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Sample records for large-scale human brain

  1. Generative models of rich clubs in Hebbian neuronal networks and large-scale human brain networks

    PubMed Central

    Vértes, Petra E.; Alexander-Bloch, Aaron; Bullmore, Edward T.

    2014-01-01

    Rich clubs arise when nodes that are ‘rich’ in connections also form an elite, densely connected ‘club’. In brain networks, rich clubs incur high physical connection costs but also appear to be especially valuable to brain function. However, little is known about the selection pressures that drive their formation. Here, we take two complementary approaches to this question: firstly we show, using generative modelling, that the emergence of rich clubs in large-scale human brain networks can be driven by an economic trade-off between connection costs and a second, competing topological term. Secondly we show, using simulated neural networks, that Hebbian learning rules also drive the emergence of rich clubs at the microscopic level, and that the prominence of these features increases with learning time. These results suggest that Hebbian learning may provide a neuronal mechanism for the selection of complex features such as rich clubs. The neural networks that we investigate are explicitly Hebbian, and we argue that the topological term in our model of large-scale brain connectivity may represent an analogous connection rule. This putative link between learning and rich clubs is also consistent with predictions that integrative aspects of brain network organization are especially important for adaptive behaviour. PMID:25180309

  2. 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.

  3. Large-Scale Brain Networks of the Human Left Temporal Pole: A Functional Connectivity MRI Study

    PubMed Central

    Pascual, Belen; Masdeu, Joseph C.; Hollenbeck, Mark; Makris, Nikos; Insausti, Ricardo; Ding, Song-Lin; Dickerson, Bradford C.

    2015-01-01

    The most rostral portion of the human temporal cortex, the temporal pole (TP), has been described as “enigmatic” because its functional neuroanatomy remains unclear. Comparative anatomy studies are only partially helpful, because the human TP is larger and cytoarchitectonically more complex than in nonhuman primates. Considered by Brodmann as a single area (BA 38), the human TP has been recently parceled into an array of cytoarchitectonic subfields. In order to clarify the functional connectivity of subregions of the TP, we undertook a study of 172 healthy adults using resting-state functional connectivity MRI. Remarkably, a hierarchical cluster analysis performed to group the seeds into distinct subsystems according to their large-scale functional connectivity grouped 87.5% of the seeds according to the recently described cytoarchitectonic subregions of the TP. Based on large-scale functional connectivity, there appear to be 4 major subregions of the TP: 1) dorsal, with predominant connectivity to auditory/somatosensory and language networks; 2) ventromedial, predominantly connected to visual networks; 3) medial, connected to paralimbic structures; and 4) anterolateral, connected to the default-semantic network. The functional connectivity of the human TP, far more complex than its known anatomic connectivity in monkey, is concordant with its hypothesized role as a cortical convergence zone. PMID:24068551

  4. Large-scale identification of coregulated enhancer networks in the adult human brain.

    PubMed

    Vermunt, Marit W; Reinink, Peter; Korving, Jeroen; de Bruijn, Ewart; Creyghton, Paul M; Basak, Onur; Geeven, Geert; Toonen, Pim W; Lansu, Nico; Meunier, Charles; van Heesch, Sebastiaan; Clevers, Hans; de Laat, Wouter; Cuppen, Edwin; Creyghton, Menno P

    2014-10-23

    Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson's disease incidence.

  5. 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.

  6. Defining face perception areas in the human brain: a large-scale factorial fMRI face localizer analysis.

    PubMed

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-07-01

    to make them correspond across individual brains. This large-scale analysis helps understanding the set of face-sensitive areas in the human brain, and encourages in-depth single participant analyses in which the whole set of areas is considered in each individual brain.

  7. Structure and function of large-scale brain systems.

    PubMed

    Koziol, Leonard F; Barker, Lauren A; Joyce, Arthur W; Hrin, Skip

    2014-01-01

    This article introduces the functional neuroanatomy of large-scale brain systems. Both the structure and functions of these brain networks are presented. All human behavior is the result of interactions within and between these brain systems. This system of brain function completely changes our understanding of how cognition and behavior are organized within the brain, replacing the traditional lesion model. Understanding behavior within the context of brain network interactions has profound implications for modifying abstract constructs such as attention, learning, and memory. These constructs also must be understood within the framework of a paradigm shift, which emphasizes ongoing interactions within a dynamically changing environment.

  8. 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

  9. Knowledge-guided robust MRI brain extraction for diverse large-scale neuroimaging studies on humans and non-human primates.

    PubMed

    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.

  10. 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…

  11. 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.

  12. Development of Large-Scale Functional Brain Networks in Children

    PubMed Central

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-01-01

    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

  13. 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

  14. 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

  15. 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

  16. Large-scale brain functional modularity is reflected in slow electroencephalographic rhythms across the human non-rapid eye movement sleep cycle.

    PubMed

    Tagliazucchi, Enzo; von Wegner, Frederic; Morzelewski, Astrid; Brodbeck, Verena; Borisov, Sergey; Jahnke, Kolja; Laufs, Helmut

    2013-04-15

    Large-scale brain functional networks (measured with functional magnetic resonance imaging, fMRI) are organized into separated but interacting modules, an architecture supporting the integration of distinct dynamical processes. In this work we study how the aforementioned modular architecture changes with the progressive loss of vigilance occurring in the descent to deep sleep and we examine the relationship between the ensuing slow electroencephalographic rhythms and large-scale network modularity as measured with fMRI. Graph theoretical methods are used to analyze functional connectivity graphs obtained from fifty-five participants at wakefulness, light and deep sleep. Network modularity (a measure of functional segregation) was found to increase during deeper sleep stages but not in light sleep. By endowing functional networks with dynamical properties, we found a direct link between increased electroencephalographic (EEG) delta power (1-4 Hz) and a breakdown of inter-modular connectivity. Both EEG slowing and increased network modularity were found to quickly decrease during awakenings from deep sleep to wakefulness, in a highly coordinated fashion. Studying the modular structure itself by means of a permutation test, we revealed different module memberships when deep sleep was compared to wakefulness. Analysis of node roles in the modular structure revealed an increase in the number of locally well-connected nodes and a decrease in the number of globally well-connected hubs, which hinders interactions between separated functional modules. Our results reveal a well-defined sequence of changes in brain modular organization occurring during the descent to sleep and establish a close parallel between modularity alterations in large-scale functional networks (accessible through whole brain fMRI recordings) and the slowing of scalp oscillations (visible on EEG). The observed re-arrangement of connectivity might play an important role in the processes underlying loss

  17. Brief Mental Training Reorganizes Large-Scale Brain Networks

    PubMed Central

    Tang, Yi-Yuan; Tang, Yan; Tang, Rongxiang; Lewis-Peacock, Jarrod A.

    2017-01-01

    Emerging evidences have shown that one form of mental training—mindfulness meditation, can improve attention, emotion regulation and cognitive performance through changing brain activity and structural connectivity. However, whether and how the short-term mindfulness meditation alters large-scale brain networks are not well understood. Here, we applied a novel data-driven technique, the multivariate pattern analysis (MVPA) to resting-state fMRI (rsfMRI) data to identify changes in brain activity patterns and assess the neural mechanisms induced by a brief mindfulness training—integrative body–mind training (IBMT), which was previously reported in our series of randomized studies. Whole brain rsfMRI was performed on an undergraduate group who received 2 weeks of IBMT with 30 min per session (5 h training in total). Classifiers were trained on measures of functional connectivity in this fMRI data, and they were able to reliably differentiate (with 72% accuracy) patterns of connectivity from before vs. after the IBMT training. After training, an increase in positive functional connections (60 connections) were detected, primarily involving bilateral superior/middle occipital gyrus, bilateral frontale operculum, bilateral superior temporal gyrus, right superior temporal pole, bilateral insula, caudate and cerebellum. These results suggest that brief mental training alters the functional connectivity of large-scale brain networks at rest that may involve a portion of the neural circuitry supporting attention, cognitive and affective processing, awareness and sensory integration and reward processing. PMID:28293180

  18. Brief Mental Training Reorganizes Large-Scale Brain Networks.

    PubMed

    Tang, Yi-Yuan; Tang, Yan; Tang, Rongxiang; Lewis-Peacock, Jarrod A

    2017-01-01

    Emerging evidences have shown that one form of mental training-mindfulness meditation, can improve attention, emotion regulation and cognitive performance through changing brain activity and structural connectivity. However, whether and how the short-term mindfulness meditation alters large-scale brain networks are not well understood. Here, we applied a novel data-driven technique, the multivariate pattern analysis (MVPA) to resting-state fMRI (rsfMRI) data to identify changes in brain activity patterns and assess the neural mechanisms induced by a brief mindfulness training-integrative body-mind training (IBMT), which was previously reported in our series of randomized studies. Whole brain rsfMRI was performed on an undergraduate group who received 2 weeks of IBMT with 30 min per session (5 h training in total). Classifiers were trained on measures of functional connectivity in this fMRI data, and they were able to reliably differentiate (with 72% accuracy) patterns of connectivity from before vs. after the IBMT training. After training, an increase in positive functional connections (60 connections) were detected, primarily involving bilateral superior/middle occipital gyrus, bilateral frontale operculum, bilateral superior temporal gyrus, right superior temporal pole, bilateral insula, caudate and cerebellum. These results suggest that brief mental training alters the functional connectivity of large-scale brain networks at rest that may involve a portion of the neural circuitry supporting attention, cognitive and affective processing, awareness and sensory integration and reward processing.

  19. Analysis of large-scale brain data for brain-computer interfaces.

    PubMed

    Das, Koel; Meyer, Joerg; Nenadic, Zoran

    2006-01-01

    We present a systematic technique for extraction of useful information from large-scale neural data in the context of brain-computer interfaces. The technique is based on a direct linear discriminant analysis, recently developed for face recognition problems. We show that this technique is capable of extracting useful information from brain data in a systematic fashion and can serve as a general analytical tool for other types of biomedical data, such as images and collections of images (movies). The performance of the method is tested on intracranial electroencephalographic data recorded from the human brain.

  20. Towards large-scale, human-based, mesoscopic neurotechnologies.

    PubMed

    Chang, Edward F

    2015-04-08

    Direct human brain recordings have transformed the scope of neuroscience in the past decade. Progress has relied upon currently available neurophysiological approaches in the context of patients undergoing neurosurgical procedures for medical treatment. While this setting has provided precious opportunities for scientific research, it also has presented significant constraints on the development of new neurotechnologies. A major challenge now is how to achieve high-resolution spatiotemporal neural recordings at a large scale. By narrowing the gap between current approaches, new directions tailored to the mesoscopic (intermediate) scale of resolution may overcome the barriers towards safe and reliable human-based neurotechnology development, with major implications for advancing both basic research and clinical translation.

  1. Dietary omega-3 fatty acids modulate large-scale systems organization in the rhesus macaque brain.

    PubMed

    Grayson, David S; Kroenke, Christopher D; Neuringer, Martha; Fair, Damien A

    2014-02-05

    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.

  2. 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

  3. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain.

    PubMed

    Barrett, Lisa Feldman; Satpute, Ajay Bhaskar

    2013-06-01

    Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain.

  4. 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.

  5. 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).

  6. 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.

  7. 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

  8. 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

    2016-05-25

    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.

  9. Unfolding large-scale online collaborative human dynamics

    PubMed Central

    Zha, Yilong; Zhou, Tao; Zhou, Changsong

    2016-01-01

    Large-scale interacting human activities underlie all social and economic phenomena, but quantitative understanding of regular patterns and mechanism is very challenging and still rare. Self-organized online collaborative activities with a precise record of event timing provide unprecedented opportunity. Our empirical analysis of the history of millions of updates in Wikipedia shows a universal double–power-law distribution of time intervals between consecutive updates of an article. We then propose a generic model to unfold collaborative human activities into three modules: (i) individual behavior characterized by Poissonian initiation of an action, (ii) human interaction captured by a cascading response to previous actions with a power-law waiting time, and (iii) population growth due to the increasing number of interacting individuals. This unfolding allows us to obtain an analytical formula that is fully supported by the universal patterns in empirical data. Our modeling approaches reveal “simplicity” beyond complex interacting human activities. PMID:27911766

  10. Integration and segregation of large-scale brain networks during short-term task automatization

    PubMed Central

    Mohr, Holger; Wolfensteller, Uta; Betzel, Richard F.; Mišić, Bratislav; Sporns, Olaf; Richiardi, Jonas; Ruge, Hannes

    2016-01-01

    The human brain is organized into large-scale functional networks that can flexibly reconfigure their connectivity patterns, supporting both rapid adaptive control and long-term learning processes. However, it has remained unclear how short-term network dynamics support the rapid transformation of instructions into fluent behaviour. Comparing fMRI data of a learning sample (N=70) with a control sample (N=67), we find that increasingly efficient task processing during short-term practice is associated with a reorganization of large-scale network interactions. Practice-related efficiency gains are facilitated by enhanced coupling between the cingulo-opercular network and the dorsal attention network. Simultaneously, short-term task automatization is accompanied by decreasing activation of the fronto-parietal network, indicating a release of high-level cognitive control, and a segregation of the default mode network from task-related networks. These findings suggest that short-term task automatization is enabled by the brain's ability to rapidly reconfigure its large-scale network organization involving complementary integration and segregation processes. PMID:27808095

  11. Large-scale brain network dynamics supporting adolescent cognitive control.

    PubMed

    Dwyer, Dominic B; Harrison, Ben J; Yücel, Murat; Whittle, Sarah; Zalesky, Andrew; Pantelis, Christos; Allen, Nicholas B; Fornito, Alex

    2014-10-15

    Adolescence is a time when the ability to engage cognitive control is linked to crucial life outcomes. Despite a historical focus on prefrontal cortex functioning, recent evidence suggests that differences between individuals may relate to interactions between distributed brain regions that collectively form a cognitive control network (CCN). Other research points to a spatially distinct and functionally antagonistic system--the default-mode network (DMN)--which typically deactivates during performance of control tasks. This literature implies that individual differences in cognitive control are determined either by activation or functional connectivity of CCN regions, deactivation or functional connectivity of DMN regions, or some combination of both. We tested between these possibilities using a multilevel fMRI characterization of CCN and DMN dynamics, measured during performance of a cognitive control task and during a task-free resting state, in 73 human adolescents. Better cognitive control performance was associated with (1) reduced activation of CCN regions, but not deactivation of the DMN; (2) variations in task-related, but not resting-state, functional connectivity within a distributed network involving both the CCN and DMN; (3) functional segregation of core elements of these two systems; and (4) task-dependent functional integration of a set of peripheral nodes into either one network or the other in response to prevailing stimulus conditions. These results indicate that individual differences in adolescent cognitive control are not solely attributable to the functioning of any single region or network, but are instead dependent on a dynamic and context-dependent interplay between the CCN and DMN.

