brain. PMID:20188158

  20. Auditory motion in the sighted and blind: Early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions.

    PubMed

    Dormal, Giulia; Rezk, Mohamed; Yakobov, Esther; Lepore, Franco; Collignon, Olivier

    2016-07-01

    How early blindness reorganizes the brain circuitry that supports auditory motion processing remains controversial. We used fMRI to characterize brain responses to in-depth, laterally moving, and static sounds in early blind and sighted individuals. Whole-brain univariate analyses revealed that the right posterior middle temporal gyrus and superior occipital gyrus selectively responded to both in-depth and laterally moving sounds only in the blind. These regions overlapped with regions selective for visual motion (hMT+/V5 and V3A) that were independently localized in the sighted. In the early blind, the right planum temporale showed enhanced functional connectivity with right occipito-temporal regions during auditory motion processing and a concomitant reduced functional connectivity with parietal and frontal regions. Whole-brain searchlight multivariate analyses demonstrated higher auditory motion decoding in the right posterior middle temporal gyrus in the blind compared to the sighted, while decoding accuracy was enhanced in the auditory cortex bilaterally in the sighted compared to the blind. Analyses targeting individually defined visual area hMT+/V5 however indicated that auditory motion information could be reliably decoded within this area even in the sighted group. Taken together, the present findings demonstrate that early visual deprivation triggers a large-scale imbalance between auditory and "visual" brain regions that typically support the processing of motion information. PMID:27107468

  1. The Neurona at Home project: Simulating a large-scale cellular automata brain in a distributed computing environment

    NASA Astrophysics Data System (ADS)

    Acedo, L.; Villanueva-Oller, J.; Moraño, J. A.; Villanueva, R.-J.

    2013-01-01

    The Berkeley Open Infrastructure for Network Computing (BOINC) has become the standard open source solution for grid computing in the Internet. Volunteers use their computers to complete an small part of the task assigned by a dedicated server. We have developed a BOINC project called Neurona@Home whose objective is to simulate a cellular automata random network with, at least, one million neurons. We consider a cellular automata version of the integrate-and-fire model in which excitatory and inhibitory nodes can activate or deactivate neighbor nodes according to a set of probabilistic rules. Our aim is to determine the phase diagram of the model and its behaviour and to compare it with the electroencephalographic signals measured in real brains.

  2. Large-Scale Production of Adeno-Associated Viral Vector Serotype-9 Carrying the Human Survival Motor Neuron Gene.

    PubMed

    Rashnonejad, Afrooz; Chermahini, Gholamhossein Amini; Li, Shaoyong; Ozkinay, Ferda; Gao, Guangping

    2016-01-01

    Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene. In this study, the large-scale production of single stranded (ss) and self-complementary (sc) AAV9 carrying the human survival motor neuron (SMN) gene (AAV9-SMN) suitable for in vivo gene therapy studies of SMA was described. SMN cDNA has been cloned into pAAV-CB6-PI and pAAVsc-CB6-PI with and without its specific UTRs, respectively. Both plasmids bear CMV enhancer/beta-actin (CB) promoter, CMV IE enhancer, and polyadenylation signal sequences. 2.5 μg of constructed pAAV-CB6-PI-SMN and pAAVsc-CB6-PI-SMN cause to, respectively, 4.853- and 2.321-fold increases in SMN protein levels in transfected cells compared to untransfected cells. Ss and scAAV9-SMN vectors were also produced from these plasmids by transient transfection of HEK293 cells using CaCl2 solution. The silver staining and electron microscopy analysis demonstrated good quality of both isolated vectors, ssAAV9-SMN and scAAV9-SMN, with the titers of 2.00E+13 and 1.00E+13 GC/ml. The results of this study show that, the plasmid containing UTR elements causes to twice more SMN gene expression in transfected cells. The quality control results show that both produced ss and scAAV9-SMN are suitable for in vivo studies. PMID:26607476

  3. Large-Scale Production of Adeno-Associated Viral Vector Serotype-9 Carrying the Human Survival Motor Neuron Gene

    PubMed Central

    RASHNONEJAD, Afrooz; CHERMAHINI, Gholamhossein AMINI; Li, Shaoyong; OZKINAY, Ferda; GAO, Guangping

    2016-01-01

    Recombinant AAV (rAAV) vectors are a suitable vector for gene therapy studies because of desired characteristics such as low immunogenicity, transfection of non-dividing and dividing cells, and long-term expression of the transgene. In this study, the large-scale production of single stranded (ss) and self-complementary (sc) AAV9 carrying the human survival motor neuron (SMN) gene (AAV9-SMN) suitable for in vivo gene therapy studies of SMA was described. SMN cDNA has been cloned into pAAV-CB6-PI and pAAVsc-CB6-PI with and without its specific UTRs, respectively. Both plasmids bear CMV enhancer/beta-actin (CB) promoter, CMV IE enhancer, and polyadenylation signal sequences. 2.5 μg of constructed pAAV-CB6-PI-SMN and pAAVsc-CB6-PI-SMN cause to, respectively, 4.853- and 2.321-fold increases in SMN protein levels in transfected cells compared to untransfected cells. Ss and scAAV9-SMN vectors were also produced from these plasmids by transient transfection of HEK293 cells using CaCl2 solution. The silver staining and electron microscopy analysis demonstrated good quality of both isolated vectors, ssAAV9-SMN and scAAV9- SMN, with the titers of 2.00E+13 and 1.00E+13 GC/ml. The results of this study show that, the plasmid containing UTR elements causes to twice more SMN gene expression in transfected cells. The quality control results show that both produced ss and scAAV9-SMN are suitable for in vivo studies. PMID:26607476

  4. Directionality of large-scale resting-state brain networks during eyes open and eyes closed conditions

    PubMed Central

    Zhang, Delong; Liang, Bishan; Wu, Xia; Wang, Zengjian; Xu, Pengfei; Chang, Song; Liu, Bo; Liu, Ming; Huang, Ruiwang

    2015-01-01

    The present study examined directional connections in the brain among resting-state networks (RSNs) when the participant had their eyes open (EO) or had their eyes closed (EC). The resting-state fMRI data were collected from 20 healthy participants (9 males, 20.17 ± 2.74 years) under the EO and EC states. Independent component analysis (ICA) was applied to identify the separated RSNs (i.e., the primary/high-level visual, primary sensory-motor, ventral motor, salience/dorsal attention, and anterior/posterior default-mode networks), and the Gaussian Bayesian network (BN) learning approach was then used to explore the conditional dependencies among these RSNs. The network-to-network directional connections related to EO and EC were depicted, and a support vector machine (SVM) was further employed to identify the directional connection patterns that could effectively discriminate between the two states. The results indicated that the connections among RSNs are directionally connected within a BN during the EO and EC states. The directional connections from the salience network (SN) to the anterior/posterior default-mode networks and the high-level to primary-level visual network were the obvious characteristics of both the EO and EC resting-state BNs. Of the directional connections in BN, the directional connections of the salience and dorsal attention network (DAN) were observed to be discriminative between the EO and EC states. In particular, we noted that the properties of the salience and DANs were in opposite directions. Overall, the present study described the directional connections of RSNs using a BN learning approach during the EO and EC states, and the results suggested that the directionality of the attention systems (i.e., mainly for the salience and the DAN) in resting state might have important roles in switching between the EO and EC conditions. PMID:25745394

  5. Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison

    PubMed Central

    De Meyer, Tim; Bady, Pierre; Trooskens, Geert; Kurscheid, Sebastian; Bloch, Jocelyne; Kros, Johan M.; Hainfellner, Johannes A.; Stupp, Roger; Delorenzi, Mauro; Hegi, Monika E.; Van Criekinge, Wim

    2015-01-01

    Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina’s Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect methylated loci rather than a quantitative analysis. MethylCap-seq and HM450 data were dichotomized and performances were compared using a gold standard free Bayesian modelling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. In addition, genome-wide characteristics were compared, revealing that HM450 probes identified substantially fewer regions compared to MethylCap-seq. Although results indicated that the latter method can detect more potentially relevant DNA-methylation, this did not translate into the discovery of more differentially methylated loci between tumours and controls compared to HM450. Our results therefore indicate that both methodologies are complementary, with a higher sensitivity for HM450 and a far larger genome-wide coverage for MethylCap-seq, but also that a more comprehensive character does not automatically imply more significant results in biomarker studies. PMID:26482909

  6. Large-scale brain networks in board game experts: insights from a domain-related task and task-free resting state.

    PubMed

    Duan, Xujun; Liao, Wei; Liang, Dongmei; Qiu, Lihua; Gao, Qing; Liu, Chengyi; Gong, Qiyong; Chen, Huafu

    2012-01-01

    Cognitive performance relies on the coordination of large-scale networks of brain regions that are not only temporally correlated during different tasks, but also networks that show highly correlated spontaneous activity during a task-free state. Both task-related and task-free network activity has been associated with individual differences in cognitive performance. Therefore, we aimed to examine the influence of cognitive expertise on four networks associated with cognitive task performance: the default mode network (DMN) and three other cognitive networks (central-executive network, dorsal attention network, and salience network). During fMRI scanning, fifteen grandmaster and master level Chinese chess players (GM/M) and fifteen novice players carried out a Chinese chess task and a task-free resting state. Modulations of network activity during task were assessed, as well as resting-state functional connectivity of those networks. Relative to novices, GM/Ms showed a broader task-induced deactivation of DMN in the chess problem-solving task, and intrinsic functional connectivity of DMN was increased with a connectivity pattern associated with the caudate nucleus in GM/Ms. The three other cognitive networks did not exhibit any difference in task-evoked activation or intrinsic functional connectivity between the two groups. These findings demonstrate the effect of long-term learning and practice in cognitive expertise on large-scale brain networks, suggesting the important role of DMN deactivation in expert performance and enhanced functional integration of spontaneous activity within widely distributed DMN-caudate circuitry, which might better support high-level cognitive control of behavior. PMID:22427852

  7. Large scale dynamic systems

    NASA Technical Reports Server (NTRS)

    Doolin, B. F.

    1975-01-01

    Classes of large scale dynamic systems were discussed in the context of modern control theory. Specific examples discussed were in the technical fields of aeronautics, water resources and electric power.

  8. Large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in Beijing, China

    PubMed Central

    2011-01-01

    Background Human metapneumovirus (hMPV), a recently identified virus, causes acute respiratory tract infections (ARTIs) in infants and children. However, studies on the seroepidemeology of hMPV are very limited in China. To assess the seroprevalence of hMPV infection in China, we tested a total of 1,156 serum specimens for the presence of anti-hMPV IgG antibody in children and adults free of acute respiratory illness in Beijing, China by using hMPV nucleocapsid (N) protein as an antigen. As a control, we used the human serum antibody against the N protein of human respiratory syncytial virus (hRSV), the most important viral agent responsible for ARIs in children. Results The seropositive rate for hMPV increased steadily with age from 67% at 1-6 mo to 100% at age 20. However, the rate dropped slightly between 6 mo and 1 yr of age. The seropositive rate for hRSV also increased steadily with age from 71% at 1-6 mo to 100% at age 20. In children aged six months to six years, the seropositive rates for the anti-hRSV IgG antibody were significantly higher than those for hMPV. Additionally, IgG antibody titers to hMPV and hRSV were significantly higher in adults than in young children. Consistent with the seropositive rates, the geometric mean titer of anti-hMPV IgG antibody was lower than that of anti-hRSV IgG antibody in children aged six months to six years. Conclusions Our results indicate that similar to hRSV, exposure to hMPV is ubiquitous in the Beijing population. However, the seroprevalence of anti-hMPV IgG antibody is lower than that of hRSV in children between six months and six years old, which suggests a different number of repeat infections or a different response to infections. PMID:21310026

  9. Large scale digital atlases in neuroscience

    NASA Astrophysics Data System (ADS)

    Hawrylycz, M.; Feng, D.; Lau, C.; Kuan, C.; Miller, J.; Dang, C.; Ng, L.

    2014-03-01

    Imaging in neuroscience has revolutionized our current understanding of brain structure, architecture and increasingly its function. Many characteristics of morphology, cell type, and neuronal circuitry have been elucidated through methods of neuroimaging. Combining this data in a meaningful, standardized, and accessible manner is the scope and goal of the digital brain atlas. Digital brain atlases are used today in neuroscience to characterize the spatial organization of neuronal structures, for planning and guidance during neurosurgery, and as a reference for interpreting other data modalities such as gene expression and connectivity data. The field of digital atlases is extensive and in addition to atlases of the human includes high quality brain atlases of the mouse, rat, rhesus macaque, and other model organisms. Using techniques based on histology, structural and functional magnetic resonance imaging as well as gene expression data, modern digital atlases use probabilistic and multimodal techniques, as well as sophisticated visualization software to form an integrated product. Toward this goal, brain atlases form a common coordinate framework for summarizing, accessing, and organizing this knowledge and will undoubtedly remain a key technology in neuroscience in the future. Since the development of its flagship project of a genome wide image-based atlas of the mouse brain, the Allen Institute for Brain Science has used imaging as a primary data modality for many of its large scale atlas projects. We present an overview of Allen Institute digital atlases in neuroscience, with a focus on the challenges and opportunities for image processing and computation.

  10. Modes of Large-Scale Brain Network Organization during Threat Processing and Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent Girls

    PubMed Central

    Cisler, Josh M.; Sigel, Benjamin A.; Kramer, Teresa L.; Smitherman, Sonet; Vanderzee, Karin; Pemberton, Joy; Kilts, Clinton D.

    2016-01-01

    Posttraumatic stress disorder (PTSD) is often chronic and disabling across the lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and mediating neural mechanisms are not well understood. Here, we test whether PTSD symptom reduction during TF-CBT is associated with individual differences in large-scale brain network organization during emotion processing. Twenty adolescent girls, aged 11–16, with PTSD related to assaultive violence completed a 12-session protocol of TF-CBT. Participants completed an emotion processing task, in which neutral and fearful facial expressions were presented either overtly or covertly during 3T fMRI, before and after treatment. Analyses focused on characterizing network properties of modularity, assortativity, and global efficiency within an 824 region-of-interest brain parcellation separately during each of the task blocks using weighted functional connectivity matrices. We similarly analyzed an existing dataset of healthy adolescent girls undergoing an identical emotion processing task to characterize normative network organization. Pre-treatment individual differences in modularity, assortativity, and global efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction. Patients who responded better to treatment had greater network modularity and assortativity but lesser efficiency, a pattern that closely resembled the control participants. At a group level, greater symptom reduction was associated with greater pre-to-post-treatment increases in network assortativity and modularity, but this was more pronounced among participants with less symptom improvement. The results support the hypothesis that modularized and resilient brain organization during emotion processing operate as mechanisms enabling symptom reduction during TF-CBT. PMID:27505076

  11. Large-scale intrinsic functional network organization along the long axis of the human medial temporal lobe.

    PubMed

    Qin, Shaozheng; Duan, Xujun; Supekar, Kaustubh; Chen, Huafu; Chen, Tianwen; Menon, Vinod

    2016-07-01

    The medial temporal lobe (MTL), encompassing the hippocampus and parahippocampal gyrus (PHG), is a heterogeneous structure which plays a critical role in memory and cognition. Here, we investigate functional architecture of the human MTL along the long axis of the hippocampus and PHG. The hippocampus showed stronger connectivity with striatum, ventral tegmental area and amygdala-regions important for integrating reward and affective signals, whereas the PHG showed stronger connectivity with unimodal and polymodal association cortices. In the hippocampus, the anterior node showed stronger connectivity with the anterior medial temporal lobe and the posterior node showed stronger connectivity with widely distributed cortical and subcortical regions including those involved in sensory and reward processing. In the PHG, differences were characterized by a gradient of increasing anterior-to-posterior connectivity with core nodes of the default mode network. Left and right MTL connectivity patterns were remarkably similar, except for stronger left than right MTL connectivity with regions in the left MTL, the ventral striatum and default mode network. Graph theoretical analysis of MTL-based networks revealed higher node centrality of the posterior, compared to anterior and middle hippocampus. The PHG showed prominent gradients in both node degree and centrality along its anterior-to-posterior axis. Our findings highlight several novel aspects of functional heterogeneity in connectivity along the long axis of the human MTL and provide new insights into how its network organization supports integration and segregation of signals from distributed brain areas. The implications of our findings for a principledunderstanding of distributed pathways that support memory and cognition are discussed. PMID:26336951

  12. Large Scale Computing

    NASA Astrophysics Data System (ADS)

    Capiluppi, Paolo

    2005-04-01

    Large Scale Computing is acquiring an important role in the field of data analysis and treatment for many Sciences and also for some Social activities. The present paper discusses the characteristics of Computing when it becomes "Large Scale" and the current state of the art for some particular application needing such a large distributed resources and organization. High Energy Particle Physics (HEP) Experiments are discussed in this respect; in particular the Large Hadron Collider (LHC) Experiments are analyzed. The Computing Models of LHC Experiments represent the current prototype implementation of Large Scale Computing and describe the level of maturity of the possible deployment solutions. Some of the most recent results on the measurements of the performances and functionalities of the LHC Experiments' testing are discussed.

  13. Validation of a two-step quality control approach for a large-scale human urine metabolomic study conducted in seven experimental batches with LC/QTOF-MS.

    PubMed

    Demetrowitsch, Tobias J; Petersen, Beate; Keppler, Julia K; Koch, Andreas; Schreiber, Stefan; Laudes, Matthias; Schwarz, Karin

    2015-01-01

    After his study of food science at the Rheinische Friedrich-Wilhelms University of Bonn, Tobias J Demetrowitsch obtained his doctoral degree in the research field of metabolomics at the Christian-Albrechts-University of Kiel. The present paper is part of his doctoral thesis and describes an extended strategy to evaluate and verify complex or large-scale experiments and data sets. Large-scale studies result in high sample numbers, requiring the analysis of samples in different batches. So far, the verification of such LC-MS-based metabolomics studies is difficult. Common approaches have not provided a reliable validation procedure to date. This article shows a novel verification process for a large-scale human urine study (analyzed by a LC/QToF-MS system) using a two-step validation procedure. The first step comprises a targeted approach that aims to examine and exclude statistical outliers. The second step consists of a principle component analysis, with the aim of a tight cluster of all quality controls and a second for all volunteer samples. The applied study design provides a reliable two-step validation procedure for large-scale studies and additionally contains an inhouse verification procedure. PMID:25558939

  14. Mapping genetic influences on human brain structure.

    PubMed

    Thompson, Paul; Cannon, Tyrone D; Toga, Arthur W

    2002-01-01

    Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain. PMID:12553492

  15. Medial Prefrontal and Anterior Insular Connectivity in Early Schizophrenia and Major Depressive Disorder: A Resting Functional MRI Evaluation of Large-Scale Brain Network Models.

    PubMed

    Penner, Jacob; Ford, Kristen A; Taylor, Reggie; Schaefer, Betsy; Théberge, Jean; Neufeld, Richard W J; Osuch, Elizabeth A; Menon, Ravi S; Rajakumar, Nagalingam; Allman, John M; Williamson, Peter C

    2016-01-01

    Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls. PMID:27064387

  16. Medial Prefrontal and Anterior Insular Connectivity in Early Schizophrenia and Major Depressive Disorder: A Resting Functional MRI Evaluation of Large-Scale Brain Network Models

    PubMed Central

    Penner, Jacob; Ford, Kristen A.; Taylor, Reggie; Schaefer, Betsy; Théberge, Jean; Neufeld, Richard W. J.; Osuch, Elizabeth A.; Menon, Ravi S.; Rajakumar, Nagalingam; Allman, John M.; Williamson, Peter C.

    2016-01-01

    Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls. PMID:27064387

  17. The many levels of causal brain network discovery. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Valdes-Sosa, Pedro A.

    2015-12-01

    Unraveling the dynamically changing networks of the brain is probably the single most important current task for the neurosciences. I wish to commend the authors on this refreshing and provocative paper [1], which not only recapitulates some of the longstanding philosophical difficulties involved in the analysis of causality in the sciences, but also summarizes current work on statistical methods for determining causal networks in the brain. I fully concur with several of the opinions defended by the authors: The most fruitful level of analysis for systems neuroscience is that of neural masses, each comprising thousands of neurons. This is what is known as the mesoscopic scale.

  18. Large-Scale Disasters

    NASA Astrophysics Data System (ADS)

    Gad-El-Hak, Mohamed

    "Extreme" events - including climatic events, such as hurricanes, tornadoes, and drought - can cause massive disruption to society, including large death tolls and property damage in the billions of dollars. Events in recent years have shown the importance of being prepared and that countries need to work together to help alleviate the resulting pain and suffering. This volume presents a review of the broad research field of large-scale disasters. It establishes a common framework for predicting, controlling and managing both manmade and natural disasters. There is a particular focus on events caused by weather and climate change. Other topics include air pollution, tsunamis, disaster modeling, the use of remote sensing and the logistics of disaster management. It will appeal to scientists, engineers, first responders and health-care professionals, in addition to graduate students and researchers who have an interest in the prediction, prevention or mitigation of large-scale disasters.

  19. Large-Scale Phosphoproteome of Human Whole Saliva Using Disulphide-Thiol-Interchange Covalent Chromatography and Mass Spectrometry

    PubMed Central

    Salih, Erdjan; Siqueira, Walter L.; Helmerhorst, Eva J.; Oppenheim, Frank G.

    2010-01-01

    Thus far only a handful of phosphoproteins with important biological functions have been identified and characterized in oral fluids and these include some of the abundant protein constituents of saliva. Whole saliva (WS) samples were trypsin digested followed by chemical derivatization using dithiothreitol (DTT) of the phospho-serine/threonine containing peptides. The DTT-phosphopeptides were enriched by covalent disulphide-thiol-interchange chromatography and analysis by nano-flow LC-ESI-MS/MS. The specificity of DTT chemical derivatization was evaluated separately under different base-catalyzed conditions with NaOH and Ba(OH)2, blocking cysteine residues by iodoacetamide and enzymatic O-deglycosylation prior to DTT reaction. Further analysis of WS samples which were subjected to either of these conditions provided supporting evidence for phosphoprotein identifications. The combined chemical strategies and mass spectrometric analyses identified 65 phosphoproteins in WS of which 28 were based on two or more peptide identification criteria with high confidence, and 37 were based on a single phosphopeptide identification. Most of the identified proteins, ~80%, were hitherto unknown phosphoprotein components. This study represents the first large-scale documentation of phosphoproteins of WS. The origins and identity of WS phosphoproteome suggest significant implications for both basic science and the development of novel biomarkers/diagnostic tools for both systemic and oral disease states. PMID:20659418

  20. Public appraisal of government efforts and participation intent in medico-ethical policymaking in Japan: a large scale national survey concerning brain death and organ transplant

    PubMed Central

    Sato, Hajime; Akabayashi, Akira; Kai, Ichiro

    2005-01-01

    Background Public satisfaction with policy process influences the legitimacy and acceptance of policies, and conditions the future political process, especially when contending ethical value judgments are involved. On the other hand, public involvement is required if effective policy is to be developed and accepted. Methods Using the data from a large-scale national opinion survey, this study evaluates public appraisal of past government efforts to legalize organ transplant from brain-dead bodies in Japan, and examines the public's intent to participate in future policy. Results A relatively large percentage of people became aware of the issue when government actions were initiated, and many increasingly formed their own opinions on the policy in question. However, a significant number (43.3%) remained unaware of any legislative efforts, and only 26.3% of those who were aware provided positive appraisals of the policymaking process. Furthermore, a majority of respondents (61.8%) indicated unwillingness to participate in future policy discussions of bioethical issues. Multivariate analysis revealed the following factors are associated with positive appraisals of policy development: greater age; earlier opinion formation; and familiarity with donor cards. Factors associated with likelihood of future participation in policy discussion include younger age, earlier attention to the issue, and knowledge of past government efforts. Those unwilling to participate cited as their reasons that experts are more knowledgeable and that the issues are too complex. Conclusions Results of an opinion survey in Japan were presented, and a set of factors statistically associated with them were discussed. Further efforts to improve policy making process on bioethical issues are desirable. PMID:15661080

  1. Large scale study on the variation of RF energy absorption in the head & brain regions of adults and children and evaluation of the SAM phantom conservativeness

    NASA Astrophysics Data System (ADS)

    Keshvari, J.; Kivento, M.; Christ, A.; Bit-Babik, G.

    2016-04-01

    This paper presents the results of two computational large scale studies using highly realistic exposure scenarios, MRI based human head and hand models, and two mobile phone models. The objectives are (i) to study the relevance of age when people are exposed to RF by comparing adult and child heads and (ii) to analyze and discuss the conservativeness of the SAM phantom for all age groups. Representative use conditions were simulated using detailed CAD models of two mobile phones operating between 900 MHz and 1950 MHz including configurations with the hand holding the phone, which were not considered in most previous studies. The peak spatial-average specific absorption rate (psSAR) in the head and the pinna tissues is assessed using anatomically accurate head and hand models. The first of the two mentioned studies involved nine head-, four hand- and two phone-models, the second study included six head-, four hand- and three simplified phone-models (over 400 configurations in total). In addition, both studies also evaluated the exposure using the SAM phantom. Results show no systematic differences between psSAR induced in the adult and child heads. The exposure level and its variation for different age groups may be different for particular phones, but no correlation between psSAR and model age was found. The psSAR from all exposure conditions was compared to the corresponding configurations using SAM, which was found to be conservative in the large majority of cases.

  2. Development of a large-scale isolation chamber system for the safe and humane care of medium-sized laboratory animals harboring infectious diseases*

    PubMed Central

    Pan, Xin; Qi, Jian-cheng; Long, Ming; Liang, Hao; Chen, Xiao; Li, Han; Li, Guang-bo; Zheng, Hao

    2010-01-01

    The close phylogenetic relationship between humans and non-human primates makes non-human primates an irreplaceable model for the study of human infectious diseases. In this study, we describe the development of a large-scale automatic multi-functional isolation chamber for use with medium-sized laboratory animals carrying infectious diseases. The isolation chamber, including the transfer chain, disinfection chain, negative air pressure isolation system, animal welfare system, and the automated system, is designed to meet all biological safety standards. To create an internal chamber environment that is completely isolated from the exterior, variable frequency drive blowers are used in the air-intake and air-exhaust system, precisely controlling the filtered air flow and providing an air-barrier protection. A double door transfer port is used to transfer material between the interior of the isolation chamber and the outside. A peracetic acid sterilizer and its associated pipeline allow for complete disinfection of the isolation chamber. All of the isolation chamber parameters can be automatically controlled by a programmable computerized menu, allowing for work with different animals in different-sized cages depending on the research project. The large-scale multi-functional isolation chamber provides a useful and safe system for working with infectious medium-sized laboratory animals in high-level bio-safety laboratories. PMID:20872984

  3. Cloning and Large-Scale Production of High-Capacity Adenoviral Vectors Based on the Human Adenovirus Type 5.

    PubMed

    Ehrke-Schulz, Eric; Zhang, Wenli; Schiwon, Maren; Bergmann, Thorsten; Solanki, Manish; Liu, Jing; Boehme, Philip; Leitner, Theo; Ehrhardt, Anja

    2016-01-01

    High-capacity adenoviral vectors (HCAdV) devoid of all viral coding sequences represent one of the most advanced gene delivery vectors due to their high packaging capacity (up to 35 kb), low immunogenicity and low toxicity. However, for many laboratories the use of HCAdV is hampered by the complicated procedure for vector genome construction and virus production. Here, a detailed protocol for efficient cloning and production of HCAdV based on the plasmid pAdFTC containing the HCAdV genome is described. The construction of HCAdV genomes is based on a cloning vector system utilizing homing endonucleases (I-CeuI and PI-SceI). Any gene of interest of up to 14 kb can be subcloned into the shuttle vector pHM5, which contains a multiple cloning site flanked by I-CeuI and PI-SceI. After I-CeuI and PI-SceI-mediated release of the transgene from the shuttle vector the transgene can be inserted into the HCAdV cloning vector pAdFTC. Because of the large size of the pAdFTC plasmid and the long recognition sites of the used enzymes associated with strong DNA binding, careful handling of the cloning fragments is needed. For virus production, the HCAdV genome is released by NotI digest and transfected into a HEK293 based producer cell line stably expressing Cre recombinase. To provide all adenoviral genes for adenovirus amplification, co-infection with a helper virus containing a packing signal flanked by loxP sites is required. Pre-amplification of the vector is performed in producer cells grown on surfaces and large-scale amplification of the vector is conducted in spinner flasks with producer cells grown in suspension. For virus purification, two ultracentrifugation steps based on cesium chloride gradients are performed followed by dialysis. Here tips, tricks and shortcuts developed over the past years working with this HCAdV vector system are presented. PMID:26863087

  4. Is Traumatic Brain Injury Associated with Reduced Inter-Hemispheric Functional Connectivity? A Study of Large-Scale Resting State Networks following Traumatic Brain Injury.

    PubMed

    Rigon, Arianna; Duff, Melissa C; McAuley, Edward; Kramer, Arthur F; Voss, Michelle W

    2016-06-01

    Traumatic brain injury (TBI) often has long-term debilitating sequelae in cognitive and behavioral domains. Understanding how TBI impacts functional integrity of brain networks that underlie these domains is key to guiding future approaches to TBI rehabilitation. In the current study, we investigated the differences in inter-hemispheric functional connectivity (FC) of resting state networks (RSNs) between chronic mild-to-severe TBI patients and normal comparisons (NC), focusing on two externally oriented networks (i.e., the fronto-parietal network [FPN] and the executive control network [ECN]), one internally oriented network (i.e., the default mode network [DMN]), and one somato-motor network (SMN). Seed voxel correlation analysis revealed that TBI patients displayed significantly less FC between lateralized seeds and both homologous and non-homologous regions in the opposite hemisphere for externally oriented networks but not for DMN or SMN; conversely, TBI patients showed increased FC within regions of the DMN, especially precuneus and parahippocampal gyrus. Region of interest correlation analyses confirmed the presence of significantly higher inter-hemispheric FC in NC for the FPN (p < 0.01), and ECN (p < 0.05), but not for the DMN (p > 0.05) or SMN (p > 0.05). Further analysis revealed that performance on a neuropsychological test measuring organizational skills and visuo-spatial abilities administered to the TBI group, the Rey-Osterrieth Complex Figure Test, positively correlated with FC between the right FPN and homologous regions. Our findings suggest that distinct RSNs display specific patterns of aberrant FC following TBI; this represents a step forward in the search for biomarkers useful for early diagnosis and treatment of TBI-related cognitive impairment. PMID:25719433

  5. Large Scale Generation and Characterization of Anti-Human IgA Monoclonal Antibody in Ascitic Fluid of Balb/c Mice

    PubMed Central

    Ezzatifar, Fatemeh; Majidi, Jafar; Baradaran, Behzad; Aghebati Maleki, Leili; Abdolalizadeh, Jalal; Yousefi, Mehdi

    2015-01-01

    Purpose: Monoclonal antibodies are potentially powerful tools used in biomedical research, diagnosis, and treatment of infectious diseases and cancers. The monoclonal antibody against Human IgA can be used as a diagnostic application to detect infectious diseases. The aim of this study was to improve an appropriate protocol for large-scale production of mAbs against IgA. Methods: For large-scale production of the monoclonal antibody, hybridoma cells that produce monoclonal antibodies against Human IgA were injected intraperitoneally into Balb/c mice that were previously primed with 0.5 ml Pristane. After ten days, ascitic fluid was harvested from the peritoneum of each mouse. The ELISA method was carried out for evaluation of the titration of produced mAbs. The ascitic fluid was investigated in terms of class and subclass by a mouse mAb isotyping kit. MAb was purified from the ascitic fluid by ion exchange chromatography. The purity of the monoclonal antibody was confirmed by SDS-PAGE, and the purified monoclonal antibody was conjugated with HRP. Results: Monoclonal antibodies with high specificity and sensitivity against Human IgA were prepared by hybridoma technology. The subclass of antibody was IgG1 and its light chain was the kappa type. Conclusion: This conjugated monoclonal antibody could have applications in designing ELISA kits in order to diagnose different infectious diseases such as toxoplasmosis and H. Pylori. PMID:25789225

  6. Shoreline Response to Climate Change and Human Manipulations in a Model of Large-Scale Coastal Change

    NASA Astrophysics Data System (ADS)

    Slott, J. M.; Murray, A. B.; Valvo, L.; Ashton, A.

    2005-12-01

    ) show that large-scale coastal features (e.g. capes and cuspate spits) may self-organize as smaller coastal features grow and merge by interacting over large distances through wave shadowing. Our current work extends this model by including the effects of beach nourishment and seawalls. These simulations start with a cape-like shoreline, resembling the Carolina coastline, which we generated using the one-line model driven by the statistical average of 20 years of hindcast wave data measured off Cape Lookout, NC (WIS Station 509). In our experiments, we explored the effects of shoreline stabilization under four different wave climate scenarios: (a) unchanged, (b) increased winter storms, (c) increased tropical storms, and (d) decreased storminess. For each of these four scenarios, we ran three simulations: a control run with no shoreline stabilization, a run with a 10 km beach nourishment project, and a run with a 10 km seawall. We identified the effects of shoreline stabilization by comparing each of the latter two simulations to the control run. In each experiment, shoreline stabilization had a large effect on shoreline position--on the order of a few kilometers--within tens of kilometers of the stabilization area. We also saw sizable effects on adjacent capes nearly 100 kilometers away. Analysis of the simulations indicate that these distant impacts occurred because shoreline stabilization altered the extent to which the stabilized cape shadowed other parts of the coast. We thank the National Science Foundation and the Duke Center on Global Change for supporting our work.

  7. Large-scale polymorphism near the ends of several human chromosomes analyzed by using fluorescence in situ hybridization (FISH)

    SciTech Connect

    Trask, B.J.; Friedman, C.; Giorgi, D.

    1994-09-01

    We have discovered a large DNA segment that is polymorphically present at the ends of several human chromosomes. The segment, f7501, was originally derived form a human chromosome 19-specific cosmid library. FISH was used to determine the cosmid`s chromosomal distribution on 44 unrelated humans and several closely related primates. The human subjects represent a diversity of reproductively isolated ethnic populations. FISH analysis revealed that sequences highly homologous to the cosmid`s insert are present on both homologs at 3q, 15q,. and 19p in almost all individuals (88, 85, and 87 of 88 homologs, respectively). Other chromosomes sites were labeled much more rarely in the sampled individuals. For example, 56 of the 88 analyzed chromosomes 11 were labeled (18+/+, 6-/-, and 20+/- individuals). In contrast, 2q was labeled on only 1/88 sampled chromosomes. The termini of 2q, 5q, 6p, 6q, 7p, 8p, 9p, 9q, 11p, 12q, 16p, 19q, and 20q and an interstitial site at 2q13-14 were labeled in at least one individual of the set. EcoR1-fragments derived from the cosmid showed the same hybridization pattern as the entire cosmid, indicating that at least 40 kbp is shared by these chromosome ends. Ethnic differences in the allele frequency of these polymorphic variants was observed. For example, signals were observed on 8/10 and 7/10 of the chromosomes 7p and 16q, respectively, derived form Biakan Pygmies, but these sites were infrequently labeled in non-Pygmy human populations (2/68, respectively). This region has undergone significant changes in chromosome location during human evolution. Strong signal was seen on chimpanzee and gorilla chromosome 3, which is homologous to human chromosome 4, a chromosome unlabeled in any of the humans we have analyzed.