  12. 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

  13. How do parcellation size and short-range connectivity affect dynamics in large-scale brain network models?

    PubMed

    Proix, Timothée; Spiegler, Andreas; Schirner, Michael; Rothmeier, Simon; Ritter, Petra; Jirsa, Viktor K

    2016-11-15

    Recent efforts to model human brain activity on the scale of the whole brain rest on connectivity estimates of large-scale networks derived from diffusion magnetic resonance imaging (dMRI). This type of connectivity describes white matter fiber tracts. The number of short-range cortico-cortical white-matter connections is, however, underrepresented in such large-scale brain models. It is still unclear on the one hand, which scale of representation of white matter fibers is optimal to describe brain activity on a large-scale such as recorded with magneto- or electroencephalography (M/EEG) or functional magnetic resonance imaging (fMRI), and on the other hand, to which extent short-range connections that are typically local should be taken into account. In this article we quantified the effect of connectivity upon large-scale brain network dynamics by (i) systematically varying the number of brain regions before computing the connectivity matrix, and by (ii) adding generic short-range connections. We used dMRI data from the Human Connectome Project. We developed a suite of preprocessing modules called SCRIPTS to prepare these imaging data for The Virtual Brain, a neuroinformatics platform for large-scale brain modeling and simulations. We performed simulations under different connectivity conditions and quantified the spatiotemporal dynamics in terms of Shannon Entropy, dwell time and Principal Component Analysis. For the reconstructed connectivity, our results show that the major white matter fiber bundles play an important role in shaping slow dynamics in large-scale brain networks (e.g. in fMRI). Faster dynamics such as gamma oscillations (around 40 Hz) are sensitive to the short-range connectivity if transmission delays are considered.

  14. 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

  15. 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

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

    PubMed Central

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

    2016-01-01

    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

  17. 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.

  18. The small-world organization of large-scale brain systems and relationships with subcortical structures.

    PubMed

    Koziol, Leonard F; Barker, Lauren A; Joyce, Arthur W; Hrin, Skip

    2014-01-01

    Brain structure and function is characterized by large-scale brain systems. However, each system has its own "small-world" organization, with sub-regions, or "hubs," that have varying degrees of specialization for certain cognitive and behavioral processes. This article describes this small-world organization, and the concepts of functional specialization and functional integration are defined and explained through practical examples. We also describe the development of large-scale brain systems and this small-world organization as a sensitive, protracted process, vulnerable to a variety of influences that generate neurodevelopmental disorders.

  19. Mathematical framework for large-scale brain network modeling in The Virtual Brain.

    PubMed

    Sanz-Leon, Paula; Knock, Stuart A; Spiegler, Andreas; Jirsa, Viktor K

    2015-05-01

    In this article, we describe the mathematical framework of the computational model at the core of the tool The Virtual Brain (TVB), designed to simulate collective whole brain dynamics by virtualizing brain structure and function, allowing simultaneous outputs of a number of experimental modalities such as electro- and magnetoencephalography (EEG, MEG) and functional Magnetic Resonance Imaging (fMRI). The implementation allows for a systematic exploration and manipulation of every underlying component of a large-scale brain network model (BNM), such as the neural mass model governing the local dynamics or the structural connectivity constraining the space time structure of the network couplings. Here, a consistent notation for the generalized BNM is given, so that in this form the equations represent a direct link between the mathematical description of BNMs and the components of the numerical implementation in TVB. Finally, we made a summary of the forward models implemented for mapping simulated neural activity (EEG, MEG, sterotactic electroencephalogram (sEEG), fMRI), identifying their advantages and limitations.

  20. Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy.

    PubMed

    Zhang, Zhiqiang; Liao, Wei; Chen, Huafu; Mantini, Dante; Ding, Ju-Rong; Xu, Qiang; Wang, Zhengge; Yuan, Cuiping; Chen, Guanghui; Jiao, Qing; Lu, Guangming

    2011-10-01

    The human brain is a large-scale integrated network in the functional and structural domain. Graph theoretical analysis provides a novel framework for analysing such complex networks. While previous neuroimaging studies have uncovered abnormalities in several specific brain networks in patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures, little is known about changes in whole-brain functional and structural connectivity networks. Regarding functional and structural connectivity, networks are intimately related and share common small-world topological features. We predict that patients with idiopathic generalized epilepsy would exhibit a decoupling between functional and structural networks. In this study, 26 patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures and 26 age- and sex-matched healthy controls were recruited. Resting-state functional magnetic resonance imaging signal correlations and diffusion tensor image tractography were used to generate functional and structural connectivity networks. Graph theoretical analysis revealed that the patients lost optimal topological organization in both functional and structural connectivity networks. Moreover, the patients showed significant increases in nodal topological characteristics in several cortical and subcortical regions, including mesial frontal cortex, putamen, thalamus and amygdala relative to controls, supporting the hypothesis that regions playing important roles in the pathogenesis of epilepsy may display abnormal hub properties in network analysis. Relative to controls, patients showed further decreases in nodal topological characteristics in areas of the default mode network, such as the posterior cingulate gyrus and inferior temporal gyrus. Most importantly, the degree of coupling between functional and structural connectivity networks was decreased, and exhibited a negative correlation with epilepsy duration in patients. Our findings

  1. 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

  2. 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).

  3. Large-scale discovery of enhancers from human heart tissue.

    PubMed

    May, Dalit; Blow, Matthew J; Kaplan, Tommy; McCulley, David J; Jensen, Brian C; Akiyama, Jennifer A; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Afzal, Veena; Simpson, Paul C; Rubin, Edward M; Black, Brian L; Bristow, James; Pennacchio, Len A; Visel, Axel

    2011-12-04

    Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.

  4. 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

  5. Weighted and directed interactions in evolving large-scale epileptic brain networks.

    PubMed

    Dickten, Henning; Porz, Stephan; Elger, Christian E; Lehnertz, Klaus

    2016-10-06

    Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess-with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics-both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only - in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control.

  6. Weighted and directed interactions in evolving large-scale epileptic brain networks

    NASA Astrophysics Data System (ADS)

    Dickten, Henning; Porz, Stephan; Elger, Christian E.; Lehnertz, Klaus

    2016-10-01

    Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess—with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics—both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only – in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control.

  7. Weighted and directed interactions in evolving large-scale epileptic brain networks

    PubMed Central

    Dickten, Henning; Porz, Stephan; Elger, Christian E.; Lehnertz, Klaus

    2016-01-01

    Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess—with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics—both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only – in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control. PMID:27708381

  8. Geomorphic and human influence on large-scale coastal change

    NASA Astrophysics Data System (ADS)

    Hapke, Cheryl J.; Kratzmann, Meredith G.; Himmelstoss, Emily A.

    2013-10-01

    An increasing need exists for regional-scale measurements of shoreline change to aid in management and planning decisions over a broad portion of the coast and to inform assessments of coastal vulnerabilities and hazards. A recent dataset of regional shoreline change, covering a large portion of the U.S. East coast (New England and Mid-Atlantic), provides rates of shoreline change over historical (~ 150 years) and recent (25-30 years) time periods making it ideal for a broad assessment of the regional variation of shoreline change, and the natural and human-induced influences on coastal behavior. The variable coastal landforms of the region provide an opportunity to investigate how specific geomorphic landforms relate to the spatial variability of shoreline change. In addition to natural influences on the rates of change, we examine the effects that development and human modifications to the coastline have on the measurements of regional shoreline change. Regional variation in the rates of shoreline change is a function of the dominant type and distribution of coastal landform as well as the relative amount of human development. Our results indicate that geomorphology has measurable influence on shoreline change rates. Anthropogenic impacts are found to be greater along the more densely developed and modified portion of the coast where jetties at engineered inlets impound large volumes of sediment resulting in extreme but discrete progradation updrift of jetties. This produces a shift in averaged values of rates that may mask the natural long-term record. Additionally, a strong correlation is found to exist between rates of shoreline change and relative level of human development. Using a geomorphic characterization of the types of coastal landform as a guide for expected relative rates of change, we found that the shoreline appears to be changing naturally only along sparsely developed coasts. Even modest amounts of development influence the rates of change and

  9. Geomorphic and human influence on large-scale coastal change

    USGS Publications Warehouse

    Hapke, Cheryl J.; Kratzmann, Meredith G.; Himmelstoss, Emily A.

    2013-01-01

    An increasing need exists for regional-scale measurements of shoreline change to aid in management and planning decisions over a broad portion of the coast and to inform assessments of coastal vulnerabilities and hazards. A recent dataset of regional shoreline change, covering a large portion of the U.S. East coast (New England and Mid-Atlantic), provides rates of shoreline change over historical (~ 150 years) and recent (25–30 years) time periods making it ideal for a broad assessment of the regional variation of shoreline change, and the natural and human-induced influences on coastal behavior. The variable coastal landforms of the region provide an opportunity to investigate how specific geomorphic landforms relate to the spatial variability of shoreline change. In addition to natural influences on the rates of change, we examine the effects that development and human modifications to the coastline have on the measurements of regional shoreline change.Regional variation in the rates of shoreline change is a function of the dominant type and distribution of coastal landform as well as the relative amount of human development. Our results indicate that geomorphology has measurable influence on shoreline change rates. Anthropogenic impacts are found to be greater along the more densely developed and modified portion of the coast where jetties at engineered inlets impound large volumes of sediment resulting in extreme but discrete progradation updrift of jetties. This produces a shift in averaged values of rates that may mask the natural long-term record. Additionally, a strong correlation is found to exist between rates of shoreline change and relative level of human development. Using a geomorphic characterization of the types of coastal landform as a guide for expected relative rates of change, we found that the shoreline appears to be changing naturally only along sparsely developed coasts. Even modest amounts of development influence the rates of change

  10. 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.

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

    PubMed

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

    2011-03-30

    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.

  12. 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.

  13. 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.

  14. Individuality manifests in the dynamic reconfiguration of large-scale brain networks during movie viewing

    PubMed Central

    Jang, Changwon; Knight, Elizabeth Quattrocki; Pae, Chongwon; Park, Bumhee; Yoon, Shin-Ae; Park, Hae-Jeong

    2017-01-01

    Individuality, the uniqueness that distinguishes one person from another, may manifest as diverse rearrangements of functional connectivity during heterogeneous cognitive demands; yet, the neurobiological substrates of individuality, reflected in inter-individual variations of large-scale functional connectivity, have not been fully evidenced. Accordingly, we explored inter-individual variations of functional connectivity dynamics, subnetwork patterns and modular architecture while subjects watched identical video clips designed to induce different arousal levels. How inter-individual variations are manifested in the functional brain networks was examined with respect to four contrasting divisions: edges within the anterior versus posterior part of the brain, edges with versus without corresponding anatomically-defined structural pathways, inter- versus intra-module connections, and rich club edge types. Inter-subject variation in dynamic functional connectivity occurred to a greater degree within edges localized to anterior rather than posterior brain regions, without adhering to structural connectivity, between modules as opposed to within modules, and in weak-tie local edges rather than strong-tie rich-club edges. Arousal level significantly modulates inter-subject variability in functional connectivity, edge patterns, and modularity, and particularly enhances the synchrony of rich-club edges. These results imply that individuality resides in the dynamic reconfiguration of large-scale brain networks in response to a stream of cognitive demands. PMID:28112247

  15. Response of human populations to large-scale emergencies

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

    Until recently, little quantitative data regarding collective human behavior during dangerous events such as bombings and riots have been available, despite its importance for emergency management, safety and urban planning. Understanding how populations react to danger is critical for prediction, detection and intervention strategies. Using a large telecommunications dataset, we study for the first time the spatiotemporal, social and demographic response properties of people during several disasters, including a bombing, a city-wide power outage, and an earthquake. Call activity rapidly increases after an event and we find that, when faced with a truly life-threatening emergency, information rapidly propagates through a population's social network. Other events, such as sports games, do not exhibit this propagation.