  8. Protein crystal growth in microgravity review of large scale temperature induction method: Bovine insulin, human insulin and human α-interferon

    NASA Astrophysics Data System (ADS)

    Long, Marianna M.; Bishop, John Bradford; Delucas, Lawrence J.; Nagabhushan, Tattanhalli L.; Reichert, Paul; Smith, G. David

    1997-01-01

    The Protein Crystal Growth Facility (PCF) is space-flight hardware that accommodates large scale protein crystal growth experiments using temperature change as the inductive step. Recent modifications include specialized instrumentation for monitoring crystal nucleation with laser light scattering. This paper reviews results from its first seven flights on the Space Shuttle, the last with laser light scattering instrumentation in place. The PCF's objective is twofold: (1) the production of high quality protein crystals for x-ray analysis and subsequent structure-based drug design and (2) preparation of a large quantity of relatively contaminant free crystals for use as time-release protein pharmaceuticals. The first three Shuttle flights with bovine insulin constituted the PCF's proof of concept, demonstrating that the space-grown crystals were larger and diffracted to higher resolution than their earth-grown counterparts. The later four PCF missions were used to grow recombinant human insulin crystals for x-ray analysis and continue productions trials aimed at the development of a processing facility for crystalline recombinant a-interferon.

  9. High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples.

    PubMed

    Abal-Fabeiro, J L; Maside, X; Llovo, J; Bello, X; Torres, M; Treviño, M; Moldes, L; Muñoz, A; Carracedo, A; Bartolomé, C

    2014-04-01

    The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high-throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90·9%) and gp60 subtype in 605 (90·2%). It displayed excellent performance, with sensitivity and specificity values of 87·3 and 98·0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61·3 and 28·3%, respectively). 96·5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming. PMID:24238396

  10. Large-Scale Production of Cardiomyocytes from Human Pluripotent Stem Cells Using a Highly Reproducible Small Molecule-Based Differentiation Protocol.

    PubMed

    Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Blue, Gillian M; Aghdami, Nasser; Winlaw, David S; Harvey, Richard P; Bosman, Alexis; Baharvand, Hossein

    2016-01-01

    Maximizing the benefit of human pluripotent stem cells (hPSCs) for research, disease modeling, pharmaceutical and clinical applications requires robust methods for the large-scale production of functional cell types, including cardiomyocytes. Here we demonstrate that the temporal manipulation of WNT, TGF-β, and SHH signaling pathways leads to highly efficient cardiomyocyte differentiation of single-cell passaged hPSC lines in both static suspension and stirred suspension bioreactor systems. Employing this strategy resulted in ~ 100% beating spheroids, consistently containing > 80% cardiac troponin T-positive cells after 15 days of culture, validated in multiple hPSC lines. We also report on a variation of this protocol for use with cell lines not currently adapted to single-cell passaging, the success of which has been verified in 42 hPSC lines. Cardiomyocytes generated using these protocols express lineage-specific markers and show expected electrophysiological functionalities. Our protocol presents a simple, efficient and robust platform for the large-scale production of human cardiomyocytes. PMID:27500408

  11. Why are We Waiting to Start Large Scale Clinical Testing of Human Chorionic Gonadotropin for the Treatment of Preterm Births?

    PubMed

    Rao, C V

    2016-07-01

    Preterm births are an expensive global health problem. Despite the basic science and clinical research advances to better understand and prevent preterm births, the rates are increasing. There are several therapeutic options. While some options such as progestins work for selected women, others such as magnesium sulfate can only be used for delaying births for 24 to 48 hours so that the patients can be treated with corticosteroids to promote fetal lung maturity. Based on the scientific and clinical evidence, we recommend testing human chorionic gonadotropin in a large multicenter, randomized, double-blind, and placebo-controlled clinical trials in women with active preterm labor and those with a previous history of preterm births. Human chorionic gonadotropin is not only inexpensive but also has not shown any side effects so far in the infants or in the mothers. PMID:26692543

  12. Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.

    PubMed

    Ivarsson, Ylva; Arnold, Roland; McLaughlin, Megan; Nim, Satra; Joshi, Rakesh; Ray, Debashish; Liu, Bernard; Teyra, Joan; Pawson, Tony; Moffat, Jason; Li, Shawn Shun-Cheng; Sidhu, Sachdev S; Kim, Philip M

    2014-02-18

    The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein-protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions. PMID:24550280

  13. Evolving networks in the human epileptic brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus; Ansmann, Gerrit; Bialonski, Stephan; Dickten, Henning; Geier, Christian; Porz, Stephan

    2014-01-01

    Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.

  14. Rapid, complete and large-scale generation of post-mitotic neurons from the human LUHMES cell line.

    PubMed

    Scholz, Diana; Pöltl, Dominik; Genewsky, Andreas; Weng, Matthias; Waldmann, Tanja; Schildknecht, Stefan; Leist, Marcel

    2011-12-01

    We characterized phenotype and function of a fetal human mesencephalic cell line (LUHMES, Lund human mesencephalic) as neuronal model system. Neurodevelopmental profiling of the proliferation stage (d0, day 0) of these conditionally-immortalized cells revealed neuronal features, expressed simultaneously with some early neuroblast and stem cell markers. An optimized 2-step differentiation procedure, triggered by shut-down of the myc transgene, resulted in uniformly post-mitotic neurons within 5 days (d5). This was associated with down-regulation of some precursor markers and further up-regulation of neuronal genes. Neurite network formation involved the outgrowth of 1-2, often > 500 μm long projections. They showed dynamic growth cone behavior, as evidenced by time-lapse imaging of stably GFP-over-expressing cells. Voltage-dependent sodium channels and spontaneous electrical activity of LUHMES continuously increased from d0 to d11, while levels of synaptic markers reached their maximum on d5. The developmental expression patterns of most genes and of the dopamine uptake- and release-machinery appeared to be intrinsically predetermined, as the differentiation proceeded similarly when external factors such as dibutyryl-cAMP and glial cell derived neurotrophic factor were omitted. Only tyrosine hydroxylase required the continuous presence of cAMP. In conclusion, LUHMES are a robust neuronal model with adaptable phenotype and high value for neurodevelopmental studies, disease modeling and neuropharmacology. PMID:21434924

  15. Large-Scaled Metabolic Profiling of Human Dermal Fibroblasts Derived from Pseudoxanthoma Elasticum Patients and Healthy Controls

    PubMed Central

    Kuzaj, Patricia; Kuhn, Joachim; Michalek, Ryan D.; Karoly, Edward D.; Faust, Isabel; Dabisch-Ruthe, Mareike; Knabbe, Cornelius; Hendig, Doris

    2014-01-01

    Mutations in the ABC transporter ABCC6 were recently identified as cause of Pseudoxanthoma elasticum (PXE), a rare genetic disorder characterized by progressive mineralization of elastic fibers. We used an untargeted metabolic approach to identify biochemical differences between human dermal fibroblasts from healthy controls and PXE patients in an attempt to find a link between ABCC6 deficiency, cellular metabolic alterations and disease pathogenesis. 358 compounds were identified by mass spectrometry covering lipids, amino acids, peptides, carbohydrates, nucleotides, vitamins and cofactors, xenobiotics and energy metabolites. We found substantial differences in glycerophospholipid composition, leucine dipeptides, and polypeptides as well as alterations in pantothenate and guanine metabolism to be significantly associated with PXE pathogenesis. These findings can be linked to extracellular matrix remodeling and increased oxidative stress, which reflect characteristic hallmarks of PXE. Our study could facilitate a better understanding of biochemical pathways involved in soft tissue mineralization. PMID:25265166

  16. Large scale tracking algorithms.

    SciTech Connect

    Hansen, Ross L.; Love, Joshua Alan; Melgaard, David Kennett; Karelitz, David B.; Pitts, Todd Alan; Zollweg, Joshua David; Anderson, Dylan Z.; Nandy, Prabal; Whitlow, Gary L.; Bender, Daniel A.; Byrne, Raymond Harry

    2015-01-01

    Low signal-to-noise data processing algorithms for improved detection, tracking, discrimination and situational threat assessment are a key research challenge. As sensor technologies progress, the number of pixels will increase signi cantly. This will result in increased resolution, which could improve object discrimination, but unfortunately, will also result in a significant increase in the number of potential targets to track. Many tracking techniques, like multi-hypothesis trackers, suffer from a combinatorial explosion as the number of potential targets increase. As the resolution increases, the phenomenology applied towards detection algorithms also changes. For low resolution sensors, "blob" tracking is the norm. For higher resolution data, additional information may be employed in the detection and classfication steps. The most challenging scenarios are those where the targets cannot be fully resolved, yet must be tracked and distinguished for neighboring closely spaced objects. Tracking vehicles in an urban environment is an example of such a challenging scenario. This report evaluates several potential tracking algorithms for large-scale tracking in an urban environment.

  17. Large scale traffic simulations

    SciTech Connect

    Nagel, K.; Barrett, C.L.; Rickert, M.

    1997-04-01

    Large scale microscopic (i.e. vehicle-based) traffic simulations pose high demands on computational speed in at least two application areas: (i) real-time traffic forecasting, and (ii) long-term planning applications (where repeated {open_quotes}looping{close_quotes} between the microsimulation and the simulated planning of individual person`s behavior is necessary). As a rough number, a real-time simulation of an area such as Los Angeles (ca. 1 million travellers) will need a computational speed of much higher than 1 million {open_quotes}particle{close_quotes} (= vehicle) updates per second. This paper reviews how this problem is approached in different projects and how these approaches are dependent both on the specific questions and on the prospective user community. The approaches reach from highly parallel and vectorizable, single-bit implementations on parallel supercomputers for Statistical Physics questions, via more realistic implementations on coupled workstations, to more complicated driving dynamics implemented again on parallel supercomputers. 45 refs., 9 figs., 1 tab.

  18. Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies.

    PubMed

    Bhadriraju, Kiran; Halter, Michael; Amelot, Julien; Bajcsy, Peter; Chalfoun, Joe; Vandecreme, Antoine; Mallon, Barbara S; Park, Kye-Yoon; Sista, Subhash; Elliott, John T; Plant, Anne L

    2016-07-01

    Identification and quantification of the characteristics of stem cell preparations is critical for understanding stem cell biology and for the development and manufacturing of stem cell based therapies. We have developed image analysis and visualization software that allows effective use of time-lapse microscopy to provide spatial and dynamic information from large numbers of human embryonic stem cell colonies. To achieve statistically relevant sampling, we examined >680 colonies from 3 different preparations of cells over 5days each, generating a total experimental dataset of 0.9 terabyte (TB). The 0.5 Giga-pixel images at each time point were represented by multi-resolution pyramids and visualized using the Deep Zoom Javascript library extended to support viewing Giga-pixel images over time and extracting data on individual colonies. We present a methodology that enables quantification of variations in nominally-identical preparations and between colonies, correlation of colony characteristics with Oct4 expression, and identification of rare events. PMID:27286574

  19. Large-scale identification of potential drug targets based on the topological features of human protein-protein interaction network.

    PubMed

    Li, Zhan-Chao; Zhong, Wen-Qian; Liu, Zhi-Qing; Huang, Meng-Hua; Xie, Yun; Dai, Zong; Zou, Xiao-Yong

    2015-04-29

    Identifying potential drug target proteins is a crucial step in the process of drug discovery and plays a key role in the study of the molecular mechanisms of disease. Based on the fact that the majority of proteins exert their functions through interacting with each other, we propose a method to recognize target proteins by using the human protein-protein interaction network and graph theory. In the network, vertexes and edges are weighted by using the confidence scores of interactions and descriptors of protein primary structure, respectively. The novel network topological features are defined and employed to characterize protein using existing databases. A widely used minimum redundancy maximum relevance and random forests algorithm are utilized to select the optimal feature subset and construct model for the identification of potential drug target proteins at the proteome scale. The accuracies of training set and test set are 89.55% and 85.23%. Using the constructed model, 2127 potential drug target proteins have been recognized and 156 drug target proteins have been validated in the database of drug target. In addition, some new drug target proteins can be considered as targets for treating diseases of mucopolysaccharidosis, non-arteritic anterior ischemic optic neuropathy, Bernard-Soulier syndrome and pseudo-von Willebrand, etc. It is anticipated that the proposed method may became a powerful high-throughput virtual screening tool of drug target. PMID:25847157

  20. Brain Organization into Resting State Networks Emerges at Criticality on a Model of the Human Connectome

    NASA Astrophysics Data System (ADS)

    Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.

    2013-04-01

    The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.

  1. Large-scale in vitro expansion of human regulatory T cells with potent xenoantigen-specific suppression.

    PubMed

    Jin, Xi; Lu, Yanrong; Zhao, Ye; Yi, Shounan

    2016-08-01

    Xenotransplantation is a potential solution to the organ donor shortage. Immunosuppression is required for successful application of xenotransplantation but may lead to infection and cancer. Thus, strategies for immune tolerance induction need to be developed. Polyclonal regulatory T cells (Treg) play a central role in the induction and maintenance of immune tolerance and have been shown to protect against islet xenograft rejection in vivo. However, global immune suppression may be mediated by polyclonal Treg immunotherapy and a simple method for in vitro expansion of xenoantigen-specific Treg for efficient Treg application becomes necessary. Human Treg isolated from peripheral blood mononuclear cells (PBMCs) were initially cultured with anti-CD3/CD28 beads, rapamycin and IL-2 for 7 days as polyclonal expansion. Expanded Treg were then cocultured with irradiated porcine PBMC as xenoantigen stimulation for three subsequent cycles with 7 days for each cycle in the presence of IL-2 and anti-CD3/CD28 beads. Treg phenotype and suppressive capacity were assessed after each cycle of xenoantigen stimulation. Treg expanded with one cycle of xenoantigen stimulation retained Treg suppressive phenotype but acquired no xenoantigen specificity along with poor expansion efficiency, whereas expansion with two-cycle xenoantigen stimulation resulted in not only more than 800-fold Treg expansion but highly suppressive xenoantigen-specific Treg with effector Treg phenotype. However further increase of stimulation cycles resulted in reduced Treg suppressive potency. This study provides a simple approach to obtain high numbers of xenoantigen-specific Treg for immune tolerance induction in xenotransplantation. PMID:25605448

  2. LARGE SCALE PURIFICATION OF BUTYRYLCHOLINESTERASE FROM HUMAN PLASMA SUITABLE FOR INJECTION INTO MONKEYS; A POTENTIAL NEW THERAPEUTIC FOR PROTECTION AGAINST COCAINE AND NERVE AGENT TOXICITY

    PubMed Central

    Lockridge, Oksana; Schopfer, Lawrence M.; Winger, Gail; Woods, James H.

    2005-01-01

    Pretreatment of animals with butyrylcholinesterase (EC 3.1.1.8 BChE) provides complete protection from the acute effects of organophosphorus nerve agents. Butyrylcholinesterase has also been shown to protect from cocaine toxicity. Large amounts of highly purified butyrylcholinesterase are needed to test the effectiveness of this new therapeutic agent in monkeys. Only a minimum amount of endotoxin can be present in a therapeutic intended for injection into monkeys. Our goal was to develop a large scale purification method for human BChE from human plasma with precautions to minimize endotoxin content. A protocol was developed that processed up to 100 L of human plasma at a time. Dialysis in pH 4.0 buffer, ion exchange chromatography at pH 4, affinity chromatography on procainamide-Sepharose, and HPLC ion exchange at pH 7.4 yielded highly purified human BChE containing a low endotoxin level of about 800 EU/ml. The purified BChE produced by this method had a mean residence time of 56 h in mice and 93 h in monkeys, and caused no toxic effects. The absence of a toxic effect in monkeys demonstrates that the endotoxin level of 800 EU/ml was well tolerated by monkeys. PMID:16788731

  3. Wiener-Granger causality for effective connectivity in the hidden states: Indication from probabilistic causality. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Tang, Wei

    2015-12-01

    Statistics and probability theory have advanced our understanding of random processes widely observed in the physical world. There is a remarkable trend in studying the brain by looking into the stochastic information processing in large-scale brain networks [1,2]. As the review by Mannino and Bressler [3] points out, the probabilistic notion of causality, with its rooted philosophical foundations, represents a revolutionary view on how different parts of the brain interact and integrate to generate function. Specifically, Probabilistic Causality (PC) asserts that a cause should increase the probability of occurrence of its effect, and PC between two brain regions entails that the probability for the activity in one region to occur increases when conditioned on the activity of the other. This definition claims inherent randomness in the causal relationship.

  4. Critical perspectives on causality and inference in brain networks: Allusions, illusions, solutions?. Comment on: "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Diwadkar, Vaibhav A.

    2015-12-01

    The human brain is an impossibly difficult cartographic landscape to map out. Within it's convoluted and labyrinthine structure is folded a million years of phylogeny, somehow expressed in the ontogeny of the specific organism; an ontogeny that conceals idiosyncratic effects of countless genes, and then the (perhaps) countably infinite effects of processes of the organism's lifespan subsequently resulting in remarkable heterogeneity [1,2]. The physical brain itself is therefore a nearly un-decodable "time machine" motivating more questions than frameworks for answering those questions: Why has evolution endowed it with the general structure that is possesses [3]; Is there regularity in macroscopic metrics of structure across species [4]; What are the most meaningful structural units in the brain: molecules, neurons, cortical columns or cortical maps [5]? Remarkably, understanding the intricacies of structure is perhaps not even the most difficult aspect of understanding the human brain. In fact, and as recently argued, a central issue lies in resolving the dialectic between structure and function: how does dynamic function arises from static (at least at the time scales at which human brain function is experimentally studied) brain structures [6]? In other words, if the mind is the brain "in action", how does it arise?

  5. A large-scale electrophoresis- and chromatography-based determination of gene expression profiles in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties

    PubMed Central

    2010-01-01

    Background Brain capillary endothelial cells (BCECs) form the physiological basis of the blood-brain barrier (BBB). The barrier function is (at least in part) due to well-known proteins such as transporters, tight junctions and metabolic barrier proteins (e.g. monoamine oxidase, gamma glutamyltranspeptidase and P-glycoprotein). Our previous 2-dimensional gel proteome analysis had identified a large number of proteins and revealed the major role of dynamic cytoskeletal remodelling in the differentiation of bovine BCECs. The aim of the present study was to elaborate a reference proteome of Triton X-100-soluble species from bovine BCECs cultured in the well-established in vitro BBB model developed in our laboratory. Results A total of 215 protein spots (corresponding to 130 distinct proteins) were identified by 2-dimensional gel electrophoresis, whereas over 350 proteins were identified by a shotgun approach. We classified around 430 distinct proteins expressed by bovine BCECs. Our large-scale gene expression analysis enabled the correction of mistakes referenced into protein databases (e.g. bovine vinculin) and constitutes valuable evidence for predictions based on genome annotation. Conclusions Elaboration of a reference proteome constitutes the first step in creating a gene expression database dedicated to capillary endothelial cells displaying BBB characteristics. It improves of our knowledge of the BBB and the key proteins in cell structures, cytoskeleton organization, metabolism, detoxification and drug resistance. Moreover, our results emphasize the need for both appropriate experimental design and correct interpretation of proteome datasets. PMID:21078152

  6. Large-Scale Purification of r28M: A Bispecific scFv Antibody Targeting Human Melanoma Produced in Transgenic Cattle

    PubMed Central

    Spiesberger, Katrin; Paulfranz, Florian; Egger, Anton; Reiser, Judith; Vogl, Claus; Rudolf-Scholik, Judith; Mayrhofer, Corina; Grosse-Hovest, Ludger; Brem, Gottfried

    2015-01-01

    Background 30 years ago, the potential of bispecific antibodies to engage cytotoxic T cells for the lysis of cancer cells was discovered. Today a variety of bispecific antibodies against diverse cell surface structures have been developed, the majority of them produced in mammalian cell culture systems. Beside the r28M, described here, no such bispecific antibody is known to be expressed by transgenic livestock, although various biologicals for medical needs are already harvested—mostly from the milk—of these transgenics. In this study we investigated the large-scale purification and biological activity of the bispecific antibody r28M, expressed in the blood of transgenic cattle. This tandem single-chain variable fragment antibody is designed to target human CD28 and the melanoma/glioblastoma-associated cell surface chondroitin sulfate proteoglycan 4 (CSPG4). Results With the described optimized purification protocol an average yield of 30 mg enriched r28M fraction out of 2 liters bovine plasma could be obtained. Separation of this enriched fraction by size exclusion chromatography into monomers, dimers and aggregates and further testing regarding the biological activity revealed the monomer fraction as being the most appropriate one to continue working with. The detailed characterization of the antibody’s activity confirmed its high specificity to induce the killing of CSPG4 positive cells. In addition, first insights into tumor cell death pathways mediated by r28M-activated peripheral blood mononuclear cells were gained. In consideration of possible applications in vivo we also tested the effect of the addition of different excipients to r28M. Conclusion Summing up, we managed to purify monomeric r28M from bovine plasma in a large-scale preparation and could prove that its biological activity is unaffected and still highly specific and thus, might be applicable for the treatment of melanoma. PMID:26469402

  7. A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

    PubMed

    Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

    2016-06-01

    Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. PMID:27199101

  8. Three Large-Scale Functional Brain Networks from Resting-State Functional MRI in Subjects with Different Levels of Cognitive Impairment

    PubMed Central

    Joo, Soo Hyun; Lim, Hyun Kook

    2016-01-01

    Normal aging and to a greater degree degenerative brain diseases such as Alzheimer's disease (AD), cause changes in the brain's structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD. PMID:26766941

  9. Three Large-Scale Functional Brain Networks from Resting-State Functional MRI in Subjects with Different Levels of Cognitive Impairment.

    PubMed

    Joo, Soo Hyun; Lim, Hyun Kook; Lee, Chang Uk

    2016-01-01

    Normal aging and to a greater degree degenerative brain diseases such as Alzheimer's disease (AD), cause changes in the brain's structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD. PMID:26766941

  10. Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate

    PubMed Central

    Datson, Nicole A; Morsink, Maarten C; Atanasova, Srebrena; Armstrong, Victor W; Zischler, Hans; Schlumbohm, Christina; Dutilh, Bas E; Huynen, Martijn A; Waegele, Brigitte; Ruepp, Andreas; de Kloet, E Ronald; Fuchs, Eberhard

    2007-01-01

    Background The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846]. Conclusion We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model. PMID:17592630

  11. Aneuploidy and Confined Chromosomal Mosaicism in the Developing Human Brain

    PubMed Central

    Liehr, Thomas; Kolotii, Alexei D.; Kutsev, Sergei I.; Pellestor, Franck; Beresheva, Alfia K.; Demidova, Irina A.; Kravets, Viktor S.; Monakhov, Viktor V.; Soloviev, Ilia V.

    2007-01-01

    Background Understanding the mechanisms underlying generation of neuronal variability and complexity remains the central challenge for neuroscience. Structural variation in the neuronal genome is likely to be one important mechanism for neuronal diversity and brain diseases. Large-scale genomic variations due to loss or gain of whole chromosomes (aneuploidy) have been described in cells of the normal and diseased human brain, which are generated from neural stem cells during intrauterine period of life. However, the incidence of aneuploidy in the developing human brain and its impact on the brain development and function are obscure. Methodology/Principal Findings To address genomic variation during development we surveyed aneuploidy/polyploidy in the human fetal tissues by advanced molecular-cytogenetic techniques at the single-cell level. Here we show that the human developing brain has mosaic nature, being composed of euploid and aneuploid neural cells. Studying over 600,000 neural cells, we have determined the average aneuploidy frequency as 1.25–1.45% per chromosome, with the overall percentage of aneuploidy tending to approach 30–35%. Furthermore, we found that mosaic aneuploidy can be exclusively confined to the brain. Conclusions/Significance Our data indicates aneuploidization to be an additional pathological mechanism for neuronal genome diversification. These findings highlight the involvement of aneuploidy in the human brain development and suggest an unexpected link between developmental chromosomal instability, intercellural/intertissular genome diversity and human brain diseases. PMID:17593959

  12. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans.

    PubMed

    Fowler, Sharon P G

    2016-10-01

    For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators' work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs - including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol+aspartame - have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or - in many cases - even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed 'Western' diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet sodas and other

  13. Do You Kiss Your Mother with That Mouth? An Authentic Large-Scale Undergraduate Research Experience in Mapping the Human Oral Microbiome†

    PubMed Central

    Wang, Jack T. H.; Daly, Joshua N.; Willner, Dana L.; Patil, Jayee; Hall, Roy A.; Schembri, Mark A.; Tyson, Gene W.; Hugenholtz, Philip

    2015-01-01

    Clinical microbiology testing is crucial for the diagnosis and treatment of community and hospital-acquired infections. Laboratory scientists need to utilize technical and problem-solving skills to select from a wide array of microbial identification techniques. The inquiry-driven laboratory training required to prepare microbiology graduates for this professional environment can be difficult to replicate within undergraduate curricula, especially in courses that accommodate large student cohorts. We aimed to improve undergraduate scientific training by engaging hundreds of introductory microbiology students in an Authentic Large-Scale Undergraduate Research Experience (ALURE). The ALURE aimed to characterize the microorganisms that reside in the healthy human oral cavity—the oral microbiome—by analyzing hundreds of samples obtained from student volunteers within the course. Students were able to choose from selective and differential culture media, Gram-staining, microscopy, as well as polymerase chain reaction (PCR) and 16S rRNA gene sequencing techniques, in order to collect, analyze, and interpret novel data to determine the collective oral microbiome of the student cohort. Pre- and postsurvey analysis of student learning gains across two iterations of the course (2012–2013) revealed significantly higher student confidence in laboratory skills following the completion of the ALURE (p < 0.05 using the Mann-Whitney U-test). Learning objectives on effective scientific communication were also met through effective student performance in laboratory reports describing the research outcomes of the project. The integration of undergraduate research in clinical microbiology has the capacity to deliver authentic research experiences and improve scientific training for large cohorts of undergraduate students. PMID:25949757

  14. Do you kiss your mother with that mouth? An authentic large-scale undergraduate research experience in mapping the human oral microbiome.

    PubMed

    Wang, Jack T H; Daly, Joshua N; Willner, Dana L; Patil, Jayee; Hall, Roy A; Schembri, Mark A; Tyson, Gene W; Hugenholtz, Philip

    2015-05-01

    Clinical microbiology testing is crucial for the diagnosis and treatment of community and hospital-acquired infections. Laboratory scientists need to utilize technical and problem-solving skills to select from a wide array of microbial identification techniques. The inquiry-driven laboratory training required to prepare microbiology graduates for this professional environment can be difficult to replicate within undergraduate curricula, especially in courses that accommodate large student cohorts. We aimed to improve undergraduate scientific training by engaging hundreds of introductory microbiology students in an Authentic Large-Scale Undergraduate Research Experience (ALURE). The ALURE aimed to characterize the microorganisms that reside in the healthy human oral cavity-the oral microbiome-by analyzing hundreds of samples obtained from student volunteers within the course. Students were able to choose from selective and differential culture media, Gram-staining, microscopy, as well as polymerase chain reaction (PCR) and 16S rRNA gene sequencing techniques, in order to collect, analyze, and interpret novel data to determine the collective oral microbiome of the student cohort. Pre- and postsurvey analysis of student learning gains across two iterations of the course (2012-2013) revealed significantly higher student confidence in laboratory skills following the completion of the ALURE (p < 0.05 using the Mann-Whitney U-test). Learning objectives on effective scientific communication were also met through effective student performance in laboratory reports describing the research outcomes of the project. The integration of undergraduate research in clinical microbiology has the capacity to deliver authentic research experiences and improve scientific training for large cohorts of undergraduate students. PMID:25949757

  15. Educating the Human Brain. Human Brain Development Series

    ERIC Educational Resources Information Center

    Posner, Michael I.; Rothbart, Mary K.

    2006-01-01

    "Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

  16. Large-Scale Information Systems

    SciTech Connect

    D. M. Nicol; H. R. Ammerlahn; M. E. Goldsby; M. M. Johnson; D. E. Rhodes; A. S. Yoshimura

    2000-12-01

    Large enterprises are ever more dependent on their Large-Scale Information Systems (LSLS), computer systems that are distinguished architecturally by distributed components--data sources, networks, computing engines, simulations, human-in-the-loop control and remote access stations. These systems provide such capabilities as workflow, data fusion and distributed database access. The Nuclear Weapons Complex (NWC) contains many examples of LSIS components, a fact that motivates this research. However, most LSIS in use grew up from collections of separate subsystems that were not designed to be components of an integrated system. For this reason, they are often difficult to analyze and control. The problem is made more difficult by the size of a typical system, its diversity of information sources, and the institutional complexities associated with its geographic distribution across the enterprise. Moreover, there is no integrated approach for analyzing or managing such systems. Indeed, integrated development of LSIS is an active area of academic research. This work developed such an approach by simulating the various components of the LSIS and allowing the simulated components to interact with real LSIS subsystems. This research demonstrated two benefits. First, applying it to a particular LSIS provided a thorough understanding of the interfaces between the system's components. Second, it demonstrated how more rapid and detailed answers could be obtained to questions significant to the enterprise by interacting with the relevant LSIS subsystems through simulated components designed with those questions in mind. In a final, added phase of the project, investigations were made on extending this research to wireless communication networks in support of telemetry applications.

  17. Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: An anatomical and behavioral analysis.

    PubMed

    You, Si-Wei; Hellström, Mats; Pollett, Margaret A; LeVaillant, Chrisna; Moses, Colette; Rigby, Paul J; Penrose, Marissa; Rodger, Jennifer; Harvey, Alan R

    2016-05-01

    Peripheral nerve (PN) grafts can be used to bridge tissue defects in the CNS. Using a PN-to-optic nerve (ON) graft model, we combined gene therapy with pharmacotherapy to promote the long-distance regeneration of injured adult retinal ganglion cells (RGCs). Autologous sciatic nerve was sutured onto the transected ON and the distal end immediately inserted into contralateral superior colliculus (SC). Control rats received intraocular injections of saline or adeno-associated virus (AAV) encoding GFP. In experimental groups, three bi-cistronic AAV vectors encoding ciliary neurotrophic factor (CNTF) were injected into different regions of the grafted eye. Each vector encoded a different fluorescent reporter to assess retinotopic order in the regenerate projection. To encourage sprouting/synaptogenesis, after 6 weeks some AAV-CNTF injected rats received an intravitreal injection of recombinant brain-derived neurotrophic factor (rBDNF) or AAV-BDNF. Four months after surgery, cholera toxin B was used to visualize regenerate RGC axons. RGC viability and axonal regrowth into SC were significantly greater in AAV-CNTF groups. In some cases, near the insertion site, regenerate axonal density resembled retinal terminal densities seen in normal SC. Complex arbors were seen in superficial but not deep SC layers and many terminals were immunopositive for presynaptic proteins vGlut2 and SV2. There was improvement in visual function via the grafted eye with significantly greater pupillary constriction in both AAV-CNTF+BDNF groups. In both control and AAV-CNTF+rBDNF groups the extent of light avoidance correlated with the maximal distance of axonal penetration into superficial SC. Despite the robust regrowth of RGC axons back into the SC, axons originating from different parts of the retina were intermixed at the PN graft/host SC interface, indicating that there remained a lack of order in this extensive regenerate projection. PMID:26970586

  18. Galaxy clustering on large scales.

    PubMed

    Efstathiou, G

    1993-06-01

    I describe some recent observations of large-scale structure in the galaxy distribution. The best constraints come from two-dimensional galaxy surveys and studies of angular correlation functions. Results from galaxy redshift surveys are much less precise but are consistent with the angular correlations, provided the distortions in mapping between real-space and redshift-space are relatively weak. The galaxy two-point correlation function, rich-cluster two-point correlation function, and galaxy-cluster cross-correlation function are all well described on large scales ( greater, similar 20h-1 Mpc, where the Hubble constant, H0 = 100h km.s-1.Mpc; 1 pc = 3.09 x 10(16) m) by the power spectrum of an initially scale-invariant, adiabatic, cold-dark-matter Universe with Gamma = Omegah approximately 0.2. I discuss how this fits in with the Cosmic Background Explorer (COBE) satellite detection of large-scale anisotropies in the microwave background radiation and other measures of large-scale structure in the Universe. PMID:11607400

  19. Very Large Scale Integration (VLSI).

    ERIC Educational Resources Information Center

    Yeaman, Andrew R. J.

    Very Large Scale Integration (VLSI), the state-of-the-art production techniques for computer chips, promises such powerful, inexpensive computing that, in the future, people will be able to communicate with computer devices in natural language or even speech. However, before full-scale VLSI implementation can occur, certain salient factors must be…

  20. Large-scale cortical correlation structure of spontaneous oscillatory activity

    PubMed Central

    Hipp, Joerg F.; Hawellek, David J.; Corbetta, Maurizio; Siegel, Markus; Engel, Andreas K.

    2013-01-01

    Little is known about the brain-wide correlation of electrophysiological signals. Here we show that spontaneous oscillatory neuronal activity exhibits frequency-specific spatial correlation structure in the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography (MEG). Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz), and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency specific power-envelope correlations. PMID:22561454

  1. Dynamics of large-scale cortical interactions at high gamma frequencies during word production: Event related causality (ERC) analysis of human electrocorticography (ECoG)

    PubMed Central

    Korzeniewska, Anna; Franaszczuk, Piotr J.; Crainiceanu, Ciprian M.; Kuś, Rafał; Crone, Nathan E.

    2011-01-01

    Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (> 60 Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC “divergence”, were also sites where high gamma power increases were most prominent and where electrocortical stimulation

  2. Progress and challenges in probing the human brain.

    PubMed

    Poldrack, Russell A; Farah, Martha J

    2015-10-15

    Perhaps one of the greatest scientific challenges is to understand the human brain. Here we review current methods in human neuroscience, highlighting the ways that they have been used to study the neural bases of the human mind. We begin with a consideration of different levels of description relevant to human neuroscience, from molecules to large-scale networks, and then review the methods that probe these levels and the ability of these methods to test hypotheses about causal mechanisms. Functional MRI is considered in particular detail, as it has been responsible for much of the recent growth of human neuroscience research. We briefly review its inferential strengths and weaknesses and present examples of new analytic approaches that allow inferences beyond simple localization of psychological processes. Finally, we review the prospects for real-world applications and new scientific challenges for human neuroscience. PMID:26469048

  3. A navigational guidance system in the human brain.

    PubMed

    Spiers, Hugo J; Maguire, Eleanor A

    2007-01-01

    Finding your way in large-scale space requires knowing where you currently are and how to get to your goal destination. While much is understood about the neural basis of one's current position during navigation, surprisingly little is known about how the human brain guides navigation to goals. Computational accounts argue that specific brain regions support navigational guidance by coding the proximity and direction to the goal, but empirical evidence for such mechanisms is lacking. Here, we scanned subjects with functional magnetic resonance imaging as they navigated to goal destinations in a highly accurate virtual simulation of a real city. Brain activity was then analyzed in combination with metric measures of proximity and direction to goal destinations that were derived from each individual subject's coordinates at every second of navigation. We found that activity in the medial prefrontal cortex was positively correlated, and activity in a right subicular/entorhinal region was negatively correlated with goal proximity. By contrast, activity in bilateral posterior parietal cortex was correlated with egocentric direction to goals. Our results provide empirical evidence for a navigational guidance system in the human brain, and define more precisely the contribution of these three brain regions to human navigation. In addition, these findings may also have wider implications for how the brain monitors and integrates different types of information in the service of goal-directed behavior in general. PMID:17492693

  4. A navigational guidance system in the human brain

    PubMed Central

    Spiers, Hugo J.; Maguire, Eleanor A.

    2008-01-01

    Finding your way in large-scale space requires knowing where you currently are and how to get to your goal destination. While much is understood about the neural basis of one’s current position during navigation, surprisingly little is known about how the human brain guides navigation to goals. Computational accounts argue that specific brain regions support navigational guidance by coding the proximity and direction to the goal, but empirical evidence for such mechanisms is lacking. Here, we scanned subjects with functional MRI (fMRI) as they navigated to goal destinations in a highly accurate virtual simulation of a real city. Brain activity was then analysed in combination with metric measures of proximity and direction to goal destinations which were derived from each individual subject’s coordinates at every second of navigation. We found that activity in the medial prefrontal cortex was positively correlated, and activity in a right subicular/entorhinal region was negatively correlated with goal proximity. By contrast, activity in bilateral posterior parietal cortex was correlated with egocentric direction to goals. Our results provide empirical evidence for a navigational guidance system in the human brain, and define more precisely the contribution of these three brain regions to human navigation. In addition, these findings may also have wider implications for how the brain monitors and integrates different types of information in the service of goal-directed behaviour in general. PMID:17492693

  5. Microfluidic large-scale integration.

    PubMed

    Thorsen, Todd; Maerkl, Sebastian J; Quake, Stephen R

    2002-10-18

    We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory. PMID:12351675

  6. INTERNATIONAL WORKSHOP ON LARGE-SCALE REFORESTATION: PROCEEDINGS

    EPA Science Inventory

    The purpose of the workshop was to identify major operational and ecological considerations needed to successfully conduct large-scale reforestation projects throughout the forested regions of the world. Large-scale" for this workshop means projects where, by human effort, approx...