  16. Criticality in large-scale brain FMRI dynamics unveiled by a novel point process analysis.

    PubMed

    Tagliazucchi, Enzo; Balenzuela, Pablo; Fraiman, Daniel; Chialvo, Dante R

    2012-01-01

    Functional magnetic resonance imaging (fMRI) techniques have contributed significantly to our understanding of brain function. Current methods are based on the analysis of gradual and continuous changes in the brain blood oxygenated level dependent (BOLD) signal. Departing from that approach, recent work has shown that equivalent results can be obtained by inspecting only the relatively large amplitude BOLD signal peaks, suggesting that relevant information can be condensed in discrete events. This idea is further explored here to demonstrate how brain dynamics at resting state can be captured just by the timing and location of such events, i.e., in terms of a spatiotemporal point process. The method allows, for the first time, to define a theoretical framework in terms of an order and control parameter derived from fMRI data, where the dynamical regime can be interpreted as one corresponding to a system close to the critical point of a second order phase transition. The analysis demonstrates that the resting brain spends most of the time near the critical point of such transition and exhibits avalanches of activity ruled by the same dynamical and statistical properties described previously for neuronal events at smaller scales. Given the demonstrated functional relevance of the resting state brain dynamics, its representation as a discrete process might facilitate large-scale analysis of brain function both in health and disease.

  17. Competitive and cooperative dynamics of large-scale brain functional networks supporting recollection.

    PubMed

    Fornito, Alex; Harrison, Ben J; Zalesky, Andrew; Simons, Jon S

    2012-07-31

    Analyses of functional interactions between large-scale brain networks have identified two broad systems that operate in apparent competition or antagonism with each other. One system, termed the default mode network (DMN), is thought to support internally oriented processing. The other system acts as a generic external attention system (EAS) and mediates attention to exogenous stimuli. Reports that the DMN and EAS show anticorrelated activity across a range of experimental paradigms suggest that competition between these systems supports adaptive behavior. Here, we used functional MRI to characterize functional interactions between the DMN and different EAS components during performance of a recollection task known to coactivate regions of both networks. Using methods to isolate task-related, context-dependent changes in functional connectivity between these systems, we show that increased cooperation between the DMN and a specific right-lateralized frontoparietal component of the EAS is associated with more rapid memory recollection. We also show that these cooperative dynamics are facilitated by a dynamic reconfiguration of the functional architecture of the DMN into core and transitional modules, with the latter serving to enhance integration with frontoparietal regions. In particular, the right posterior cingulate cortex may act as a critical information-processing hub that provokes these context-dependent reconfigurations from an intrinsic or default state of antagonism. Our findings highlight the dynamic, context-dependent nature of large-scale brain dynamics and shed light on their contribution to individual differences in behavior.

  18. Large-scale extraction of brain connectivity from the neuroscientific literature

    PubMed Central

    Richardet, Renaud; Chappelier, Jean-Cédric; Telefont, Martin; Hill, Sean

    2015-01-01

    Motivation: In neuroscience, as in many other scientific domains, the primary form of knowledge dissemination is through published articles. One challenge for modern neuroinformatics is finding methods to make the knowledge from the tremendous backlog of publications accessible for search, analysis and the integration of such data into computational models. A key example of this is metascale brain connectivity, where results are not reported in a normalized repository. Instead, these experimental results are published in natural language, scattered among individual scientific publications. This lack of normalization and centralization hinders the large-scale integration of brain connectivity results. In this article, we present text-mining models to extract and aggregate brain connectivity results from 13.2 million PubMed abstracts and 630 216 full-text publications related to neuroscience. The brain regions are identified with three different named entity recognizers (NERs) and then normalized against two atlases: the Allen Brain Atlas (ABA) and the atlas from the Brain Architecture Management System (BAMS). We then use three different extractors to assess inter-region connectivity. Results: NERs and connectivity extractors are evaluated against a manually annotated corpus. The complete in litero extraction models are also evaluated against in vivo connectivity data from ABA with an estimated precision of 78%. The resulting database contains over 4 million brain region mentions and over 100 000 (ABA) and 122 000 (BAMS) potential brain region connections. This database drastically accelerates connectivity literature review, by providing a centralized repository of connectivity data to neuroscientists. Availability and implementation: The resulting models are publicly available at github.com/BlueBrain/bluima. Contact: renaud.richardet@epfl.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25609795

  19. Bursty properties revealed in large-scale brain networks with a point-based method for dynamic functional connectivity

    PubMed Central

    Thompson, William Hedley; Fransson, Peter

    2016-01-01

    The brain is organized into large scale spatial networks that can be detected during periods of rest using fMRI. The brain is also a dynamic organ with activity that changes over time. We developed a method and investigated properties where the connections as a function of time are derived and quantified. The point based method (PBM) presented here derives covariance matrices after clustering individual time points based upon their global spatial pattern. This method achieved increased temporal sensitivity, together with temporal network theory, allowed us to study functional integration between resting-state networks. Our results show that functional integrations between two resting-state networks predominately occurs in bursts of activity. This is followed by varying intermittent periods of less connectivity. The described point-based method of dynamic resting-state functional connectivity allows for a detailed and expanded view on the temporal dynamics of resting-state connectivity that provides novel insights into how neuronal information processing is integrated in the human brain at the level of large-scale networks. PMID:27991540

  20. 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.

  1. 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.

  2. Large-scale brain networks emerge from dynamic processing of musical timbre, key and rhythm.

    PubMed

    Alluri, Vinoo; Toiviainen, Petri; Jääskeläinen, Iiro P; Glerean, Enrico; Sams, Mikko; Brattico, Elvira

    2012-02-15

    We investigated the neural underpinnings of timbral, tonal, and rhythmic features of a naturalistic musical stimulus. Participants were scanned with functional Magnetic Resonance Imaging (fMRI) while listening to a stimulus with a rich musical structure, a modern tango. We correlated temporal evolutions of timbral, tonal, and rhythmic features of the stimulus, extracted using acoustic feature extraction procedures, with the fMRI time series. Results corroborate those obtained with controlled stimuli in previous studies and highlight additional areas recruited during musical feature processing. While timbral feature processing was associated with activations in cognitive areas of the cerebellum, and sensory and default mode network cerebrocortical areas, musical pulse and tonality processing recruited cortical and subcortical cognitive, motor and emotion-related circuits. In sum, by combining neuroimaging, acoustic feature extraction and behavioral methods, we revealed the large-scale cognitive, motor and limbic brain circuitry dedicated to acoustic feature processing during listening to a naturalistic stimulus. In addition to these novel findings, our study has practical relevance as it provides a powerful means to localize neural processing of individual acoustical features, be it those of music, speech, or soundscapes, in ecological settings.

  3. General relationship of global topology, local dynamics, and directionality in large-scale brain networks.

    PubMed

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

    2015-04-01

    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.

  4. 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

  5. The co-evolution of social institutions, demography, and large-scale human cooperation.

    PubMed

    Powers, Simon T; Lehmann, Laurent

    2013-11-01

    Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small- to large-scale societies involves understanding how these institutions co-evolve with demography. We study this using a demographically explicit model of institution formation in a patch-structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co-evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small- to large-scale social groups.

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

    PubMed

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

    2015-10-01

    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.

  7. Large-scale brain networks in the awake, truly resting marmoset monkey.

    PubMed

    Belcher, Annabelle M; Yen, Cecil C; Stepp, Haley; Gu, Hong; Lu, Hanbing; Yang, Yihong; Silva, Afonso C; Stein, Elliot A

    2013-10-16

    Resting-state functional MRI is a powerful tool that is increasingly used as a noninvasive method for investigating whole-brain circuitry and holds great potential as a possible diagnostic for disease. Despite this potential, few resting-state studies have used animal models (of which nonhuman primates represent our best opportunity of understanding complex human neuropsychiatric disease), and no work has characterized networks in awake, truly resting animals. Here we present results from a small New World monkey that allows for the characterization of resting-state networks in the awake state. Six adult common marmosets (Callithrix jacchus) were acclimated to light, comfortable restraint using individualized helmets. Following behavioral training, resting BOLD data were acquired during eight consecutive 10 min scans for each conscious subject. Group independent component analysis revealed 12 brain networks that overlap substantially with known anatomically constrained circuits seen in the awake human. Specifically, we found eight sensory and "lower-order" networks (four visual, two somatomotor, one cerebellar, and one caudate-putamen network), and four "higher-order" association networks (one default mode-like network, one orbitofrontal, one frontopolar, and one network resembling the human salience network). In addition to their functional relevance, these network patterns bear great correspondence to those previously described in awake humans. This first-of-its-kind report in an awake New World nonhuman primate provides a platform for mechanistic neurobiological examination for existing disease models established in the marmoset.

  8. 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.

  9. Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays

    PubMed Central

    Ferrea, E.; Maccione, A.; Medrihan, L.; Nieus, T.; Ghezzi, D.; Baldelli, P.; Benfenati, F.; Berdondini, L.

    2012-01-01

    Multielectrode arrays (MEAs) are extensively used for electrophysiological studies on brain slices, but the spatial resolution and field of recording of conventional arrays are limited by the low number of electrodes available. Here, we present a large-scale array recording simultaneously from 4096 electrodes used to study propagating spontaneous and evoked network activity in acute murine cortico-hippocampal brain slices at unprecedented spatial and temporal resolution. We demonstrate that multiple chemically induced epileptiform episodes in the mouse cortex and hippocampus can be classified according to their spatio-temporal dynamics. Additionally, the large-scale and high-density features of our recording system enable the topological localization and quantification of the effects of antiepileptic drugs in local neuronal microcircuits, based on the distinct field potential propagation patterns. This novel high-resolution approach paves the way to detailed electrophysiological studies in brain circuits spanning spatial scales from single neurons up to the entire slice network. PMID:23162432

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

    PubMed

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

    2016-02-05

    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.

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

    PubMed Central

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

    2016-01-01

    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

  12. Effects on aquatic and human health due to large scale bioenergy crop expansion.

    PubMed

    Love, Bradley J; Einheuser, Matthew D; Nejadhashemi, A Pouyan

    2011-08-01

    In this study, the environmental impacts of large scale bioenergy crops were evaluated using the Soil and Water Assessment Tool (SWAT). Daily pesticide concentration data for a study area consisting of four large watersheds located in Michigan (totaling 53,358 km²) was estimated over a six year period (2000-2005). Model outputs for atrazine, bromoxynil, glyphosate, metolachlor, pendimethalin, sethoxydim, triflualin, and 2,4-D model output were used to predict the possible long-term implications that large-scale bioenergy crop expansion may have on the bluegill (Lepomis macrochirus) and humans. Threshold toxicity levels were obtained for the bluegill and for human consumption for all pesticides being evaluated through an extensive literature review. Model output was compared to each toxicity level for the suggested exposure time (96-hour for bluegill and 24-hour for humans). The results suggest that traditional intensive row crops such as canola, corn and sorghum may negatively impact aquatic life, and in most cases affect the safe drinking water availability. The continuous corn rotation, the most representative rotation for current agricultural practices for a starch-based ethanol economy, delivers the highest concentrations of glyphosate to the stream. In addition, continuous canola contributed to a concentration of 1.11 ppm of trifluralin, a highly toxic herbicide, which is 8.7 times the 96-hour ecotoxicity of bluegills and 21 times the safe drinking water level. Also during the period of study, continuous corn resulted in the impairment of 541,152 km of stream. However, there is promise with second-generation lignocellulosic bioenergy crops such as switchgrass, which resulted in a 171,667 km reduction in total stream length that exceeds the human threshold criteria, as compared to the base scenario. Results of this study may be useful in determining the suitability of bioenergy crop rotations and aid in decision making regarding the adaptation of large-scale

  13. 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.

  14. 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

    2016-03-10

    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.

  15. 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.

  16. Dynamic adaptation of large-scale brain networks in response to acute stressors.

    PubMed

    Hermans, Erno J; Henckens, Marloes J A G; Joëls, Marian; Fernández, Guillén

    2014-06-01

    Stress initiates an intricate response that affects diverse cognitive and affective domains, with the goal of improving survival chances in the light of changing environmental challenges. Here, we bridge animal data at cellular and systems levels with human work on brain-wide networks to propose a framework describing how stress-related neuromodulators trigger dynamic shifts in network balance, enabling an organism to comprehensively reallocate its neural resources according to cognitive demands. We argue that exposure to acute stress prompts a reallocation of resources to a salience network, promoting fear and vigilance, at the cost of an executive control network. After stress subsides, resource allocation to these two networks reverses, which normalizes emotional reactivity and enhances higher-order cognitive processes important for long-term survival.

  17. Meta-Analysis in Human Neuroimaging: Computational Modeling of Large-Scale Databases

    PubMed Central

    Fox, Peter T.; Lancaster, Jack L.; Laird, Angela R.; Eickhoff, Simon B.

    2016-01-01

    Spatial normalization—applying standardized coordinates as anatomical addresses within a reference space—was introduced to human neuroimaging research nearly 30 years ago. Over these three decades, an impressive series of methodological advances have adopted, extended, and popularized this standard. Collectively, this work has generated a methodologically coherent literature of unprecedented rigor, size, and scope. Large-scale online databases have compiled these observations and their associated meta-data, stimulating the development of meta-analytic methods to exploit this expanding corpus. Coordinate-based meta-analytic methods have emerged and evolved in rigor and utility. Early methods computed cross-study consensus, in a manner roughly comparable to traditional (nonimaging) meta-analysis. Recent advances now compute coactivation-based connectivity, connectivity-based functional parcellation, and complex network models powered from data sets representing tens of thousands of subjects. Meta-analyses of human neuroimaging data in large-scale databases now stand at the forefront of computational neurobiology. PMID:25032500

  18. Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution.