  7. Epigenetics in the Human Brain

    PubMed Central

    Houston, Isaac; Peter, Cyril J; Mitchell, Amanda; Straubhaar, Juerg; Rogaev, Evgeny; Akbarian, Schahram

    2013-01-01

    Many cellular constituents in the human brain permanently exit from the cell cycle during pre- or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether >100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size. PMID:22643929

  8. Scaling and Criticality in Large-Scale Neuronal Activity

    NASA Astrophysics Data System (ADS)

    Linkenkaer-Hansen, K.

    The human brain during wakeful rest spontaneously generates large-scale neuronal network oscillations at around 10 and 20 Hz that can be measured non-invasively using magnetoencephalography (MEG) or electroencephalography (EEG). In this chapter, spontaneous oscillations are viewed as the outcome of a self-organizing stochastic process. The aim is to introduce the general prerequisites for stochastic systems to evolve to the critical state and to explain their neurophysiological equivalents. I review the recent evidence that the theory of self-organized criticality (SOC) may provide a unifying explanation for the large variability in amplitude, duration, and recurrence of spontaneous network oscillations, as well as the high susceptibility to perturbations and the long-range power-law temporal correlations in their amplitude envelope.

  9. Large scale topography of Io

    NASA Technical Reports Server (NTRS)

    Gaskell, R. W.; Synnott, S. P.

    1987-01-01

    To investigate the large scale topography of the Jovian satellite Io, both limb observations and stereographic techniques applied to landmarks are used. The raw data for this study consists of Voyager 1 images of Io, 800x800 arrays of picture elements each of which can take on 256 possible brightness values. In analyzing this data it was necessary to identify and locate landmarks and limb points on the raw images, remove the image distortions caused by the camera electronics and translate the corrected locations into positions relative to a reference geoid. Minimizing the uncertainty in the corrected locations is crucial to the success of this project. In the highest resolution frames, an error of a tenth of a pixel in image space location can lead to a 300 m error in true location. In the lowest resolution frames, the same error can lead to an uncertainty of several km.

  10. Challenges for Large Scale Simulations

    NASA Astrophysics Data System (ADS)

    Troyer, Matthias

    2010-03-01

    With computational approaches becoming ubiquitous the growing impact of large scale computing on research influences both theoretical and experimental work. I will review a few examples in condensed matter physics and quantum optics, including the impact of computer simulations in the search for supersolidity, thermometry in ultracold quantum gases, and the challenging search for novel phases in strongly correlated electron systems. While only a decade ago such simulations needed the fastest supercomputers, many simulations can now be performed on small workstation clusters or even a laptop: what was previously restricted to a few experts can now potentially be used by many. Only part of the gain in computational capabilities is due to Moore's law and improvement in hardware. Equally impressive is the performance gain due to new algorithms - as I will illustrate using some recently developed algorithms. At the same time modern peta-scale supercomputers offer unprecedented computational power and allow us to tackle new problems and address questions that were impossible to solve numerically only a few years ago. While there is a roadmap for future hardware developments to exascale and beyond, the main challenges are on the algorithmic and software infrastructure side. Among the problems that face the computational physicist are: the development of new algorithms that scale to thousands of cores and beyond, a software infrastructure that lifts code development to a higher level and speeds up the development of new simulation programs for large scale computing machines, tools to analyze the large volume of data obtained from such simulations, and as an emerging field provenance-aware software that aims for reproducibility of the complete computational workflow from model parameters to the final figures. Interdisciplinary collaborations and collective efforts will be required, in contrast to the cottage-industry culture currently present in many areas of computational

  11. What is the nature of causality in the brain? - Inherently probabilistic. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Dhamala, Mukesh

    2015-12-01

    Understanding cause-and-effect (causal) relations from observations concerns all sciences including neuroscience. Appropriately defining causality and its nature, though, has been a topic of active discussion for philosophers and scientists for centuries. Although brain research, particularly functional neuroimaging research, is now moving rapidly beyond identification of brain regional activations towards uncovering causal relations between regions, the nature of causality has not be been thoroughly described and resolved. In the current review article [1], Mannino and Bressler take us on a beautiful journey into the history of the work on causality and make a well-reasoned argument that the causality in the brain is inherently probabilistic. This notion is consistent with brain anatomy and functions, and is also inclusive of deterministic cases of inputs leading to outputs in the brain.

  12. Mapping human brain networks with cortico-cortical evoked potentials

    PubMed Central

    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  13. Mapping human brain networks with cortico-cortical evoked potentials.

    PubMed

    Keller, Corey J; Honey, Christopher J; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D

    2014-10-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  14. Deterministic versus probabilistic causality in the brain: To cut or not to cut. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Zhang, Mengsen; Nordham, Craig; Kelso, J. A. Scott

    2015-12-01

    In recent decades the rapid growth of new imaging technologies and measurement tools has dramatically changed how neuroscientists explore the function of the brain. A careful examination of the conceptual basis of causal inference using such methods is long overdue. Mannino and Bressler (M&B) [1] provide an informative review on the notion of causality from the perspectives of philosophy, physics, complex systems and brain sciences.

  15. Large Scale Homing in Honeybees

    PubMed Central

    Pahl, Mario; Zhu, Hong; Tautz, Jürgen; Zhang, Shaowu

    2011-01-01

    Honeybee foragers frequently fly several kilometres to and from vital resources, and communicate those locations to their nest mates by a symbolic dance language. Research has shown that they achieve this feat by memorizing landmarks and the skyline panorama, using the sun and polarized skylight as compasses and by integrating their outbound flight paths. In order to investigate the capacity of the honeybees' homing abilities, we artificially displaced foragers to novel release spots at various distances up to 13 km in the four cardinal directions. Returning bees were individually registered by a radio frequency identification (RFID) system at the hive entrance. We found that homing rate, homing speed and the maximum homing distance depend on the release direction. Bees released in the east were more likely to find their way back home, and returned faster than bees released in any other direction, due to the familiarity of global landmarks seen from the hive. Our findings suggest that such large scale homing is facilitated by global landmarks acting as beacons, and possibly the entire skyline panorama. PMID:21602920

  16. Modeling of Large-Scale Functional Brain Networks Based on Structural Connectivity from DTI: Comparison with EEG Derived Phase Coupling Networks and Evaluation of Alternative Methods along the Modeling Path

    PubMed Central

    Cheng, Bastian; Messé, Arnaud; Thomalla, Götz; Gerloff, Christian; König, Peter

    2016-01-01

    In this study, we investigate if phase-locking of fast oscillatory activity relies on the anatomical skeleton and if simple computational models informed by structural connectivity can help further to explain missing links in the structure-function relationship. We use diffusion tensor imaging data and alpha band-limited EEG signal recorded in a group of healthy individuals. Our results show that about 23.4% of the variance in empirical networks of resting-state functional connectivity is explained by the underlying white matter architecture. Simulating functional connectivity using a simple computational model based on the structural connectivity can increase the match to 45.4%. In a second step, we use our modeling framework to explore several technical alternatives along the modeling path. First, we find that an augmentation of homotopic connections in the structural connectivity matrix improves the link to functional connectivity while a correction for fiber distance slightly decreases the performance of the model. Second, a more complex computational model based on Kuramoto oscillators leads to a slight improvement of the model fit. Third, we show that the comparison of modeled and empirical functional connectivity at source level is much more specific for the underlying structural connectivity. However, different source reconstruction algorithms gave comparable results. Of note, as the fourth finding, the model fit was much better if zero-phase lag components were preserved in the empirical functional connectome, indicating a considerable amount of functionally relevant synchrony taking place with near zero or zero-phase lag. The combination of the best performing alternatives at each stage in the pipeline results in a model that explains 54.4% of the variance in the empirical EEG functional connectivity. Our study shows that large-scale brain circuits of fast neural network synchrony strongly rely upon the structural connectome and simple computational

  17. Modeling of Large-Scale Functional Brain Networks Based on Structural Connectivity from DTI: Comparison with EEG Derived Phase Coupling Networks and Evaluation of Alternative Methods along the Modeling Path.

    PubMed

    Finger, Holger; Bönstrup, Marlene; Cheng, Bastian; Messé, Arnaud; Hilgetag, Claus; Thomalla, Götz; Gerloff, Christian; König, Peter

    2016-08-01

    In this study, we investigate if phase-locking of fast oscillatory activity relies on the anatomical skeleton and if simple computational models informed by structural connectivity can help further to explain missing links in the structure-function relationship. We use diffusion tensor imaging data and alpha band-limited EEG signal recorded in a group of healthy individuals. Our results show that about 23.4% of the variance in empirical networks of resting-state functional connectivity is explained by the underlying white matter architecture. Simulating functional connectivity using a simple computational model based on the structural connectivity can increase the match to 45.4%. In a second step, we use our modeling framework to explore several technical alternatives along the modeling path. First, we find that an augmentation of homotopic connections in the structural connectivity matrix improves the link to functional connectivity while a correction for fiber distance slightly decreases the performance of the model. Second, a more complex computational model based on Kuramoto oscillators leads to a slight improvement of the model fit. Third, we show that the comparison of modeled and empirical functional connectivity at source level is much more specific for the underlying structural connectivity. However, different source reconstruction algorithms gave comparable results. Of note, as the fourth finding, the model fit was much better if zero-phase lag components were preserved in the empirical functional connectome, indicating a considerable amount of functionally relevant synchrony taking place with near zero or zero-phase lag. The combination of the best performing alternatives at each stage in the pipeline results in a model that explains 54.4% of the variance in the empirical EEG functional connectivity. Our study shows that large-scale brain circuits of fast neural network synchrony strongly rely upon the structural connectome and simple computational

  18. Large Scale Nanolaminate Deformable Mirror

    SciTech Connect

    Papavasiliou, A; Olivier, S; Barbee, T; Miles, R; Chang, K

    2005-11-30

    This work concerns the development of a technology that uses Nanolaminate foils to form light-weight, deformable mirrors that are scalable over a wide range of mirror sizes. While MEMS-based deformable mirrors and spatial light modulators have considerably reduced the cost and increased the capabilities of adaptive optic systems, there has not been a way to utilize the advantages of lithography and batch-fabrication to produce large-scale deformable mirrors. This technology is made scalable by using fabrication techniques and lithography that are not limited to the sizes of conventional MEMS devices. Like many MEMS devices, these mirrors use parallel plate electrostatic actuators. This technology replicates that functionality by suspending a horizontal piece of nanolaminate foil over an electrode by electroplated nickel posts. This actuator is attached, with another post, to another nanolaminate foil that acts as the mirror surface. Most MEMS devices are produced with integrated circuit lithography techniques that are capable of very small line widths, but are not scalable to large sizes. This technology is very tolerant of lithography errors and can use coarser, printed circuit board lithography techniques that can be scaled to very large sizes. These mirrors use small, lithographically defined actuators and thin nanolaminate foils allowing them to produce deformations over a large area while minimizing weight. This paper will describe a staged program to develop this technology. First-principles models were developed to determine design parameters. Three stages of fabrication will be described starting with a 3 x 3 device using conventional metal foils and epoxy to a 10-across all-metal device with nanolaminate mirror surfaces.

  19. Large-scale databases of proper names.

    PubMed

    Conley, P; Burgess, C; Hage, D

    1999-05-01

    Few tools for research in proper names have been available--specifically, there is no large-scale corpus of proper names. Two corpora of proper names were constructed, one based on U.S. phone book listings, the other derived from a database of Usenet text. Name frequencies from both corpora were compared with human subjects' reaction times (RTs) to the proper names in a naming task. Regression analysis showed that the Usenet frequencies contributed to predictions of human RT, whereas phone book frequencies did not. In addition, semantic neighborhood density measures derived from the HAL corpus were compared with the subjects' RTs and found to be a better predictor of RT than was frequency in either corpus. These new corpora are freely available on line for download. Potentials for these corpora range from using the names as stimuli in experiments to using the corpus data in software applications. PMID:10495803

  20. A Direct Brain-to-Brain Interface in Humans

    PubMed Central

    Rao, Rajesh P. N.; Stocco, Andrea; Bryan, Matthew; Sarma, Devapratim; Youngquist, Tiffany M.; Wu, Joseph; Prat, Chantel S.

    2014-01-01

    We describe the first direct brain-to-brain interface in humans and present results from experiments involving six different subjects. Our non-invasive interface, demonstrated originally in August 2013, combines electroencephalography (EEG) for recording brain signals with transcranial magnetic stimulation (TMS) for delivering information to the brain. We illustrate our method using a visuomotor task in which two humans must cooperate through direct brain-to-brain communication to achieve a desired goal in a computer game. The brain-to-brain interface detects motor imagery in EEG signals recorded from one subject (the “sender”) and transmits this information over the internet to the motor cortex region of a second subject (the “receiver”). This allows the sender to cause a desired motor response in the receiver (a press on a touchpad) via TMS. We quantify the performance of the brain-to-brain interface in terms of the amount of information transmitted as well as the accuracies attained in (1) decoding the sender’s signals, (2) generating a motor response from the receiver upon stimulation, and (3) achieving the overall goal in the cooperative visuomotor task. Our results provide evidence for a rudimentary form of direct information transmission from one human brain to another using non-invasive means. PMID:25372285

  1. Technology for Large-Scale Translation of Clinical Practice Guidelines: A Pilot Study of the Performance of a Hybrid Human and Computer-Assisted Approach

    PubMed Central

    2015-01-01

    Background The construction of EBMPracticeNet, a national electronic point-of-care information platform in Belgium, began in 2011 to optimize quality of care by promoting evidence-based decision making. The project involved, among other tasks, the translation of 940 EBM Guidelines of Duodecim Medical Publications from English into Dutch and French. Considering the scale of the translation process, it was decided to make use of computer-aided translation performed by certificated translators with limited expertise in medical translation. Our consortium used a hybrid approach, involving a human translator supported by a translation memory (using SDL Trados Studio), terminology recognition (using SDL MultiTerm terminology databases) from medical terminology databases, and support from online machine translation. This resulted in a validated translation memory, which is now in use for the translation of new and updated guidelines. Objective The objective of this experiment was to evaluate the performance of the hybrid human and computer-assisted approach in comparison with translation unsupported by translation memory and terminology recognition. A comparison was also made with the translation efficiency of an expert medical translator. Methods We conducted a pilot study in which two sets of 30 new and 30 updated guidelines were randomized to one of three groups. Comparable guidelines were translated (1) by certificated junior translators without medical specialization using the hybrid method, (2) by an experienced medical translator without this support, and (3) by the same junior translators without the support of the validated translation memory. A medical proofreader who was blinded for the translation procedure, evaluated the translated guidelines for acceptability and adequacy. Translation speed was measured by recording translation and post-editing time. The human translation edit rate was calculated as a metric to evaluate the quality of the translation. A

  2. From details to large scale: the representation of environmental positions follows a granularity gradient along the human hippocampal and entorhinal anterior-posterior axis.

    PubMed

    Evensmoen, Hallvard Røe; Ladstein, Jarle; Hansen, Tor Ivar; Møller, Jarle Alexander; Witter, Menno P; Nadel, Lynn; Håberg, Asta K

    2015-01-01

    In rodents representations of environmental positions follow a granularity gradient along the hippocampal and entorhinal anterior-posterior axis; with fine-grained representations most posteriorly. To investigate if such a gradient exists in humans, functional magnetic resonance imaging data were acquired during virtual environmental learning of the objects' positions and the association between the objects and room geometry. The Objects-room geometry binding led to increased activation throughout the hippocampus and in the posterior entorhinal cortex. Within subject comparisons related specifically to the level of spatial granularity of the object position encoding showed that activation in the posterior and intermediate hippocampus was highest for fine-grained and medium-grained representations, respectively. In addition, the level of fine granularity in the objects' positions encoded between subjects correlated with posterior hippocampal activation. For the anterior hippocampus increased activation was observed for coarse-grained representations as compared to failed encoding. Activation in anterior hippocampus correlated with the number of environments in which the objects positions were remembered when permitting a coarse representation of positions. In the entorhinal cortex, activation in the posterior part correlated with level of fine granularity for the objects' positions encoded between subjects, and activation in the posterior and intermediate entorhinal cortex increased for medium-grained representations. This demonstrates directly that positional granularity is represented in a graded manner along the anterior-posterior axis of the human hippocampus, and to some extent entorhinal cortex, with most fine-grained positional representations posteriorly. PMID:25155295

  3. Large-scale cloning of human chromosome 2-specific yeast artificial chromosomes (YACs) using an interspersed repetitive sequences (IRS)-PCR approach

    SciTech Connect

    Liu, J.; Rezonzew, R. |; Stanton, V.P. Jr.

    1995-03-20

    We report here an efficient approach to the establishment of extended YAC contigs on human chromosome 2 by using an interspersed repetitive sequences (IRS)-PCR-based screening strategy for YAC DNA pools. Genomic DNA was extracted from 1152 YAC pools comprised of 55,296 YACs mostly derived from the CEPH Mark I library. Alu-element-mediated PCR was performed for each pool, and amplification products were spotted on hybridization membranes (IRS filters). IRS probes for the screening of the IRS filters were obtained by Alu-element-mediated PCR. Of 708 distinct probes obtained from chromosome 2-specific somatic cell hybrids, 85% were successfully used for library screening. Similarly, 80% of 80 YAC walking probes were successfully used for library screening. Each probe detected an average of 6.6 YACs, which is in good agreement with the 7- to 7.5-fold genome coverage provided by the library. In a preliminary analysis, we have identified 188 YAC groups that are the basis for building contigs for chromosome 2. The coverage of the telomeric half of chromosome 2q was considered to be good since 31 of 34 microsatellites and 22 of 23 expressed sequence tags that were chosen from chromosome region 2q13-q37 were contained in a chromosome 2 YAC sublibrary generated by our experiments. We have identified a minimum of 1610 distinct chromosome 2-specific YACs, which will be a valuable asset for the physical mapping of the second largest human chromosome. 81 refs., 8 figs., 3 tabs.

  4. Development of large-scale functional networks over the lifespan.

    PubMed

    Schlee, Winfried; Leirer, Vera; Kolassa, Stephan; Thurm, Franka; Elbert, Thomas; Kolassa, Iris-Tatjana

    2012-10-01

    The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence. PMID:22236372

  5. Engineering management of large scale systems

    NASA Technical Reports Server (NTRS)

    Sanders, Serita; Gill, Tepper L.; Paul, Arthur S.

    1989-01-01

    The organization of high technology and engineering problem solving, has given rise to an emerging concept. Reasoning principles for integrating traditional engineering problem solving with system theory, management sciences, behavioral decision theory, and planning and design approaches can be incorporated into a methodological approach to solving problems with a long range perspective. Long range planning has a great potential to improve productivity by using a systematic and organized approach. Thus, efficiency and cost effectiveness are the driving forces in promoting the organization of engineering problems. Aspects of systems engineering that provide an understanding of management of large scale systems are broadly covered here. Due to the focus and application of research, other significant factors (e.g., human behavior, decision making, etc.) are not emphasized but are considered.

  6. Phylogeographic Refinement and Large Scale Genotyping of Human Y Chromosome Haplogroup E Provide New Insights into the Dispersal of Early Pastoralists in the African Continent.

    PubMed

    Trombetta, Beniamino; D'Atanasio, Eugenia; Massaia, Andrea; Ippoliti, Marco; Coppa, Alfredo; Candilio, Francesca; Coia, Valentina; Russo, Gianluca; Dugoujon, Jean-Michel; Moral, Pedro; Akar, Nejat; Sellitto, Daniele; Valesini, Guido; Novelletto, Andrea; Scozzari, Rosaria; Cruciani, Fulvio

    2015-07-01

    Haplogroup E, defined by mutation M40, is the most common human Y chromosome clade within Africa. To increase the level of resolution of haplogroup E, we disclosed the phylogenetic relationships among 729 mutations found in 33 haplogroup DE Y-chromosomes sequenced at high coverage in previous studies. Additionally, we dissected the E-M35 subclade by genotyping 62 informative markers in 5,222 samples from 118 worldwide populations. The phylogeny of haplogroup E showed novel features compared with the previous topology, including a new basal dichotomy. Within haplogroup E-M35, we resolved all the previously known polytomies and assigned all the E-M35* chromosomes to five new different clades, all belonging to a newly identified subhaplogroup (E-V1515), which accounts for almost half of the E-M35 chromosomes from the Horn of Africa. Moreover, using a Bayesian phylogeographic analysis and a single nucleotide polymorphism-based approach we localized and dated the origin of this new lineage in the northern part of the Horn, about 12 ka. Time frames, phylogenetic structuring, and sociogeographic distribution of E-V1515 and its subclades are consistent with a multistep demic spread of pastoralism within north-eastern Africa and its subsequent diffusion to subequatorial areas. In addition, our results increase the discriminative power of the E-M35 haplogroup for use in forensic genetics through the identification of new ancestry-informative markers. PMID:26108492

  7. Phylogeographic Refinement and Large Scale Genotyping of Human Y Chromosome Haplogroup E Provide New Insights into the Dispersal of Early Pastoralists in the African Continent

    PubMed Central

    Trombetta, Beniamino; D’Atanasio, Eugenia; Massaia, Andrea; Ippoliti, Marco; Coppa, Alfredo; Candilio, Francesca; Coia, Valentina; Russo, Gianluca; Dugoujon, Jean-Michel; Moral, Pedro; Akar, Nejat; Sellitto, Daniele; Valesini, Guido; Novelletto, Andrea; Scozzari, Rosaria; Cruciani, Fulvio

    2015-01-01

    Haplogroup E, defined by mutation M40, is the most common human Y chromosome clade within Africa. To increase the level of resolution of haplogroup E, we disclosed the phylogenetic relationships among 729 mutations found in 33 haplogroup DE Y-chromosomes sequenced at high coverage in previous studies. Additionally, we dissected the E-M35 subclade by genotyping 62 informative markers in 5,222 samples from 118 worldwide populations. The phylogeny of haplogroup E showed novel features compared with the previous topology, including a new basal dichotomy. Within haplogroup E-M35, we resolved all the previously known polytomies and assigned all the E-M35* chromosomes to five new different clades, all belonging to a newly identified subhaplogroup (E-V1515), which accounts for almost half of the E-M35 chromosomes from the Horn of Africa. Moreover, using a Bayesian phylogeographic analysis and a single nucleotide polymorphism-based approach we localized and dated the origin of this new lineage in the northern part of the Horn, about 12 ka. Time frames, phylogenetic structuring, and sociogeographic distribution of E-V1515 and its subclades are consistent with a multistep demic spread of pastoralism within north-eastern Africa and its subsequent diffusion to subequatorial areas. In addition, our results increase the discriminative power of the E-M35 haplogroup for use in forensic genetics through the identification of new ancestry-informative markers. PMID:26108492

  8. Human Brain Reacts to Transcranial Extraocular Light.

    PubMed

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H; Karhunen, Pekka J; Hartikainen, Kaisa M

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain. PMID:26910350

  9. Human Brain Reacts to Transcranial Extraocular Light

    PubMed Central

    Sun, Lihua; Peräkylä, Jari; Kovalainen, Anselmi; Ogawa, Keith H.; Karhunen, Pekka J.; Hartikainen, Kaisa M.

    2016-01-01

    Transcranial extraocular light affects the brains of birds and modulates their seasonal changes in physiology and behavior. However, whether the human brain is sensitive to extraocular light is unknown. To test whether extraocular light has any effect on human brain functioning, we measured brain electrophysiology of 18 young healthy subjects using event-related potentials while they performed a visual attention task embedded with emotional distractors. Extraocular light delivered via ear canals abolished normal emotional modulation of attention related brain responses. With no extraocular light delivered, emotional distractors reduced centro-parietal P300 amplitude compared to neutral distractors. This phenomenon disappeared with extraocular light delivery. Extraocular light delivered through the ear canals was shown to penetrate at the base of the scull of a cadaver. Thus, we have shown that extraocular light impacts human brain functioning calling for further research on the mechanisms of action of light on the human brain. PMID:26910350

  10. Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

    PubMed Central

    Koscik, Timothy R.; Tranel, Daniel

    2013-01-01

    Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

  11. Evaluating effective reaction rates of kinetically driven solutes in large-scale, anisotropic media: human health risk implications in CO2 leakage

    NASA Astrophysics Data System (ADS)

    Siirila, E. R.; Maxwell, R. M.

    2011-12-01

    The role of high and low hydraulic conductivity (K) regions in heterogeneous, stratified and non-stratified flow fields and the subsequent effect of rate dependent geochemical reactions are investigated with regards to mobilized arsenic from CO2 leakage at a Carbon Capture and Storage (CCS) site. Following the methodology of previous work, human health risk is used as an endpoint for comparison via a two-stage or nested Monte Carlo scheme, explicitly considering joint uncertainty and variability for a hypothetical population of individuals. This study identifies geo-hydrologic conditions where solute reactions are either rate limited (non-reactive), in equilibrium (linear equilibrium assumption, LEA, is appropriate), or are sensitive to time-dependent kinetic reaction rates. Potential interplay between multiple parameters (i.e. positive or negative feedbacks) is shown utilizing stochastic ensembles. In particular, the effect of preferential flow pathways and solute mixing on the field-scale (macrodispersion) and sub-grid (local dispersion) is examined for varying degrees of stratification and regional groundwater velocities. Results show effective reaction rates of kinetic ensembles are dissimilar from LEA ensembles with the inclusion of local dispersion, resulting in an additive tailing effect of the solute plume, a retarded peak time, and an increased cancer risk. This discrepancy between kinetic and LEA ensembles is augmented in highly anisotropic media, especially at intermediate regional groundwater velocities. The distribution, magnitude, and associated uncertainty of cancer risk are controlled by these factors, but are also strongly dependent on the regional groundwater velocity. We demonstrate a higher associated uncertainty of cancer risk in stratified domains is linked to higher aquifer connectivity and less macrodispersion in the flow field. This study has implications in CCS site selection and groundwater driven risk assessment modeling.

  12. Supporting large-scale computational science

    SciTech Connect

    Musick, R

    1998-10-01

    A study has been carried out to determine the feasibility of using commercial database management systems (DBMSs) to support large-scale computational science. Conventional wisdom in the past has been that DBMSs are too slow for such data. Several events over the past few years have muddied the clarity of this mindset: 1. 2. 3. 4. Several commercial DBMS systems have demonstrated storage and ad-hoc quer access to Terabyte data sets. Several large-scale science teams, such as EOSDIS [NAS91], high energy physics [MM97] and human genome [Kin93] have adopted (or make frequent use of) commercial DBMS systems as the central part of their data management scheme. Several major DBMS vendors have introduced their first object-relational products (ORDBMSs), which have the potential to support large, array-oriented data. In some cases, performance is a moot issue. This is true in particular if the performance of legacy applications is not reduced while new, albeit slow, capabilities are added to the system. The basic assessment is still that DBMSs do not scale to large computational data. However, many of the reasons have changed, and there is an expiration date attached to that prognosis. This document expands on this conclusion, identifies the advantages and disadvantages of various commercial approaches, and describes the studies carried out in exploring this area. The document is meant to be brief, technical and informative, rather than a motivational pitch. The conclusions within are very likely to become outdated within the next 5-7 years, as market forces will have a significant impact on the state of the art in scientific data management over the next decade.

  13. Large-scale topology and the default mode network in the mouse connectome.

    PubMed

    Stafford, James M; Jarrett, Benjamin R; Miranda-Dominguez, Oscar; Mills, Brian D; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P; Lattal, K Matthew; Mitchell, Suzanne H; David, Stephen V; Fryer, John D; Nigg, Joel T; Fair, Damien A

    2014-12-30

    Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)--a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

  14. Large-scale topology and the default mode network in the mouse connectome

    PubMed Central

    Stafford, James M.; Jarrett, Benjamin R.; Miranda-Dominguez, Oscar; Mills, Brian D.; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P.; Lattal, K. Matthew; Mitchell, Suzanne H.; David, Stephen V.; Fryer, John D.; Nigg, Joel T.; Fair, Damien A.

    2014-01-01

    Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

  15. Probabilistic Cuing in Large-Scale Environmental Search

    ERIC Educational Resources Information Center

    Smith, Alastair D.; Hood, Bruce M.; Gilchrist, Iain D.

    2010-01-01

    Finding an object in our environment is an important human ability that also represents a critical component of human foraging behavior. One type of information that aids efficient large-scale search is the likelihood of the object being in one location over another. In this study we investigated the conditions under which individuals respond to…

  16. Large-Scale Reform Comes of Age

    ERIC Educational Resources Information Center

    Fullan, Michael

    2009-01-01

    This article reviews the history of large-scale education reform and makes the case that large-scale or whole system reform policies and strategies are becoming increasingly evident. The review briefly addresses the pre 1997 period concluding that while the pressure for reform was mounting that there were very few examples of deliberate or…

  17. Large-scale infrared scene projectors

    NASA Astrophysics Data System (ADS)

    Murray, Darin A.

    1999-07-01

    Large-scale infrared scene projectors, typically have unique opto-mechanical characteristics associated to their application. This paper outlines two large-scale zoom lens assemblies with different environmental and package constraints. Various challenges and their respective solutions are discussed and presented.

  18. [Planimetric volumetry of human brains].

    PubMed

    Orthner, H; Seler, W

    1975-04-01

    1) Coronal sections measuring exactly 4 mm in thickness of 106 human brains (212 cerebral hemispheres) were cut with the Göttinger Hirnmakrotom. Planimetric volumetry of various macroscopically delineated structures was performed on photographs of the sections. 2) The volumes ovtained from 58 "normal cases" were used for determining preliminary standards as well as mean values and standard deviations for age and sex. The female-male ratio of the structures measured varies between 86 and 92%. Comparing right and left a predominance of the left pallidum for both sexes is apparent showing an error probability of less than 5%. In "normal" men a significant predominance of the rightsided frontal structures, located anterior to the anterior commissure, have been found (error probability of less than 1%). 3) Regarding the 48 "abnormal cases", striatum and pallidum show a uniform picture in Huntington's disease, namely an extreme shrinkage. The pallidum shrinks to a similar extent as the striatum, although its neurones are not substantially affected by this system atrophy. Other structures do not display similarly uniform changes in this disease. 4) In Parkinson's syndrome a tendency of the pallidum to enlarge -- though statistically not significant -- is seen. This raises the question whether a constitutional hyperplasia of this structure is sometimes involved in the pathogenesis. 5) In Pick's disease, it is not only the histologically impressive centers of shrinkage of the cerebral cortex that are atrophic, but, to a somewhat lesser degree, also the whole telencephalon. 6) In an 18-year-old girl with malignant obsessional neurosis (schizophrenia?) the volume of the striatum was highly above average values enlarged. 7) Bibliographical data of macroscopic-quantitative brain research reveal many problems which can be solved today due to improved methods. PMID:125721

  19. Synthesis of small and large scale dynamos

    NASA Astrophysics Data System (ADS)

    Subramanian, Kandaswamy

    Using a closure model for the evolution of magnetic correlations, we uncover an interesting plausible saturated state of the small-scale fluctuation dynamo (SSD) and a novel analogy between quantum mechanical tunnelling and the generation of large-scale fields. Large scale fields develop via the α-effect, but as magnetic helicity can only change on a resistive timescale, the time it takes to organize the field into large scales increases with magnetic Reynolds number. This is very similar to the results which obtain from simulations using the full MHD equations.

  20. Large-scale regions of antimatter

    SciTech Connect

    Grobov, A. V. Rubin, S. G.

    2015-07-15

    Amodified mechanism of the formation of large-scale antimatter regions is proposed. Antimatter appears owing to fluctuations of a complex scalar field that carries a baryon charge in the inflation era.

  1. Protein phosphorylation systems in postmortem human brain

    SciTech Connect

    Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P. )

    1989-01-01

    Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders.

  2. Transcriptional neoteny in the human brain

    PubMed Central

    Somel, Mehmet; Franz, Henriette; Yan, Zheng; Lorenc, Anna; Guo, Song; Giger, Thomas; Kelso, Janet; Nickel, Birgit; Dannemann, Michael; Bahn, Sabine; Webster, Maree J.; Weickert, Cynthia S.; Lachmann, Michael; Pääbo, Svante; Khaitovich, Philipp

    2009-01-01

    In development, timing is of the utmost importance, and the timing of developmental processes often changes as organisms evolve. In human evolution, developmental retardation, or neoteny, has been proposed as a possible mechanism that contributed to the rise of many human-specific features, including an increase in brain size and the emergence of human-specific cognitive traits. We analyzed mRNA expression in the prefrontal cortex of humans, chimpanzees, and rhesus macaques to determine whether human-specific neotenic changes are present at the gene expression level. We show that the brain transcriptome is dramatically remodeled during postnatal development and that developmental changes in the human brain are indeed delayed relative to other primates. This delay is not uniform across the human transcriptome but affects a specific subset of genes that play a potential role in neural development. PMID:19307592

  3. DESIGN OF LARGE-SCALE AIR MONITORING NETWORKS

    EPA Science Inventory

    The potential effects of air pollution on human health have received much attention in recent years. In the U.S. and other countries, there are extensive large-scale monitoring networks designed to collect data to inform the public of exposure risks to air pollution. A major crit...

  4. Large-scale cortical network properties predict future sound-to-word learning success.

    PubMed

    Sheppard, John Patrick; Wang, Ji-Ping; Wong, Patrick C M

    2012-05-01

    The human brain possesses a remarkable capacity to interpret and recall novel sounds as spoken language. These linguistic abilities arise from complex processing spanning a widely distributed cortical network and are characterized by marked individual variation. Recently, graph theoretical analysis has facilitated the exploration of how such aspects of large-scale brain functional organization may underlie cognitive performance. Brain functional networks are known to possess small-world topologies characterized by efficient global and local information transfer, but whether these properties relate to language learning abilities remains unknown. Here we applied graph theory to construct large-scale cortical functional networks from cerebral hemodynamic (fMRI) responses acquired during an auditory pitch discrimination task and found that such network properties were associated with participants' future success in learning words of an artificial spoken language. Successful learners possessed networks with reduced local efficiency but increased global efficiency relative to less successful learners and had a more cost-efficient network organization. Regionally, successful and less successful learners exhibited differences in these network properties spanning bilateral prefrontal, parietal, and right temporal cortex, overlapping a core network of auditory language areas. These results suggest that efficient cortical network organization is associated with sound-to-word learning abilities among healthy, younger adults. PMID:22360625

  5. Robust regression for large-scale neuroimaging studies.

    PubMed

    Fritsch, Virgile; Da Mota, Benoit; Loth, Eva; Varoquaux, Gaël; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Brühl, Rüdiger; Butzek, Brigitte; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Lemaitre, Hervé; Mann, Karl; Nees, Frauke; Paus, Tomas; Schad, Daniel J; Schümann, Gunter; Frouin, Vincent; Poline, Jean-Baptiste; Thirion, Bertrand

    2015-05-01

    Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. PMID:25731989

  6. Large-scale inhomogeneities and galaxy statistics

    NASA Technical Reports Server (NTRS)

    Schaeffer, R.; Silk, J.

    1984-01-01

    The density fluctuations associated with the formation of large-scale cosmic pancake-like and filamentary structures are evaluated using the Zel'dovich approximation for the evolution of nonlinear inhomogeneities in the expanding universe. It is shown that the large-scale nonlinear density fluctuations in the galaxy distribution due to pancakes modify the standard scale-invariant correlation function xi(r) at scales comparable to the coherence length of adiabatic fluctuations. The typical contribution of pancakes and filaments to the J3 integral, and more generally to the moments of galaxy counts in a volume of approximately (15-40 per h Mpc)exp 3, provides a statistical test for the existence of large scale inhomogeneities. An application to several recent three dimensional data sets shows that despite large observational uncertainties over the relevant scales characteristic features may be present that can be attributed to pancakes in most, but not all, of the various galaxy samples.

  7. Survey on large scale system control methods

    NASA Technical Reports Server (NTRS)

    Mercadal, Mathieu

    1987-01-01

    The problem inherent to large scale systems such as power network, communication network and economic or ecological systems were studied. The increase in size and flexibility of future spacecraft has put those dynamical systems into the category of large scale systems, and tools specific to the class of large systems are being sought to design control systems that can guarantee more stability and better performance. Among several survey papers, reference was found to a thorough investigation on decentralized control methods. Especially helpful was the classification made of the different existing approaches to deal with large scale systems. A very similar classification is used, even though the papers surveyed are somehow different from the ones reviewed in other papers. Special attention is brought to the applicability of the existing methods to controlling large mechanical systems like large space structures. Some recent developments are added to this survey.

  8. The large-scale distribution of galaxies

    NASA Technical Reports Server (NTRS)

    Geller, Margaret J.

    1989-01-01

    The spatial distribution of galaxies in the universe is characterized on the basis of the six completed strips of the Harvard-Smithsonian Center for Astrophysics redshift-survey extension. The design of the survey is briefly reviewed, and the results are presented graphically. Vast low-density voids similar to the void in Bootes are found, almost completely surrounded by thin sheets of galaxies. Also discussed are the implications of the results for the survey sampling problem, the two-point correlation function of the galaxy distribution, the possibility of detecting large-scale coherent flows, theoretical models of large-scale structure, and the identification of groups and clusters of galaxies.

  9. Large-scale quantum effects in biological systems

    NASA Astrophysics Data System (ADS)

    Mesquita, Marcus V.; Vasconcellos, Áurea R.; Luzzi, Roberto; Mascarenhas, Sergio

    Particular aspects of large-scale quantum effects in biological systems, such as biopolymers and also microtubules in the cytoskeleton of neurons which can have relevance in brain functioning, are discussed. The microscopic (quantum mechanical) and macroscopic (quantum statistical mechanical) aspects, and the emergence of complex behavior, are described. This phenomena consists of the large-scale coherent process of Fröhlich-Bose-Einstein condensation in open and sufficiently far-from-equilibrium biopolymers. Associated with this phenomenon is the presence of Schrödinger-Davydov solitons, which propagate, undistorted and undamped, when embedded in the Fröhlich-Bose-Einstein condensate, thus allowing for the transmission of signals at long distances, involving a question relevant to bioenergetics.

  10. Large-scale network-level processes during entrainment.

    PubMed

    Lithari, Chrysa; Sánchez-García, Carolina; Ruhnau, Philipp; Weisz, Nathan

    2016-03-15

    Visual rhythmic stimulation evokes a robust power increase exactly at the stimulation frequency, the so-called steady-state response (SSR). Localization of visual SSRs normally shows a very focal modulation of power in visual cortex and led to the treatment and interpretation of SSRs as a local phenomenon. Given the brain network dynamics, we hypothesized that SSRs have additional large-scale effects on the brain functional network that can be revealed by means of graph theory. We used rhythmic visual stimulation at a range of frequencies (4-30 Hz), recorded MEG and investigated source level connectivity across the whole brain. Using graph theoretical measures we observed a frequency-unspecific reduction of global density in the alpha band "disconnecting" visual cortex from the rest of the network. Also, a frequency-specific increase of connectivity between occipital cortex and precuneus was found at the stimulation frequency that exhibited the highest resonance (30 Hz). In conclusion, we showed that SSRs dynamically re-organized the brain functional network. These large-scale effects should be taken into account not only when attempting to explain the nature of SSRs, but also when used in various experimental designs. PMID:26835557

  11. Large-scale network-level processes during entrainment

    PubMed Central

    Lithari, Chrysa; Sánchez-García, Carolina; Ruhnau, Philipp; Weisz, Nathan

    2016-01-01

    Visual rhythmic stimulation evokes a robust power increase exactly at the stimulation frequency, the so-called steady-state response (SSR). Localization of visual SSRs normally shows a very focal modulation of power in visual cortex and led to the treatment and interpretation of SSRs as a local phenomenon. Given the brain network dynamics, we hypothesized that SSRs have additional large-scale effects on the brain functional network that can be revealed by means of graph theory. We used rhythmic visual stimulation at a range of frequencies (4–30 Hz), recorded MEG and investigated source level connectivity across the whole brain. Using graph theoretical measures we observed a frequency-unspecific reduction of global density in the alpha band “disconnecting” visual cortex from the rest of the network. Also, a frequency-specific increase of connectivity between occipital cortex and precuneus was found at the stimulation frequency that exhibited the highest resonance (30 Hz). In conclusion, we showed that SSRs dynamically re-organized the brain functional network. These large-scale effects should be taken into account not only when attempting to explain the nature of SSRs, but also when used in various experimental designs. PMID:26835557

  12. The human parental brain: In vivo neuroimaging

    PubMed Central

    Swain, James E.

    2015-01-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

  13. Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

    PubMed Central

    Shu, Ni; Liu, Yaou; Duan, Yunyun; Li, Kuncheng

    2015-01-01

    The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

  14. Large Scale Commodity Clusters for Lattice QCD

    SciTech Connect

    A. Pochinsky; W. Akers; R. Brower; J. Chen; P. Dreher; R. Edwards; S. Gottlieb; D. Holmgren; P. Mackenzie; J. Negele; D. Richards; J. Simone; W. Watson

    2002-06-01

    We describe the construction of large scale clusters for lattice QCD computing being developed under the umbrella of the U.S. DoE SciDAC initiative. We discuss the study of floating point and network performance that drove the design of the cluster, and present our plans for future multi-Terascale facilities.

  15. Management of large-scale technology

    NASA Technical Reports Server (NTRS)

    Levine, A.

    1985-01-01

    Two major themes are addressed in this assessment of the management of large-scale NASA programs: (1) how a high technology agency was a decade marked by a rapid expansion of funds and manpower in the first half and almost as rapid contraction in the second; and (2) how NASA combined central planning and control with decentralized project execution.

  16. A Large Scale Computer Terminal Output Controller.

    ERIC Educational Resources Information Center

    Tucker, Paul Thomas

    This paper describes the design and implementation of a large scale computer terminal output controller which supervises the transfer of information from a Control Data 6400 Computer to a PLATO IV data network. It discusses the cost considerations leading to the selection of educational television channels rather than telephone lines for…

  17. Large-scale CFB combustion demonstration project

    SciTech Connect

    Nielsen, P.T.; Hebb, J.L.; Aquino, R.

    1998-07-01

    The Jacksonville Electric Authority's large-scale CFB demonstration project is described. Given the early stage of project development, the paper focuses on the project organizational structure, its role within the Department of Energy's Clean Coal Technology Demonstration Program, and the projected environmental performance. A description of the CFB combustion process in included.

  18. Large-scale CFB combustion demonstration project

    SciTech Connect

    Nielsen, P.T.; Hebb, J.L.; Aquino, R.

    1998-04-01

    The Jacksonville Electric Authority`s large-scale CFB demonstration project is described. Given the early stage of project development, the paper focuses on the project organizational structure, its role within the Department of Energy`s Clean Coal Technology Demonstration Program, and the projected environmental performance. A description of the CFB combustion process is included.

  19. Evaluating Large-Scale Interactive Radio Programmes

    ERIC Educational Resources Information Center

    Potter, Charles; Naidoo, Gordon

    2009-01-01

    This article focuses on the challenges involved in conducting evaluations of interactive radio programmes in South Africa with large numbers of schools, teachers, and learners. It focuses on the role such large-scale evaluation has played during the South African radio learning programme's development stage, as well as during its subsequent…

  20. ARPACK: Solving large scale eigenvalue problems

    NASA Astrophysics Data System (ADS)

    Lehoucq, Rich; Maschhoff, Kristi; Sorensen, Danny; Yang, Chao

    2013-11-01

    ARPACK is a collection of Fortran77 subroutines designed to solve large scale eigenvalue problems. The package is designed to compute a few eigenvalues and corresponding eigenvectors of a general n by n matrix A. It is most appropriate for large sparse or structured matrices A where structured means that a matrix-vector product w

  1. Human brain mapping: Experimental and computational approaches

    SciTech Connect

    Wood, C.C.; George, J.S.; Schmidt, D.M.; Aine, C.J.; Sanders, J.; Belliveau, J.

    1998-11-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). This program developed project combined Los Alamos' and collaborators' strengths in noninvasive brain imaging and high performance computing to develop potential contributions to the multi-agency Human Brain Project led by the National Institute of Mental Health. The experimental component of the project emphasized the optimization of spatial and temporal resolution of functional brain imaging by combining: (a) structural MRI measurements of brain anatomy; (b) functional MRI measurements of blood flow and oxygenation; and (c) MEG measurements of time-resolved neuronal population currents. The computational component of the project emphasized development of a high-resolution 3-D volumetric model of the brain based on anatomical MRI, in which structural and functional information from multiple imaging modalities can be integrated into a single computational framework for modeling, visualization, and database representation.

  2. Symmetry and asymmetry in the human brain

    NASA Astrophysics Data System (ADS)

    Hugdahl, Kenneth

    2005-10-01

    Structural and functional asymmetry in the human brain and nervous system is reviewed in a historical perspective, focusing on the pioneering work of Broca, Wernicke, Sperry, and Geschwind. Structural and functional asymmetry is exemplified from work done in our laboratory on auditory laterality using an empirical procedure called dichotic listening. This also involves different ways of validating the dichotic listening procedure against both invasive and non-invasive techniques, including PET and fMRI blood flow recordings. A major argument is that the human brain shows a substantial interaction between structurally, or "bottom-up" asymmetry and cognitively, or "top-down" modulation, through a focus of attention to the right or left side in auditory space. These results open up a more dynamic and interactive view of functional brain asymmetry than the traditional static view that the brain is lateralized, or asymmetric, only for specific stimuli and stimulus properties.

  3. Expression of EGFP-amino-tagged human mu opioid receptor in Drosophila Schneider 2 cells: a potential expression system for large-scale production of G-protein coupled receptors.

    PubMed

    Perret, Bénédicte G; Wagner, Renaud; Lecat, Sandra; Brillet, Karl; Rabut, Gwénaël; Bucher, Bernard; Pattus, Franc

    2003-09-01

    The G-protein coupled receptor (GPCR) human mu opioid receptor (hMOR) fused to the carboxy-terminus of the enhanced green fluorescent protein (EGFP) has been successfully and stably expressed in Drosophila Schneider 2 cells under the control of an inducible metallothionein promoter. Polyclonal cells expressing EGFPhMOR display high-affinity, saturable, and specific binding sites for the opioid antagonist diprenorphine. Competition studies with opioid agonists and antagonists defined the pharmacological profile of a mu opioid receptor similar to that observed in mammalian cells, suggesting proper folding of EGFPhMOR in a high-affinity state in Drosophila cells. The functionality of the fusion protein was demonstrated by the ability of agonist to reduce forskolin-stimulated cyclic AMP production and to induce [35S]GTPgammaS incorporation. The EGFPhMOR protein had the expected molecular weight (70kDa), as demonstrated by protein immunoblotting with anti-EGFP and anti-C-terminus hMOR antibodies. However, quantitative EGFP fluorescence intensity analysis revealed that the total level of expressed EGFPhMOR is 8-fold higher than the level of diprenorphine binding sites, indicating that part of the receptor is not in a high-affinity state. This may in part be due to a population of receptors localized in intracellular compartments, as shown by the distribution of fluorescence between the plasma membrane and the cell interior. This study shows that EGFP is a valuable and versatile tool for monitoring and quantifying expression levels as well as for optimizing and characterizing an expression system. Optimization of the Drosophila Schneider 2 cell expression system will allow large-scale purification of GPCRs, thus enabling structural studies to be undertaken. PMID:12963349

  4. Multiple aldehyde reductases of human brain.

    PubMed

    Hoffman, P L; Wermuth, B; von Wartburg, J P

    1980-01-01

    Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC 1.1.1.2. The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme ("SSA reductase") differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of gamma-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles. PMID:7424738

  5. Cytogenetics of human brain tumors

    SciTech Connect

    Finkernagel, S.W.; Kletz, T.; Day-Salvatore, D.L.

    1994-09-01

    Chromosome studies of 55 brain tumors, including meningiomas, gliomas, astrocyomas and pituatary adenomas, were performed. Primary and first passage cultures were successfully obtained in 75% of these samples with an average of 18 G-banded metaphases analyzed per tumor. 44% of all the brain tumors showed numerical and or structural abnormalities. 46% of the primary and 38% of the first passage cultures showed similar numerical gains/losses and complex karyotypic changes. The most frequent numerical abnormalities (n {ge} 5) included loss of chromosomes 10, 22, and Y. The structural abnormalities most often seen involved 1p, 2, 5, 7, 17q and 19. This is an ongoing study which will attempt to correlate tumor type with specific karyotypic changes and to see if any of the observed chromosomal abnormalities provide prognostic indicators.

  6. Transcriptional Landscape of the Prenatal Human Brain

    PubMed Central

    Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick F.; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Player, Allison Stevens; Pletikos, Mihovil; Reding, Melissa; Royall, Joshua J.; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B.; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael J.; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.

    2014-01-01

    Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229

  7. Hierarchical features of large-scale cortical connectivity

    NASA Astrophysics Data System (ADS)

    da F. Costa, L.; Sporns, O.

    2005-12-01

    The analysis of complex networks has revealed patterns of organization in a variety of natural and artificial systems, including neuronal networks of the brain at multiple scales. In this paper, we describe a novel analysis of the large-scale connectivity between regions of the mammalian cerebral cortex, utilizing a set of hierarchical measurements proposed recently. We examine previously identified functional clusters of brain regions in macaque visual cortex and cat cortex and find significant differences between such clusters in terms of several hierarchical measures, revealing differences in how these clusters are embedded in the overall cortical architecture. For example, the ventral cluster of visual cortex maintains structurally more segregated, less divergent connections than the dorsal cluster, which may point to functionally different roles of their constituent brain regions.

  8. Seasonality in human cognitive brain responses.

    PubMed

    Meyer, Christelle; Muto, Vincenzo; Jaspar, Mathieu; Kussé, Caroline; Lambot, Erik; Chellappa, Sarah L; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Middleton, Benita; Archer, Simon N; Collette, Fabienne; Dijk, Derk-Jan; Phillips, Christophe; Maquet, Pierre; Vandewalle, Gilles

    2016-03-15

    Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations. PMID:26858432

  9. Magnetic resonance spectroscopy of the human brain

    NASA Astrophysics Data System (ADS)

    Strózik-Kotlorz, D.

    2014-01-01

    I give a brief description of the magnetic resonance spectroscopy (MRS) in the human brain examinations. MRS allows a noninvasive chemical analysis of the brain using a standard high field MR system. Nowadays, the dominant form of MR brain spectroscopy is proton spectroscopy. Two main techniques of MRS, which utilize the chemical shift of metabolites in the external magnetic field, are SVS (single voxel) and CSI (single slice). The major peaks in the spectrum of a normal brain include NAA, Cr, Cho and m-Ins, which are neuronal, energetic, membrane turnover and glial markers, respectively. In disease, two pathological metabolites can be found in the brain spectra: Lac, which is end product of anaerobic glycolysis and Lip, which is a marker of membrane breakdown, occurring in necrosis. The common way to analyze clinical spectra is to determine metabolite ratios, e.g. NAA/Cr, Cho/Cr, Cho/NAA. This analysis permits a safe and noninvasive examination of the brain tissue as each disease state has its own characteristic spectroscopic image. MRS is a valuable diagnostic tool in such clinical applications as detecting brain tumors and differentiating tumors from inflammatory and infectious processes. Proton MRS is also very helpful in diagnostic of ischemic lesions, Alzheimer's disease and hepatic encephalopathy. The MRS brain spectra should always be correlated with the Magnetic Resonance Imaging (MRI) results and alone cannot make neurological diagnosis.

  10. Cholesterol metabolites exported from human brain.

    PubMed

    Iuliano, Luigi; Crick, Peter J; Zerbinati, Chiara; Tritapepe, Luigi; Abdel-Khalik, Jonas; Poirot, Marc; Wang, Yuqin; Griffiths, William J

    2015-07-01

    The human brain contains approximately 25% of the body's cholesterol. The brain is separated from the circulation by the blood brain barrier. While cholesterol will not passes this barrier, oxygenated forms of cholesterol can cross the barrier. Here by measuring the difference in the oxysterol content of blood plasma in the jugular vein and in a forearm vein by mass spectrometry (MS) we were able to determine the flux of more than 20 cholesterol metabolites between brain and the circulation. We confirm that 24S-hydroxycholesterol is exported from brain at a rate of about 2-3mg/24h. Gas chromatography (GC)-MS data shows that the cholesterol metabolites 5α-hydroxy-6-oxocholesterol (3β,5α-dihydroxycholestan-6-one), 7β-hydroxycholesterol and 7-oxocholesterol, generally considered to be formed through reactive oxygen species, are similarly exported from brain at rates of about 0.1, 2 and 2mg/24h, respectively. Although not to statistical significance both GC-MS and liquid chromatography (LC)-MS methods indicate that (25R)26-hydroxycholesterol is imported to brain, while LC-MS indicates that 7α-hydroxy-3-oxocholest-4-enoic acid is exported from brain. PMID:25668615

  11. Direction of information flow in large-scale resting-state networks is frequency-dependent.

    PubMed

    Hillebrand, Arjan; Tewarie, Prejaas; van Dellen, Edwin; Yu, Meichen; Carbo, Ellen W S; Douw, Linda; Gouw, Alida A; van Straaten, Elisabeth C W; Stam, Cornelis J

    2016-04-01

    Normal brain function requires interactions between spatially separated, and functionally specialized, macroscopic regions, yet the directionality of these interactions in large-scale functional networks is unknown. Magnetoencephalography was used to determine the directionality of these interactions, where directionality was inferred from time series of beamformer-reconstructed estimates of neuronal activation, using a recently proposed measure of phase transfer entropy. We observed well-organized posterior-to-anterior patterns of information flow in the higher-frequency bands (alpha1, alpha2, and beta band), dominated by regions in the visual cortex and posterior default mode network. Opposite patterns of anterior-to-posterior flow were found in the theta band, involving mainly regions in the frontal lobe that were sending information to a more distributed network. Many strong information senders in the theta band were also frequent receivers in the alpha2 band, and vice versa. Our results provide evidence that large-scale resting-state patterns of information flow in the human brain form frequency-dependent reentry loops that are dominated by flow from parieto-occipital cortex to integrative frontal areas in the higher-frequency bands, which is mirrored by a theta band anterior-to-posterior flow. PMID:27001844

  12. Human Maternal Brain Plasticity: Adaptation to Parenting.

    PubMed

    Kim, Pilyoung

    2016-09-01

    New mothers undergo dynamic neural changes that support positive adaptation to parenting and the development of mother-infant relationships. In this article, I review important psychological adaptations that mothers experience during pregnancy and the early postpartum period. I then review evidence of structural and functional plasticity in human mothers' brains, and explore how such plasticity supports mothers' psychological adaptation to parenting and sensitive maternal behaviors. Last, I discuss pregnancy and the early postpartum period as a window of vulnerabilities and opportunities when the human maternal brain is influenced by stress and psychopathology, but also receptive to interventions. PMID:27589497

  13. Revisiting Glycogen Content in the Human Brain.

    PubMed

    Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

    2015-12-01

    Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain. PMID:26202425

  14. Human intelligence and brain networks

    PubMed Central

    Colom, Roberto; Karama, Sherif; Jung, Rex E.; Haier, Richard J.

    2010-01-01

    Intelligence can be defined as a general mental ability for reasoning, problem solving, and learning. Because of its general nature, intelligence integrates cognitive functions such as perception, attention, memory, language, or planning. On the basis of this definition, intelligence can be reliably measured by standardized tests with obtained scores predicting several broad social outcomes such as educational achievement, job performance, health, and longevity. A detailed understanding of the brain mechanisms underlying this general mental ability could provide significant individual and societal benefits. Structural and functional neuroimaging studies have generally supported a frontoparietal network relevant for intelligence. This same network has also been found to underlie cognitive functions related to perception, short-term memory storage, and language. The distributed nature of this network and its involvement in a wide range of cognitive functions fits well with the integrative nature of intelligence. A new key phase of research is beginning to investigate how functional networks relate to structural networks, with emphasis on how distributed brain areas communicate with each other. PMID:21319494

  15. Fractals and cosmological large-scale structure

    NASA Technical Reports Server (NTRS)

    Luo, Xiaochun; Schramm, David N.

    1992-01-01

    Observations of galaxy-galaxy and cluster-cluster correlations as well as other large-scale structure can be fit with a 'limited' fractal with dimension D of about 1.2. This is not a 'pure' fractal out to the horizon: the distribution shifts from power law to random behavior at some large scale. If the observed patterns and structures are formed through an aggregation growth process, the fractal dimension D can serve as an interesting constraint on the properties of the stochastic motion responsible for limiting the fractal structure. In particular, it is found that the observed fractal should have grown from two-dimensional sheetlike objects such as pancakes, domain walls, or string wakes. This result is generic and does not depend on the details of the growth process.

  16. Condition Monitoring of Large-Scale Facilities

    NASA Technical Reports Server (NTRS)

    Hall, David L.

    1999-01-01

    This document provides a summary of the research conducted for the NASA Ames Research Center under grant NAG2-1182 (Condition-Based Monitoring of Large-Scale Facilities). The information includes copies of view graphs presented at NASA Ames in the final Workshop (held during December of 1998), as well as a copy of a technical report provided to the COTR (Dr. Anne Patterson-Hine) subsequent to the workshop. The material describes the experimental design, collection of data, and analysis results associated with monitoring the health of large-scale facilities. In addition to this material, a copy of the Pennsylvania State University Applied Research Laboratory data fusion visual programming tool kit was also provided to NASA Ames researchers.

  17. Large scale processes in the solar nebula.

    NASA Astrophysics Data System (ADS)

    Boss, A. P.

    Most proposed chondrule formation mechanisms involve processes occurring inside the solar nebula, so the large scale (roughly 1 to 10 AU) structure of the nebula is of general interest for any chrondrule-forming mechanism. Chondrules and Ca, Al-rich inclusions (CAIs) might also have been formed as a direct result of the large scale structure of the nebula, such as passage of material through high temperature regions. While recent nebula models do predict the existence of relatively hot regions, the maximum temperatures in the inner planet region may not be high enough to account for chondrule or CAI thermal processing, unless the disk mass is considerably greater than the minimum mass necessary to restore the planets to solar composition. Furthermore, it does not seem to be possible to achieve both rapid heating and rapid cooling of grain assemblages in such a large scale furnace. However, if the accretion flow onto the nebula surface is clumpy, as suggested by observations of variability in young stars, then clump-disk impacts might be energetic enough to launch shock waves which could propagate through the nebula to the midplane, thermally processing any grain aggregates they encounter, and leaving behind a trail of chondrules.

  18. Large-scale extraction of proteins.

    PubMed

    Cunha, Teresa; Aires-Barros, Raquel

    2002-01-01

    The production of foreign proteins using selected host with the necessary posttranslational modifications is one of the key successes in modern biotechnology. This methodology allows the industrial production of proteins that otherwise are produced in small quantities. However, the separation and purification of these proteins from the fermentation media constitutes a major bottleneck for the widespread commercialization of recombinant proteins. The major production costs (50-90%) for typical biological product resides in the purification strategy. There is a need for efficient, effective, and economic large-scale bioseparation techniques, to achieve high purity and high recovery, while maintaining the biological activity of the molecule. Aqueous two-phase systems (ATPS) allow process integration as simultaneously separation and concentration of the target protein is achieved, with posterior removal and recycle of the polymer. The ease of scale-up combined with the high partition coefficients obtained allow its potential application in large-scale downstream processing of proteins produced by fermentation. The equipment and the methodology for aqueous two-phase extraction of proteins on a large scale using mixer-settlerand column contractors are described. The operation of the columns, either stagewise or differential, are summarized. A brief description of the methods used to account for mass transfer coefficients, hydrodynamics parameters of hold-up, drop size, and velocity, back mixing in the phases, and flooding performance, required for column design, is also provided. PMID:11876297

  19. Spontaneous functional network dynamics and associated structural substrates in the human brain

    PubMed Central

    Liao, Xuhong; Yuan, Lin; Zhao, Tengda; Dai, Zhengjia; Shu, Ni; Xia, Mingrui; Yang, Yihong; Evans, Alan; He, Yong

    2015-01-01

    Recent imaging connectomics studies have demonstrated that the spontaneous human brain functional networks derived from resting-state functional MRI (R-fMRI) include many non-trivial topological properties, such as highly efficient small-world architecture and densely connected hub regions. However, very little is known about dynamic functional connectivity (D-FC) patterns of spontaneous human brain networks during rest and about how these spontaneous brain dynamics are constrained by the underlying structural connectivity. Here, we combined sub-second multiband R-fMRI data with graph-theoretical approaches to comprehensively investigate the dynamic characteristics of the topological organization of human whole-brain functional networks, and then employed diffusion imaging data in the same participants to further explore the associated structural substrates. At the connection level, we found that human whole-brain D-FC patterns spontaneously fluctuated over time, while homotopic D-FC exhibited high connectivity strength and low temporal variability. At the network level, dynamic functional networks exhibited time-varying but evident small-world and assortativity architecture, with several regions (e.g., insula, sensorimotor cortex and medial prefrontal cortex) emerging as functionally persistent hubs (i.e., highly connected regions) while possessing large temporal variability in their degree centrality. Finally, the temporal characteristics (i.e., strength and variability) of the connectional and nodal properties of the dynamic brain networks were significantly associated with their structural counterparts. Collectively, we demonstrate the economical, efficient, and flexible characteristics of dynamic functional coordination in large-scale human brain networks during rest, and highlight their relationship with underlying structural connectivity, which deepens our understandings of spontaneous brain network dynamics in humans. PMID:26388757

  20. Causal influence in neural systems: Reconciling mechanistic-reductionist and statistical perspectives. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino & S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Griffiths, John D.

    2015-12-01

    The modern understanding of the brain as a large, complex network of interacting elements is a natural consequence of the Neuron Doctrine [1,2] that has been bolstered in recent years by the tools and concepts of connectomics. In this abstracted, network-centric view, the essence of neural and cognitive function derives from the flows between network elements of activity and information - or, more generally, causal influence. The appropriate characterization of causality in neural systems, therefore, is a question at the very heart of systems neuroscience.

  1. CARBOXYHEMOGLOBIN AND BRAIN BLOOD FLOW IN HUMANS

    EPA Science Inventory

    It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. he BBF response in humans has been shown to be quite variable. wo experiments were conducted in wh...

  2. 'What' and 'where' in the human brain.

    PubMed

    Ungerleider, L G; Haxby, J V

    1994-04-01

    Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms. PMID:8038571

  3. Large-scale objective phenotyping of 3D facial morphology

    PubMed Central

    Hammond, Peter; Suttie, Michael

    2012-01-01

    Abnormal phenotypes have played significant roles in the discovery of gene function, but organized collection of phenotype data has been overshadowed by developments in sequencing technology. In order to study phenotypes systematically, large-scale projects with standardized objective assessment across populations are considered necessary. The report of the 2006 Human Variome Project meeting recommended documentation of phenotypes through electronic means by collaborative groups of computational scientists and clinicians using standard, structured descriptions of disease-specific phenotypes. In this report, we describe progress over the past decade in 3D digital imaging and shape analysis of the face, and future prospects for large-scale facial phenotyping. Illustrative examples are given throughout using a collection of 1107 3D face images of healthy controls and individuals with a range of genetic conditions involving facial dysmorphism. PMID:22434506

  4. Zika virus impairs growth in human neurospheres and brain organoids.

    PubMed

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. PMID:27064148

  5. Epilepsy: Extreme Events in the Human Brain

    NASA Astrophysics Data System (ADS)

    Lehnertz, Klaus

    The analysis of Xevents arising in dynamical systems with many degrees of freedom represents a challenge for many scientific fields. This is especially true for the open, dissipative, and adaptive system known as the human brain. Due to its complex structure, its immense functionality, and — as in the case of epilepsy — due to the coexistence of normal and abnormal functions, the brain can be regarded as one of the most complex and fascinating systems in nature. Data gathered so far show that the epileptic process exhibits a high spatial and temporal variability. Small, specific, regions of the brain are responsible for the generation of focal epileptic seizures, and the amount of time a patient spends actually having seizures is only a small fraction of his/her lifetime. In between these Xevents large parts of the brain exhibit normal functioning. Since the occurrence of seizures usually can not be explained by exogenous factors, and since the brain recovers its normal state after a seizure in the majority of cases, this might indicate that endogenous nonlinear (deterministic and/or stochastic) properties are involved in the control of these Xevents. In fact, converging evidence now indicates that (particularly) nonlinear approaches to the analysis of brain activity allow us to define precursors which, provided sufficient sensitivity and specificity can be obtained, might lead to the development of patient-specific seizure anticipation and seizure prevention strategies.

  6. Methylomic trajectories across human fetal brain development.

    PubMed

    Spiers, Helen; Hannon, Eilis; Schalkwyk, Leonard C; Smith, Rebecca; Wong, Chloe C Y; O'Donovan, Michael C; Bray, Nicholas J; Mill, Jonathan

    2015-03-01

    Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity. PMID:25650246

  7. Large-Scale PV Integration Study

    SciTech Connect

    Lu, Shuai; Etingov, Pavel V.; Diao, Ruisheng; Ma, Jian; Samaan, Nader A.; Makarov, Yuri V.; Guo, Xinxin; Hafen, Ryan P.; Jin, Chunlian; Kirkham, Harold; Shlatz, Eugene; Frantzis, Lisa; McClive, Timothy; Karlson, Gregory; Acharya, Dhruv; Ellis, Abraham; Stein, Joshua; Hansen, Clifford; Chadliev, Vladimir; Smart, Michael; Salgo, Richard; Sorensen, Rahn; Allen, Barbara; Idelchik, Boris

    2011-07-29

    This research effort evaluates the impact of large-scale photovoltaic (PV) and distributed generation (DG) output on NV Energy’s electric grid system in southern Nevada. It analyzes the ability of NV Energy’s generation to accommodate increasing amounts of utility-scale PV and DG, and the resulting cost of integrating variable renewable resources. The study was jointly funded by the United States Department of Energy and NV Energy, and conducted by a project team comprised of industry experts and research scientists from Navigant Consulting Inc., Sandia National Laboratories, Pacific Northwest National Laboratory and NV Energy.

  8. Large-scale planar lightwave circuits

    NASA Astrophysics Data System (ADS)

    Bidnyk, Serge; Zhang, Hua; Pearson, Matt; Balakrishnan, Ashok

    2011-01-01

    By leveraging advanced wafer processing and flip-chip bonding techniques, we have succeeded in hybrid integrating a myriad of active optical components, including photodetectors and laser diodes, with our planar lightwave circuit (PLC) platform. We have combined hybrid integration of active components with monolithic integration of other critical functions, such as diffraction gratings, on-chip mirrors, mode-converters, and thermo-optic elements. Further process development has led to the integration of polarization controlling functionality. Most recently, all these technological advancements have been combined to create large-scale planar lightwave circuits that comprise hundreds of optical elements integrated on chips less than a square inch in size.

  9. Neutrinos and large-scale structure

    SciTech Connect

    Eisenstein, Daniel J.

    2015-07-15

    I review the use of cosmological large-scale structure to measure properties of neutrinos and other relic populations of light relativistic particles. With experiments to measure the anisotropies of the cosmic microwave anisotropies and the clustering of matter at low redshift, we now have securely measured a relativistic background with density appropriate to the cosmic neutrino background. Our limits on the mass of the neutrino continue to shrink. Experiments coming in the next decade will greatly improve the available precision on searches for the energy density of novel relativistic backgrounds and the mass of neutrinos.

  10. Experimental Simulations of Large-Scale Collisions

    NASA Technical Reports Server (NTRS)

    Housen, Kevin R.

    2002-01-01

    This report summarizes research on the effects of target porosity on the mechanics of impact cratering. Impact experiments conducted on a centrifuge provide direct simulations of large-scale cratering on porous asteroids. The experiments show that large craters in porous materials form mostly by compaction, with essentially no deposition of material into the ejecta blanket that is a signature of cratering in less-porous materials. The ratio of ejecta mass to crater mass is shown to decrease with increasing crater size or target porosity. These results are consistent with the observation that large closely-packed craters on asteroid Mathilde appear to have formed without degradation to earlier craters.

  11. Colloquium: Large scale simulations on GPU clusters

    NASA Astrophysics Data System (ADS)

    Bernaschi, Massimo; Bisson, Mauro; Fatica, Massimiliano

    2015-06-01

    Graphics processing units (GPU) are currently used as a cost-effective platform for computer simulations and big-data processing. Large scale applications require that multiple GPUs work together but the efficiency obtained with cluster of GPUs is, at times, sub-optimal because the GPU features are not exploited at their best. We describe how it is possible to achieve an excellent efficiency for applications in statistical mechanics, particle dynamics and networks analysis by using suitable memory access patterns and mechanisms like CUDA streams, profiling tools, etc. Similar concepts and techniques may be applied also to other problems like the solution of Partial Differential Equations.

  12. Nonthermal Components in the Large Scale Structure

    NASA Astrophysics Data System (ADS)

    Miniati, Francesco

    2004-12-01

    I address the issue of nonthermal processes in the large scale structure of the universe. After reviewing the properties of cosmic shocks and their role as particle accelerators, I discuss the main observational results, from radio to γ-ray and describe the processes that are thought be responsible for the observed nonthermal emissions. Finally, I emphasize the important role of γ-ray astronomy for the progress in the field. Non detections at these photon energies have already allowed us important conclusions. Future observations will tell us more about the physics of the intracluster medium, shocks dissipation and CR acceleration.

  13. Large scale phononic metamaterials for seismic isolation

    SciTech Connect

    Aravantinos-Zafiris, N.; Sigalas, M. M.

    2015-08-14

    In this work, we numerically examine structures that could be characterized as large scale phononic metamaterials. These novel structures could have band gaps in the frequency spectrum of seismic waves when their dimensions are chosen appropriately, thus raising the belief that they could be serious candidates for seismic isolation structures. Different and easy to fabricate structures were examined made from construction materials such as concrete and steel. The well-known finite difference time domain method is used in our calculations in order to calculate the band structures of the proposed metamaterials.