    PubMed

    Ghedin, Elodie; Sengamalay, Naomi A; Shumway, Martin; Zaborsky, Jennifer; Feldblyum, Tamara; Subbu, Vik; Spiro, David J; Sitz, Jeff; Koo, Hean; Bolotov, Pavel; Dernovoy, Dmitry; Tatusova, Tatiana; Bao, Yiming; St George, Kirsten; Taylor, Jill; Lipman, David J; Fraser, Claire M; Taubenberger, Jeffery K; Salzberg, Steven L

    2005-10-20

    Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.

  19. 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.

  20. 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.

  1. A Large-Scale, Energetic Model of Cardiovascular Homeostasis Predicts Dynamics of Arterial Pressure in Humans

    PubMed Central

    Roytvarf, Alexander; Shusterman, Vladimir

    2008-01-01

    The energetic balance of forces in the cardiovascular system is vital to the stability of blood flow to all physiological systems in mammals. Yet, a large-scale, theoretical model, summarizing the energetic balance of major forces in a single, mathematically closed system has not been described. Although a number of computer simulations have been successfully performed with the use of analog models, the analysis of energetic balance of forces in such models is obscured by a big number of interacting elements. Hence, the goal of our study was to develop a theoretical model that represents large-scale, energetic balance in the cardiovascular system, including the energies of arterial pressure wave, blood flow, and the smooth muscle tone of arterial walls. Because the emphasis of our study was on tracking beat-to-beat changes in the balance of forces, we used a simplified representation of the blood pressure wave as a trapezoidal pressure-pulse with a strong-discontinuity leading front. This allowed significant reduction in the number of required parameters. Our approach has been validated using theoretical analysis, and its accuracy has been confirmed experimentally. The model predicted the dynamics of arterial pressure in human subjects undergoing physiological tests and provided insights into the relationships between arterial pressure and pressure wave velocity. PMID:18269976

  2. 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.

  3. Investigation of the large-scale functional brain networks modulated by acupuncture.

    PubMed

    Feng, Yuanyuan; Bai, Lijun; Ren, Yanshuang; Wang, Hu; Liu, Zhenyu; Zhang, Wensheng; Tian, Jie

    2011-09-01

    Previous neuroimaging studies have primarily focused on the neural activities involving the acute effects of acupuncture. Considering that acupuncture can induce long-lasting effects, several researchers have begun to pay attention to the sustained effects of acupuncture on the resting brain. Most of these researchers adopted functional connectivity analysis based on one or a few preselected brain regions and demonstrated various function-guided brain networks underlying the specific effect of acupuncture. Few have investigated how these brain networks interacted at the whole-brain level. In this study, we sought to investigate the functional correlations throughout the entire brain following acupuncture at acupoint ST36 (ACUP) in comparison with acupuncture at nearby nonacupoint (SHAM). We divided the whole brain into 90 regions and constructed functional brain network for each condition. Then we examined the network hubs and identified statistically significant differences in functional correlations between the two conditions. Following ACUP, but not SHAM, the limbic/paralimbic regions such as the amygdala, hippocampus and anterior cingulate gyrus emerged as network hubs. For direct comparisons, increased correlations for ACUP compared to SHAM were primarily related with the limbic/paralimbic and subcortical regions such as the insula, amygdala, anterior cingulate gyrus, and thalamus, whereas decreased correlations were mainly related with the sensory and frontal cortex. The heterogeneous modulation patterns between the two conditions may relate to the functional specific modulatory effects of acupuncture. The preliminary findings may help us to better understand the long-lasting effects of acupuncture on the entire resting brain, as well as the neurophysiological mechanisms underlying acupuncture.

  4. Sleep Deprivation Makes the Young Brain Resemble the Elderly Brain: A Large-Scale Brain Networks Study.

    PubMed

    Zhou, Xinqi; Wu, Taoyu; Yu, Jing; Lei, Xu

    2017-02-01

    Decreased cognition performance and impaired brain function are similar results of sleep deprivation (SD) and aging, according to mounted supporting evidence. Some investigators even proposed SD as a model of aging. However, few direct comparisons were ever explored between the effects of SD and aging by network module analysis with the resting-state functional magnetic resonance imaging. In this study, both within-module and between-module (BT) connectivities were calculated in the whole brain to describe a complete picture of brain networks' functional connectivity among three groups (young normal sleep, young SD, and old group). The results showed that the BT connectivities in subcortical and cerebellar networks were significantly declined in both the young SD group and old group. There were six other networks, that is, ventral attention, dorsal attention, default mode, auditory, cingulo-opercular, and memory retrieval networks, significantly influenced by aging. Therefore, we speculated that the effects of SD on the young group can be regarded as a simplified model of aging. Moreover, this provided a possible explanation, that is, the old were more tolerable for SD than the young. However, SD may not be a considerable model for aging when discussing the brain regions related to those SD-uninfluenced networks.

  5. Large-Scale Analysis of Gene Expression and Connectivity in the Rodent Brain: Insights through Data Integration

    PubMed Central

    French, Leon; Tan, Powell Patrick Cheng; Pavlidis, Paul

    2011-01-01

    Recent research in C. elegans and the rodent has identified correlations between gene expression and connectivity. Here we extend this type of approach to examine complex patterns of gene expression in the rodent brain in the context of regional brain connectivity and differences in cellular populations. Using multiple large-scale data sets obtained from public sources, we identified two novel patterns of mouse brain gene expression showing a strong degree of anti-correlation, and relate this to multiple data modalities including macroscale connectivity. We found that these signatures are associated with differences in expression of neuronal and oligodendrocyte markers, suggesting they reflect regional differences in cellular populations. We also find that the expression level of these genes is correlated with connectivity degree, with regions expressing the neuron-enriched pattern having more incoming and outgoing connections with other regions. Our results exemplify what is possible when increasingly detailed large-scale cell- and gene-level data sets are integrated with connectivity data. PMID:21863139

  6. Pattern classification of large-scale functional brain networks: identification of informative neuroimaging markers for epilepsy.

    PubMed

    Zhang, Jie; Cheng, Wei; Wang, ZhengGe; Zhang, ZhiQiang; Lu, WenLian; Lu, GuangMing; Feng, Jianfeng

    2012-01-01

    The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology

  7. 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

  8. Communication efficiency and congestion of signal traffic in large-scale brain networks.

    PubMed

    Mišić, Bratislav; Sporns, Olaf; McIntosh, Anthony R

    2014-01-01

    The complex connectivity of the cerebral cortex suggests that inter-regional communication is a primary function. Using computational modeling, we show that anatomical connectivity may be a major determinant for global information flow in brain networks. A macaque brain network was implemented as a communication network in which signal units flowed between grey matter nodes along white matter paths. Compared to degree-matched surrogate networks, information flow on the macaque brain network was characterized by higher loss rates, faster transit times and lower throughput, suggesting that neural connectivity may be optimized for speed rather than fidelity. Much of global communication was mediated by a "rich club" of hub regions: a sub-graph comprised of high-degree nodes that are more densely interconnected with each other than predicted by chance. First, macaque communication patterns most closely resembled those observed for a synthetic rich club network, but were less similar to those seen in a synthetic small world network, suggesting that the former is a more fundamental feature of brain network topology. Second, rich club regions attracted the most signal traffic and likewise, connections between rich club regions carried more traffic than connections between non-rich club regions. Third, a number of rich club regions were significantly under-congested, suggesting that macaque connectivity actively shapes information flow, funneling traffic towards some nodes and away from others. Together, our results indicate a critical role of the rich club of hub nodes in dynamic aspects of global brain communication.

  9. A statistical model for brain networks inferred from large-scale electrophysiological signals.

    PubMed

    Obando, Catalina; De Vico Fallani, Fabrizio

    2017-03-01

    Network science has been extensively developed to characterize the structural properties of complex systems, including brain networks inferred from neuroimaging data. As a result of the inference process, networks estimated from experimentally obtained biological data represent one instance of a larger number of realizations with similar intrinsic topology. A modelling approach is therefore needed to support statistical inference on the bottom-up local connectivity mechanisms influencing the formation of the estimated brain networks. Here, we adopted a statistical model based on exponential random graph models (ERGMs) to reproduce brain networks, or connectomes, estimated by spectral coherence between high-density electroencephalographic (EEG) signals. ERGMs are made up by different local graph metrics, whereas the parameters weight the respective contribution in explaining the observed network. We validated this approach in a dataset of N = 108 healthy subjects during eyes-open (EO) and eyes-closed (EC) resting-state conditions. Results showed that the tendency to form triangles and stars, reflecting clustering and node centrality, better explained the global properties of the EEG connectomes than other combinations of graph metrics. In particular, the synthetic networks generated by this model configuration replicated the characteristic differences found in real brain networks, with EO eliciting significantly higher segregation in the alpha frequency band (8-13 Hz) than EC. Furthermore, the fitted ERGM parameter values provided complementary information showing that clustering connections are significantly more represented from EC to EO in the alpha range, but also in the beta band (14-29 Hz), which is known to play a crucial role in cortical processing of visual input and externally oriented attention. Taken together, these findings support the current view of the functional segregation and integration of the brain in terms of modules and hubs, and provide a

  10. Criticality in Large-Scale Brain fMRI Dynamics Unveiled by a Novel Point Process Analysis

    PubMed Central

    Tagliazucchi, Enzo; Balenzuela, Pablo; Fraiman, Daniel; Chialvo, Dante R.

    2012-01-01

    Functional magnetic resonance imaging (fMRI) techniques have contributed significantly to our understanding of brain function. Current methods are based on the analysis of gradual and continuous changes in the brain blood oxygenated level dependent (BOLD) signal. Departing from that approach, recent work has shown that equivalent results can be obtained by inspecting only the relatively large amplitude BOLD signal peaks, suggesting that relevant information can be condensed in discrete events. This idea is further explored here to demonstrate how brain dynamics at resting state can be captured just by the timing and location of such events, i.e., in terms of a spatiotemporal point process. The method allows, for the first time, to define a theoretical framework in terms of an order and control parameter derived from fMRI data, where the dynamical regime can be interpreted as one corresponding to a system close to the critical point of a second order phase transition. The analysis demonstrates that the resting brain spends most of the time near the critical point of such transition and exhibits avalanches of activity ruled by the same dynamical and statistical properties described previously for neuronal events at smaller scales. Given the demonstrated functional relevance of the resting state brain dynamics, its representation as a discrete process might facilitate large-scale analysis of brain function both in health and disease. PMID:22347863

  11. Large scale brain functional networks support sentence comprehension: evidence from both explicit and implicit language tasks.

    PubMed

    Zhu, Zude; Fan, Yuanyuan; Feng, Gangyi; Huang, Ruiwang; Wang, Suiping

    2013-01-01

    Previous studies have indicated that sentences are comprehended via widespread brain regions in the fronto-temporo-parietal network in explicit language tasks (e.g., semantic congruency judgment tasks), and through restricted temporal or frontal regions in implicit language tasks (e.g., font size judgment tasks). This discrepancy has raised questions regarding a common network for sentence comprehension that acts regardless of task effect and whether different tasks modulate network properties. To this end, we constructed brain functional networks based on 27 subjects' fMRI data that was collected while performing explicit and implicit language tasks. We found that network properties and network hubs corresponding to the implicit language task were similar to those associated with the explicit language task. We also found common hubs in occipital, temporal and frontal regions in both tasks. Compared with the implicit language task, the explicit language task resulted in greater global efficiency and increased integrated betweenness centrality of the left inferior frontal gyrus, which is a key region related to sentence comprehension. These results suggest that brain functional networks support both explicit and implicit sentence comprehension; in addition, these two types of language tasks may modulate the properties of brain functional networks.

  12. 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

  13. Genomic divergences among cattle, dog and human estimated from large-scale alignments of genomic sequences

    PubMed Central

    Liu, George E; Matukumalli, Lakshmi K; Sonstegard, Tad S; Shade, Larry L; Van Tassell, Curtis P

    2006-01-01

    Background Approximately 11 Mb of finished high quality genomic sequences were sampled from cattle, dog and human to estimate genomic divergences and their regional variation among these lineages. Results Optimal three-way multi-species global sequence alignments for 84 cattle clones or loci (each >50 kb of genomic sequence) were constructed using the human and dog genome assemblies as references. Genomic divergences and substitution rates were examined for each clone and for various sequence classes under different functional constraints. Analysis of these alignments revealed that the overall genomic divergences are relatively constant (0.32–0.37 change/site) for pairwise comparisons among cattle, dog and human; however substitution rates vary across genomic regions and among different sequence classes. A neutral mutation rate (2.0–2.2 × 10(-9) change/site/year) was derived from ancestral repetitive sequences, whereas the substitution rate in coding sequences (1.1 × 10(-9) change/site/year) was approximately half of the overall rate (1.9–2.0 × 10(-9) change/site/year). Relative rate tests also indicated that cattle have a significantly faster rate of substitution as compared to dog and that this difference is about 6%. Conclusion This analysis provides a large-scale and unbiased assessment of genomic divergences and regional variation of substitution rates among cattle, dog and human. It is expected that these data will serve as a baseline for future mammalian molecular evolution studies. PMID:16759380

  14. Large Scale 7436-bp Deletions in Human Sperm Mitochondrial DNA with Spermatozoa Dysfunction and Male Infertility

    PubMed Central

    Ambulkar, Prafulla S.; Waghmare, Jwalant E.; Chaudhari, Ajay R.; Wankhede, Vandana R.; Tarnekar, Aaditya M.; Shende, Moreshwar R.