  14. Magnetite biomineralization in the human brain.

    PubMed Central

    Kirschvink, J L; Kobayashi-Kirschvink, A; Woodford, B J

    1992-01-01

    Although the mineral magnetite (Fe3O4) is precipitated biochemically by bacteria, protists, and a variety of animals, it has not been documented previously in human tissue. Using an ultrasensitive superconducting magnetometer in a clean-lab environment, we have detected the presence of ferromagnetic material in a variety of tissues from the human brain. Magnetic particle extracts from solubilized brain tissues examined with high-resolution transmission electron microscopy, electron diffraction, and elemental analyses identify minerals in the magnetite-maghemite family, with many of the crystal morphologies and structures resembling strongly those precipitated by magnetotactic bacteria and fish. These magnetic and high-resolution transmission electron microscopy measurements imply the presence of a minimum of 5 million single-domain crystals per gram for most tissues in the brain and greater than 100 million crystals per gram for pia and dura. Magnetic property data indicate the crystals are in clumps of between 50 and 100 particles. Biogenic magnetite in the human brain may account for high-field saturation effects observed in the T1 and T2 values of magnetic resonance imaging and, perhaps, for a variety of biological effects of low-frequency magnetic fields. Images PMID:1502184

  15. The Human Brain Project and neuromorphic computing

    PubMed Central

    Calimera, Andrea; Macii, Enrico; Poncino, Massimo

    Summary Understanding how the brain manages billions of processing units connected via kilometers of fibers and trillions of synapses, while consuming a few tens of Watts could provide the key to a completely new category of hardware (neuromorphic computing systems). In order to achieve this, a paradigm shift for computing as a whole is needed, which will see it moving away from current “bit precise” computing models and towards new techniques that exploit the stochastic behavior of simple, reliable, very fast, low-power computing devices embedded in intensely recursive architectures. In this paper we summarize how these objectives will be pursued in the Human Brain Project. PMID:24139655

  16. Human freedom and the brain.

    PubMed

    Kornhuber, Hans Helmut

    2009-06-01

    Freedom of will does exist, it is self-leadership of man based on reason and ethos. Evidence comes from truth. Determinism cannot be proved since if you try, you mean to prove a truth; but there is no truth without freedom. By contrast for freedom there are many pieces of evidence e.g. science, arts, technology. Freedom utilizes creative abstract thinking with phantasy. Freedom is graded, limited, based on nature, but not developed without good will. We perceive reliably freedom by self-consciousness and in other persons as long as we are sober. Freedom needs intelligence, but is more, it is a creative and moral virtue. The basis for freedom is phylogenesis and culture, in the individual learning and experimenting. Factors in the becoming of freedom are not only genes and environment but also self-discipline. But the creativity of free will is dangerous. Man therefore needs morale. Drives and feelings become humanized, cultural interests are developed. There is a humane nobility from long good will. PMID:25384854

  17. Energy landscape and dynamics of brain activity during human bistable perception

    PubMed Central

    Watanabe, Takamitsu; Masuda, Naoki; Megumi, Fukuda; Kanai, Ryota; Rees, Geraint

    2014-01-01

    Individual differences in the structure of parietal and prefrontal cortex predict the stability of bistable visual perception. However, the mechanisms linking such individual differences in brain structures to behaviour remain elusive. Here we demonstrate a systematic relationship between the dynamics of brain activity, cortical structure and behaviour underpinning bistable perception. Using fMRI in humans, we find that the activity dynamics during bistable perception are well described as fluctuating between three spatially distributed energy minimums: visual-area-dominant, frontal-area-dominant and intermediate states. Transitions between these energy minimums predicted behaviour, with participants whose brain activity tend to reflect the visual-area-dominant state exhibiting more stable perception and those whose activity transits to frontal-area-dominant states reporting more frequent perceptual switches. Critically, these brain activity dynamics are correlated with individual differences in grey matter volume of the corresponding brain areas. Thus, individual differences in the large-scale dynamics of brain activity link focal brain structure with bistable perception. PMID:25163855

  18. Large-scale Globally Propagating Coronal Waves

    NASA Astrophysics Data System (ADS)

    Warmuth, Alexander

    2015-09-01

    Large-scale, globally propagating wave-like disturbances have been observed in the solar chromosphere and by inference in the corona since the 1960s. However, detailed analysis of these phenomena has only been conducted since the late 1990s. This was prompted by the availability of high-cadence coronal imaging data from numerous spaced-based instruments, which routinely show spectacular globally propagating bright fronts. Coronal waves, as these perturbations are usually referred to, have now been observed in a wide range of spectral channels, yielding a wealth of information. Many findings have supported the "classical" interpretation of the disturbances: fast-mode MHD waves or shocks that are propagating in the solar corona. However, observations that seemed inconsistent with this picture have stimulated the development of alternative models in which "pseudo waves" are generated by magnetic reconfiguration in the framework of an expanding coronal mass ejection. This has resulted in a vigorous debate on the physical nature of these disturbances. This review focuses on demonstrating how the numerous observational findings of the last one and a half decades can be used to constrain our models of large-scale coronal waves, and how a coherent physical understanding of these disturbances is finally emerging.

  19. Local gravity and large-scale structure

    NASA Technical Reports Server (NTRS)

    Juszkiewicz, Roman; Vittorio, Nicola; Wyse, Rosemary F. G.

    1990-01-01

    The magnitude and direction of the observed dipole anisotropy of the galaxy distribution can in principle constrain the amount of large-scale power present in the spectrum of primordial density fluctuations. This paper confronts the data, provided by a recent redshift survey of galaxies detected by the IRAS satellite, with the predictions of two cosmological models with very different levels of large-scale power: the biased Cold Dark Matter dominated model (CDM) and a baryon-dominated model (BDM) with isocurvature initial conditions. Model predictions are investigated for the Local Group peculiar velocity, v(R), induced by mass inhomogeneities distributed out to a given radius, R, for R less than about 10,000 km/s. Several convergence measures for v(R) are developed, which can become powerful cosmological tests when deep enough samples become available. For the present data sets, the CDM and BDM predictions are indistinguishable at the 2 sigma level and both are consistent with observations. A promising discriminant between cosmological models is the misalignment angle between v(R) and the apex of the dipole anisotropy of the microwave background.

  20. Segmentation of human brain using structural MRI.

    PubMed

    Helms, Gunther

    2016-04-01

    Segmentation of human brain using structural MRI is a key step of processing in imaging neuroscience. The methods have undergone a rapid development in the past two decades and are now widely available. This non-technical review aims at providing an overview and basic understanding of the most common software. Starting with the basis of structural MRI contrast in brain and imaging protocols, the concepts of voxel-based and surface-based segmentation are discussed. Special emphasis is given to the typical contrast features and morphological constraints of cortical and sub-cortical grey matter. In addition to the use for voxel-based morphometry, basic applications in quantitative MRI, cortical thickness estimations, and atrophy measurements as well as assignment of cortical regions and deep brain nuclei are briefly discussed. Finally, some fields for clinical applications are given. PMID:26739264

  1. Line segment extraction for large scale unorganized point clouds

    NASA Astrophysics Data System (ADS)

    Lin, Yangbin; Wang, Cheng; Cheng, Jun; Chen, Bili; Jia, Fukai; Chen, Zhonggui; Li, Jonathan

    2015-04-01

    Line segment detection in images is already a well-investigated topic, although it has received considerably less attention in 3D point clouds. Benefiting from current LiDAR devices, large-scale point clouds are becoming increasingly common. Most human-made objects have flat surfaces. Line segments that occur where pairs of planes intersect give important information regarding the geometric content of point clouds, which is especially useful for automatic building reconstruction and segmentation. This paper proposes a novel method that is capable of accurately extracting plane intersection line segments from large-scale raw scan points. The 3D line-support region, namely, a point set near a straight linear structure, is extracted simultaneously. The 3D line-support region is fitted by our Line-Segment-Half-Planes (LSHP) structure, which provides a geometric constraint for a line segment, making the line segment more reliable and accurate. We demonstrate our method on the point clouds of large-scale, complex, real-world scenes acquired by LiDAR devices. We also demonstrate the application of 3D line-support regions and their LSHP structures on urban scene abstraction.

  2. Infrasounds and biorhythms of the human brain

    NASA Astrophysics Data System (ADS)

    Panuszka, Ryszard; Damijan, Zbigniew; Kasprzak, Cezary; McGlothlin, James

    2002-05-01

    Low Frequency Noise (LFN) and infrasound has begun a new public health hazard. Evaluations of annoyance of (LFN) on human occupational health were based on standards where reactions of human auditory system and vibrations of parts of human body were small. Significant sensitivity has been observed on the central nervous system from infrasonic waves especially below 10 Hz. Observed follow-up effects in the brain gives incentive to study the relationship between parameters of waves and reactions obtained of biorhythms (EEG) and heart action (EKG). New results show the impact of LFN on the electrical potentials of the brain are dependent on the pressure waves on the human body. Electrical activity of circulatory system was also affected. Signals recorded in industrial workplaces were duplicated by loudspeakers and used to record data from a typical LFN spectra with 5 and 7 Hz in a laboratory chamber. External noise, electromagnetic fields, temperature, dust, and other elements were controlled. Results show not only a follow-up effect in the brain but also a result similar to arrhythmia in the heart. Relaxations effects were observed of people impacted by waves generated from natural sources such as streams and waterfalls.

  3. Molecular genetic determinants of human brain size.

    PubMed

    Tang, Bor Luen

    2006-07-01

    Cognitive skills such as tool use, syntactical languages, and self-awareness differentiate humans from other primates. The underlying basis for this cognitive difference has been widely associated with a high encephalization quotient and an anatomically distinct, exceptionally large cerebral cortex. Investigations on congenital microcephaly had revealed several genes that affect mammalian brain size when mutated. At least four of these, microcephalin (MCPH1), abnormal spindle-like microcephaly-associated (ASPM), cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), and centromere-associated protein J (CENPJ) are known to have undergone significant positive selection in the great apes and human lineages during primate evolution. MCPH1 and ASPM both have very young single nucleotide polymorphism haplotypes associated with modern humans, and these genes are presumably still evolving in Homo sapiens. Microcephalin has a role in DNA damage response and regulation of cell cycle checkpoints. The other known microcephaly-associated genes encode microtubule-associated centrosomal proteins that might regulate neural progenitor cell division and cell number. Recent reports have also unveiled a previously unknown function of ephrins and Eph in the regulation of neural progenitor cell death with a consequential effect on brain size. Understanding the mechanism for developmental control of brain organogenesis by these genes, and others such as FOXP2, shall provide fresh perspectives on the evolution of human intelligence. PMID:16716254

  4. Human brain disease recreated in mice

    SciTech Connect

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  5. Large-scale Granger causality analysis on resting-state functional MRI

    NASA Astrophysics Data System (ADS)

    D'Souza, Adora M.; Abidin, Anas Zainul; Leistritz, Lutz; Wismüller, Axel

    2016-03-01

    We demonstrate an approach to measure the information flow between each pair of time series in resting-state functional MRI (fMRI) data of the human brain and subsequently recover its underlying network structure. By integrating dimensionality reduction into predictive time series modeling, large-scale Granger Causality (lsGC) analysis method can reveal directed information flow suggestive of causal influence at an individual voxel level, unlike other multivariate approaches. This method quantifies the influence each voxel time series has on every other voxel time series in a multivariate sense and hence contains information about the underlying dynamics of the whole system, which can be used to reveal functionally connected networks within the brain. To identify such networks, we perform non-metric network clustering, such as accomplished by the Louvain method. We demonstrate the effectiveness of our approach to recover the motor and visual cortex from resting state human brain fMRI data and compare it with the network recovered from a visuomotor stimulation experiment, where the similarity is measured by the Dice Coefficient (DC). The best DC obtained was 0.59 implying a strong agreement between the two networks. In addition, we thoroughly study the effect of dimensionality reduction in lsGC analysis on network recovery. We conclude that our approach is capable of detecting causal influence between time series in a multivariate sense, which can be used to segment functionally connected networks in the resting-state fMRI.

  6. Imaging Monoamine Oxidase in the Human Brain

    SciTech Connect

    Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Logan, Jean

    1999-11-10

    Positron emission tomography (PET) studies mapping monoamine oxidase in the human brain have been used to measure the turnover rate for MAO B; to determine the minimum effective dose of a new MAO inhibitor drug lazabemide and to document MAO inhibition by cigarette smoke. These studies illustrate the power of PET and radiotracer chemistry to measure normal biochemical processes and to provide information on the effect of drug exposure on specific molecular targets.

  7. Multitree Algorithms for Large-Scale Astrostatistics

    NASA Astrophysics Data System (ADS)

    March, William B.; Ozakin, Arkadas; Lee, Dongryeol; Riegel, Ryan; Gray, Alexander G.

    2012-03-01

    this number every week, resulting in billions of objects. At such scales, even linear-time analysis operations present challenges, particularly since statistical analyses are inherently interactive processes, requiring that computations complete within some reasonable human attention span. The quadratic (or worse) runtimes of straightforward implementations become quickly unbearable. Examples of applications. These analysis subroutines occur ubiquitously in astrostatistical work. We list just a few examples. The need to cross-match objects across different catalogs has led to various algorithms, which at some point perform an AllNN computation. 2-point and higher-order spatial correlations for the basis of spatial statistics, and are utilized in astronomy to compare the spatial structures of two datasets, such as an observed sample and a theoretical sample, for example, forming the basis for two-sample hypothesis testing. Friends-of-friends clustering is often used to identify halos in data from astrophysical simulations. Minimum spanning tree properties have also been proposed as statistics of large-scale structure. Comparison of the distributions of different kinds of objects requires accurate density estimation, for which KDE is the overall statistical method of choice. The prediction of redshifts from optical data requires accurate regression, for which kernel regression is a powerful method. The identification of objects of various types in astronomy, such as stars versus galaxies, requires accurate classification, for which KDA is a powerful method. Overview. In this chapter, we will briefly sketch the main ideas behind recent fast algorithms which achieve, for example, linear runtimes for pairwise-distance problems, or similarly dramatic reductions in computational growth. In some cases, the runtime orders for these algorithms are mathematically provable statements, while in others we have only conjectures backed by experimental observations for the time being

  8. Large scale water lens for solar concentration.

    PubMed

    Mondol, A S; Vogel, B; Bastian, G

    2015-06-01

    Properties of large scale water lenses for solar concentration were investigated. These lenses were built from readily available materials, normal tap water and hyper-elastic linear low density polyethylene foil. Exposed to sunlight, the focal lengths and light intensities in the focal spot were measured and calculated. Their optical properties were modeled with a raytracing software based on the lens shape. We have achieved a good match of experimental and theoretical data by considering wavelength dependent concentration factor, absorption and focal length. The change in light concentration as a function of water volume was examined via the resulting load on the foil and the corresponding change of shape. The latter was extracted from images and modeled by a finite element simulation. PMID:26072893

  9. Large Scale Quantum Simulations of Nuclear Pasta

    NASA Astrophysics Data System (ADS)

    Fattoyev, Farrukh J.; Horowitz, Charles J.; Schuetrumpf, Bastian

    2016-03-01

    Complex and exotic nuclear geometries collectively referred to as ``nuclear pasta'' are expected to naturally exist in the crust of neutron stars and in supernovae matter. Using a set of self-consistent microscopic nuclear energy density functionals we present the first results of large scale quantum simulations of pasta phases at baryon densities 0 . 03 < ρ < 0 . 10 fm-3, proton fractions 0 . 05

  10. Large-scale simulations of reionization

    SciTech Connect

    Kohler, Katharina; Gnedin, Nickolay Y.; Hamilton, Andrew J.S.; /JILA, Boulder

    2005-11-01

    We use cosmological simulations to explore the large-scale effects of reionization. Since reionization is a process that involves a large dynamic range--from galaxies to rare bright quasars--we need to be able to cover a significant volume of the universe in our simulation without losing the important small scale effects from galaxies. Here we have taken an approach that uses clumping factors derived from small scale simulations to approximate the radiative transfer on the sub-cell scales. Using this technique, we can cover a simulation size up to 1280h{sup -1} Mpc with 10h{sup -1} Mpc cells. This allows us to construct synthetic spectra of quasars similar to observed spectra of SDSS quasars at high redshifts and compare them to the observational data. These spectra can then be analyzed for HII region sizes, the presence of the Gunn-Peterson trough, and the Lyman-{alpha} forest.

  11. Estimation of large-scale dimension densities.

    PubMed

    Raab, C; Kurths, J

    2001-07-01

    We propose a technique to calculate large-scale dimension densities in both higher-dimensional spatio-temporal systems and low-dimensional systems from only a few data points, where known methods usually have an unsatisfactory scaling behavior. This is mainly due to boundary and finite-size effects. With our rather simple method, we normalize boundary effects and get a significant correction of the dimension estimate. This straightforward approach is based on rather general assumptions. So even weak coherent structures obtained from small spatial couplings can be detected with this method, which is impossible by using the Lyapunov-dimension density. We demonstrate the efficiency of our technique for coupled logistic maps, coupled tent maps, the Lorenz attractor, and the Roessler attractor. PMID:11461376

  12. The challenge of large-scale structure

    NASA Astrophysics Data System (ADS)

    Gregory, S. A.

    1996-03-01

    The tasks that I have assumed for myself in this presentation include three separate parts. The first, appropriate to the particular setting of this meeting, is to review the basic work of the founding of this field; the appropriateness comes from the fact that W. G. Tifft made immense contributions that are not often realized by the astronomical community. The second task is to outline the general tone of the observational evidence for large scale structures. (Here, in particular, I cannot claim to be complete. I beg forgiveness from any workers who are left out by my oversight for lack of space and time.) The third task is to point out some of the major aspects of the field that may represent the clues by which some brilliant sleuth will ultimately figure out how galaxies formed.

  13. Large scale cryogenic fluid systems testing

    NASA Technical Reports Server (NTRS)

    1992-01-01

    NASA Lewis Research Center's Cryogenic Fluid Systems Branch (CFSB) within the Space Propulsion Technology Division (SPTD) has the ultimate goal of enabling the long term storage and in-space fueling/resupply operations for spacecraft and reusable vehicles in support of space exploration. Using analytical modeling, ground based testing, and on-orbit experimentation, the CFSB is studying three primary categories of fluid technology: storage, supply, and transfer. The CFSB is also investigating fluid handling, advanced instrumentation, and tank structures and materials. Ground based testing of large-scale systems is done using liquid hydrogen as a test fluid at the Cryogenic Propellant Tank Facility (K-site) at Lewis' Plum Brook Station in Sandusky, Ohio. A general overview of tests involving liquid transfer, thermal control, pressure control, and pressurization is given.

  14. Batteries for Large Scale Energy Storage

    SciTech Connect

    Soloveichik, Grigorii L.

    2011-07-15

    In recent years, with the deployment of renewable energy sources, advances in electrified transportation, and development in smart grids, the markets for large-scale stationary energy storage have grown rapidly. Electrochemical energy storage methods are strong candidate solutions due to their high energy density, flexibility, and scalability. This review provides an overview of mature and emerging technologies for secondary and redox flow batteries. New developments in the chemistry of secondary and flow batteries as well as regenerative fuel cells are also considered. Advantages and disadvantages of current and prospective electrochemical energy storage options are discussed. The most promising technologies in the short term are high-temperature sodium batteries with β”-alumina electrolyte, lithium-ion batteries, and flow batteries. Regenerative fuel cells and lithium metal batteries with high energy density require further research to become practical.

  15. Grid sensitivity capability for large scale structures

    NASA Technical Reports Server (NTRS)

    Nagendra, Gopal K.; Wallerstein, David V.

    1989-01-01

    The considerations and the resultant approach used to implement design sensitivity capability for grids into a large scale, general purpose finite element system (MSC/NASTRAN) are presented. The design variables are grid perturbations with a rather general linking capability. Moreover, shape and sizing variables may be linked together. The design is general enough to facilitate geometric modeling techniques for generating design variable linking schemes in an easy and straightforward manner. Test cases have been run and validated by comparison with the overall finite difference method. The linking of a design sensitivity capability for shape variables in MSC/NASTRAN with an optimizer would give designers a powerful, automated tool to carry out practical optimization design of real life, complicated structures.

  16. Large-Scale Astrophysical Visualization on Smartphones

    NASA Astrophysics Data System (ADS)

    Becciani, U.; Massimino, P.; Costa, A.; Gheller, C.; Grillo, A.; Krokos, M.; Petta, C.

    2011-07-01

    Nowadays digital sky surveys and long-duration, high-resolution numerical simulations using high performance computing and grid systems produce multidimensional astrophysical datasets in the order of several Petabytes. Sharing visualizations of such datasets within communities and collaborating research groups is of paramount importance for disseminating results and advancing astrophysical research. Moreover educational and public outreach programs can benefit greatly from novel ways of presenting these datasets by promoting understanding of complex astrophysical processes, e.g., formation of stars and galaxies. We have previously developed VisIVO Server, a grid-enabled platform for high-performance large-scale astrophysical visualization. This article reviews the latest developments on VisIVO Web, a custom designed web portal wrapped around VisIVO Server, then introduces VisIVO Smartphone, a gateway connecting VisIVO Web and data repositories for mobile astrophysical visualization. We discuss current work and summarize future developments.

  17. The XMM Large Scale Structure Survey

    NASA Astrophysics Data System (ADS)

    Pierre, Marguerite

    2005-10-01

    We propose to complete, by an additional 5 deg2, the XMM-LSS Survey region overlying the Spitzer/SWIRE field. This field already has CFHTLS and Integral coverage, and will encompass about 10 deg2. The resulting multi-wavelength medium-depth survey, which complements XMM and Chandra deep surveys, will provide a unique view of large-scale structure over a wide range of redshift, and will show active galaxies in the full range of environments. The complete coverage by optical and IR surveys provides high-quality photometric redshifts, so that cosmological results can quickly be extracted. In the spirit of a Legacy survey, we will make the raw X-ray data immediately public. Multi-band catalogues and images will also be made available on short time scales.

  18. Estimation of large-scale dimension densities

    NASA Astrophysics Data System (ADS)

    Raab, Corinna; Kurths, Jürgen

    2001-07-01

    We propose a technique to calculate large-scale dimension densities in both higher-dimensional spatio-temporal systems and low-dimensional systems from only a few data points, where known methods usually have an unsatisfactory scaling behavior. This is mainly due to boundary and finite-size effects. With our rather simple method, we normalize boundary effects and get a significant correction of the dimension estimate. This straightforward approach is based on rather general assumptions. So even weak coherent structures obtained from small spatial couplings can be detected with this method, which is impossible by using the Lyapunov-dimension density. We demonstrate the efficiency of our technique for coupled logistic maps, coupled tent maps, the Lorenz attractor, and the Roessler attractor.

  19. Large-Scale Organization of Glycosylation Networks

    NASA Astrophysics Data System (ADS)

    Kim, Pan-Jun; Lee, Dong-Yup; Jeong, Hawoong

    2009-03-01

    Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are frequently attached to proteins and lipids. Glycans participate in fundamental biological processes including molecular trafficking and clearance, cell proliferation and apoptosis, developmental biology, immune response, and pathogenesis. N-linked glycans found on proteins are formed by sequential attachments of monosaccharides with the help of a relatively small number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thus generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigate the large-scale organization of such N-glycosylation pathways in a mammalian cell. The uncovered results give the experimentally-testable predictions for glycosylation process, and can be applied to the engineering of therapeutic glycoproteins.

  20. Large-scale sequential quadratic programming algorithms

    SciTech Connect

    Eldersveld, S.K.

    1992-09-01

    The problem addressed is the general nonlinear programming problem: finding a local minimizer for a nonlinear function subject to a mixture of nonlinear equality and inequality constraints. The methods studied are in the class of sequential quadratic programming (SQP) algorithms, which have previously proved successful for problems of moderate size. Our goal is to devise an SQP algorithm that is applicable to large-scale optimization problems, using sparse data structures and storing less curvature information but maintaining the property of superlinear convergence. The main features are: 1. The use of a quasi-Newton approximation to the reduced Hessian of the Lagrangian function. Only an estimate of the reduced Hessian matrix is required by our algorithm. The impact of not having available the full Hessian approximation is studied and alternative estimates are constructed. 2. The use of a transformation matrix Q. This allows the QP gradient to be computed easily when only the reduced Hessian approximation is maintained. 3. The use of a reduced-gradient form of the basis for the null space of the working set. This choice of basis is more practical than an orthogonal null-space basis for large-scale problems. The continuity condition for this choice is proven. 4. The use of incomplete solutions of quadratic programming subproblems. Certain iterates generated by an active-set method for the QP subproblem are used in place of the QP minimizer to define the search direction for the nonlinear problem. An implementation of the new algorithm has been obtained by modifying the code MINOS. Results and comparisons with MINOS and NPSOL are given for the new algorithm on a set of 92 test problems.

  1. Supporting large-scale computational science

    SciTech Connect

    Musick, R., LLNL

    1998-02-19

    Business needs have driven the development of commercial database systems since their inception. As a result, there has been a strong focus on supporting many users, minimizing the potential corruption or loss of data, and maximizing performance metrics like transactions per second, or TPC-C and TPC-D results. It turns out that these optimizations have little to do with the needs of the scientific community, and in particular have little impact on improving the management and use of large-scale high-dimensional data. At the same time, there is an unanswered need in the scientific community for many of the benefits offered by a robust DBMS. For example, tying an ad-hoc query language such as SQL together with a visualization toolkit would be a powerful enhancement to current capabilities. Unfortunately, there has been little emphasis or discussion in the VLDB community on this mismatch over the last decade. The goal of the paper is to identify the specific issues that need to be resolved before large-scale scientific applications can make use of DBMS products. This topic is addressed in the context of an evaluation of commercial DBMS technology applied to the exploration of data generated by the Department of Energy`s Accelerated Strategic Computing Initiative (ASCI). The paper describes the data being generated for ASCI as well as current capabilities for interacting with and exploring this data. The attraction of applying standard DBMS technology to this domain is discussed, as well as the technical and business issues that currently make this an infeasible solution.

  2. Introducing Large-Scale Innovation in Schools

    NASA Astrophysics Data System (ADS)

    Sotiriou, Sofoklis; Riviou, Katherina; Cherouvis, Stephanos; Chelioti, Eleni; Bogner, Franz X.

    2016-08-01

    Education reform initiatives tend to promise higher effectiveness in classrooms especially when emphasis is given to e-learning and digital resources. Practical changes in classroom realities or school organization, however, are lacking. A major European initiative entitled Open Discovery Space (ODS) examined the challenge of modernizing school education via a large-scale implementation of an open-scale methodology in using technology-supported innovation. The present paper describes this innovation scheme which involved schools and teachers all over Europe, embedded technology-enhanced learning into wider school environments and provided training to teachers. Our implementation scheme consisted of three phases: (1) stimulating interest, (2) incorporating the innovation into school settings and (3) accelerating the implementation of the innovation. The scheme's impact was monitored for a school year using five indicators: leadership and vision building, ICT in the curriculum, development of ICT culture, professional development support, and school resources and infrastructure. Based on about 400 schools, our study produced four results: (1) The growth in digital maturity was substantial, even for previously high scoring schools. This was even more important for indicators such as vision and leadership" and "professional development." (2) The evolution of networking is presented graphically, showing the gradual growth of connections achieved. (3) These communities became core nodes, involving numerous teachers in sharing educational content and experiences: One out of three registered users (36 %) has shared his/her educational resources in at least one community. (4) Satisfaction scores ranged from 76 % (offer of useful support through teacher academies) to 87 % (good environment to exchange best practices). Initiatives such as ODS add substantial value to schools on a large scale.

  3. Introducing Large-Scale Innovation in Schools

    NASA Astrophysics Data System (ADS)

    Sotiriou, Sofoklis; Riviou, Katherina; Cherouvis, Stephanos; Chelioti, Eleni; Bogner, Franz X.

    2016-02-01

    Education reform initiatives tend to promise higher effectiveness in classrooms especially when emphasis is given to e-learning and digital resources. Practical changes in classroom realities or school organization, however, are lacking. A major European initiative entitled Open Discovery Space (ODS) examined the challenge of modernizing school education via a large-scale implementation of an open-scale methodology in using technology-supported innovation. The present paper describes this innovation scheme which involved schools and teachers all over Europe, embedded technology-enhanced learning into wider school environments and provided training to teachers. Our implementation scheme consisted of three phases: (1) stimulating interest, (2) incorporating the innovation into school settings and (3) accelerating the implementation of the innovation. The scheme's impact was monitored for a school year using five indicators: leadership and vision building, ICT in the curriculum, development of ICT culture, professional development support, and school resources and infrastructure. Based on about 400 schools, our study produced four results: (1) The growth in digital maturity was substantial, even for previously high scoring schools. This was even more important for indicators such as vision and leadership" and "professional development." (2) The evolution of networking is presented graphically, showing the gradual growth of connections achieved. (3) These communities became core nodes, involving numerous teachers in sharing educational content and experiences: One out of three registered users (36 %) has shared his/her educational resources in at least one community. (4) Satisfaction scores ranged from 76 % (offer of useful support through teacher academies) to 87 % (good environment to exchange best practices). Initiatives such as ODS add substantial value to schools on a large scale.

  4. Large-scale electrophysiology: acquisition, compression, encryption, and storage of big data.

    PubMed

    Brinkmann, Benjamin H; Bower, Mark R; Stengel, Keith A; Worrell, Gregory A; Stead, Matt

    2009-05-30

    The use of large-scale electrophysiology to obtain high spatiotemporal resolution brain recordings (>100 channels) capable of probing the range of neural activity from local field potential oscillations to single-neuron action potentials presents new challenges for data acquisition, storage, and analysis. Our group is currently performing continuous, long-term electrophysiological recordings in human subjects undergoing evaluation for epilepsy surgery using hybrid intracranial electrodes composed of up to 320 micro- and clinical macroelectrode arrays. DC-capable amplifiers, sampling at 32kHz per channel with 18-bits of A/D resolution are capable of resolving extracellular voltages spanning single-neuron action potentials, high frequency oscillations, and high amplitude ultra-slow activity, but this approach generates 3 terabytes of data per day (at 4 bytes per sample) using current data formats. Data compression can provide several practical benefits, but only if data can be compressed and appended to files in real-time in a format that allows random access to data segments of varying size. Here we describe a state-of-the-art, scalable, electrophysiology platform designed for acquisition, compression, encryption, and storage of large-scale data. Data are stored in a file format that incorporates lossless data compression using range-encoded differences, a 32-bit cyclically redundant checksum to ensure data integrity, and 128-bit encryption for protection of patient information. PMID:19427545

  5. Ascorbic acid in fetal human brain

    PubMed Central

    Adlard, B. P. F.; De Souza, S. W.; Moon, Susan

    1974-01-01

    Ascorbic acid concentrations in fetal human forebrain in the period 11 to 19 weeks' gestational age were 4 to 11 times higher than those of adults. Levels fell progressively with increasing gestational age but, in term babies dying within 4 weeks of birth, were still at least 3 times those of adults. It was confirmed that, in women delivering at term, ascorbic acid concentrations are approximately 4 times higher in cord blood plasma than in maternal blood plasma. The possible importance of ascorbic acid for normal human brain development is discussed. PMID:4830116

  6. MRI and MRS of human brain tumors.

    PubMed

    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM). PMID:19381963

  7. Toward Developmental Connectomics of the Human Brain.

    PubMed

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  8. Toward Developmental Connectomics of the Human Brain

    PubMed Central

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental

  9. A geometric network model of intrinsic grey-matter connectivity of the human brain

    PubMed Central

    Lo, Yi-Ping; O’Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-01-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections. PMID:26503036

  10. A geometric network model of intrinsic grey-matter connectivity of the human brain

    NASA Astrophysics Data System (ADS)

    Lo, Yi-Ping; O'Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-10-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections.

  11. On the analysis of large-scale genomic structures.

    PubMed

    Oiwa, Nestor Norio; Goldman, Carla

    2005-01-01

    We apply methods from statistical physics (histograms, correlation functions, fractal dimensions, and singularity spectra) to characterize large-scale structure of the distribution of nucleotides along genomic sequences. We discuss the role of the extension of noncoding segments ("junk DNA") for the genomic organization, and the connection between the coding segment distribution and the high-eukaryotic chromatin condensation. The following sequences taken from GenBank were analyzed: complete genome of Xanthomonas campestri, complete genome of yeast, chromosome V of Caenorhabditis elegans, and human chromosome XVII around gene BRCA1. The results are compared with the random and periodic sequences and those generated by simple and generalized fractal Cantor sets. PMID:15858230

  12. Brain structures in the sciences and humanities.

    PubMed

    Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

    2015-11-01

    The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia). PMID:25079346

  13. Relationship Between Large-Scale Functional and Structural Covariance Networks in Idiopathic Generalized Epilepsy

    PubMed Central

    Zhang, Zhiqiang; Mantini, Dante; Xu, Qiang; Wang, Zhengge; Chen, Guanghui; Jiao, Qing; Zang, Yu-Feng

    2013-01-01

    Abstract The human brain can be modeled as a network, whose structure can be revealed by either anatomical or functional connectivity analyses. Little is known, so far, about the topological features of the large-scale interregional functional covariance network (FCN) in the brain. Further, the relationship between the FCN and the structural covariance network (SCN) has not been characterized yet, in the intact as well as in the diseased brain. Here, we studied 59 patients with idiopathic generalized epilepsy characterized by tonic–clonic seizures and 59 healthy controls. We estimated the FCN and the SCN by measuring amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV), respectively, and then we conducted graph theoretical analyses. Our ALFF-based FCN and GMV-based results revealed that the normal human brain is characterized by specific topological properties such as small worldness and highly-connected hub regions. The patients had an altered overall topology compared to the controls, suggesting that epilepsy is primarily a disorder of the cerebral network organization. Further, the patients had altered nodal characteristics in the subcortical and medial temporal regions and default-mode regions, for both the FCN and SCN. Importantly, the correspondence between the FCN and SCN was significantly larger in patients than in the controls. These results support the hypothesis that the SCN reflects shared long-term trophic mechanisms within functionally synchronous systems. They can also provide crucial information for understanding the interactions between the whole-brain network organization and pathology in generalized tonic–clonic seizures. PMID:23510272

  14. Structural brain correlates of human sleep oscillations.

    PubMed

    Saletin, Jared M; van der Helm, Els; Walker, Matthew P

    2013-12-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Gray matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, gray matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, gray matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure. PMID:23770411

  15. Perfusion harmonic imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Metzler, Volker H.; Seidel, Guenter; Wiesmann, Martin; Meyer, Karsten; Aach, Til

    2003-05-01

    The fast visualisation of cerebral microcirculation supports diagnosis of acute cerebrovascular diseases. However, the commonly used CT/MRI-based methods are time consuming and, moreover, costly. Therefore we propose an alternative approach to brain perfusion imaging by means of ultrasonography. In spite of the low signal/noise-ratio of transcranial ultrasound and the high impedance of the skull, flow images of cerebral blood flow can be derived by capturing the kinetics of appropriate contrast agents by harmonic ultrasound image sequences. In this paper we propose three different methods for human brain perfusion imaging, each of which yielding flow images indicating the status of the patient's cerebral microcirculation by visualising local flow parameters. Bolus harmonic imaging (BHI) displays the flow kinetics of bolus injections, while replenishment (RHI) and diminution harmonic imaging (DHI) compute flow characteristics from contrast agent continuous infusions. RHI measures the contrast agents kinetics in the influx phase and DHI displays the diminution kinetics of the contrast agent acquired from the decay phase. In clinical studies, BHI- and RHI-parameter images were found to represent comprehensive and reproducible distributions of physiological cerebral blood flow. For DHI it is shown, that bubble destruction and hence perfusion phenomena principally can be displayed. Generally, perfusion harmonic imaging enables reliable and fast bedside imaging of human brain perfusion. Due to its cost efficiency it complements cerebrovascular diagnostics by established CT/MRI-based methods.

  16. Structural Brain Correlates of Human Sleep Oscillations

    PubMed Central

    Saletin, Jared M.; van der Helm, Els; Walker, Matthew P.

    2014-01-01

    Sleep is strongly conserved within species, yet marked and perplexing inter-individual differences in sleep physiology are observed. Combining EEG sleep recordings and high-resolution structural brain imaging, here we demonstrate that the morphology of the human brain offers one explanatory factor of such inter-individual variability. Grey matter volume in interoceptive and exteroceptive cortices correlated with the expression of slower NREM sleep spindle frequencies, supporting their proposed role in sleep protection against conscious perception. Conversely, and consistent with an involvement in declarative memory processing, grey matter volume in bilateral hippocampus was associated with faster NREM sleep spindle frequencies. In contrast to spindles, grey matter volume in the homeostatic sleep-regulating center of the basal forebrain/hypothalamus, together with the medial prefrontal cortex, accounted for individual differences in NREM slow wave oscillations. Together, such findings indicate that the qualitative and quantitative expression of human sleep physiology is significantly related to anatomically specific differences in macroscopic brain structure. PMID:23770411

  17. Gravity and large-scale nonlocal bias

    NASA Astrophysics Data System (ADS)

    Chan, Kwan Chuen; Scoccimarro, Román; Sheth, Ravi K.