    2016-01-01

    Introduction Mitochondria and mitochondrial DNA are essential to sperm motility and fertility. It controls growth, development and differentiation through oxidation energy supply. Mitochondrial (mtDNA) deletions or mutation are frequently attributed to defects of sperm motility and finally these deletions lead to sperm dysfunction and causes infertility in male. Aim To investigate the correlation between large scale 7436-bp deletions in sperm mtDNA and non-motility of sperm in asthenozoospermia and Oligoasthenoteratozoospermia (OAT) infertile men. Materials and Methods The present prospective study was carried out in Human Genetic Division, Department of Anatomy, Mahatma Gandhi Institute of Medical Sciences, Sevagram from June 2014 to July 2016. We have studied 110 asthenozoospermia and OAT infertile men whose semen profile indicated abnormal motility and 50 normal fertile controls. Of 110 infertile men, 70 had asthenozoospermia and 40 had OAT. Fractionations of spermatozoa were done in each semen sample on the basis of their motility by percoll gradients discontinuous technique. Long-range PCR was used for detection of 7436-bp deletions in sperm mtDNA and was confirmed by primer shift technique. Results Overall eight subjects (8/110; 7.2%) of which six (6/70; 8.57%) asthenozoospermia and two (2/40; 5%) OAT had shown deletions of 7436-bp. In 40% percoll fraction had more non-motile spermatozoa than 80% percoll fraction. The non-motile spermatozoa in 40% percoll fractions showed more mtDNA deletions (7.2%) than the motile spermatozoa in 80% percoll fraction (2.7%). The sequencing of flanking regions of deleted mtDNA confirmed 7436-bp deletions. Interestingly, no deletions were found in control subjects. Conclusion Though, the frequency of 7436-bp deletions in sperm mtDNA was low in infertile cases but meaningful indications were there when results were compared with controls. It is indicated that large scale deletions 7436-bp of mtDNA is associated with abnormal

  15. Unsupervised learning framework for large-scale flight data analysis of cockpit human machine interaction issues

    NASA Astrophysics Data System (ADS)

    Vaidya, Abhishek B.

    As the level of automation within an aircraft increases, the interactions between the pilot and autopilot play a crucial role in its proper operation. Issues with human machine interactions (HMI) have been cited as one of the main causes behind many aviation accidents. Due to the complexity of such interactions, it is challenging to identify all possible situations and develop the necessary contingencies. In this thesis, we propose a data-driven analysis tool to identify potential HMI issues in large-scale Flight Operational Quality Assurance (FOQA) dataset. The proposed tool is developed using a multi-level clustering framework, where a set of basic clustering techniques are combined with a consensus-based approach to group HMI events and create a data-driven model from the FOQA data. The proposed framework is able to effectively compress a large dataset into a small set of representative clusters within a data-driven model, enabling subject matter experts to effectively investigate identified potential HMI issues.

  16. 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

  17. 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.

  18. Large Scale Functional Brain Networks Underlying Temporal Integration of Audio-Visual Speech Perception: An EEG Study.

    PubMed

    Kumar, G Vinodh; Halder, Tamesh; Jaiswal, Amit K; Mukherjee, Abhishek; Roy, Dipanjan; Banerjee, Arpan

    2016-01-01

    Observable lip movements of the speaker influence perception of auditory speech. A classical example of this influence is reported by listeners who perceive an illusory (cross-modal) speech sound (McGurk-effect) when presented with incongruent audio-visual (AV) speech stimuli. Recent neuroimaging studies of AV speech perception accentuate the role of frontal, parietal, and the integrative brain sites in the vicinity of the superior temporal sulcus (STS) for multisensory speech perception. However, if and how does the network across the whole brain participates during multisensory perception processing remains an open question. We posit that a large-scale functional connectivity among the neural population situated in distributed brain sites may provide valuable insights involved in processing and fusing of AV speech. Varying the psychophysical parameters in tandem with electroencephalogram (EEG) recordings, we exploited the trial-by-trial perceptual variability of incongruent audio-visual (AV) speech stimuli to identify the characteristics of the large-scale cortical network that facilitates multisensory perception during synchronous and asynchronous AV speech. We evaluated the spectral landscape of EEG signals during multisensory speech perception at varying AV lags. Functional connectivity dynamics for all sensor pairs was computed using the time-frequency global coherence, the vector sum of pairwise coherence changes over time. During synchronous AV speech, we observed enhanced global gamma-band coherence and decreased alpha and beta-band coherence underlying cross-modal (illusory) perception compared to unisensory perception around a temporal window of 300-600 ms following onset of stimuli. During asynchronous speech stimuli, a global broadband coherence was observed during cross-modal perception at earlier times along with pre-stimulus decreases of lower frequency power, e.g., alpha rhythms for positive AV lags and theta rhythms for negative AV lags. Thus, our

  19. Large Scale Functional Brain Networks Underlying Temporal Integration of Audio-Visual Speech Perception: An EEG Study

    PubMed Central

    Kumar, G. Vinodh; Halder, Tamesh; Jaiswal, Amit K.; Mukherjee, Abhishek; Roy, Dipanjan; Banerjee, Arpan

    2016-01-01

    Observable lip movements of the speaker influence perception of auditory speech. A classical example of this influence is reported by listeners who perceive an illusory (cross-modal) speech sound (McGurk-effect) when presented with incongruent audio-visual (AV) speech stimuli. Recent neuroimaging studies of AV speech perception accentuate the role of frontal, parietal, and the integrative brain sites in the vicinity of the superior temporal sulcus (STS) for multisensory speech perception. However, if and how does the network across the whole brain participates during multisensory perception processing remains an open question. We posit that a large-scale functional connectivity among the neural population situated in distributed brain sites may provide valuable insights involved in processing and fusing of AV speech. Varying the psychophysical parameters in tandem with electroencephalogram (EEG) recordings, we exploited the trial-by-trial perceptual variability of incongruent audio-visual (AV) speech stimuli to identify the characteristics of the large-scale cortical network that facilitates multisensory perception during synchronous and asynchronous AV speech. We evaluated the spectral landscape of EEG signals during multisensory speech perception at varying AV lags. Functional connectivity dynamics for all sensor pairs was computed using the time-frequency global coherence, the vector sum of pairwise coherence changes over time. During synchronous AV speech, we observed enhanced global gamma-band coherence and decreased alpha and beta-band coherence underlying cross-modal (illusory) perception compared to unisensory perception around a temporal window of 300–600 ms following onset of stimuli. During asynchronous speech stimuli, a global broadband coherence was observed during cross-modal perception at earlier times along with pre-stimulus decreases of lower frequency power, e.g., alpha rhythms for positive AV lags and theta rhythms for negative AV lags. Thus

  20. Attentional load modulates large-scale functional brain connectivity beyond the core attention networks.

    PubMed

    Alnæs, Dag; Kaufmann, Tobias; Richard, Geneviève; Duff, Eugene P; Sneve, Markus H; Endestad, Tor; Nordvik, Jan Egil; Andreassen, Ole A; Smith, Stephen M; Westlye, Lars T

    2015-04-01

    In line with the notion of a continuously active and dynamic brain, functional networks identified during rest correspond with those revealed by task-fMRI. Characterizing the dynamic cross-talk between these network nodes is key to understanding the successful implementation of effortful cognitive processing in healthy individuals and its breakdown in a variety of conditions involving aberrant brain biology and cognitive dysfunction. We employed advanced network modeling on fMRI data collected during a task involving sustained attentive tracking of objects at two load levels and during rest. Using multivariate techniques, we demonstrate that attentional load levels can be significantly discriminated, and from a resting-state condition, the accuracy approaches 100%, by means of estimates of between-node functional connectivity. Several network edges were modulated during task engagement: The dorsal attention network increased connectivity with a visual node, while decreasing connectivity with motor and sensory nodes. Also, we observed a decoupling between left and right hemisphere dorsal visual streams. These results support the notion of dynamic network reconfigurations based on attentional effort. No simple correspondence between node signal amplitude change and node connectivity modulations was found, thus network modeling provides novel information beyond what is revealed by conventional task-fMRI analysis. The current decoding of attentional states confirms that edge connectivity contains highly predictive information about the mental state of the individual, and the approach shows promise for the utilization in clinical contexts.

  1. Dysfunction of Large-Scale Brain Networks in Schizophrenia: A Meta-analysis of Resting-State Functional Connectivity.

    PubMed

    Dong, Debo; Wang, Yulin; Chang, Xuebin; Luo, Cheng; Yao, Dezhong

    2017-03-11

    Schizophrenia is a complex mental disorder with disorganized communication among large-scale brain networks, as demonstrated by impaired resting-state functional connectivity (rsFC). Individual rsFC studies, however, vary greatly in their methods and findings. We searched for consistent patterns of network dysfunction in schizophrenia by using a coordinate-based meta-analysis. Fifty-six seed-based voxel-wise rsFC datasets from 52 publications (2115 patients and 2297 healthy controls) were included in this meta-analysis. Then, coordinates of seed regions of interest (ROI) and between-group effects were extracted and coded. Seed ROIs were categorized into seed networks by their location within an a priori template. Multilevel kernel density analysis was used to identify brain networks in which schizophrenia was linked to hyper-connectivity or hypo-connectivity with each a priori network. Our results showed that schizophrenia was characterized by hypo-connectivity within the default network (DN, self-related thought), affective network (AN, emotion processing), ventral attention network (VAN, processing of salience), thalamus network (TN, gating information) and somatosensory network (SS, involved in sensory and auditory perception). Additionally, hypo-connectivity between the VAN and TN, VAN and DN, VAN and frontoparietal network (FN, external goal-directed regulation), FN and TN, and FN and DN were found in schizophrenia. Finally, the only instance of hyper-connectivity in schizophrenia was observed between the AN and VAN. Our meta-analysis motivates an empirical foundation for a disconnected large-scale brain networks model of schizophrenia in which the salience processing network (VAN) plays the core role, and its imbalanced communication with other functional networks may underlie the core difficulty of patients to differentiate self-representation (inner world) and environmental salience processing (outside world).

  2. 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.

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

    USGS Publications Warehouse

    Leu, Matthias

    2003-01-01

    Background Humans have dramatically altered wildlands in the western United States over the past 100 years by using these lands and the resources they provide. Anthropogenic changes to the landscape, such as urban expansion and development of rural areas, influence the number and kinds of plants and wildlife that remain. In addition, western ecosystems are also affected by roads, powerlines, and other networks and land uses necessary to maintain human populations. The cumulative impacts of human presence and actions on a landscape are called the "human footprint." These impacts may affect plants and wildlife by increasing the number of synanthropic (species that benefit from human activities) bird and mammal predators and facilitating their movements through the landscape or by creating unsuitable habitats. These actions can impact plants and wildlife to such an extent that the persistence of populations or entire species is questionable. For example, greater sage-grouse (Centrocercus urophasianus) once were widespread throughout the Great Basin, but now are a focus of conservation concern because populations have declined for the past three decades across most of their range. At the USGS Forest and Rangeland Ecosystem Science Center, we are developing spatial models to better understand potential influences of the human footprint on shrubland ecosystems and associated wildlife in the western United States.

  4. 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…

  5. Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization

    PubMed Central

    Chang, Luke J.; Banich, Marie T.; Wager, Tor D.; Yarkoni, Tal

    2016-01-01

    The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2–4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. SIGNIFICANCE STATEMENT Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex

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

    PubMed Central

    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

  7. 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.

  8. 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.

  9. 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

  10. A Triple Network Connectivity Study of Large-Scale Brain Systems in Cognitively Normal APOE4 Carriers

    PubMed Central

    Wu, Xia; Li, Qing; Yu, Xinyu; Chen, Kewei; Fleisher, Adam S.; Guo, Xiaojuan; Zhang, Jiacai; Reiman, Eric M.; Yao, Li; Li, Rui

    2016-01-01

    The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer’s disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach. Our findings indicated altered within-network connectivity that suggests future cognitive decline risk, and preserved between-network connectivity that may support their current preserved cognition in the cognitively normal APOE4 allele carriers. The study provides novel sights into our understanding of the risk factors for AD and their influence on the triple network model of major psychopathology. PMID:27733827

  11. 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

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

    PubMed

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

    2014-11-01

    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.

  13. Large-scale purification of IgM from human sera. Comparison of three optimized procedures utilizing protein A chromatography.

    PubMed

    Mauch, H; Kümel, G; Hammer, H J

    1980-01-01

    for the preparation of gram amounts of IgM from human sera sedimentation at 100,000 g or treatment with ZnSO4 of the redissolved "euglobulin"-precipitate was compared to direct precipitation from the clarified serum by boric acid. Three alternative large scale purification procedures were developed, leading to an IgM-sample characterized as pure by various criteria. Inclusion of protein A chromatography proved to enhance the yield very considerably.

  14. 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

  15. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells

    PubMed Central

    Jong, Ambrose Y.; Wu, Chun-Hua; Li, Jingbo; Sun, Jianping; Fabbri, Muller; Wayne, Alan S.; Seeger, Robert C.