    2012-04-01

    For Gaussian primordial fluctuations the relationship between galaxy and matter overdensities, bias, is most often assumed to be local at the time of observation in the large-scale limit. This hypothesis is however unstable under time evolution, we provide proofs under several (increasingly more realistic) sets of assumptions. In the simplest toy model galaxies are created locally and linearly biased at a single formation time, and subsequently move with the dark matter (no velocity bias) conserving their comoving number density (no merging). We show that, after this formation time, the bias becomes unavoidably nonlocal and nonlinear at large scales. We identify the nonlocal gravitationally induced fields in which the galaxy overdensity can be expanded, showing that they can be constructed out of the invariants of the deformation tensor (Galileons), the main signature of which is a quadrupole field in second-order perturbation theory. In addition, we show that this result persists if we include an arbitrary evolution of the comoving number density of tracers. We then include velocity bias, and show that new contributions appear; these are related to the breaking of Galilean invariance of the bias relation, a dipole field being the signature at second order. We test these predictions by studying the dependence of halo overdensities in cells of fixed dark matter density: measurements in simulations show that departures from the mean bias relation are strongly correlated with the nonlocal gravitationally induced fields identified by our formalism, suggesting that the halo distribution at the present time is indeed more closely related to the mass distribution at an earlier rather than present time. However, the nonlocality seen in the simulations is not fully captured by assuming local bias in Lagrangian space. The effects on nonlocal bias seen in the simulations are most important for the most biased halos, as expected from our predictions. Accounting for these

  18. Large-Scale Statistics for Cu Electromigration

    NASA Astrophysics Data System (ADS)

    Hauschildt, M.; Gall, M.; Hernandez, R.

    2009-06-01

    Even after the successful introduction of Cu-based metallization, the electromigration failure risk has remained one of the important reliability concerns for advanced process technologies. The observation of strong bimodality for the electron up-flow direction in dual-inlaid Cu interconnects has added complexity, but is now widely accepted. The failure voids can occur both within the via ("early" mode) or within the trench ("late" mode). More recently, bimodality has been reported also in down-flow electromigration, leading to very short lifetimes due to small, slit-shaped voids under vias. For a more thorough investigation of these early failure phenomena, specific test structures were designed based on the Wheatstone Bridge technique. The use of these structures enabled an increase of the tested sample size close to 675000, allowing a direct analysis of electromigration failure mechanisms at the single-digit ppm regime. Results indicate that down-flow electromigration exhibits bimodality at very small percentage levels, not readily identifiable with standard testing methods. The activation energy for the down-flow early failure mechanism was determined to be 0.83±0.02 eV. Within the small error bounds of this large-scale statistical experiment, this value is deemed to be significantly lower than the usually reported activation energy of 0.90 eV for electromigration-induced diffusion along Cu/SiCN interfaces. Due to the advantages of the Wheatstone Bridge technique, we were also able to expand the experimental temperature range down to 150° C, coming quite close to typical operating conditions up to 125° C. As a result of the lowered activation energy, we conclude that the down-flow early failure mode may control the chip lifetime at operating conditions. The slit-like character of the early failure void morphology also raises concerns about the validity of the Blech-effect for this mechanism. A very small amount of Cu depletion may cause failure even before a

  19. Visualization of monoamine oxidase in human brain

    SciTech Connect

    Fowler, J.S.; Volkow, N.D.; Wang, G.J.; Pappas, N.; Shea, C.; MacGregor, R.R.; Logan, J.

    1996-12-31

    Monoamine oxidase is a flavin enzyme which exists in two subtypes, MAO A and MAO B. In human brain MAO B predominates and is largely compartmentalized in cell bodies of serotonergic neurons and glia. Regional distribution of MAO B was determined by positron computed tomography with volunteers after the administration of deuterium substituted [11C]L-deprenyl. The basal ganglia and thalamus exhibited the greatest concentrations of MAO B with intermediate levels in the frontal cortex and cingulate gyrus while lowest levels were observed in the parietal and temporal cortices and cerebellum. We observed that brain MAO B increases with are in health normal subjects, however the increases were generally smaller than those revealed with post-mortem studies.

  20. Blocking monocyte transmigration in in vitro system by a human antibody scFv anti-CD99. Efficient large scale purification from periplasmic inclusion bodies in E. coli expression system.

    PubMed

    Moricoli, Diego; Muller, William Anthony; Carbonella, Damiano Cosimo; Balducci, Maria Cristina; Dominici, Sabrina; Watson, Richard; Fiori, Valentina; Weber, Evan; Cianfriglia, Maurizio; Scotlandi, Katia; Magnani, Mauro

    2014-06-01

    Migration of leukocytes into site of inflammation involves several steps mediated by various families of adhesion molecules. CD99 play a significant role in transendothelial migration (TEM) of leukocytes. Inhibition of TEM by specific monoclonal antibody (mAb) can provide a potent therapeutic approach to treating inflammatory conditions. However, the therapeutic utilization of whole IgG can lead to an inappropriate activation of Fc receptor-expressing cells, inducing serious adverse side effects due to cytokine release. In this regard, specific recombinant antibody in single chain variable fragments (scFvs) originated by phage library may offer a solution by affecting TEM function in a safe clinical context. However, this consideration requires large scale production of functional scFv antibodies and the absence of toxic reagents utilized for solubilization and refolding step of inclusion bodies that may discourage industrial application of these antibody fragments. In order to apply the scFv anti-CD99 named C7A in a clinical setting, we herein describe an efficient and large scale production of the antibody fragments expressed in E. coli as periplasmic insoluble protein avoiding gel filtration chromatography approach, and laborious refolding step pre- and post-purification. Using differential salt elution which is a simple, reproducible and effective procedure we are able to separate scFv in monomer format from aggregates. The purified scFv antibody C7A exhibits inhibitory activity comparable to an antagonistic conventional mAb, thus providing an excellent agent for blocking CD99 signaling. This protocol can be useful for the successful purification of other monomeric scFvs which are expressed as periplasmic inclusion bodies in bacterial systems. PMID:24798881

  1. Curvature constraints from large scale structure

    NASA Astrophysics Data System (ADS)

    Di Dio, Enea; Montanari, Francesco; Raccanelli, Alvise; Durrer, Ruth; Kamionkowski, Marc; Lesgourgues, Julien

    2016-06-01

    We modified the CLASS code in order to include relativistic galaxy number counts in spatially curved geometries; we present the formalism and study the effect of relativistic corrections on spatial curvature. The new version of the code is now publicly available. Using a Fisher matrix analysis, we investigate how measurements of the spatial curvature parameter ΩK with future galaxy surveys are affected by relativistic effects, which influence observations of the large scale galaxy distribution. These effects include contributions from cosmic magnification, Doppler terms and terms involving the gravitational potential. As an application, we consider angle and redshift dependent power spectra, which are especially well suited for model independent cosmological constraints. We compute our results for a representative deep, wide and spectroscopic survey, and our results show the impact of relativistic corrections on spatial curvature parameter estimation. We show that constraints on the curvature parameter may be strongly biased if, in particular, cosmic magnification is not included in the analysis. Other relativistic effects turn out to be subdominant in the studied configuration. We analyze how the shift in the estimated best-fit value for the curvature and other cosmological parameters depends on the magnification bias parameter, and find that significant biases are to be expected if this term is not properly considered in the analysis.

  2. Large-scale carbon fiber tests

    NASA Technical Reports Server (NTRS)

    Pride, R. A.

    1980-01-01

    A realistic release of carbon fibers was established by burning a minimum of 45 kg of carbon fiber composite aircraft structural components in each of five large scale, outdoor aviation jet fuel fire tests. This release was quantified by several independent assessments with various instruments developed specifically for these tests. The most likely values for the mass of single carbon fibers released ranged from 0.2 percent of the initial mass of carbon fiber for the source tests (zero wind velocity) to a maximum of 0.6 percent of the initial carbon fiber mass for dissemination tests (5 to 6 m/s wind velocity). Mean fiber lengths for fibers greater than 1 mm in length ranged from 2.5 to 3.5 mm. Mean diameters ranged from 3.6 to 5.3 micrometers which was indicative of significant oxidation. Footprints of downwind dissemination of the fire released fibers were measured to 19.1 km from the fire.

  3. Large-scale wind turbine structures

    NASA Technical Reports Server (NTRS)

    Spera, David A.

    1988-01-01

    The purpose of this presentation is to show how structural technology was applied in the design of modern wind turbines, which were recently brought to an advanced stage of development as sources of renewable power. Wind turbine structures present many difficult problems because they are relatively slender and flexible; subject to vibration and aeroelastic instabilities; acted upon by loads which are often nondeterministic; operated continuously with little maintenance in all weather; and dominated by life-cycle cost considerations. Progress in horizontal-axis wind turbines (HAWT) development was paced by progress in the understanding of structural loads, modeling of structural dynamic response, and designing of innovative structural response. During the past 15 years a series of large HAWTs was developed. This has culminated in the recent completion of the world's largest operating wind turbine, the 3.2 MW Mod-5B power plane installed on the island of Oahu, Hawaii. Some of the applications of structures technology to wind turbine will be illustrated by referring to the Mod-5B design. First, a video overview will be presented to provide familiarization with the Mod-5B project and the important components of the wind turbine system. Next, the structural requirements for large-scale wind turbines will be discussed, emphasizing the difficult fatigue-life requirements. Finally, the procedures used to design the structure will be presented, including the use of the fracture mechanics approach for determining allowable fatigue stresses.

  4. Large-scale wind turbine structures

    NASA Astrophysics Data System (ADS)

    Spera, David A.

    1988-05-01

    The purpose of this presentation is to show how structural technology was applied in the design of modern wind turbines, which were recently brought to an advanced stage of development as sources of renewable power. Wind turbine structures present many difficult problems because they are relatively slender and flexible; subject to vibration and aeroelastic instabilities; acted upon by loads which are often nondeterministic; operated continuously with little maintenance in all weather; and dominated by life-cycle cost considerations. Progress in horizontal-axis wind turbines (HAWT) development was paced by progress in the understanding of structural loads, modeling of structural dynamic response, and designing of innovative structural response. During the past 15 years a series of large HAWTs was developed. This has culminated in the recent completion of the world's largest operating wind turbine, the 3.2 MW Mod-5B power plane installed on the island of Oahu, Hawaii. Some of the applications of structures technology to wind turbine will be illustrated by referring to the Mod-5B design. First, a video overview will be presented to provide familiarization with the Mod-5B project and the important components of the wind turbine system. Next, the structural requirements for large-scale wind turbines will be discussed, emphasizing the difficult fatigue-life requirements. Finally, the procedures used to design the structure will be presented, including the use of the fracture mechanics approach for determining allowable fatigue stresses.

  5. Food appropriation through large scale land acquisitions

    NASA Astrophysics Data System (ADS)

    Rulli, Maria Cristina; D'Odorico, Paolo

    2014-05-01

    The increasing demand for agricultural products and the uncertainty of international food markets has recently drawn the attention of governments and agribusiness firms toward investments in productive agricultural land, mostly in the developing world. The targeted countries are typically located in regions that have remained only marginally utilized because of lack of modern technology. It is expected that in the long run large scale land acquisitions (LSLAs) for commercial farming will bring the technology required to close the existing crops yield gaps. While the extent of the acquired land and the associated appropriation of freshwater resources have been investigated in detail, the amount of food this land can produce and the number of people it could feed still need to be quantified. Here we use a unique dataset of land deals to provide a global quantitative assessment of the rates of crop and food appropriation potentially associated with LSLAs. We show how up to 300-550 million people could be fed by crops grown in the acquired land, should these investments in agriculture improve crop production and close the yield gap. In contrast, about 190-370 million people could be supported by this land without closing of the yield gap. These numbers raise some concern because the food produced in the acquired land is typically exported to other regions, while the target countries exhibit high levels of malnourishment. Conversely, if used for domestic consumption, the crops harvested in the acquired land could ensure food security to the local populations.

  6. Large Scale Computer Simulation of Erthocyte Membranes

    NASA Astrophysics Data System (ADS)

    Harvey, Cameron; Revalee, Joel; Laradji, Mohamed

    2007-11-01

    The cell membrane is crucial to the life of the cell. Apart from partitioning the inner and outer environment of the cell, they also act as a support of complex and specialized molecular machinery, important for both the mechanical integrity of the cell, and its multitude of physiological functions. Due to its relative simplicity, the red blood cell has been a favorite experimental prototype for investigations of the structural and functional properties of the cell membrane. The erythrocyte membrane is a composite quasi two-dimensional structure composed essentially of a self-assembled fluid lipid bilayer and a polymerized protein meshwork, referred to as the cytoskeleton or membrane skeleton. In the case of the erythrocyte, the polymer meshwork is mainly composed of spectrin, anchored to the bilayer through specialized proteins. Using a coarse-grained model, recently developed by us, of self-assembled lipid membranes with implicit solvent and using soft-core potentials, we simulated large scale red-blood-cells bilayers with dimensions ˜ 10-1 μm^2, with explicit cytoskeleton. Our aim is to investigate the renormalization of the elastic properties of the bilayer due to the underlying spectrin meshwork.

  7. An informal paper on large-scale dynamic systems

    NASA Technical Reports Server (NTRS)

    Ho, Y. C.

    1975-01-01

    Large scale systems are defined as systems requiring more than one decision maker to control the system. Decentralized control and decomposition are discussed for large scale dynamic systems. Information and many-person decision problems are analyzed.

  8. Physical biology of human brain development.

    PubMed

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia. PMID:26217183

  9. Physical biology of human brain development

    PubMed Central

    Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

    2015-01-01

    Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales–from phenomena on the cellular level toward form and function on the organ level–to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia. PMID:26217183

  10. Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain

    PubMed Central

    Krienen, Fenna M.; Yeo, B. T. Thomas; Ge, Tian; Buckner, Randy L.; Sherwood, Chet C.

    2016-01-01

    The human brain is patterned with disproportionately large, distributed cerebral networks that connect multiple association zones in the frontal, temporal, and parietal lobes. The expansion of the cortical surface, along with the emergence of long-range connectivity networks, may be reflected in changes to the underlying molecular architecture. Using the Allen Institute’s human brain transcriptional atlas, we demonstrate that genes particularly enriched in supragranular layers of the human cerebral cortex relative to mouse distinguish major cortical classes. The topography of transcriptional expression reflects large-scale brain network organization consistent with estimates from functional connectivity MRI and anatomical tracing in nonhuman primates. Microarray expression data for genes preferentially expressed in human upper layers (II/III), but enriched only in lower layers (V/VI) of mouse, were cross-correlated to identify molecular profiles across the cerebral cortex of postmortem human brains (n = 6). Unimodal sensory and motor zones have similar molecular profiles, despite being distributed across the cortical mantle. Sensory/motor profiles were anticorrelated with paralimbic and certain distributed association network profiles. Tests of alternative gene sets did not consistently distinguish sensory and motor regions from paralimbic and association regions: (i) genes enriched in supragranular layers in both humans and mice, (ii) genes cortically enriched in humans relative to nonhuman primates, (iii) genes related to connectivity in rodents, (iv) genes associated with human and mouse connectivity, and (v) 1,454 gene sets curated from known gene ontologies. Molecular innovations of upper cortical layers may be an important component in the evolution of long-range corticocortical projections. PMID:26739559

  11. Molecular biology of the human brain

    SciTech Connect

    Jones, E.G.

    1988-01-01

    This book examines new methods of molecular biology that are providing valuable insights into the human brain, the genes that govern its assembly and function, and the many genetic defects that cause neurological diseases such as Alzheimer's, Cri du Chat syndrome, Huntington's disease, and bipolar depression disorder. In addition, the book reviews techniques in molecular neurobiological research, including the use of affinity reagents, chimeric receptors, and site-directed mutagenesis in localizing the ion channel and cholinergic binding site, and the application of somatic cell genetics in isolating specific chromosomes or chromosomal segments.

  12. Sensitivity technologies for large scale simulation.

    SciTech Connect

    Collis, Samuel Scott; Bartlett, Roscoe Ainsworth; Smith, Thomas Michael; Heinkenschloss, Matthias; Wilcox, Lucas C.; Hill, Judith C.; Ghattas, Omar; Berggren, Martin Olof; Akcelik, Volkan; Ober, Curtis Curry; van Bloemen Waanders, Bart Gustaaf; Keiter, Eric Richard

    2005-01-01

    Sensitivity analysis is critically important to numerous analysis algorithms, including large scale optimization, uncertainty quantification,reduced order modeling, and error estimation. Our research focused on developing tools, algorithms and standard interfaces to facilitate the implementation of sensitivity type analysis into existing code and equally important, the work was focused on ways to increase the visibility of sensitivity analysis. We attempt to accomplish the first objective through the development of hybrid automatic differentiation tools, standard linear algebra interfaces for numerical algorithms, time domain decomposition algorithms and two level Newton methods. We attempt to accomplish the second goal by presenting the results of several case studies in which direct sensitivities and adjoint methods have been effectively applied, in addition to an investigation of h-p adaptivity using adjoint based a posteriori error estimation. A mathematical overview is provided of direct sensitivities and adjoint methods for both steady state and transient simulations. Two case studies are presented to demonstrate the utility of these methods. A direct sensitivity method is implemented to solve a source inversion problem for steady state internal flows subject to convection diffusion. Real time performance is achieved using novel decomposition into offline and online calculations. Adjoint methods are used to reconstruct initial conditions of a contamination event in an external flow. We demonstrate an adjoint based transient solution. In addition, we investigated time domain decomposition algorithms in an attempt to improve the efficiency of transient simulations. Because derivative calculations are at the root of sensitivity calculations, we have developed hybrid automatic differentiation methods and implemented this approach for shape optimization for gas dynamics using the Euler equations. The hybrid automatic differentiation method was applied to a first

  13. International space station. Large scale integration approach

    NASA Astrophysics Data System (ADS)

    Cohen, Brad

    The International Space Station is the most complex large scale integration program in development today. The approach developed for specification, subsystem development, and verification lay a firm basis on which future programs of this nature can be based. International Space Station is composed of many critical items, hardware and software, built by numerous International Partners, NASA Institutions, and U.S. Contractors and is launched over a period of five years. Each launch creates a unique configuration that must be safe, survivable, operable, and support ongoing assembly (assemblable) to arrive at the assembly complete configuration in 2003. The approaches to integrating each of the modules into a viable spacecraft and continue the assembly is a challenge in itself. Added to this challenge are the severe schedule constraints and lack of an "Iron Bird", which prevents assembly and checkout of each on-orbit configuration prior to launch. This paper will focus on the following areas: 1) Specification development process explaining how the requirements and specifications were derived using a modular concept driven by launch vehicle capability. Each module is composed of components of subsystems versus completed subsystems. 2) Approach to stage (each stage consists of the launched module added to the current on-orbit spacecraft) specifications. Specifically, how each launched module and stage ensures support of the current and future elements of the assembly. 3) Verification approach, due to the schedule constraints, is primarily analysis supported by testing. Specifically, how are the interfaces ensured to mate and function on-orbit when they cannot be mated before launch. 4) Lessons learned. Where can we improve this complex system design and integration task?

  14. Large Scale Flame Spread Environmental Characterization Testing

    NASA Technical Reports Server (NTRS)

    Clayman, Lauren K.; Olson, Sandra L.; Gokoghi, Suleyman A.; Brooker, John E.; Ferkul, Paul V.; Kacher, Henry F.

    2013-01-01

    Under the Advanced Exploration Systems (AES) Spacecraft Fire Safety Demonstration Project (SFSDP), as a risk mitigation activity in support of the development of a large-scale fire demonstration experiment in microgravity, flame-spread tests were conducted in normal gravity on thin, cellulose-based fuels in a sealed chamber. The primary objective of the tests was to measure pressure rise in a chamber as sample material, burning direction (upward/downward), total heat release, heat release rate, and heat loss mechanisms were varied between tests. A Design of Experiments (DOE) method was imposed to produce an array of tests from a fixed set of constraints and a coupled response model was developed. Supplementary tests were run without experimental design to additionally vary select parameters such as initial chamber pressure. The starting chamber pressure for each test was set below atmospheric to prevent chamber overpressure. Bottom ignition, or upward propagating burns, produced rapid acceleratory turbulent flame spread. Pressure rise in the chamber increases as the amount of fuel burned increases mainly because of the larger amount of heat generation and, to a much smaller extent, due to the increase in gaseous number of moles. Top ignition, or downward propagating burns, produced a steady flame spread with a very small flat flame across the burning edge. Steady-state pressure is achieved during downward flame spread as the pressure rises and plateaus. This indicates that the heat generation by the flame matches the heat loss to surroundings during the longer, slower downward burns. One heat loss mechanism included mounting a heat exchanger directly above the burning sample in the path of the plume to act as a heat sink and more efficiently dissipate the heat due to the combustion event. This proved an effective means for chamber overpressure mitigation for those tests producing the most total heat release and thusly was determined to be a feasible mitigation

  15. Synchronization of coupled large-scale Boolean networks

    SciTech Connect

    Li, Fangfei

    2014-03-15

    This paper investigates the complete synchronization and partial synchronization of two large-scale Boolean networks. First, the aggregation algorithm towards large-scale Boolean network is reviewed. Second, the aggregation algorithm is applied to study the complete synchronization and partial synchronization of large-scale Boolean networks. Finally, an illustrative example is presented to show the efficiency of the proposed results.

  16. Mouse Genetic Models of Human Brain Disorders.

    PubMed

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  17. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  18. Building a Large-Scale Computational Model of a Cortical Neuronal Network

    NASA Astrophysics Data System (ADS)

    Zemanová, Lucia; Zhou, Changsong; Kurths, Jürgen

    We introduce the general framework of the large-scale neuronal model used in the 5th Helmholtz Summer School — Complex Brain Networks. The main aim is to build a universal large-scale model of a cortical neuronal network, structured as a network of networks, which is flexible enough to implement different kinds of topology and neuronal models and which exhibits behavior in various dynamical regimes. First, we describe important biological aspects of brain topology and use them in the construction of a large-scale cortical network. Second, the general dynamical model is presented together with explanations of the major dynamical properties of neurons. Finally, we discuss the implementation of the model into parallel code and its possible modifications and improvements.

  19. Two phylogenetic specializations in the human brain.

    PubMed

    Allman, John; Hakeem, Atiya; Watson, Karli

    2002-08-01

    In this study, two anatomical specializations of the brain in apes and humans are considered. One of these is a whole cortical area located in the frontal polar cortex (Brodmann's area 10), and the other is a morphologically distinctive cell type, the spindle neuron of the anterior cingulate cortex. The authors suggest that the spindle cells may relay to other parts of the brain--especially to area 10, the outcome of processing within the anterior cingulate cortex. This relay conveys the motivation to act. It particularly concerns the recognition of having committed an error that leads to the initiation of adaptive responses to these adverse events so as to reduce error commission. This capacity is related to the development of self-control as an individual matures and gains social insight. Although the anterior cingulate deals with the individual's immediate response to changing conditions, area 10 is involved in the retrieval of memories from the individual's past experience and the capacity to plan adaptive responses. The authors suggest that these neurobehavioral specializations are crucial aspects of intelligence as defined as the capacity to make adaptive responses to changing conditions. The authors further hypothesize that these specializations facilitated the evolution of the unique capacity for the intergenerational transfer of the food and information characteristic of human extended families. PMID:12194502

  20. Large-Scale Spacecraft Fire Safety Tests

    NASA Technical Reports Server (NTRS)

    Urban, David; Ruff, Gary A.; Ferkul, Paul V.; Olson, Sandra; Fernandez-Pello, A. Carlos; T'ien, James S.; Torero, Jose L.; Cowlard, Adam J.; Rouvreau, Sebastien; Minster, Olivier; Toth, Balazs; Legros, Guillaume; Eigenbrod, Christian; Smirnov, Nickolay; Fujita, Osamu; Jomaas, Grunde

    2014-01-01

    An international collaborative program is underway to address open issues in spacecraft fire safety. Because of limited access to long-term low-gravity conditions and the small volume generally allotted for these experiments, there have been relatively few experiments that directly study spacecraft fire safety under low-gravity conditions. Furthermore, none of these experiments have studied sample sizes and environment conditions typical of those expected in a spacecraft fire. The major constraint has been the size of the sample, with prior experiments limited to samples of the order of 10 cm in length and width or smaller. This lack of experimental data forces spacecraft designers to base their designs and safety precautions on 1-g understanding of flame spread, fire detection, and suppression. However, low-gravity combustion research has demonstrated substantial differences in flame behavior in low-gravity. This, combined with the differences caused by the confined spacecraft environment, necessitates practical scale spacecraft fire safety research to mitigate risks for future space missions. To address this issue, a large-scale spacecraft fire experiment is under development by NASA and an international team of investigators. This poster presents the objectives, status, and concept of this collaborative international project (Saffire). The project plan is to conduct fire safety experiments on three sequential flights of an unmanned ISS re-supply spacecraft (the Orbital Cygnus vehicle) after they have completed their delivery of cargo to the ISS and have begun their return journeys to earth. On two flights (Saffire-1 and Saffire-3), the experiment will consist of a flame spread test involving a meter-scale sample ignited in the pressurized volume of the spacecraft and allowed to burn to completion while measurements are made. On one of the flights (Saffire-2), 9 smaller (5 x 30 cm) samples will be tested to evaluate NASAs material flammability screening tests

  1. Ecohydrological modeling for large-scale environmental impact assessment.

    PubMed

    Woznicki, Sean A; Nejadhashemi, A Pouyan; Abouali, Mohammad; Herman, Matthew R; Esfahanian, Elaheh; Hamaamin, Yaseen A; Zhang, Zhen

    2016-02-01

    Ecohydrological models are frequently used to assess the biological integrity of unsampled streams. These models vary in complexity and scale, and their utility depends on their final application. Tradeoffs are usually made in model scale, where large-scale models are useful for determining broad impacts of human activities on biological conditions, and regional-scale (e.g. watershed or ecoregion) models provide stakeholders greater detail at the individual stream reach level. Given these tradeoffs, the objective of this study was to develop large-scale stream health models with reach level accuracy similar to regional-scale models thereby allowing for impacts assessments and improved decision-making capabilities. To accomplish this, four measures of biological integrity (Ephemeroptera, Plecoptera, and Trichoptera taxa (EPT), Family Index of Biotic Integrity (FIBI), Hilsenhoff Biotic Index (HBI), and fish Index of Biotic Integrity (IBI)) were modeled based on four thermal classes (cold, cold-transitional, cool, and warm) of streams that broadly dictate the distribution of aquatic biota in Michigan. The Soil and Water Assessment Tool (SWAT) was used to simulate streamflow and water quality in seven watersheds and the Hydrologic Index Tool was used to calculate 171 ecologically relevant flow regime variables. Unique variables were selected for each thermal class using a Bayesian variable selection method. The variables were then used in development of adaptive neuro-fuzzy inference systems (ANFIS) models of EPT, FIBI, HBI, and IBI. ANFIS model accuracy improved when accounting for stream thermal class rather than developing a global model. PMID:26595397

  2. Functional interactions between large-scale networks during memory search.

    PubMed

    Kragel, James E; Polyn, Sean M

    2015-03-01

    Neuroimaging studies have identified two major large-scale brain networks, the default mode network (DMN) and the dorsal attention network (DAN), which are engaged for internally and externally directed cognitive tasks respectively, and which show anticorrelated activity during cognitively demanding tests and at rest. We identified these brain networks using independent component analysis (ICA) of functional magnetic resonance imaging data, and examined their interactions during the free-recall task, a self-initiated memory search task in which retrieval is performed in the absence of external cues. Despite the internally directed nature of the task, the DAN showed transient engagement in the seconds leading up to successful retrieval. ICA revealed a fractionation of the DMN into 3 components. A posteromedial network increased engagement during memory search, while the two others showed suppressed activity during memory search. Cooperative interactions between this posteromedial network, a right-lateralized frontoparietal control network, and a medial prefrontal network were maintained during memory search. The DAN demonstrated heterogeneous task-dependent shifts in functional coupling with various subnetworks within the DMN. This functional reorganization suggests a broader role of the DAN in the absence of externally directed cognition, and highlights the contribution of the posteromedial network to episodic retrieval. PMID:24084128

  3. The Human Brain in Numbers: A Linearly Scaled-up Primate Brain

    PubMed Central

    Herculano-Houzel, Suzana

    2009-01-01

    The human brain has often been viewed as outstanding among mammalian brains: the most cognitively able, the largest-than-expected from body size, endowed with an overdeveloped cerebral cortex that represents over 80% of brain mass, and purportedly containing 100 billion neurons and 10× more glial cells. Such uniqueness was seemingly necessary to justify the superior cognitive abilities of humans over larger-brained mammals such as elephants and whales. However, our recent studies using a novel method to determine the cellular composition of the brain of humans and other primates as well as of rodents and insectivores show that, since different cellular scaling rules apply to the brains within these orders, brain size can no longer be considered a proxy for the number of neurons in the brain. These studies also showed that the human brain is not exceptional in its cellular composition, as it was found to contain as many neuronal and non-neuronal cells as would be expected of a primate brain of its size. Additionally, the so-called overdeveloped human cerebral cortex holds only 19% of all brain neurons, a fraction that is similar to that found in other mammals. In what regards absolute numbers of neurons, however, the human brain does have two advantages compared to other mammalian brains: compared to rodents, and probably to whales and elephants as well, it is built according to the very economical, space-saving scaling rules that apply to other primates; and, among economically built primate brains, it is the largest, hence containing the most neurons. These findings argue in favor of a view of cognitive abilities that is centered on absolute numbers of neurons, rather than on body size or encephalization, and call for a re-examination of several concepts related to the exceptionality of the human brain. PMID:19915731

  4. [Neuroethics: Ethical Endowments of Human Brain].

    PubMed

    López Moratalla, Natalia

    2015-01-01

    The neurobiological processes underlying moral judgement have been the focus of Neuroethics. Neurosciences demonstrate which cerebral areas are active and inactive whilst people decide how to act when facing a moral dilemma; in this way we know the correlation between determined cerebral areas and our human acts. We can explain how the ″ethical endowments″ of each person, common to all human beings, is ″embedded″ in the dynamic of cerebral flows. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion related areas of the brain contribute to moral judgement. The outcome of man's natural inclinations is on one hand linked to instinctive systems of animal survival and to basic emotions, and on the other, to the life of each individual human uninhibited by automatism of the biological laws, because he is governed by the laws of freedom. The capacity to formulate an ethical judgement is an innate asset of the human mind. PMID:26546796

  5. Development and optimisation of a procedure for the production of Parapoxvirus ovis by large-scale microcarrier cell culture in a non-animal, non-human and non-plant-derived medium.

    PubMed

    Pohlscheidt, M; Langer, U; Minuth, T; Bödeker, B; Apeler, H; Hörlein, H-D; Paulsen, D; Rübsamen-Waigmann, H; Henzler, H-J; Reichl, U

    2008-03-17

    For the production of a chemically inactivated Parapoxvirus ovis (PPVO), an adherent bovine kidney cell line was cultivated on Cytodex-3 microcarriers in suspension culture. The inactivated and purified virus particles have shown immune modulatory activity in several animal models. PPVO was produced by a biphasic batch process at the 3.5 and 10 L scale. Aeration was realised by bubble-free membrane oxygenation via a tube stator with a central two-blade anchor impeller. In order to increase efficiency, process robustness and safety, the established process was optimised. The cell line was adapted to a protein-free medium (except recombinant insulin) in order to increase biosafety. A scale up to a 50 L pilot plant with direct cell expansion was performed successfully. In parallel, the biphasic batch process was optimised with special emphasis on different operating conditions (cell number, Multiplicity of Infection (MOI), etc.) and process management (fed-batch, dialysis, etc.). The quality and concentration of the purified virus particles was assessed by quantitative electron microscopy, residual host cell protein and DNA-content and, finally, biologic activity in a transgenic mouse model. This integrated approach led to a new, safe, robust and highly productive large-scale production process, called "Volume-Expanded-Fed" Batch with cell densities up to 6-7e06 cells/mL. By subsequent dilution of infected cells into the next process scale, an increase in total productivity by a factor of 40 (related to an established biphasic batch process) was achieved. PMID:18295380

  6. Left Brain to Right Brain: Notes from the Human Laboratory.

    ERIC Educational Resources Information Center

    Baumli, Francis

    1982-01-01

    Examines the implications of the left brain-right brain theory on communications styles in male-female relationships. The author contends that women tend to use the vagueness of their emotional responses manipulatively. Men need to apply rational approaches to increase clarity in communication. (AM)

  7. Large-scale assembly of colloidal particles

    NASA Astrophysics Data System (ADS)

    Yang, Hongta

    This study reports a simple, roll-to-roll compatible coating technology for producing three-dimensional highly ordered colloidal crystal-polymer composites, colloidal crystals, and macroporous polymer membranes. A vertically beveled doctor blade is utilized to shear align silica microsphere-monomer suspensions to form large-area composites in a single step. The polymer matrix and the silica microspheres can be selectively removed to create colloidal crystals and self-standing macroporous polymer membranes. The thickness of the shear-aligned crystal is correlated with the viscosity of the colloidal suspension and the coating speed, and the correlations can be qualitatively explained by adapting the mechanisms developed for conventional doctor blade coating. Five important research topics related to the application of large-scale three-dimensional highly ordered macroporous films by doctor blade coating are covered in this study. The first topic describes the invention in large area and low cost color reflective displays. This invention is inspired by the heat pipe technology. The self-standing macroporous polymer films exhibit brilliant colors which originate from the Bragg diffractive of visible light form the three-dimensional highly ordered air cavities. The colors can be easily changed by tuning the size of the air cavities to cover the whole visible spectrum. When the air cavities are filled with a solvent which has the same refractive index as that of the polymer, the macroporous polymer films become completely transparent due to the index matching. When the solvent trapped in the cavities is evaporated by in-situ heating, the sample color changes back to brilliant color. This process is highly reversible and reproducible for thousands of cycles. The second topic reports the achievement of rapid and reversible vapor detection by using 3-D macroporous photonic crystals. Capillary condensation of a condensable vapor in the interconnected macropores leads to the

  8. Population generation for large-scale simulation

    NASA Astrophysics Data System (ADS)

    Hannon, Andrew C.; King, Gary; Morrison, Clayton; Galstyan, Aram; Cohen, Paul

    2005-05-01

    Computer simulation is used to research phenomena ranging from the structure of the space-time continuum to population genetics and future combat.1-3 Multi-agent simulations in particular are now commonplace in many fields.4, 5 By modeling populations whose complex behavior emerges from individual interactions, these simulations help to answer questions about effects where closed form solutions are difficult to solve or impossible to derive.6 To be useful, simulations must accurately model the relevant aspects of the underlying domain. In multi-agent simulation, this means that the modeling must include both the agents and their relationships. Typically, each agent can be modeled as a set of attributes drawn from various distributions (e.g., height, morale, intelligence and so forth). Though these can interact - for example, agent height is related to agent weight - they are usually independent. Modeling relations between agents, on the other hand, adds a new layer of complexity, and tools from graph theory and social network analysis are finding increasing application.7, 8 Recognizing the role and proper use of these techniques, however, remains the subject of ongoing research. We recently encountered these complexities while building large scale social simulations.9-11 One of these, the Hats Simulator, is designed to be a lightweight proxy for intelligence analysis problems. Hats models a "society in a box" consisting of many simple agents, called hats. Hats gets its name from the classic spaghetti western, in which the heroes and villains are known by the color of the hats they wear. The Hats society also has its heroes and villains, but the challenge is to identify which color hat they should be wearing based on how they behave. There are three types of hats: benign hats, known terrorists, and covert terrorists. Covert terrorists look just like benign hats but act like terrorists. Population structure can make covert hat identification significantly more

  9. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Penetration of the brain microvascular endothelial layer is one of the routes L. monocytogenes use to breach the blood-brain barrier. Because host factors in the blood severely limit direct invasion of human brain microvascular endothelial cells (HBMECs) by L. monocytogenes, alternative mechanisms m...