    2017-01-01

    ABSTRACT Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically. In this report, we present a simple, robust, and cost-effective method to isolate a large quantity of NK EVs. After propagating and activating NK cells ex vivo and then incubating them in exosome-free medium for 48 h, EVs were isolated using a polymer precipitation method. The isolated vesicles contain the tetraspanin CD63, an EV marker, and associated proteins (fibronectin), but are devoid of cytochrome C, a cytoplasmic marker. Nanoparticle tracking analysis showed a size distribution between 100 and 200 nm while transmission electron microscopy imaging displayed vesicles with an oval shape and comparable sizes, fulfilling the definition of EV. Importantly, isolated EV fractions were cytotoxic against cancer cells. Furthermore, our results demonstrate for the first time that isolated activated NK (aNK) cell EVs contain the cytotoxic proteins perforin, granulysin, and granzymes A and B, incorporated from the aNK cells. Activation of caspase -3, -7 and -9 was detected in cancer cells incubated with aNK EVs, and caspase inhibitors blocked aNK EV-induced cytotoxicity, suggesting that aNK EVs activate caspase pathways in target cells. The ability to isolate functional aNK EVs on a large scale may lead to new clinical applications. Abbreviations: NK: natural killer cells; activated NK (aNK) cells; EVs: extracellular vesicles; ALL: acute lymphoblastic leukaemia; aAPC: artificial antigen-presenting cell; TEM: transmission

  16. Influence of wiring cost on the large-scale architecture of human cortical connectivity.

    PubMed

    Samu, David; Seth, Anil K; Nowotny, Thomas

    2014-04-01

    In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained ('random'), connection length preserving ('spatial'), and connection length optimised ('reduced') surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast

  17. 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

    2014-05-06

    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.

  18. 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

    2015-07-20

    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.

  19. Large Scale Immune Profiling of Infected Humans and Goats Reveals Differential Recognition of Brucella melitensis Antigens

    PubMed Central

    Liang, Li; Leng, Diana; Burk, Chad; Nakajima-Sasaki, Rie; Kayala, Matthew A.; Atluri, Vidya L.; Pablo, Jozelyn; Unal, Berkay; Ficht, Thomas A.; Gotuzzo, Eduardo; Saito, Mayuko; Morrow, W. John W.; Liang, Xiaowu; Baldi, Pierre; Gilman, Robert H.; Vinetz, Joseph M.; Tsolis, Renée M.; Felgner, Philip L.

    2010-01-01

    Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host. PMID:20454614

  20. Large scale immune profiling of infected humans and goats reveals differential recognition of Brucella melitensis antigens.

    PubMed

    Liang, Li; Leng, Diana; Burk, Chad; Nakajima-Sasaki, Rie; Kayala, Matthew A; Atluri, Vidya L; Pablo, Jozelyn; Unal, Berkay; Ficht, Thomas A; Gotuzzo, Eduardo; Saito, Mayuko; Morrow, W John W; Liang, Xiaowu; Baldi, Pierre; Gilman, Robert H; Vinetz, Joseph M; Tsolis, Renée M; Felgner, Philip L

    2010-05-04

    Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.

  1. 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

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

    USGS Publications Warehouse

    Leu, M.; Hanser, S.E.; Knick, S.T.

    2008-01-01

    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

  3. 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

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

    PubMed

    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.

  5. 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.

  6. Large-scale oscillation of structure-related DNA sequence features in human chromosome 21

    NASA Astrophysics Data System (ADS)

    Li, Wentian; Miramontes, Pedro

    2006-08-01

    Human chromosome 21 is the only chromosome in the human genome that exhibits oscillation of the (G+C) content of a cycle length of hundreds kilobases (kb) ( 500kb near the right telomere). We aim at establishing the existence of a similar periodicity in structure-related sequence features in order to relate this (G+C)% oscillation to other biological phenomena. The following quantities are shown to oscillate with the same 500kb periodicity in human chromosome 21: binding energy calculated by two sets of dinucleotide-based thermodynamic parameters, AA/TT and AAA/TTT bi- and tri-nucleotide density, 5'-TA-3' dinucleotide density, and signal for 10- or 11-base periodicity of AA/TT or AAA/TTT. These intrinsic quantities are related to structural features of the double helix of DNA molecules, such as base-pair binding, untwisting or unwinding, stiffness, and a putative tendency for nucleosome formation.

  7. 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.

  8. 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.

  9. 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

  10. Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry

    PubMed Central

    Sadowski, Tomasz; Klose, Christian; Gerl, Mathias J.; Wójcik-Maciejewicz, Anna; Herzog, Ronny; Simons, Kai; Reich, Adam; Surma, Michal A.

    2017-01-01

    The lipid composition of human skin is essential for its function; however the simultaneous quantification of a wide range of stratum corneum (SC) and sebaceous lipids is not trivial. We developed and validated a quantitative high-throughput shotgun mass spectrometry-based platform for lipid analysis of tape-stripped SC skin samples. It features coverage of 16 lipid classes; total quantification to the level of individual lipid molecules; high reproducibility and high-throughput capabilities. With this method we conducted a large lipidomic survey of 268 human SC samples, where we investigated the relationship between sampling depth and lipid composition, lipidome variability in samples from 14 different sampling sites on the human body and finally, we assessed the impact of age and sex on lipidome variability in 104 healthy subjects. We found sebaceous lipids to constitute an abundant component of the SC lipidome as they diffuse into the topmost SC layers forming a gradient. Lipidomic variability with respect to sampling depth, site and subject is considerable, and mainly accredited to sebaceous lipids, while stratum corneum lipids vary less. This stresses the importance of sampling design and the role of sebaceous lipids in skin studies. PMID:28266621

  11. Development of a large scale human complement source for use in bacterial immunoassays.

    PubMed

    Brookes, Charlotte; Kuisma, Eeva; Alexander, Frances; Allen, Lauren; Tipton, Thomas; Ram, Sanjay; Gorringe, Andrew; Taylor, Stephen

    2013-05-31

    The serum bactericidal assay is the correlate of protection for meningococcal disease but the use and comparison of functional immunological assays for the assessment of meningococcal vaccines is complicated by the sourcing of human complement. This is due to high levels of immunity in the population acquired through natural meningococcal carriage and means that many individuals must be screened to find donors with suitably low bactericidal titres against the target strain. The use of different donors for each meningococcal strain means that comparisons of assay responses between strains and between laboratories is difficult. We have developed a method for IgG-depletion of 300 ml batches of pooled human lepirudin-derived plasma using Protein G sepharose affinity chromatography that retains complement activity. However, IgG-depletion also removed C1q. This was also eluted from the affinity matrix, concentrated and added to the complement source. The final complement source retained mean alternative pathway activity of 96.8% and total haemolytic activity of 84.2% in four batches. Complement components C3, C5, properdin and factor H were retained following the process and the IgG-depleted complement was shown to be suitable for use in antibody-mediated complement deposition and serum bactericidal activity assays against serogroup B meningococci. The generation of large IgG-depleted batches of pooled human plasma allows for the comparison of immunological responses to diverse meningococcal strain panels in large clinical trials.

  12. Multi-modal analysis of functional connectivity and cerebral blood flow reveals shared and unique effects of propofol in large-scale brain networks.

    PubMed

    Qiu, Maolin; Scheinost, Dustin; Ramani, Ramachandran; Constable, R Todd

    2017-03-01

    Anesthesia-induced changes in functional connectivity and cerebral blow flow (CBF) in large-scale brain networks have emerged as key markers of reduced consciousness. However, studies of functional connectivity disagree on which large-scale networks are altered or preserved during anesthesia, making it difficult to find a consensus amount studies. Additionally, pharmacological alterations in CBF could amplify or occlude changes in connectivity due to the shared variance between CBF and connectivity. Here, we used data-driven connectivity methods and multi-modal imaging to investigate shared and unique neural correlates of reduced consciousness for connectivity in large-scale brain networks. Rs-fMRI and CBF data were collected from the same subjects during an awake and deep sedation condition induced by propofol. We measured whole-brain connectivity using the intrinsic connectivity distribution (ICD), a method not reliant on pre-defined seed regions, networks of interest, or connectivity thresholds. The shared and unique variance between connectivity and CBF were investigated. Finally, to account for shared variance, we present a novel extension to ICD that incorporates cerebral blood flow (CBF) as a scaling factor in the calculation of global connectivity, labeled CBF-adjusted ICD). We observed altered connectivity in multiple large-scale brain networks including the default mode (DMN), salience, visual, and motor networks and reduced CBF in the DMN, frontoparietal network, and thalamus. Regional connectivity and CBF were significantly correlated during both the awake and propofol condition. Nevertheless changes in connectivity and CBF between the awake and deep sedation condition were only significantly correlated in a subsystem of the DMN, suggesting that, while there is significant shared variance between the modalities, changes due to propofol are relatively unique. Similar, but less significant, results were observed in the CBF-adjusted ICD analysis, providing

  13. 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.

  14. Human Problem Solving in Dynamic Environments. Understanding and Supporting Operators in Large-Scale, Complex Systems

    DTIC Science & Technology

    1987-10-01

    AUTHOR(*) S. CONTRACT OR GRANT NUMBER(*) Richard L. Henneman and William B. Rouse MDA903-2- C -Ol45 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM...n measure Qf c Rlity. The literature review [ Henneman and I’ Rouse 1986] also suggested that an appropriate dependent measure of complexity is the... Henneman , R.L., and W.B. Rouse. Measures of human performance in fault diagnosis tasks. j= Kansactions on Sysems, Man and C .7Xkiat i’. its, SMC-14, (1):99

  15. Large scale DNA sequencing: new challenges emerge--the 2007 Human Genome Variation Society scientific meeting.

    PubMed

    Oetting, William S

    2008-05-01

    The annual scientific meeting of the Human Genome Variation Society (HGVS) was held on 23 October 2007, in San Diego, CA. The major theme of this meeting was "New DNA Sequencing Technologies & Human Genome Variation." A series of speakers provided information on several new technologies that produce DNA sequence data on a scale far beyond what was possible even a few years ago. These new technologies produce up to gigabases of nucleotides on a single run. Already, two individuals have had their entire genome sequenced, resulting in the identification of many novel DNA variants. Several new questions now need to be answered. What impact do these novel variants have on the phenotypes? How are we to associate private variants in a single individual with disease, especially when current association studies require genotyping thousands of individuals? Further work will be required to create methodologies to analyze these variants to determine if they are potentially disease-producing or are phenotypically silent. For the technology to be useful in a medical setting it will be crucial to answer to these questions.

  16. 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

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

    PubMed Central

    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

    2016-01-01

    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

  18. 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.

  19. 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

  20. TALEN-mediated modification of the bovine genome for large-scale production of human serum albumin.

    PubMed

    Moghaddassi, Shaida; Eyestone, Will; Bishop, Colin E

    2014-01-01

    As an initial step towards creating genetically modified cattle as a biopharming source of recombinant human serum albumin (rHSA), we report modification of the bovine albumin (bA) locus by transcription activator-like effector nuclease (TALEN)-stimulated homology-directed repair (HDR). Pedigreed bovine fibroblasts were co-transfected with TALENs and an 11.5-kb human serum albumin (HSA) minigene donor construct, designed to simultaneously disrupt and replace bovine serum albumin (BSA) expression with controlled rHSA expression in both the liver and the milk. Targeted integration of the HSA minigene was confirmed in transfected fibroblasts at a frequency of approximately 11% and transgenic bovine embryos were produced from targeted fibroblasts using somatic cell nuclear transfer (SCNT). The research delineated here lays the foundation for the future generation of transgenic rHSA cattle with the potential to provide a large-scale, reliable, and quality-controlled source of rHSA.

  1. Sequence Diversity and Large-Scale Typing of SNPs in the Human Apolipoprotein E Gene

    PubMed Central

    Nickerson, Deborah A.; Taylor, Scott L.; Fullerton, Stephanie M.; Weiss, Kenneth M.; Clark, Andrew G.; Stengård, Jari H.; Salomaa, Veikko; Boerwinkle, Eric; Sing, Charles F.

    2000-01-01

    A common strategy for genotyping large samples begins with the characterization of human single nucleotide polymorphisms (SNPs) by sequencing candidate regions in a small sample for SNP discovery. This is usually followed by typing in a large sample those sites observed to vary in a smaller sample. We present results from a systematic investigation of variation at the human apolipoprotein E locus (APOE), as well as the evaluation of the two-tiered sampling strategy based on these data. We sequenced 5.5 kb spanning the entire APOE genomic region in a core sample of 72 individuals, including 24 each of African-Americans from Jackson, Mississippi; European-Americans from Rochester, Minnesota; and Europeans from North Karelia, Finland. This sequence survey detected 21 SNPs and 1 multiallelic indel, 14 of which had not been previously reported. Alleles varied in relative frequency among the populations, and 10 sites were polymorphic in only a single population sample. Oligonucleotide ligation assays (OLA) were developed for 20 of these sites (omitting the indel and a closely-linked SNP). These were then scored in 2179 individuals sampled from the same three populations (n = 843, 884, and 452, respectively). Relative allele frequencies were generally consistent with estimates from the core sample, although variation was found in some populations in the larger sample at SNPs that were monomorphic in the corresponding smaller core sample. Site variation in the larger samples showed no systematic deviation from Hardy-Weinberg expectation. The large OLA sample clearly showed that variation in many, but not all, of OLA-typed SNPs is significantly correlated with the classical protein-coding variants, implying that there may be important substructure within the classical ɛ2, ɛ3, and ɛ4 alleles. Comparison of the levels and patterns of polymorphism in the core samples with those estimated for the OLA-typed samples shows how nucleotide diversity is underestimated when

  2. 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

  3. 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.

  4. Large-scale identification of human protein function using topological features of interaction network

    PubMed Central

    Li, Zhanchao; Liu, Zhiqing; Zhong, Wenqian; Huang, Menghua; Wu, Na; Xie, Yun; Dai, Zong; Zou, Xiaoyong

    2016-01-01

    The annotation of protein function is a vital step to elucidate the essence of life at a molecular level, and it is also meritorious in biomedical and pharmaceutical industry. Developments of sequencing technology result in constant expansion of the gap between the number of the known sequences and their functions. Therefore, it is indispensable to develop a computational method for the annotation of protein function. Herein, a novel method is proposed to identify protein function based on the weighted human protein-protein interaction network and graph theory. The network topology features with local and global information are presented to characterise proteins. The minimum redundancy maximum relevance algorithm is used to select 227 optimized feature subsets and support vector machine technique is utilized to build the prediction models. The performance of current method is assessed through 10-fold cross-validation test, and the range of accuracies is from 67.63% to 100%. Comparing with other annotation methods, the proposed way possesses a 50% improvement in the predictive accuracy. Generally, such network topology features provide insights into the relationship between protein functions and network architectures. The source code of Matlab is freely available on request from the authors. PMID:27849060

  5. 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.

  6. 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

    2015-11-16

    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.

  7. Large-scale identification of human protein function using topological features of interaction network

    NASA Astrophysics Data System (ADS)

    Li, Zhanchao; Liu, Zhiqing; Zhong, Wenqian; Huang, Menghua; Wu, Na; Xie, Yun; Dai, Zong; Zou, Xiaoyong

    2016-11-01

    The annotation of protein function is a vital step to elucidate the essence of life at a molecular level, and it is also meritorious in biomedical and pharmaceutical industry. Developments of sequencing technology result in constant expansion of the gap between the number of the known sequences and their functions. Therefore, it is indispensable to develop a computational method for the annotation of protein function. Herein, a novel method is proposed to identify protein function based on the weighted human protein-protein interaction network and graph theory. The network topology features with local and global information are presented to characterise proteins. The minimum redundancy maximum relevance algorithm is used to select 227 optimized feature subsets and support vector machine technique is utilized to build the prediction models. The performance of current method is assessed through 10-fold cross-validation test, and the range of accuracies is from 67.63% to 100%. Comparing with other annotation methods, the proposed way possesses a 50% improvement in the predictive accuracy. Generally, such network topology features provide insights into the relationship between protein functions and network architectures. The source code of Matlab is freely available on request from the authors.

  8. 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

  9. Large-scale Top-down Proteomics of the Human Proteome: Membrane Proteins, Mitochondria, and Senescence*

    PubMed Central

    Catherman, Adam D.; Durbin, Kenneth R.; Ahlf, Dorothy R.; Early, Bryan P.; Fellers, Ryan T.; Tran, John C.; Thomas, Paul M.; Kelleher, Neil L.

    2013-01-01

    Top-down proteomics is emerging as a viable method for the routine identification of hundreds to thousands of proteins. In this work we report the largest top-down study to date, with the identification of 1,220 proteins from the transformed human cell line H1299 at a false discovery rate of 1%. Multiple separation strategies were utilized, including the focused isolation of mitochondria, resulting in significantly improved proteome coverage relative to previous work. In all, 347 mitochondrial proteins were identified, including ∼50% of the mitochondrial proteome below 30 kDa and over 75% of the subunits constituting the large complexes of oxidative phosphorylation. Three hundred of the identified proteins were found to be integral membrane proteins containing between 1 and 12 transmembrane helices, requiring no specific enrichment or modified LC-MS parameters. Over 5,000 proteoforms were observed, many harboring post-translational modifications, including over a dozen proteins containing lipid anchors (some previously unknown) and many others with phosphorylation and methylation modifications. Comparison between untreated and senescent H1299 cells revealed several changes to the proteome, including the hyperphosphorylation of HMGA2. This work illustrates the burgeoning ability of top-down proteomics to characterize large numbers of intact proteoforms in a high-throughput fashion. PMID:24023390

  10. 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

    2013-08-07

    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.

  11. Reconstruction of micron resolution mouse brain surface from large-scale imaging dataset using resampling-based variational model

    PubMed Central

    Li, Jing; Quan, Tingwei; Li, Shiwei; Zhou, Hang; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

    2015-01-01

    Brain surface profile is essential for brain studies, including registration, segmentation of brain structure and drawing neuronal circuits. Recent advances in high-throughput imaging techniques enable imaging whole mouse brain at micron spatial resolution and provide a basis for more fine quantitative studies in neuroscience. However, reconstructing micron resolution brain surface from newly produced neuronal dataset still faces challenges. Most current methods apply global analysis, which are neither applicable to a large imaging dataset nor to a brain surface with an inhomogeneous signal intensity. Here, we proposed a resampling-based variational model for this purpose. In this model, the movement directions of the initial boundary elements are fixed, the final positions of the initial boundary elements that form the brain surface are determined by the local signal intensity. These features assure an effective reconstruction of the brain surface from a new brain dataset. Compared with conventional typical methods, such as level set based method and active contour method, our method significantly increases the recall and precision rates above 97% and is approximately hundreds-fold faster. We demonstrated a fast reconstruction at micron level of the whole brain surface from a large dataset of hundreds of GB in size within 6 hours. PMID:26245266

  12. Evaluation of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury: A Large-Scale Network Analysis Using Network-Based Statistic.

    PubMed

    Kaushal, Mayank; Oni-Orisan, Akinwunmi; Chen, Gang; Li, Wenjun; Leschke, Jack; Ward, B Douglas; Kalinosky, Benjamin; Budde, Matthew D; Schmit, Brian D; Li, Shi-Jiang; Muqeet, Vaishnavi; Kurpad, Shekar N

    2017-03-15

    Large-scale network analysis characterizes the brain as a complex network of nodes and edges to evaluate functional connectivity patterns. The utility of graph-based techniques has been demonstrated in an increasing number of resting-state functional MRI (rs-fMRI) studies in the normal and diseased brain. However, to our knowledge, graph theory has not been used to study the reorganization pattern of resting-state brain networks in patients with traumatic complete spinal cord injury (SCI). In the present analysis, we applied a graph-theoretical approach to explore changes to global brain network architecture as a result of SCI. Fifteen subjects with chronic (> 2 years) complete (American Spinal Injury Association [ASIA] A) cervical SCI and 15 neurologically intact controls were scanned using rs-fMRI. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI) or nodes. The average time series was extracted at each node, and correlation analysis was performed between every pair of nodes. A functional connectivity matrix for each subject was then generated. Subsequently, the matrices were averaged across groups, and network changes were evaluated between groups using the network-based statistic (NBS) method. Our results showed decreased connectivity in a subnetwork of the whole brain in SCI compared with control subjects. Upon further examination, increased connectivity was observed in a subnetwork of the sensorimotor cortex and cerebellum network in SCI. In conclusion, our findings emphasize the applicability of NBS to study functional connectivity architecture in diseased brain states. Further, we show reorganization of large-scale resting-state brain networks in traumatic SCI, with potential prognostic and therapeutic implications.

  13. Large-Scale Metabolite Analysis of Standards and Human Serum by Laser Desorption Ionization Mass Spectrometry from Silicon Nanopost Arrays.

    PubMed

    Korte, Andrew R; Stopka, Sylwia A; Morris, Nicholas; Razunguzwa, Trust; Vertes, Akos

    2016-09-20

    The unique challenges presented by metabolomics have driven the development of new mass spectrometry (MS)-based techniques for small molecule analysis. We have previously demonstrated silicon nanopost arrays (NAPA) to be an effective substrate for laser desorption ionization (LDI) of small molecules for MS. However, the utility of NAPA-LDI-MS for a wide range of metabolite classes has not been investigated. Here we apply NAPA-LDI-MS to the large-scale acquisition of high-resolution mass spectra and tandem mass spectra from a collection of metabolite standards covering a range of compound classes including amino acids, nucleotides, carbohydrates, xenobiotics, lipids, and other classes. In untargeted analysis of metabolite standard mixtures, detection was achieved for 374 compounds and useful MS/MS spectra were obtained for 287 compounds, without individual optimization of ionization or fragmentation conditions. Metabolite detection was evaluated in the context of 31 metabolic pathways, and NAPA-LDI-MS was found to provide detection for 63% of investigated pathway metabolites. Individual, targeted analysis of the 20 common amino acids provided detection of 100% of the investigated compounds, demonstrating that improved coverage is possible through optimization and targeting of individual analytes or analyte classes. In direct analysis of aqueous and organic extracts from human serum samples, spectral features were assigned to a total of 108 small metabolites and lipids. Glucose and amino acids were quantitated within their physiological concentration ranges. The broad coverage demonstrated by this large-scale screening experiment opens the door for use of NAPA-LDI-MS in numerous metabolite analysis applications.

  14. 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

  15. 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.

  16. 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)

  17. 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

  18. 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

  19. Microelectronics, bioinformatics and neurocomputation for massive neuronal recordings in brain circuits with large scale multielectrode array probes.

    PubMed

    Maccione, Alessandro; Gandolfo, Mauro; Zordan, Stefano; Amin, Hayder; Di Marco, Stefano; Nieus, Thierry; Angotzi, Gian Nicola; Berdondini, Luca

    2015-10-01

    Deciphering neural network function in health and disease requires recording from many active neurons simultaneously. Developing approaches to increase their numbers is a major neurotechnological challenge. Parallel to recent advances in optical Ca(2+) imaging, an emerging approach consists in adopting complementary-metal-oxide-semiconductor (CMOS) technology to realize MultiElectrode Array (MEA) devices. By implementing signal conditioning and multiplexing circuits, these devices allow nowadays to record from several thousands of single neurons at sub-millisecond temporal resolution. At the same time, these recordings generate very large data streams which become challenging to analyze. Here, at first we shortly review the major approaches developed for data management and analysis for conventional, low-resolution MEAs. We highlight how conventional computational tools cannot be easily up-scaled to very large electrode array recordings, and custom bioinformatics tools are an emerging need in this field. We then introduce a novel approach adapted for the acquisition, compression and analysis of extracellular signals acquired simultaneously from 4096 electrodes with CMOS MEAs. Finally, as a case study, we describe how this novel large scale recording platform was used to record and analyze extracellular spikes from the ganglion cell layer in the wholemount retina at pan-retinal scale following patterned light stimulation.

  20. 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

  1. Large scale expansion of human umbilical cord cells in a rotating bed system bioreactor for cardiovascular tissue engineering applications.

    PubMed

    Reichardt, Anne; Polchow, Bianca; Shakibaei, Mehdi; Henrich, Wolfgang; Hetzer, Roland; Lueders, Cora

    2013-01-01

    Widespread use of human umbilical cord cells for cardiovascular tissue engineering requires production of large numbers of well-characterized cells under controlled conditions. In current research projects, the expansion of cells to be used to create a tissue construct is usually performed in static cell culture systems which are, however, often not satisfactory due to limitations in nutrient and oxygen supply. To overcome these limitations dynamic cell expansion in bioreactor systems under controllable conditions could be an important tool providing continuous perfusion for the generation of large numbers of viable pre-conditioned cells in a short time period. For this purpose cells derived from human umbilical cord arteries were expanded in a rotating bed system bioreactor for up to 9 days. For a comparative study, cells were cultivated under static conditions in standard culture devices. Our results demonstrated that the microenvironment in the perfusion bioreactor was more favorable than that of the standard cell culture flasks. Data suggested that cells in the bioreactor expanded 39 fold (38.7 ± 6.1 fold) in comparison to statically cultured cells (31.8 ± 3.0 fold). Large-scale production of cells in the bioreactor resulted in more than 3 x 10(8) cells from a single umbilical cord fragment within 9 days. Furthermore cell doubling time was lower in the bioreactor system and production of extracellular matrix components was higher. With this study, we present an appropriate method to expand human umbilical cord artery derived cells with high cellular proliferation rates in a well-defined bioreactor system under GMP conditions.

  2. A Case Study for Large-Scale Human Microbiome Analysis Using JCVI’s Metagenomics Reports (METAREP)

    PubMed Central

    Goll, Johannes; Thiagarajan, Mathangi; Abubucker, Sahar; Huttenhower, Curtis; Yooseph, Shibu; Methé, Barbara A.

    2012-01-01

    As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code

  3. 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.

  4. 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

  5. Modern muddy deposit along the Zhejiang coast in the East China Sea: Response to large-scale human projects

    NASA Astrophysics Data System (ADS)

    Xu, Gang; Liu, Jian; Liu, Shengfa; Wang, Zhongbo; Hu, Gang; Kong, Xianghuai

    2016-11-01

    Grain size and clay minerals in the surface sediment off Zhejiang Province, China, of the East China Sea were analyzed to study changes in grain size, muddy deposit boundary, and major riverine and other derived matters transport paths in the Zhejiang coastal muddy deposit since the impoundment of the Three Gorges Dam and after other large-scale human projects. The results show that the sediment types are mainly silt and mud in the muddy deposit, divided based on the 10% isoline of the sand-sized component. The sources of sediment in the muddy deposit are mainly the Yangtze River and simultaneously supplies from the Qiantang Jiang, Ou Jiang, relict fine-grain matter, and hydrolyzed volcanic rocks around the Zhoushan Islands. The transport and dispersal of sediments in the study area are largely controlled by the Zhejiang-Fujian coastal current and the Taiwan Warm Current and appear seasonally. The contributions from the Ou Jiang, relict matter, local hydrolyzed matter, and the Qiantang Jiang are enlarged owing to the decline of Yangtze suspended matter and the constructions of major human projects in the Hangzhou Bay, respectively. In addition, the sediment grain size exhibits a fining trend because of the influence of the Three Gorges Dam. The boundary of the muddy deposit is relatively stable after the Three Gorges Dam impoundment north of the city of Zhoushan. In contrast, south of the city of Zhoushan the boundary of the muddy deposit lies toward the east because the sediment supply from the relict fine-grained matters resuspended by the Taiwan Warm Current east of the study area. The changes in the grain size and contributions from smaller rivers and other derived matter as well as the boundary of the muddy deposit there will probably become more pronounced in the future.