  10. Dynamic analysis of the human brain with complex cerebral sulci.

    PubMed

    Tseng, Jung-Ge; Huang, Bo-Wun; Ou, Yi-Wen; Yen, Ke-Tien; Wu, Yi-Te

    2016-07-01

    The brain is one of the most vulnerable organs inside the human body. Head accidents often appear in daily life and are easy to cause different level of brain damage inside the skull. Once the brain suffered intense locomotive impact, external injuries, falls, or other accidents, it will result in different degrees of concussion. This study employs finite element analysis to compare the dynamic characteristics between the geometric models of an assumed simple brain tissue and a brain tissue with complex cerebral sulci. It is aimed to understand the free vibration of the internal brain tissue and then to protect the brain from injury caused by external influences. Reverse engineering method is used for a Classic 5-Part Brain (C18) model produced by 3B Scientific Corporation. 3D optical scanner is employed to scan the human brain structure model with complex cerebral sulci and imported into 3D graphics software to construct a solid brain model to simulate the real complex brain tissue. Obtaining the normal mode analysis by inputting the material properties of the true human brain into finite element analysis software, and then to compare the simplified and the complex of brain models. PMID:27459595

  11. Large-scale recording of astrocyte activity

    PubMed Central

    Nimmerjahn, Axel; Bergles, Dwight E.

    2015-01-01

    Astrocytes are highly ramified glial cells found throughout the central nervous system (CNS). They express a variety of neurotransmitter receptors that can induce widespread chemical excitation, placing these cells in an optimal position to exert global effects on brain physiology. However, the activity patterns of only a small fraction of astrocytes have been examined and techniques to manipulate their behavior are limited. As a result, little is known about how astrocytes modulate CNS function on synaptic, microcircuit, or systems levels. Here, we review current and emerging approaches for visualizing and manipulating astrocyte activity in vivo. Deciphering how astrocyte network activity is controlled in different physiological and pathological contexts is critical for defining their roles in the healthy and diseased CNS. PMID:25665733

  12. Spread of epileptic activity in human brain

    NASA Astrophysics Data System (ADS)

    Milton, John

    1997-03-01

    For many patients with medically refractory epilepsy surgical resection of the site of seizure onset (epileptic focus) offers the best hope for cure. Determination of the nature of seizure propagation should lead to improved methods for locating the epileptic focus (and hence reduce patient morbidity) and possibly to new treatment modalities directed at blocking seizure spread. Theoretical studies of neural networks emphasize the role of traveling waves for the propagation of activity. However, the nature of seizure propagation in human brain remains poorly characterized. The spread of epileptic activity in patients undergoing presurgical evaluation for epilepsy surgery was measured by placing subdural grids of electrodes (interelectrode spacings of 3-10 mm) over the frontal and temporal lobes. The exact location of each electrode relative to the surface of the brain was determined using 3--D MRI imaging techniques. Thus it is possible to monitor the spread of epileptic activity in both space and time. The observations are discussed in light of models for seizure propagation.

  13. Proton spectroscopic imaging of human brain

    NASA Astrophysics Data System (ADS)

    Moonen, Chrit T. W.; Sobering, Geoffrey; Van Zijl, Peter C. M.; Gillen, Joe; Von Kienlin, Markus; Bizzi, Alberto

    Signals from water and fat can cause artifacts in proton spectroscopic imaging in the human brain. The major problem is variation of the B0 field over a range of several ppm within the sensitive volume of the standard whole-head coil. Here, the coherence-pathway formalism is used to describe and evaluate the origin of artifacts in a double spin-echo (PRESS) sequence. The attenuation of unwanted coherences using pulsed field gradients is described for homogeneous and inhomogeneous B0 fields. The effect of the following parameters on the quality of the spectroscopic images is analyzed: (a) directional order of plane selection, (b) positioning of phase-encode gradients in the sequence, (c) postprocessing spatial windowing, and (d) motion. It is shown that, for a typical echo time of 272 ms, it is not necessary to first select a region of interest within the brain borders when sufficient phase-encode steps are used. Examples of 2D proton spectroscopic images with a nominal voxel volume of 0.85 ml are given for a healthy volunteer and a patient with a low-grade glioma.

  14. Moment-to-moment brain signal variability: A next frontier in human brain mapping?

    PubMed Central

    Garrett, Douglas D.; Samanez-Larkin, Gregory R.; MacDonald, Stuart W.S.; Lindenberger, Ulman; McIntosh, Anthony R.; Grady, Cheryl L.

    2013-01-01

    Neuroscientists have long observed that brain activity is naturally variable from moment-to-moment, but neuroimaging research has largely ignored the potential importance of this phenomenon. An emerging research focus on within-person brain signal variability is providing novel insights, and offering highly predictive, complementary, and even orthogonal views of brain function in relation to human life-span development, cognitive performance, and various clinical conditions. As a result, brain signal variability is evolving as a bona fide signal of interest, and should no longer be dismissed as meaningless noise when mapping the human brain. PMID:23458776

  15. Areal and laminar differentiation in the mouse neocortex using large scale gene expression data.

    PubMed

    Hawrylycz, Mike; Bernard, Amy; Lau, Chris; Sunkin, Susan M; Chakravarty, M Mallar; Lein, Ed S; Jones, Allan R; Ng, Lydia

    2010-02-01

    Although cytoarchitectonic organization of the mammalian cortex into different lamina has been well-studied, identifying the architectural differences that distinguish cortical areas from one another is more challenging. Localization of large anatomical structures is possible using magnetic resonance imaging or invasive techniques (such as anterograde or retrograde tracing), but identifying patterns in gene expression architecture is limited as gene products do not necessarily identify an immediate functional consequence of a specialized area. Expression of specific genes in the mouse and human cortex is most often identified across entire lamina, and areal patterning of expression (when it exists) is most easily differentiated on a layer-by-layer basis. Since cortical organization is defined by the expression of large sets of genes, the task of identifying individual (or groups of structures) cannot be done using individual areal markers. In this manuscript we describe a methodology for clustering gene expression correlation profiles in the C57Bl/6J mouse cortex to identify large-scale genetic relationships between layers and areas. By using the Anatomic Gene Expression Atlas (http://mouse.brain-map.org/agea/) derived from in situ hybridization data in the Allen Brain Atlas, we show that a consistent expression based organization of areal patterning in the mouse cortex exists when clustered on a laminar basis. Surface-based mapping and visualization techniques are used as a representation to clarify these relationships. PMID:19800006

  16. Self-* and Adaptive Mechanisms for Large Scale Distributed Systems

    NASA Astrophysics Data System (ADS)

    Fragopoulou, P.; Mastroianni, C.; Montero, R.; Andrjezak, A.; Kondo, D.

    Large-scale distributed computing systems and infrastructure, such as Grids, P2P systems and desktop Grid platforms, are decentralized, pervasive, and composed of a large number of autonomous entities. The complexity of these systems is such that human administration is nearly impossible and centralized or hierarchical control is highly inefficient. These systems need to run on highly dynamic environments, where content, network topologies and workloads are continuously changing. Moreover, they are characterized by the high degree of volatility of their components and the need to provide efficient service management and to handle efficiently large amounts of data. This paper describes some of the areas for which adaptation emerges as a key feature, namely, the management of computational Grids, the self-management of desktop Grid platforms and the monitoring and healing of complex applications. It also elaborates on the use of bio-inspired algorithms to achieve self-management. Related future trends and challenges are described.

  17. A large-scale crop protection bioassay data set.

    PubMed

    Gaulton, Anna; Kale, Namrata; van Westen, Gerard J P; Bellis, Louisa J; Bento, A Patrícia; Davies, Mark; Hersey, Anne; Papadatos, George; Forster, Mark; Wege, Philip; Overington, John P

    2015-01-01

    ChEMBL is a large-scale drug discovery database containing bioactivity information primarily extracted from scientific literature. Due to the medicinal chemistry focus of the journals from which data are extracted, the data are currently of most direct value in the field of human health research. However, many of the scientific use-cases for the current data set are equally applicable in other fields, such as crop protection research: for example, identification of chemical scaffolds active against a particular target or endpoint, the de-convolution of the potential targets of a phenotypic assay, or the potential targets/pathways for safety liabilities. In order to broaden the applicability of the ChEMBL database and allow more widespread use in crop protection research, an extensive data set of bioactivity data of insecticidal, fungicidal and herbicidal compounds and assays was collated and added to the database. PMID:26175909

  18. Measuring Large-Scale Social Networks with High Resolution

    PubMed Central

    Stopczynski, Arkadiusz; Sekara, Vedran; Sapiezynski, Piotr; Cuttone, Andrea; Madsen, Mette My; Larsen, Jakob Eg; Lehmann, Sune

    2014-01-01

    This paper describes the deployment of a large-scale study designed to measure human interactions across a variety of communication channels, with high temporal resolution and spanning multiple years—the Copenhagen Networks Study. Specifically, we collect data on face-to-face interactions, telecommunication, social networks, location, and background information (personality, demographics, health, politics) for a densely connected population of 1 000 individuals, using state-of-the-art smartphones as social sensors. Here we provide an overview of the related work and describe the motivation and research agenda driving the study. Additionally, the paper details the data-types measured, and the technical infrastructure in terms of both backend and phone software, as well as an outline of the deployment procedures. We document the participant privacy procedures and their underlying principles. The paper is concluded with early results from data analysis, illustrating the importance of multi-channel high-resolution approach to data collection. PMID:24770359

  19. Large-scale climatic control on European precipitation

    NASA Astrophysics Data System (ADS)

    Lavers, David; Prudhomme, Christel; Hannah, David

    2010-05-01

    Precipitation variability has a significant impact on society. Sectors such as agriculture and water resources management are reliant on predictable and reliable precipitation supply with extreme variability having potentially adverse socio-economic impacts. Therefore, understanding the climate drivers of precipitation is of human relevance. This research examines the strength, location and seasonality of links between precipitation and large-scale Mean Sea Level Pressure (MSLP) fields across Europe. In particular, we aim to evaluate whether European precipitation is correlated with the same atmospheric circulation patterns or if there is a strong spatial and/or seasonal variation in the strength and location of centres of correlations. The work exploits time series of gridded ERA-40 MSLP on a 2.5˚×2.5˚ grid (0˚N-90˚N and 90˚W-90˚E) and gridded European precipitation from the Ensemble project on a 0.5°×0.5° grid (36.25˚N-74.25˚N and 10.25˚W-24.75˚E). Monthly Spearman rank correlation analysis was performed between MSLP and precipitation. During winter, a significant MSLP-precipitation correlation dipole pattern exists across Europe. Strong negative (positive) correlation located near the Icelandic Low and positive (negative) correlation near the Azores High pressure centres are found in northern (southern) Europe. These correlation dipoles resemble the structure of the North Atlantic Oscillation (NAO). The reversal in the correlation dipole patterns occurs at the latitude of central France, with regions to the north (British Isles, northern France, Scandinavia) having a positive relationship with the NAO, and regions to the south (Italy, Portugal, southern France, Spain) exhibiting a negative relationship with the NAO. In the lee of mountain ranges of eastern Britain and central Sweden, correlation with North Atlantic MSLP is reduced, reflecting a reduced influence of westerly flow on precipitation generation as the mountains act as a barrier to moist

  20. Dynamic reconfiguration of frontal brain networks during executive cognition in humans

    PubMed Central

    Braun, Urs; Schäfer, Axel; Walter, Henrik; Erk, Susanne; Romanczuk-Seiferth, Nina; Haddad, Leila; Schweiger, Janina I.; Grimm, Oliver; Heinz, Andreas; Tost, Heike; Meyer-Lindenberg, Andreas; Bassett, Danielle S.

    2015-01-01

    The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of “dynamic network neuroscience” to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the “n-back” task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes “network flexibility,” employs transient and heterogeneous connectivity between frontal systems, which we refer to as “integration.” Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia. PMID:26324898

  1. Dynamic reconfiguration of frontal brain networks during executive cognition in humans.

    PubMed

    Braun, Urs; Schäfer, Axel; Walter, Henrik; Erk, Susanne; Romanczuk-Seiferth, Nina; Haddad, Leila; Schweiger, Janina I; Grimm, Oliver; Heinz, Andreas; Tost, Heike; Meyer-Lindenberg, Andreas; Bassett, Danielle S

    2015-09-15

    The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of "dynamic network neuroscience" to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the "n-back" task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes "network flexibility," employs transient and heterogeneous connectivity between frontal systems, which we refer to as "integration." Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia. PMID:26324898

  2. Representing and Retrieving Video Shots in Human-Centric Brain Imaging Space

    PubMed Central

    Han, Junwei; Ji, Xiang; Hu, Xintao; Zhu, Dajiang; Li, Kaiming; Jiang, Xi; Cui, Guangbin; Guo, Lei; Liu, Tianming

    2014-01-01

    Meaningful representation and effective retrieval of video shots in a large-scale database has been a profound challenge for the image/video processing and computer vision communities. A great deal of effort has been devoted to the extraction of low-level visual features such as color, shape, texture, and motion for characterizing and retrieving video shots. However, the accuracy of these feature descriptors is still far from satisfaction due to the well-known semantic gap. In order to alleviate the problem, this paper investigates a novel methodology of representing and retrieving video shots using human-centric high-level features derived in brain imaging space (BIS) where brain responses to natural stimulus of video watching can be explored and interpreted. At first, our recently developed Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOL) system is employed to locate large-scale functional brain networks and their ROIs (regions of interests) that are involved in the comprehension of video stimulus. Then, functional connectivities between various functional ROI pairs are utilized as BIS features to characterize the brain’s comprehension of video semantics. Then an effective feature selection procedure is applied to learn the most relevant features while removing redundancy, which results in the formation of the final BIS features. Afterwards, a mapping from low-level visual features to high-level semantic features in the BIS is built via the Gaussian Process Regression (GPR) algorithm, and a manifold structure is then inferred in which video key frames are represented by the mapped feature vectors in the BIS. Finally, the manifold-ranking algorithm concerning the relationship among all data is applied to measure the similarity between key frames of video shots. Experimental results on the TRECVID 2005 dataset have demonstrated the superiority of the proposed work in comparison with traditional methods. PMID:23568507

  3. Probes of large-scale structure in the universe

    NASA Technical Reports Server (NTRS)

    Suto, Yasushi; Gorski, Krzysztof; Juszkiewicz, Roman; Silk, Joseph

    1988-01-01

    A general formalism is developed which shows that the gravitational instability theory for the origin of the large-scale structure of the universe is now capable of critically confronting observational results on cosmic background radiation angular anisotropies, large-scale bulk motions, and large-scale clumpiness in the galaxy counts. The results indicate that presently advocated cosmological models will have considerable difficulty in simultaneously explaining the observational results.

  4. Studying brain functions with mesoscopic measurements: advances in electrocorticography for non-human primates

    PubMed Central

    Fukushima, Makoto; Chao, Zenas C.

    2015-01-01

    Our brain is organized in a modular structure. Information in different modalities is processed within distinct cortical areas. However, individual cortical areas cannot enable complex cognitive functions without interacting with other cortical areas. Electrocorticography (ECoG) has recently become an important tool for studying global network activity across cortical areas in animal models. With stable recordings of electrical field potentials from multiple cortical areas, ECoG provides an opportunity to systematically study large-scale cortical activity at a mesoscopic spatiotemporal resolution under various experimental conditions. Recent developments in thin, flexible ECoG electrodes permit recording field potentials from not only gyral but intrasulcal cortical surfaces. Our review here focuses on the recent advances of ECoG applications to non-human primates. PMID:25889531

  5. Large-scale sequencing trials begin

    SciTech Connect

    Roberts, L.

    1990-12-07

    As genome sequencing gets under way, investigators are grappling not just with new techniques but also with questions about what is acceptable accuracy and when data should be released. Four groups are embarking on projects that could make or break the human genome project. They are setting out to sequence the longest stretches of DNA ever tackled-several million bases each-and to do it faster and cheaper than anyone has before. If these groups can't pull it off, then prospects for knocking off the entire human genome, all 3 billion bases, in 15 years and for $3 billion will look increasingly unlikely. Harvard's Walter Gilbert, is first tackling the genome of Mycoplasma capricolum. At Stanford, David Botstein and Ron Davis are sequencing Saccharomyces cerevisiae. In a collaborative effort, Robert Waterson at Washington University and John Sulston at the Medical Research Council lab in Cambridge, England, have already started on the nematode Caenorhabditis elegans. And in the only longstanding project of the bunch, University of Wisconsin geneticist Fred Blattner is already several hundred kilobases into the Escherichia coli genome.

  6. Ongoing dynamics in large-scale functional connectivity predict perception

    PubMed Central

    Sadaghiani, Sepideh; Poline, Jean-Baptiste; Kleinschmidt, Andreas; D’Esposito, Mark

    2015-01-01

    Most brain activity occurs in an ongoing manner not directly locked to external events or stimuli. Regional ongoing activity fluctuates in unison with some brain regions but not others, and the degree of long-range coupling is called functional connectivity, often measured with correlation. Strength and spatial distributions of functional connectivity dynamically change in an ongoing manner over seconds to minutes, even when the external environment is held constant. Direct evidence for any behavioral relevance of these continuous large-scale dynamics has been limited. Here, we investigated whether ongoing changes in baseline functional connectivity correlate with perception. In a continuous auditory detection task, participants perceived the target sound in roughly one-half of the trials. Very long (22–40 s) interstimulus intervals permitted investigation of baseline connectivity unaffected by preceding evoked responses. Using multivariate classification, we observed that functional connectivity before the target predicted whether it was heard or missed. Using graph theoretical measures, we characterized the difference in functional connectivity between states that lead to hits vs. misses. Before misses compared with hits and task-free rest, connectivity showed reduced modularity, a measure of integrity of modular network structure. This effect was strongest in the default mode and visual networks and caused by both reduced within-network connectivity and enhanced across-network connections before misses. The relation of behavior to prestimulus connectivity was dissociable from that of prestimulus activity amplitudes. In conclusion, moment to moment dynamic changes in baseline functional connectivity may shape subsequent behavioral performance. A highly modular network structure seems beneficial to perceptual efficiency. PMID:26106164

  7. Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy

    PubMed Central

    Bonilha, Leonardo; Tabesh, Ali; Dabbs, Kevin; Hsu, David A.; Stafstrom, Carl E.; Hermann, Bruce P.; Lin, Jack J.

    2014-01-01

    Recent neuroimaging and behavioral studies have revealed that children with new onset epilepsy already exhibit brain structural abnormalities and cognitive impairment. How the organization of large-scale brain structural networks is altered near the time of seizure onset and whether network changes are related to cognitive performances remain unclear. Recent studies also suggest that regional brain volume covariance reflects synchronized brain developmental changes. Here, we test the hypothesis that epilepsy during early-life is associated with abnormalities in brain network organization and cognition. We used graph theory to study structural brain networks based on regional volume covariance in 39 children with new-onset seizures and 28 healthy controls. Children with new-onset epilepsy showed a suboptimal topological structural organization with enhanced network segregation and reduced global integration compared to controls. At the regional level, structural reorganization was evident with redistributed nodes from the posterior to more anterior head regions. The epileptic brain network was more vulnerable to targeted but not random attacks. Finally, a subgroup of children with epilepsy, namely those with lower IQ and poorer executive function, had a reduced balance between network segregation and integration. Taken together, the findings suggest that the neurodevelopmental impact of new onset childhood epilepsies alters large-scale brain networks, resulting in greater vulnerability to network failure and cognitive impairment. PMID:24453089

  8. Food security through large scale investments in agriculture

    NASA Astrophysics Data System (ADS)

    Rulli, M.; D'Odorico, P.

    2013-12-01

    Most of the human appropriation of freshwater resources is for food production. There is some concern that in the near future the finite freshwater resources available on Earth might not be sufficient to meet the increasing human demand for agricultural products. In the late 1700s Malthus argued that in the long run the humanity would not have enough resources to feed itself. Malthus' analysis, however, did not account for the emergence of technological innovations that could increase the rate of food production. The modern and contemporary history has seen at least three major technological advances that have increased humans' access to food, namely, the industrial revolution, the green revolution, and the intensification of global trade. Here we argue that a fourth revolution has just started to happen. It involves foreign direct investments in agriculture, which intensify the crop yields of potentially highly productive agricultural lands by introducing the use of more modern technologies. The increasing demand for agricultural products and the uncertainty of international food markets has recently drawn the attention of governments and agribusiness firms toward investments in productive agricultural land, mostly in the developing world. The targeted countries are typically located in regions that have remained only marginally utilized because of lack of modern technology. It is expected that in the long run large scale land acquisitions for commercial farming will bring the technology required to close the existing yield gaps. While the extent of the acquired land and the associated appropriation of freshwater resources have been investigated in detail, the amount of food this land can produce and the number of people it could feed still need to be quantified. Here we use a unique dataset of verified land deals to provide a global quantitative assessment of the rates of crop and food appropriation potentially associated with large scale land acquisitions. We

  9. Metabolic costs and evolutionary implications of human brain development.

    PubMed

    Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

    2014-09-01

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149

  10. Punishment sustains large-scale cooperation in prestate warfare.

    PubMed

    Mathew, Sarah; Boyd, Robert

    2011-07-12

    Understanding cooperation and punishment in small-scale societies is crucial for explaining the origins of human cooperation. We studied warfare among the Turkana, a politically uncentralized, egalitarian, nomadic pastoral society in East Africa. Based on a representative sample of 88 recent raids, we show that the Turkana sustain costly cooperation in combat at a remarkably large scale, at least in part, through punishment of free-riders. Raiding parties comprised several hundred warriors and participants are not kin or day-to-day interactants. Warriors incur substantial risk of death and produce collective benefits. Cowardice and desertions occur, and are punished by community-imposed sanctions, including collective corporal punishment and fines. Furthermore, Turkana norms governing warfare benefit the ethnolinguistic group, a population of a half-million people, at the expense of smaller social groupings. These results challenge current views that punishment is unimportant in small-scale societies and that human cooperation evolved in small groups of kin and familiar individuals. Instead, these results suggest that cooperation at the larger scale of ethnolinguistic units enforced by third-party sanctions could have a deep evolutionary history in the human species. PMID:21670285

  11. Punishment sustains large-scale cooperation in prestate warfare

    PubMed Central

    Mathew, Sarah; Boyd, Robert

    2011-01-01

    Understanding cooperation and punishment in small-scale societies is crucial for explaining the origins of human cooperation. We studied warfare among the Turkana, a politically uncentralized, egalitarian, nomadic pastoral society in East Africa. Based on a representative sample of 88 recent raids, we show that the Turkana sustain costly cooperation in combat at a remarkably large scale, at least in part, through punishment of free-riders. Raiding parties comprised several hundred warriors and participants are not kin or day-to-day interactants. Warriors incur substantial risk of death and produce collective benefits. Cowardice and desertions occur, and are punished by community-imposed sanctions, including collective corporal punishment and fines. Furthermore, Turkana norms governing warfare benefit the ethnolinguistic group, a population of a half-million people, at the expense of smaller social groupings. These results challenge current views that punishment is unimportant in small-scale societies and that human cooperation evolved in small groups of kin and familiar individuals. Instead, these results suggest that cooperation at the larger scale of ethnolinguistic units enforced by third-party sanctions could have a deep evolutionary history in the human species. PMID:21670285

  12. Territorial Polymers and Large Scale Genome Organization

    NASA Astrophysics Data System (ADS)

    Grosberg, Alexander

    2012-02-01

    Chromatin fiber in interphase nucleus represents effectively a very long polymer packed in a restricted volume. Although polymer models of chromatin organization were considered, most of them disregard the fact that DNA has to stay not too entangled in order to function properly. One polymer model with no entanglements is the melt of unknotted unconcatenated rings. Extensive simulations indicate that rings in the melt at large length (monomer numbers) N approach the compact state, with gyration radius scaling as N^1/3, suggesting every ring being compact and segregated from the surrounding rings. The segregation is consistent with the known phenomenon of chromosome territories. Surface exponent β (describing the number of contacts between neighboring rings scaling as N^β) appears only slightly below unity, β 0.95. This suggests that the loop factor (probability to meet for two monomers linear distance s apart) should decay as s^-γ, where γ= 2 - β is slightly above one. The later result is consistent with HiC data on real human interphase chromosomes, and does not contradict to the older FISH data. The dynamics of rings in the melt indicates that the motion of one ring remains subdiffusive on the time scale well above the stress relaxation time.

  13. Human brain networks function in connectome-specific harmonic waves

    PubMed Central

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call ‘connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory–inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation–inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness. PMID:26792267

  14. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  15. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

    PubMed Central

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  16. The Challenge of Large-Scale Literacy Improvement

    ERIC Educational Resources Information Center

    Levin, Ben

    2010-01-01

    This paper discusses the challenge of making large-scale improvements in literacy in schools across an entire education system. Despite growing interest and rhetoric, there are very few examples of sustained, large-scale change efforts around school-age literacy. The paper reviews 2 instances of such efforts, in England and Ontario. After…

  17. Using Large-Scale Assessment Scores to Determine Student Grades

    ERIC Educational Resources Information Center

    Miller, Tess

    2013-01-01

    Many Canadian provinces provide guidelines for teachers to determine students' final grades by combining a percentage of students' scores from provincial large-scale assessments with their term scores. This practice is thought to hold students accountable by motivating them to put effort into completing the large-scale assessment, thereby…

  18. From baseline to epileptiform activity: A path to synchronized rhythmicity in large-scale neural networks

    NASA Astrophysics Data System (ADS)

    Shusterman, Vladimir; Troy, William C.

    2008-06-01

    In large-scale neural networks in the brain the emergence of global behavioral patterns, manifested by electroencephalographic activity, is driven by the self-organization of local neuronal groups into synchronously functioning ensembles. However, the laws governing such macrobehavior and its disturbances, in particular epileptic seizures, are poorly understood. Here we use a mean-field population network model to describe a state of baseline physiological activity and the transition from the baseline state to rhythmic epileptiform activity. We describe principles which explain how this rhythmic activity arises in the form of spatially uniform self-sustained synchronous oscillations. In addition, we show how the rate of migration of the leading edge of the synchronous oscillations can be theoretically predicted, and compare the accuracy of this prediction with that measured experimentally using multichannel electrocorticographic recordings obtained from a human subject experiencing epileptic seizures. The comparison shows that the experimentally measured rate of migration of the leading edge of synchronous oscillations is within the theoretically predicted range of values. Computer simulations have been performed to investigate the interactions between different regions of the brain and to show how organization in one spatial region can promote or inhibit organization in another. Our theoretical predictions are also consistent with the results of functional magnetic resonance imaging (fMRI), in particular with observations that lower-frequency electroencephalographic (EEG) rhythms entrain larger areas of the brain than higher-frequency rhythms. These findings advance the understanding of functional behavior of interconnected populations and might have implications for the analysis of diverse classes of networks.

  19. Sex beyond the genitalia: The human brain mosaic.

    PubMed

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-12-15

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains ("female brain" or "male brain"). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only "male" or only "female" features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the "maleness-femaleness" continuum are rare. Rather, most brains are comprised of unique "mosaics" of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

  20. Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

    NASA Astrophysics Data System (ADS)

    Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

    2014-03-01

    The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

  1. Parental brain and socioeconomic epigenetic effects in human development

    PubMed Central

    Swain, James E.; Perkins, Suzanne C.; Dayton, Carolyn J.; Finegood, Eric D.; Ho, S. Shaun

    2015-01-01

    Critically significant parental effects in behavioral genetics may be partly understood as a consequence of maternal brain structure and function of caregiving systems recently studied in humans as well as rodents. Key parental brain areas regulate emotions, motivation/reward, and decision making, as well as more complex social-cognitive circuits. Additional key environmental factors must include socioeconomic status and paternal brain physiology. These have implications for developmental and evolutionary biology as well as public policy. PMID:23095400

  2. Resonance of human brain under head acceleration.

    PubMed

    Laksari, Kaveh; Wu, Lyndia C; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C

    2015-07-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull-brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull-brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain-skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  3. Can global hydrological models reproduce large scale river flood regimes?

    NASA Astrophysics Data System (ADS)

    Eisner, Stephanie; Flörke, Martina

    2013-04-01

    River flooding remains one of the most severe natural hazards. On the one hand, major flood events pose a serious threat to human well-being, causing deaths and considerable economic damage. On the other hand, the periodic occurrence of flood pulses is crucial to maintain the functioning of riverine floodplains and wetlands, and to preserve the ecosystem services the latter provide. In many regions, river floods reveal a distinct seasonality, i.e. they occur at a particular time during the year. This seasonality is related to regionally dominant flood generating processes which can be expressed in river flood types. While in data-rich regions (esp. Europe and North America) the analysis of flood regimes can be based on observed river discharge time series, this data is sparse or lacking in many other regions of the world. This gap of knowledge can be filled by global modeling approaches. However, to date most global modeling studies have focused on mean annual or monthly water availability and their change over time while simulating discharge extremes, both floods and droughts, still remains a challenge for large scale hydrological models. This study will explore the ability of the global hydrological model WaterGAP3 to simulate the large scale patterns of river flood regimes, represented by seasonal pattern and the dominant flood type. WaterGAP3 simulates the global terrestrial water balance on a 5 arc minute spatial grid (excluding Greenland and Antarctica) at a daily time step. The model accounts for human interference on river flow, i.e. water abstraction for various purposes, e.g. irrigation, and flow regulation by large dams and reservoirs. Our analysis will provide insight in the general ability of global hydrological models to reproduce river flood regimes and thus will promote the creation of a global map of river flood regimes to provide a spatially inclusive and comprehensive picture. Understanding present-day flood regimes can support both flood risk

  4. Distribution probability of large-scale landslides in central Nepal

    NASA Astrophysics Data System (ADS)

    Timilsina, Manita; Bhandary, Netra P.; Dahal, Ranjan Kumar; Yatabe, Ryuichi

    2014-12-01

    Large-scale landslides in the Himalaya are defined as huge, deep-seated landslide masses that occurred in the geological past. They are widely distributed in the Nepal Himalaya. The steep topography and high local relief provide high potential for such failures, whereas the dynamic geology and adverse climatic conditions play a key role in the occurrence and reactivation of such landslides. The major geoscientific problems related with such large-scale landslides are 1) difficulties in their identification and delineation, 2) sources of small-scale failures, and 3) reactivation. Only a few scientific publications have been published concerning large-scale landslides in Nepal. In this context, the identification and quantification of large-scale landslides and their potential distribution are crucial. Therefore, this study explores the distribution of large-scale landslides in the Lesser Himalaya. It provides simple guidelines to identify large-scale landslides based on their typical characteristics and using a 3D schematic diagram. Based on the spatial distribution of landslides, geomorphological/geological parameters and logistic regression, an equation of large-scale landslide distribution is also derived. The equation is validated by applying it to another area. For the new area, the area under the receiver operating curve of the landslide distribution probability in the new area is 0.699, and a distribution probability value could explain > 65% of existing landslides. Therefore, the regression equation can be applied to areas of the Lesser Himalaya of central Nepal with similar geological and geomorphological conditions.

  5. Metabolic costs and evolutionary implications of human brain development

    PubMed Central

    Kuzawa, Christopher W.; Chugani, Harry T.; Grossman, Lawrence I.; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R.; Wildman, Derek E.; Sherwood, Chet C.; Leonard, William R.; Lange, Nicholas

    2014-01-01

    The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149

  6. Advanced Connectivity Analysis (ACA): a Large Scale Functional Connectivity Data Mining Environment.

    PubMed

    Chen, Rong; Nixon, Erika; Herskovits, Edward

    2016-04-01

    Using resting-state functional magnetic resonance imaging (rs-fMRI) to study functional connectivity is of great importance to understand normal development and function as well as a host of neurological and psychiatric disorders. Seed-based analysis is one of the most widely used rs-fMRI analysis methods. Here we describe a freely available large scale functional connectivity data mining software package called Advanced Connectivity Analysis (ACA). ACA enables large-scale seed-based analysis and brain-behavior analysis. It can seamlessly examine a large number of seed regions with minimal user input. ACA has a brain-behavior analysis component to delineate associations among imaging biomarkers and one or more behavioral variables. We demonstrate applications of ACA to rs-fMRI data sets from a study of autism. PMID:26662457

  7. Alcohol-Related Brain Damage in Humans

    PubMed Central

    Erdozain, Amaia M.; Morentin, Benito; Bedford, Lynn; King, Emma; Tooth, David; Brewer, Charlotte; Wayne, Declan; Johnson, Laura; Gerdes, Henry K.; Wigmore, Peter; Callado, Luis F.; Carter, Wayne G.

    2014-01-01

    Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics. PMID:24699688

  8. General Anesthesia and Human Brain Connectivity

    PubMed Central

    2012-01-01

    Abstract General anesthesia consists of amnesia, hypnosis, analgesia, and areflexia. Of these, the mechanism of hypnosis, or loss of consciousness, has been the most elusive, yet a fascinating problem. How anesthetic agents suppress human consciousness has been investigated with neuroimaging for two decades. Anesthetics substantially reduce the global cerebral metabolic rate and blood flow with a degree of regional heterogeneity characteristic to the anesthetic agent. The thalamus appears to be a common site of modulation by several anesthetics, but this may be secondary to cortical effects. Stimulus-dependent brain activation is preserved in primary sensory areas, suggesting that unconsciousness cannot be explained by cortical deafferentation or a diminution of cortical sensory reactivity. The effect of general anesthetics in functional and effective connectivity is varied depending on the agent, dose, and network studied. At an anesthetic depth characterized by the subjects' unresponsiveness, a partial, but not complete, reduction in connectivity is generally observed. Functional connectivity of the frontoparietal association cortex is often reduced, but a causal role of this change for the loss of consciousness remains uncertain. Functional connectivity of the nonspecific (intralaminar) thalamic nuclei is preferentially reduced by propofol. Higher-order thalamocortical connectivity is also reduced with certain anesthetics. The changes in functional connectivity during anesthesia induction and emergence do not mirror each other; the recovery from anesthesia may involve increases in functional connectivity above the normal wakeful baseline. Anesthetic loss of consciousness is not a block of corticofugal information transfer, but a disruption of higher-order cortical information integration. The prime candidates for functional networks of the forebrain that play a critical role in maintaining the state of consciousness are those based on the posterior parietal

  9. Reconstituting a human brain in animals: a Jewish perspective on human sanctity.

    PubMed

    Loike, John D; Tendler, Moshe

    2008-12-01

    The potential use of stem cells in the treatment of a variety of human diseases has been a major driving force for embryonic stem cell research. Another productive area of research has been the use of human stem cells to reconstitute human organ systems in animals in an attempt to create new animal models for human diseases. However, the possibility of transplanting human embryonic brain cells or precursor brain cells into an animal fetus presents numerous ethical challenges. This paper examines, from a Jewish perspective on human dignity, several bioethical concerns related to the reconstitution of animal brains with human neurons. PMID:19143409

  10. Resonance of human brain under head acceleration

    PubMed Central

    Laksari, Kaveh; Wu, Lyndia C.; Kurt, Mehmet; Kuo, Calvin; Camarillo, David C.

    2015-01-01

    Although safety standards have reduced fatal head trauma due to single severe head impacts, mild trauma from repeated head exposures may carry risks of long-term chronic changes in the brain's function and structure. To study the physical sensitivities of the brain to mild head impacts, we developed the first dynamic model of the skull–brain based on in vivo MRI data. We showed that the motion of the brain can be described by a rigid-body with constrained kinematics. We further demonstrated that skull–brain dynamics can be approximated by an under-damped system with a low-frequency resonance at around 15 Hz. Furthermore, from our previous field measurements, we found that head motions in a variety of activities, including contact sports, show a primary frequency of less than 20 Hz. This implies that typical head exposures may drive the brain dangerously close to its mechanical resonance and lead to amplified brain–skull relative motions. Our results suggest a possible cause for mild brain trauma, which could occur due to repetitive low-acceleration head oscillations in a variety of recreational and occupational activities. PMID:26063824

  11. Wireless gigabit data telemetry for large-scale neural recording.

    PubMed

    Kuan, Yen-Cheng; Lo, Yi-Kai; Kim, Yanghyo; Chang, Mau-Chung Frank; Liu, Wentai

    2015-05-01

    Implantable wireless neural recording from a large ensemble of simultaneously acting neurons is a critical component to thoroughly investigate neural interactions and brain dynamics from freely moving animals. Recent researches have shown the feasibility of simultaneously recording from hundreds of neurons and suggested that the ability of recording a larger number of neurons results in better signal quality. This massive recording inevitably demands a large amount of data transfer. For example, recording 2000 neurons while keeping the signal fidelity ( > 12 bit, > 40 KS/s per neuron) needs approximately a 1-Gb/s data link. Designing a wireless data telemetry system to support such (or higher) data rate while aiming to lower the power consumption of an implantable device imposes a grand challenge on neuroscience community. In this paper, we present a wireless gigabit data telemetry for future large-scale neural recording interface. This telemetry comprises of a pair of low-power gigabit transmitter and receiver operating at 60 GHz, and establishes a short-distance wireless link to transfer the massive amount of neural signals outward from the implanted device. The transmission distance of the received neural signal can be further extended by an externally rendezvous wireless transceiver, which is less power/heat-constraint since it is not at the immediate proximity of the cortex and its radiated signal is not seriously attenuated by the lossy tissue. The gigabit data link has been demonstrated to achieve a high data rate of 6 Gb/s with a bit-error-rate of 10(-12) at a transmission distance of 6 mm, an applicable separation between transmitter and receiver. This high data rate is able to support thousands of recording channels while ensuring a low energy cost per bit of 2.08 pJ/b. PMID:25823050

  12. Large-scale functional models of visual cortex for remote sensing

    SciTech Connect

    Brumby, Steven P; Kenyon, Garrett; Rasmussen, Craig E; Swaminarayan, Sriram; Bettencourt, Luis; Landecker, Will

    2009-01-01

    Neuroscience has revealed many properties of neurons and of the functional organization of visual cortex that are believed to be essential to human vision, but are missing in standard artificial neural networks. Equally important may be the sheer scale of visual cortex requiring {approx}1 petaflop of computation. In a year, the retina delivers {approx}1 petapixel to the brain, leading to massively large opportunities for learning at many levels of the cortical system. We describe work at Los Alamos National Laboratory (LANL) to develop large-scale functional models of visual cortex on LANL's Roadrunner petaflop supercomputer. An initial run of a simple region VI code achieved 1.144 petaflops during trials at the IBM facility in Poughkeepsie, NY (June 2008). Here, we present criteria for assessing when a set of learned local representations is 'complete' along with general criteria for assessing computer vision models based on their projected scaling behavior. Finally, we extend one class of biologically-inspired learning models to problems of remote sensing imagery.

  13. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App.

    PubMed

    Teki, Sundeep; Kumar, Sukhbinder; Griffiths, Timothy D

    2016-01-01

    The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance-the capacity to make sense of complex 'auditory scenes' is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the 'stochastic figure-ground' stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10) performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a 'game' featured in a smartphone app (The Great Brain Experiment) and obtained data from a large population with diverse demographical patterns (n = 5148). Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders. PMID:27096165

  14. The PREP pipeline: standardized preprocessing for large-scale EEG analysis.

    PubMed

    Bigdely-Shamlo, Nima; Mullen, Tim; Kothe, Christian; Su, Kyung-Min; Robbins, Kay A

    2015-01-01

    The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real-world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode. PMID:26150785

  15. The PREP pipeline: standardized preprocessing for large-scale EEG analysis

    PubMed Central

    Bigdely-Shamlo, Nima; Mullen, Tim; Kothe, Christian; Su, Kyung-Min; Robbins, Kay A.

    2015-01-01

    The technology to collect brain imaging and physiological measures has become portable and ubiquitous, opening the possibility of large-scale analysis of real-world human imaging. By its nature, such data is large and complex, making automated processing essential. This paper shows how lack of attention to the very early stages of an EEG preprocessing pipeline can reduce the signal-to-noise ratio and introduce unwanted artifacts into the data, particularly for computations done in single precision. We demonstrate that ordinary average referencing improves the signal-to-noise ratio, but that noisy channels can contaminate the results. We also show that identification of noisy channels depends on the reference and examine the complex interaction of filtering, noisy channel identification, and referencing. We introduce a multi-stage robust referencing scheme to deal with the noisy channel-reference interaction. We propose a standardized early-stage EEG processing pipeline (PREP) and discuss the application of the pipeline to more than 600 EEG datasets. The pipeline includes an automatically generated report for each dataset processed. Users can download the PREP pipeline as a freely available MATLAB library from http://eegstudy.org/prepcode. PMID:26150785

  16. Large-Scale Analysis of Auditory Segregation Behavior Crowdsourced via a Smartphone App

    PubMed Central

    Kumar, Sukhbinder; Griffiths, Timothy D.

    2016-01-01

    The human auditory system is adept at detecting sound sources of interest from a complex mixture of several other simultaneous sounds. The ability to selectively attend to the speech of one speaker whilst ignoring other speakers and background noise is of vital biological significance—the capacity to make sense of complex ‘auditory scenes’ is significantly impaired in aging populations as well as those with hearing loss. We investigated this problem by designing a synthetic signal, termed the ‘stochastic figure-ground’ stimulus that captures essential aspects of complex sounds in the natural environment. Previously, we showed that under controlled laboratory conditions, young listeners sampled from the university subject pool (n = 10) performed very well in detecting targets embedded in the stochastic figure-ground signal. Here, we presented a modified version of this cocktail party paradigm as a ‘game’ featured in a smartphone app (The Great Brain Experiment) and obtained data from a large population with diverse demographical patterns (n = 5148). Despite differences in paradigms and experimental settings, the observed target-detection performance by users of the app was robust and consistent with our previous results from the psychophysical study. Our results highlight the potential use of smartphone apps in capturing robust large-scale auditory behavioral data from normal healthy volunteers, which can also be extended to study auditory deficits in clinical populations with hearing impairments and central auditory disorders. PMID:27096165

  17. [Brain evolution of the human from the paleoneurologic viewpoint].

    PubMed

    Brandt, M

    1993-12-01

    Paleoneurology interprets natural or artificial endocasts. It is, therefore, the only method which is able to provide direct information on the ancestry of the human brain. Australopithecus, Homo habilis and Homo erectus are of outstanding importance concerning human evolution. This short review deals with some well-preserved endocasts of these forms. Possibilities and limitations of paleoneurology are discussed with respect to the taxonomic attribution of fossil specimens. Functional aspects of the cortical sulcus pattern can be interpreted rather strictly and is, therefore, of considerably phylogenetic significance. It indicates that even some early hominids exhibit a human-like brain organization (e.g. KNM-ER 1470) while others (such a KNM-ER 1805) feature a rather pongid-like brain organization. However, controversy over the interpretation of endocasts from early hominids continues: It has not been possible to unequivocally demonstrate a human-like feature of the Australopithecus brain. PMID:8285598

  18. Sex beyond the genitalia: The human brain mosaic

    PubMed Central

    Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

    2015-01-01

    Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

  19. Genetic Changes Shaping the Human Brain

    PubMed Central

    Bae, Byoung-il; Jayaraman, Divya; Walsh, Christopher A.

    2015-01-01

    Summary The development and function of our brain are governed by a genetic blueprint, which reflects dynamic changes over the history of evolution. Recent progress in genetics and genomics, facilitated by next-generation sequencing and single-cell sorting, has identified numerous genomic loci that are associated with a neuroanatomical or neurobehavioral phenotype. Here, we review some of the genetic changes in both protein-coding and noncoding regions that affect brain development and evolution, as well as recent progress in brain transcriptomics. Understanding these genetic changes may provide novel insights into neurological and neuropsychiatric disorders, such as autism and schizophrenia. PMID:25710529

  20. Reflectance Diffuse Optical Tomography: Its Application to Human Brain Mapping

    NASA Astrophysics Data System (ADS)

    Ueda, Yukio; Yamanaka, Takeshi; Yamashita, Daisuke; Suzuki, Toshihiko; Ohmae, Etsuko; Oda, Motoki; Yamashita, Yutaka

    2005-09-01

    We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases.

  1. Optogenetic control of human neurons in organotypic brain cultures.

    PubMed

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H; Jespersen, Bo; Christiansen, Søren H; Bengzon, Johan; Woldbye, David P D; Kokaia, Merab

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. PMID:27098488

  2. Optogenetic control of human neurons in organotypic brain cultures

    PubMed Central

    Andersson, My; Avaliani, Natalia; Svensson, Andreas; Wickham, Jenny; Pinborg, Lars H.; Jespersen, Bo; Christiansen, Søren H.; Bengzon, Johan; Woldbye, David P.D.; Kokaia, Merab

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies. PMID:27098488

  3. Overview of the human brain as a distributed computing network

    SciTech Connect

    Gevins, A.S.

    1983-01-01

    The hierarchically organized human brain is viewed as a prime example of a massively parallel, adaptive information processing and process control system. A brief overview of the human brain is provided for computer architects, in hopes that the principles of massive parallelism, dense connectivity and self-organization of assemblies of processing elements will prove relevant to the design of fifth generation VLSI computing networks. 6 references.

  4. Dissociable large-scale networks anchored in the right anterior insula subserve affective experience and attention1

    PubMed Central

    Touroutoglou, Alexandra; Hollenbeck, Mark; Dickerson, Bradford C.; Barrett, Lisa Feldman

    2012-01-01

    Meta-analytic summaries of neuroimaging studies point to at least two major functional-anatomic subdivisions within the anterior insula that contribute to the detection and processing of salient information: a dorsal region that is routinely active during attention tasks and a ventral region that is routinely active during affective experience. In two independent samples of cognitively normal human adults, we used intrinsic functional connectivity magnetic resonance imaging to demonstrate that the right dorsal and right ventral anterior insula are nodes in separable large-scale functional networks. Furthermore, stronger intrinsic connectivity within the right dorsal anterior insula network was associated with better performance on a task involving attention and processing speed whereas stronger connectivity within the right ventral anterior insula network was associated with more intense affective experience. These results support the hypothesis that the identification and manipulation of salient information is subserved by at least two brain networks anchored in the right anterior insula that exhibit distinct large-scale topography and dissociable behavioral correlates. PMID:22361166

  5. Understanding complexity in the human brain

    PubMed Central

    Bassett, Danielle S.; Gazzaniga, Michael S.

    2011-01-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind–brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind–brain mechanisms. PMID:21497128

  6. Large-scale spatial population databases in infectious disease research

    PubMed Central

    2012-01-01

    Modelling studies on the spatial distribution and spread of infectious diseases are becoming increasingly detailed and sophisticated, with global risk mapping and epidemic modelling studies now popular. Yet, in deriving populations at risk of disease estimates, these spatial models must rely on existing global and regional datasets on population distribution, which are often based on outdated and coarse resolution data. Moreover, a variety of different methods have been used to model population distribution at large spatial scales. In this review we describe the main global gridded population datasets that are freely available for health researchers and compare their construction methods, and highlight the uncertainties inherent in these population datasets. We review their application in past studies on disease risk and dynamics, and discuss how the choice of dataset can affect results. Moreover, we highlight how the lack of contemporary, detailed and reliable data on human population distribution in low income countries is proving a barrier to obtaining accurate large-scale estimates of population at risk and constructing reliable models of disease spread, and suggest research directions required to further reduce these barriers. PMID:22433126

  7. Large Scale Applications of HTS in New Zealand

    NASA Astrophysics Data System (ADS)

    Wimbush, Stuart C.

    New Zealand has one of the longest-running and most consistently funded (relative to GDP) programmes in high temperature superconductor (HTS) development and application worldwide. As a consequence, it has a sustained breadth of involvement in HTS technology development stretching from the materials discovery right through to burgeoning commercial exploitation. This review paper outlines the present large scale projects of the research team at the newly-established Robinson Research Institute of Victoria University of Wellington. These include the construction and grid-based testing of a three-phase 1 MVA 2G HTS distribution transformer utilizing Roebel cable for its high-current secondary windings and the development of a cryogen-free conduction-cooled 1.5 T YBCO-based human extremity magnetic resonance imaging system. Ongoing activities supporting applications development such as low-temperature full-current characterization of commercial superconducting wires and the implementation of inductive flux-pump technologies for efficient brushless coil excitation in superconducting magnets and rotating machines are also described.

  8. A novel methodology for large-scale phylogeny partition.

    PubMed

    Prosperi, Mattia C F; Ciccozzi, Massimo; Fanti, Iuri; Saladini, Francesco; Pecorari, Monica; Borghi, Vanni; Di Giambenedetto, Simona; Bruzzone, Bianca; Capetti, Amedeo; Vivarelli, Angela; Rusconi, Stefano; Re, Maria Carla; Gismondo, Maria Rita; Sighinolfi, Laura; Gray, Rebecca R; Salemi, Marco; Zazzi, Maurizio; De Luca, Andrea

    2011-01-01

    Understanding the determinants of virus transmission is a fundamental step for effective design of screening and intervention strategies to control viral epidemics. Phylogenetic analysis can be a valid approach for the identification of transmission chains, and very-large data sets can be analysed through parallel computation. Here we propose and validate a new methodology for the partition of large-scale phylogenies and the inference of transmission clusters. This approach, on the basis of a depth-first search algorithm, conjugates the evaluation of node reliability, tree topology and patristic distance analysis. The method has been applied to identify transmission clusters of a phylogeny of 11,541 human immunodeficiency virus-1 subtype B pol gene sequences from a large Italian cohort. Molecular transmission chains were characterized by means of different clinical/demographic factors, such as the interaction between male homosexuals and male heterosexuals. Our method takes an advantage of a flexible notion of transmission cluster and can become a general framework to analyse other epidemics. PMID:21610724

  9. Large-scale spatial population databases in infectious disease research.

    PubMed

    Linard, Catherine; Tatem, Andrew J

    2012-01-01

    Modelling studies on the spatial distribution and spread of infectious diseases are becoming increasingly detailed and sophisticated, with global risk mapping and epidemic modelling studies now popular. Yet, in deriving populations at risk of disease estimates, these spatial models must rely on existing global and regional datasets on population distribution, which are often based on outdated and coarse resolution data. Moreover, a variety of different methods have been used to model population distribution at large spatial scales. In this review we describe the main global gridded population datasets that are freely available for health researchers and compare their construction methods, and highlight the uncertainties inherent in these population datasets. We review their application in past studies on disease risk and dynamics, and discuss how the choice of dataset can affect results. Moreover, we highlight how the lack of contemporary, detailed and reliable data on human population distribution in low income countries is proving a barrier to obtaining accurate large-scale estimates of population at risk and constructing reliable models of disease spread, and suggest research directions required to further reduce these barriers. PMID:22433126

  10. Determining Environmental Impacts of Large Scale Irrigation in Turkey

    NASA Astrophysics Data System (ADS)

    Simpson, K.; Douglas, E. M.; Limbrunner, J. F.; Ozertan, G.

    2010-12-01

    In 1989, the Turkish government launched their most comprehensive regional development plan in history entitled the Southeastern Anatolia Project (SAP) which focuses on improving the quality of life and income level within the most underdeveloped region in Turkey. This project aims to integrate sustainable human development through agriculture, industry, transportation, education, health and rural and urban infrastructure building. In May 2008, a new action plan was announced for the region which includes the designation of almost 800,000 hectares of previously unirrigated land to be open for irrigation within the next five years. If not done in a sustainable manner, such a large-scale irrigation project could cause severe environmental impacts. The first objective of our research is to use computer simulations to reproduce the observed environmental impacts of irrigated agriculture in this arid region, primarily by simulating the effects of soil salinization. The second objective of our research is to estimate soil salinization that could result from expanded irrigation and suggest sustainable strategies for the newly irrigated land in Turkey in order to minimize these environmental impacts.

  11. Large-Scale Functional Purification of Recombinant HIV-1 Capsid

    PubMed Central

    Jin, Debi; Wong, Melanie; Leavitt, Stephanie; Brendza, Katherine M.; Liu, Xiaohong; Sakowicz, Roman

    2013-01-01

    During human immunodeficiency virus type-1 (HIV-1) virion maturation, capsid proteins undergo a major rearrangement to form a conical core that protects the viral nucleoprotein complexes. Mutations in the capsid sequence that alter the stability of the capsid core are deleterious to viral infectivity and replication. Recently, capsid assembly has become an attractive target for the development of a new generation of anti-retroviral agents. Drug screening efforts and subsequent structural and mechanistic studies require gram quantities of active, homogeneous and pure protein. Conventional means of laboratory purification of Escherichia coli expressed recombinant capsid protein rely on column chromatography steps that are not amenable to large-scale production. Here we present a function-based purification of wild-type and quadruple mutant capsid proteins, which relies on the inherent propensity of capsid protein to polymerize and depolymerize. This method does not require the packing of sizable chromatography columns and can generate double-digit gram quantities of functionally and biochemically well-behaved proteins with greater than 98% purity. We have used the purified capsid protein to characterize two known assembly inhibitors in our in-house developed polymerization assay and to measure their binding affinities. Our capsid purification procedure provides a robust method for purifying large quantities of a key protein in the HIV-1 life cycle, facilitating identification of the next generation anti-HIV agents. PMID:23472130

  12. Large-scale functional purification of recombinant HIV-1 capsid.

    PubMed

    Hung, Magdeleine; Niedziela-Majka, Anita; Jin, Debi; Wong, Melanie; Leavitt, Stephanie; Brendza, Katherine M; Liu, Xiaohong; Sakowicz, Roman

    2013-01-01

    During human immunodeficiency virus type-1 (HIV-1) virion maturation, capsid proteins undergo a major rearrangement to form a conical core that protects the viral nucleoprotein complexes. Mutations in the capsid sequence that alter the stability of the capsid core are deleterious to viral infectivity and replication. Recently, capsid assembly has become an attractive target for the development of a new generation of anti-retroviral agents. Drug screening efforts and subsequent structural and mechanistic studies require gram quantities of active, homogeneous and pure protein. Conventional means of laboratory purification of Escherichia coli expressed recombinant capsid protein rely on column chromatography steps that are not amenable to large-scale production. Here we present a function-based purification of wild-type and quadruple mutant capsid proteins, which relies on the inherent propensity of capsid protein to polymerize and depolymerize. This method does not require the packing of sizable chromatography columns and can generate double-digit gram quantities of functionally and biochemically well-behaved proteins with greater than 98% purity. We have used the purified capsid protein to characterize two known assembly inhibitors in our in-house developed polymerization assay and to measure their binding affinities. Our capsid purification procedure provides a robust method for purifying large quantities of a key protein in the HIV-1 life cycle, facilitating identification of the next generation anti-HIV agents. PMID:23472130

  13. Needs, opportunities, and options for large scale systems research

    SciTech Connect

    Thompson, G.L.

    1984-10-01

    The Office of Energy Research was recently asked to perform a study of Large Scale Systems in order to facilitate the development of a true large systems theory. It was decided to ask experts in the fields of electrical engineering, chemical engineering and manufacturing/operations research for their ideas concerning large scale systems research. The author was asked to distribute a questionnaire among these experts to find out their opinions concerning recent accomplishments and future research directions in large scale systems research. He was also requested to convene a conference which included three experts in each area as panel members to discuss the general area of large scale systems research. The conference was held on March 26--27, 1984 in Pittsburgh with nine panel members, and 15 other attendees. The present report is a summary of the ideas presented and the recommendations proposed by the attendees.

  14. Increased morphological asymmetry, evolvability and plasticity in human brain evolution

    PubMed Central

    Gómez-Robles, Aida; Hopkins, William D.; Sherwood, Chet C.

    2013-01-01

    The study of hominin brain evolution relies mostly on evaluation of the endocranial morphology of fossil skulls. However, only some general features of external brain morphology are evident from endocasts, and many anatomical details can be difficult or impossible to examine. In this study, we use geometric morphometric techniques to evaluate inter- and intraspecific differences in cerebral morphology in a sample of in vivo magnetic resonance imaging scans of chimpanzees and humans, with special emphasis on the study of asymmetric variation. Our study reveals that chimpanzee–human differences in cerebral morphology are mainly symmetric; by contrast, there is continuity in asymmetric variation between species, with humans showing an increased range of variation. Moreover, asymmetric variation does not appear to be the result of allometric scaling at intraspecific levels, whereas symmetric changes exhibit very slight allometric effects within each species. Our results emphasize two key properties of brain evolution in the hominine clade: first, evolution of chimpanzee and human brains (and probably their last common ancestor and related species) is not strongly morphologically constrained, thus making their brains highly evolvable and responsive to selective pressures; second, chimpanzee and, especially, human brains show high levels of fluctuating asymmetry indicative of pronounced developmental plasticity. We infer that these two characteristics can have a role in human cognitive evolution. PMID:23615289

  15. Brain development is similar in Neanderthals and modern humans.

    PubMed

    Ponce de León, Marcia S; Bienvenu, Thibaut; Akazawa, Takeru; Zollikofer, Christoph P E

    2016-07-25

    While the braincase of adult Neanderthals had a similar volume to that of modern humans from the same period, differences in endocranial shape suggest that brain morphology differed between modern humans and Neanderthals. When and how these differences arose during evolution and development is a topic of ongoing research, with potential implications for species-specific differences in brain and cognitive development, and in life history [1,2]. Earlier research suggested that Neanderthals followed an ancestral mode of brain development, similar to that of our closest living relatives, the chimpanzees [2-4]. Modern humans, by contrast, were suggested to follow a uniquely derived mode of brain development just after birth, giving rise to the characteristically globular shape of the adult human brain case [2,4,5]. Here, we re-examine this hypothesis using an extended sample of Neanderthal infants. We document endocranial development during the decisive first two years of postnatal life. The new data indicate that Neanderthals followed largely similar modes of endocranial development to modern humans. These findings challenge the notion that human brain and cognitive development after birth is uniquely derived [2,4]. PMID:27458909

  16. Interpretation of large-scale deviations from the Hubble flow

    NASA Astrophysics Data System (ADS)

    Grinstein, B.; Politzer, H. David; Rey, S.-J.; Wise, Mark B.

    1987-03-01

    The theoretical expectation for large-scale streaming velocities relative to the Hubble flow is expressed in terms of statistical correlation functions. Only for objects that trace the mass would these velocities have a simple cosmological interpretation. If some biasing effects the objects' formation, then nonlinear gravitational evolution is essential to predicting the expected large-scale velocities, which also depend on the nature of the biasing.

  17. Large scale suppression of scalar power on a spatial condensation

    NASA Astrophysics Data System (ADS)

    Kouwn, Seyen; Kwon, O.-Kab; Oh, Phillial

    2015-03-01

    We consider a deformed single-field inflation model in terms of three SO(3) symmetric moduli fields. We find that spatially linear solutions for the moduli fields induce a phase transition during the early stage of the inflation and the suppression of scalar power spectrum at large scales. This suppression can be an origin of anomalies for large-scale perturbation modes in the cosmological observation.

  18. Near infrared Raman spectra of human brain lipids

    NASA Astrophysics Data System (ADS)

    Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

    2005-05-01

    Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

  19. Large-scale motions in a plane wall jet

    NASA Astrophysics Data System (ADS)

    Gnanamanickam, Ebenezer; Jonathan, Latim; Shibani, Bhatt

    2015-11-01

    The dynamic significance of large-scale motions in turbulent boundary layers have been the focus of several recent studies, primarily focussing on canonical flows - zero pressure gradient boundary layers, flows within pipes and channels. This work presents an investigation into the large-scale motions in a boundary layer that is used as the prototypical flow field for flows with large-scale mixing and reactions, the plane wall jet. An experimental investigation is carried out in a plane wall jet facility designed to operate at friction Reynolds numbers Reτ > 1000 , which allows for the development of a significant logarithmic region. The streamwise turbulent intensity across the boundary layer is decomposed into small-scale (less than one integral length-scale δ) and large-scale components. The small-scale energy has a peak in the near-wall region associated with the near-wall turbulent cycle as in canonical boundary layers. However, eddies of large-scales are the dominating eddies having significantly higher energy, than the small-scales across almost the entire boundary layer even at the low to moderate Reynolds numbers under consideration. The large-scales also appear to amplitude and frequency modulate the smaller scales across the entire boundary layer.

  20. Do glutathione levels decline in aging human brain?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. PMID:26845616

  1. Evolution of the human brain: when bigger is better

    PubMed Central

    Hofman, Michel A.

    2014-01-01

    Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain's complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power. PMID:24723857

  2. Conscious brain-to-brain communication in humans using non-invasive technologies.

    PubMed

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID:25137064

  3. Conscious Brain-to-Brain Communication in Humans Using Non-Invasive Technologies

    PubMed Central

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L.; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues. PMID:25137064

  4. EFFECTS OF LARGE-SCALE POULTRY FARMS ON AQUATIC MICROBIAL COMMUNITIES: A MOLECULAR INVESTIGATION.

    EPA Science Inventory

    The effects of large-scale poultry production operations on water quality and human health are largely unknown. Poultry litter is frequently applied as fertilizer to agricultural lands adjacent to large poultry farms. Run-off from the land introduces a variety of stressors into t...

  5. Estimating Variance Components from Sparse Data Matrices in Large-Scale Educational Assessments

    ERIC Educational Resources Information Center

    DeMars, Christine

    2015-01-01

    In generalizability theory studies in large-scale testing contexts, sometimes a facet is very sparsely crossed with the object of measurement. For example, when assessments are scored by human raters, it may not be practical to have every rater score all students. Sometimes the scoring is systematically designed such that the raters are…

  6. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  7. BrainKnowledge: a human brain function mapping knowledge-base system.

    PubMed

    Hsiao, Mei-Yu; Chen, Chien-Chung; Chen, Jyh-Horng

    2011-03-01

    Associating fMRI image datasets with the available literature is crucial for the analysis and interpretation of fMRI data. Here, we present a human brain function mapping knowledge-base system (BrainKnowledge) that associates fMRI data analysis and literature search functions. BrainKnowledge not only contains indexed literature, but also provides the ability to compare experimental data with those derived from the literature. BrainKnowledge provides three major functions: (1) to search for brain activation models by selecting a particular brain function; (2) to query functions by brain structure; (3) to compare the fMRI data with data extracted from the literature. All these functions are based on our literature extraction and mining module developed earlier (Hsiao, Chen, Chen. Journal of Biomedical Informatics 42, 912-922, 2009), which automatically downloads and extracts information from a vast amount of fMRI literature and generates co-occurrence models and brain association patterns to illustrate the relevance of brain structures and functions. BrainKnowledge currently provides three co-occurrence models: (1) a structure-to-function co-occurrence model; (2) a function-to-structure co-occurrence model; and (3) a brain structure co-occurrence model. Each model has been generated from over 15,000 extracted Medline abstracts. In this study, we illustrate the capabilities of BrainKnowledge and provide an application example with the studies of affect. BrainKnowledge, which combines fMRI experimental results with Medline abstracts, may be of great assistance to scientists not only by freeing up resources and valuable time, but also by providing a powerful tool that collects and organizes over ten thousand abstracts into readily usable and relevant sources of information for researchers. PMID:20857233

  8. The large-scale landslide risk classification in catchment scale

    NASA Astrophysics Data System (ADS)

    Liu, Che-Hsin; Wu, Tingyeh; Chen, Lien-Kuang; Lin, Sheng-Chi

    2013-04-01

    The landslide disasters caused heavy casualties during Typhoon Morakot, 2009. This disaster is defined as largescale landslide due to the casualty numbers. This event also reflects the survey on large-scale landslide potential is so far insufficient and significant. The large-scale landslide potential analysis provides information about where should be focused on even though it is very difficult to distinguish. Accordingly, the authors intend to investigate the methods used by different countries, such as Hong Kong, Italy, Japan and Switzerland to clarify the assessment methodology. The objects include the place with susceptibility of rock slide and dip slope and the major landslide areas defined from historical records. Three different levels of scales are confirmed necessarily from country to slopeland, which are basin, catchment, and slope scales. Totally ten spots were classified with high large-scale landslide potential in the basin scale. The authors therefore focused on the catchment scale and employ risk matrix to classify the potential in this paper. The protected objects and large-scale landslide susceptibility ratio are two main indexes to classify the large-scale landslide risk. The protected objects are the constructions and transportation facilities. The large-scale landslide susceptibility ratio is based on the data of major landslide area and dip slope and rock slide areas. Totally 1,040 catchments are concerned and are classified into three levels, which are high, medium, and low levels. The proportions of high, medium, and low levels are 11%, 51%, and 38%, individually. This result represents the catchments with high proportion of protected objects or large-scale landslide susceptibility. The conclusion is made and it be the base material for the slopeland authorities when considering slopeland management and the further investigation.

  9. Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

    PubMed

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-08-26

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  10. Mitochondrial viability in mouse and human postmortem brain

    PubMed Central

    Barksdale, Keri A.; Perez-Costas, Emma; Gandy, Johanna C.; Melendez-Ferro, Miguel; Roberts, Rosalinda C.; Bijur, Gautam N.

    2010-01-01

    Neuronal function in the brain requires energy in the form of ATP, and mitochondria are canonically associated with ATP production in neurons. The electrochemical gradient, which underlies the mitochondrial transmembrane potential (ΔΨmem), is harnessed for ATP generation. Here we show that ΔΨmem and ATP-production can be engaged in mitochondria isolated from human brains up to 8.5 h postmortem. Also, a time course of postmortem intervals from 0 to 24 h using mitochondria isolated from mouse cortex reveals that ΔΨmem in mitochondria can be reconstituted beyond 10 h postmortem. It was found that complex I of the mitochondrial electron transport chain was affected adversely with increasing postmortem intervals. Mitochondria isolated from postmortem mouse brains maintain the ability to produce ATP, but rates of production decreased with longer postmortem intervals. Furthermore, we show that postmortem brain mitochondria retain their ΔΨmem and ATP-production capacities following cryopreservation. Our finding that ΔΨmem and ATP-generating capacity can be reinitiated in brain mitochondria hours after death indicates that human postmortem brains can be an abundant source of viable mitochondria to study metabolic processes in health and disease. It is also possible to archive these mitochondria for future studies.—Barksdale, K. A., Perez-Costas, E., Gandy, J. C., Melendez-Ferro, M., Roberts, R. C., Bijur, G. N. Mitochondrial viability in mouse and human postmortem brain. PMID:20466876

  11. Progress on the paternal brain: theory, animal models, human brain research, and mental health implications.

    PubMed

    Swain, J E; Dayton, C J; Kim, P; Tolman, R M; Volling, B L

    2014-01-01

    With a secure foundation in basic research across mammalian species in which fathers participate in the raising of young, novel brain-imaging approaches are outlining a set of consistent brain circuits that regulate paternal thoughts and behaviors in humans. The newest experimental paradigms include increasingly realistic baby-stimuli to provoke paternal cognitions and behaviors with coordinated hormone measures to outline brain networks that regulate motivation, reflexive caring, emotion regulation, and social brain networks with differences and similarities to those found in mothers. In this article, on the father brain, we review all brain-imaging studies on PubMed to date on the human father brain and introduce the topic with a selection of theoretical models and foundational neurohormonal research on animal models in support of the human work. We discuss potentially translatable models for the identification and treatment of paternal mood and father-child relational problems, which could improve infant mental health and developmental trajectories with potentially broad public health importance. PMID:25798491

  12. On Expression Patterns and Developmental Origin of Human Brain Regions

    PubMed Central

    Kirsch, Lior; Chechik, Gal

    2016-01-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

  13. BrainNet Viewer: a network visualization tool for human brain connectomics.

    PubMed

    Xia, Mingrui; Wang, Jinhui; He, Yong

    2013-01-01

    The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/). PMID:23861951

  14. Neurochemical modulation of repetition suppression and novelty signals in the human brain.

    PubMed

    Bunzeck, Nico; Thiel, Christiane

    2016-07-01

    The repeated processing of a sensory stimulus, such as a picture or sound, leads to a decrement in response in neurons that fired to the initial presentation. These effects are well known from single cell recordings in the inferior temporal cortex in monkeys, and functional neuroimaging in humans on large-scale neural activity could show similar effects in extrastriate, frontal and medial temporal lobe (MTL) regions. The role of specific neurotransmitters in repeated processing of information is, however, less clear. In the first part of this article, we will introduce the two concepts of repetition suppression and novelty signals, which is followed by a brief overview of pharmacological neuroimaging in humans. We will then summarize human studies suggesting that gamma-aminobutyric-acid (GABA) and acetylcholine (ACh) play an important role in modulating behavioral priming and associated repetition suppression in extrastriate and frontal brain regions. Finally, we review studies on neural novelty signals in the dopaminergic mesolimbic system, and conclude that dopamine (DA) regulates the temporal aspects of novelty processing and closely relates to long-term memory encoding rather than behavioral priming. As such, this review describes differential roles of GABA, ACh and DA in repeated stimulus processing, and further suggests that repetition suppression and neural novelty signals may not be two sides of the same coin but rather independent processes. PMID:26625882

  15. TV, Brain Waves and Human Behavior

    ERIC Educational Resources Information Center

    Science News, 1978

    1978-01-01

    Describes the procedure to test the hypothesis that subjects' brain waves in response to a television flicker (distraction) would be smaller in amplitude during television programs of high, in contrast to low, interest. Results from 12 viewers support the hypothesis. (CP)

  16. Human and rat brain lipofuscin proteome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The accumulation of an autofluorescent pigment called lipofuscin in neurons is an invariable hallmark of brain aging. So far, this material has been considered to be waste material without particular relevance for cellular pathology. However, two lines of evidence argue that lipofuscin may have yet ...

  17. Development of Human Brain Structural Networks Through Infancy and Childhood

    PubMed Central

    Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

    2015-01-01

    During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

  18. Comparative genetic approaches to the evolution of human brain and behavior

    PubMed Central

    Vallender, Eric J.

    2012-01-01

    With advances in genomic technologies the amount of genetic data available to scientists today is vast. Genomes are now available or planned for fourteen different primate species and complete resequencing of numerous human individuals from numerous populations is underway. Moreover, high-throughput deep sequencing is quickly making whole genome efforts within the reach of single laboratories allowing for unprecedented studies. Comparative genetic approaches to the identification of the underlying basis of human brain, behavior and cognitive ability are moving to the forefront. Two approaches predominate: inter-species divergence comparisons and intra-species polymorphism studies. These methodological differences are useful for different time scales of evolution and necessarily focus on different evolutionary events in the history of primate and hominin evolution. Inter-species divergence is more useful in studying large scale primate, or hominoid, evolution whereas intra-species polymorphism can be more illuminating of recent hominin evolution. These differences in methodological utility also extend to studies of differing genetic substrates; current divergence studies focus primarily on protein evolution while polymorphism studies are substrate ambivalent. Some of the issues inherent in these studies can be ameliorated by current sequencing capabilities while others remain intractable. New avenues are also being opened that allow for the incorporation of novel substrates and approaches. In the post-genomic era the study of human evolution, specifically as it relates to the brain, is becoming more complete focusing increasingly on the totality of the system and better conceptualizing the entirety of the genetic changes that have lead to the human phenotype today. PMID:21140466

  19. Genetic regulation of human brain development: lessons from Mendelian diseases

    PubMed Central

    Dixon-Salazar, Tracy J.; Gleeson, Joseph G.

    2016-01-01

    One of the fundamental goals in human genetics is to link gene function to phenotype, yet the function of the majority of the genes in the human body is still poorly understood. This is especially true for the developing human brain<