  6. 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.

  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 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.

  9. Large Scale Gene Expression Meta-Analysis Reveals Tissue-Specific, Sex-Biased Gene Expression in Humans

    PubMed Central

    Mayne, Benjamin T.; Bianco-Miotto, Tina; Buckberry, Sam; Breen, James; Clifton, Vicki; Shoubridge, Cheryl; Roberts, Claire T.

    2016-01-01

    The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases. PMID:27790248

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Large-Scale Overproduction and Purification of Recombinant Histone Deacetylase 8 (HDAC8) from the Human-Pathogenic Flatworm Schistosoma mansoni.

    PubMed

    Marek, Martin; Shaik, Tajith B; Duclaud, Sylvie; Pierce, Raymond J; Romier, Christophe

    2016-01-01

    Epigenetic mechanisms underlie the morphological transformations and shifts in virulence of eukaryotic pathogens. The targeting of epigenetics-driven cellular programs thus represents an Achilles' heel of human parasites. Today, zinc-dependent histone deacetylases (HDACs) belong to the most explored epigenetic drug targets in eukaryotic parasites. Here, we describe an optimized protocol for the large-scale overproduction and purification of recombinant smHDAC8, an emerging epigenetic drug target in the multicellular human-pathogenic flatworm Schistosoma mansoni. The strategy employs the robustness of recombinant expression in Escherichia coli together with initial purification through a poly-histidine affinity tag that can be removed by the thrombin protease. This protocol is divided into two steps: (1) large-scale production of smHDAC8 in E. coli, and (2) purification of the target smHDAC8 protein through multiple purification steps.

  15. Scientific Accomplishments for ARL Brain Structure-Function Couplings Research on Large-Scale Brain Networks from FY11-FY13 (DSI Final Report)

    DTIC Science & Technology

    2014-03-01

    changes in blood flow as a proxy measure of brain activity and electroencephalography (EEG) data that records electrical activity on the scalp that...neuroimaging technologies: Magnetic resonance imaging (MRI) and Electroencephalography (EEG). The first can provide both structural and functional brain data...Michigan, Ann Arbor, and the University of California, San Diego. Electroencephalography (EEG) records the synchronous electrical activity of

  16. Inter- and intrahemispheric dissociations in ideomotor apraxia: a large-scale lesion-symptom mapping study in subacute brain-damaged patients.

    PubMed

    Manuel, Aurelie L; Radman, Narges; Mesot, Delphine; Chouiter, Leila; Clarke, Stephanie; Annoni, Jean-Marie; Spierer, Lucas

    2013-12-01

    Pantomimes of object use require accurate representations of movements and a selection of the most task-relevant gestures. Prominent models of praxis, corroborated by functional neuroimaging studies, predict a critical role for left parietal cortices in pantomime and advance that these areas store representations of tool use. In contrast, lesion data points to the involvement of left inferior frontal areas, suggesting that defective selection of movement features is the cause of pantomime errors. We conducted a large-scale voxel-based lesion-symptom mapping analyses with configural/spatial (CS) and body-part-as-object (BPO) pantomime errors of 150 left and right brain-damaged patients. Our results confirm the left hemisphere dominance in pantomime. Both types of error were associated with damage to left inferior frontal regions in tumor and stroke patients. While CS pantomime errors were associated with left temporoparietal lesions in both stroke and tumor patients, these errors appeared less associated with parietal areas in stroke than in tumor patients and less associated with temporal in tumor than stroke patients. BPO errors were associated with left inferior frontal lesions in both tumor and stroke patients. Collectively, our results reveal a left intrahemispheric dissociation for various aspects of pantomime, but with an unspecific role for inferior frontal regions.

  17. 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.

  18. 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

  19. Large-scale phosphoproteome of human whole saliva using disulfide-thiol interchange covalent chromatography and mass spectrometry.

    PubMed

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

    2010-12-01

    To date, 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 disulfide-thiol interchange chromatography and analysis by nanoflow liquid chromatography and electrospray ionization tandem mass spectrometry (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 that 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 these, 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 previously 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 systemic and oral disease states.

  20. 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.

  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.

    PubMed

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

    2016-04-21

    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. 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.

  3. 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

  4. 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.

  5. 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.

  6. Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging.

    PubMed

    Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; Lu, Guang-Ming; Zuo, Xi-Nian

    2015-10-01

    Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging.

  7. SNP-based large-scale identification of allele-specific gene expression in human B cells.

    PubMed

    Song, Min-Young; Kim, Hye-Eun; Kim, Sun; Choi, Ick-Hwa; Lee, Jong-Keuk

    2012-02-10

    Polymorphism and variations in gene expression provide the genetic basis for human variation. Allelic variation of gene expression, in particular, may play a crucial role in phenotypic variation and disease susceptibility. To identify genes with allelic expression in human cells, we genotyped genomic DNA and cDNA isolated from 31 immortalized B cell lines from three Centre d'Etude du Polymorphisme Humain (CEPH) families using high-density single-nucleotide polymorphism (SNP) chips containing 13,900 exonic SNPs. We identified seven SNPs in five genes with monoallelic expression, 146 SNPs in 125 genes with allelic imbalance in expression with preferentially higher expression of one allele in a heterozygous individual. The monoallelically expressed genes (ERAP2, MDGA1, LOC644422, SDCCAG3P1 and CLTCL1) were regulated by cis-acting, non-imprinted differential allelic control. In addition, all monoallelic gene expression patterns and allelic imbalances in gene expression in B cells were transmitted from parents to offspring in the pedigree, indicating genetic transmission of allelic gene expression. Furthermore, frequent allele substitution, probably due to RNA editing, was also observed in 21 genes in 23 SNPs as well as in 48 SNPs located in regions containing no known genes. In this study, we demonstrated that allelic gene expression is frequently observed in human B cells, and SNP chips are very useful tools for detecting allelic gene expression. Overall, our data provide a valuable framework for better understanding allelic gene expression in human B cells.

  8. Human platelet lysate is an alternative to fetal bovine serum for large-scale expansion of bone marrow-derived mesenchymal stromal cells.

    PubMed

    Gottipamula, Sanjay; Sharma, Archana; Krishnamurthy, Sagar; Majumdar, Anish Sen; Seetharam, Raviraja N

    2012-07-01

    Human platelet lysate (HPL) was evaluated as an alternative to fetal bovine serum (FBS) in large-scale culturing of bone marrow-derived mesenchymal stromal cells (BM-MSCs) for therapeutic applications. Dulbecco's modified Eagle medium (DMEM)of low glucose (LG) and Knock Out (KO) were used with human platelet lysate (HPL) as LG-HPL and KO-HPL, and with FBS as LG-FBS and KO-FBS to culture the BM-MSCs. HPL at 10 % (v/v) supported BM-MSCs growth and subsequent isolation efficiency generated >90 × 10(6) MSCs in LG-HPL. Population doublings (PDs) and population doubling times of LG-HPL and KO-HPL (PDT) were not significantly different but LG-HPL showed a significant clonogenic potential and HPL cultures had an average PDT of 36.5 ± 6.5 h and an average PDs of 5 ± 0.7/passage. BM-MSCs cultured with LG-HPL had significantly higher immunosuppression compared to LG-FBS, but KO-HPL and KO-FBS-grown cultures were not significantly different. HPL is therefore alternative to FBS for large-scale production of BM-MSCs for therapeutic applications.

  9. Quantifying unobserved protein-coding variants in human populations provides a roadmap for large-scale sequencing projects

    PubMed Central

    Zou, James; Valiant, Gregory; Valiant, Paul; Karczewski, Konrad; Chan, Siu On; Samocha, Kaitlin; Lek, Monkol; Sunyaev, Shamil; Daly, Mark; MacArthur, Daniel G.

    2016-01-01

    As new proposals aim to sequence ever larger collection of humans, it is critical to have a quantitative framework to evaluate the statistical power of these projects. We developed a new algorithm, UnseenEst, and applied it to the exomes of 60,706 individuals to estimate the frequency distribution of all protein-coding variants, including rare variants that have not been observed yet in the current cohorts. Our results quantified the number of new variants that we expect to identify as sequencing cohorts reach hundreds of thousands of individuals. With 500K individuals, we find that we expect to capture 7.5% of all possible loss-of-function variants and 12% of all possible missense variants. We also estimate that 2,900 genes have loss-of-function frequency of <0.00001 in healthy humans, consistent with very strong intolerance to gene inactivation. PMID:27796292

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Large-scale expansion of human skin-derived precursor cells (hSKPs) in stirred suspension bioreactors.

    PubMed

    Surrao, Denver C; Boon, Kathryn; Borys, Breanna; Sinha, Sarthak; Kumar, Ranjan; Biernaskie, Jeff; Kallos, Michael S

    2016-12-01

    Human skin-derived precursor cells (hSKPs) are multipotent adult stem cells found in the dermis of human skin. Incorporation of hSKPs into split-thickness skin grafts (STSGs), the current gold standard to treat severe burns or tissue resections, has been proposed as a treatment option to enhance skin wound healing and tissue function. For this approach to be clinically viable substantial quantities of hSKPs are required, which is the rate-limiting step, as only a few thousand hSKPs can be isolated from an autologous skin biopsy without causing donor site morbidity. In order to produce sufficient quantities of clinically viable cells, we have developed a bioprocess capable of expanding hSKPs as aggregates in stirred suspension bioreactors (SSBs). In this study, we found hSKPs from adult donors to expand significantly more (P < 0.05) at 60 rpm in SSBs than in static cultures. Furthermore, the utility of the SSBs, at 60 rpm is demonstrated by serial passaging of hSKPs from a small starting population, which can be isolated from an autologous skin biopsy without causing donor site morbidity. At 60 rpm, aggregates were markedly smaller and did not experience oxygen diffusional limitations, as seen in hSKPs cultured at 40 rpm. While hSKPs also grew at 80 rpm (0.74 Pa) and 100 rpm (1 Pa), they produced smaller aggregates due to high shear stress. The pH of the media in all the SSBs was closer to biological conditions and significantly different (P < 0.05) from static cultures, which recorded acidic pH conditions. The nutrient concentrations of the media in all the SSBs and static cultures did not drop below acceptable limits. Furthermore, there was no significant build-up of waste products to limit hSKP expansion in the SSBs. In addition, hSKP markers were maintained in the 60 rpm SSB as demonstrated by immunocytochemistry. This method of growing hSKPs in a batch culture at 60 rpm in a SSB represents an important first step in developing an

  15. Simplified Large-Scale Refolding, Purification, and Characterization of Recombinant Human Granulocyte-Colony Stimulating Factor in Escherichia coli

    PubMed Central

    Kim, Chang Kyu; Lee, Chi Ho; Lee, Seung-Bae; Oh, Jae-Wook

    2013-01-01

    Granulocyte-colony stimulating factor (G-CSF) is a pleiotropic cytokine that stimulates the development of committed hematopoietic progenitor cells and enhances the functional activity of mature cells. Here, we report a simplified method for fed-batch culture as well as the purification of recombinant human (rh) G-CSF. The new system for rhG-CSF purification was performed using not only temperature shift strategy without isopropyl-l-thio-β-d-galactoside (IPTG) induction but also the purification method by a single step of prep-HPLC after the pH precipitation of the refolded samples. Through these processes, the final cell density and overall yield of homogenous rhG-CSF were obtained 42.8 g as dry cell weights, 1.75 g as purified active proteins, from 1 L culture broth, respectively. The purity of rhG-CSF was finally 99% since the isoforms of rhG-CSF could be separated through the prep-HPLC step. The result of biological activity indicated that purified rhG-CSF has a similar profile to the World Health Organization (WHO) 2nd International Standard for G-CSF. Taken together, our results demonstrate that the simple purification through a single step of prep-HPLC may be valuable for the industrial-scale production of biologically active proteins. PMID:24224041

  16. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes

    PubMed Central

    Margolin, Adam A.; Palomero, Teresa; Sumazin, Pavel; Califano, Andrea; Ferrando, Adolfo A.; Stolovitzky, Gustavo

    2009-01-01

    ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed at minimizing false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T cells, followed by extensive biochemical validation, reveals that 3 oncogenic transcription factors, NOTCH1, MYC, and HES1, bind to several thousand target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC cobinds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs. PMID:19118200

  17. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.

    PubMed

    Margolin, Adam A; Palomero, Teresa; Sumazin, Pavel; Califano, Andrea; Ferrando, Adolfo A; Stolovitzky, Gustavo

    2009-01-06

    ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed at minimizing false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T cells, followed by extensive biochemical validation, reveals that 3 oncogenic transcription factors, NOTCH1, MYC, and HES1, bind to several thousand target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC cobinds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs.

  18. Toward Elimination of Dog-Mediated Human Rabies: Experiences from Implementing a Large-scale Demonstration Project in Southern Tanzania

    PubMed Central

    Mpolya, Emmanuel Abraham; Lembo, Tiziana; Lushasi, Kennedy; Mancy, Rebecca; Mbunda, Eberhard M.; Makungu, Selemani; Maziku, Matthew; Sikana, Lwitiko; Jaswant, Gurdeep; Townsend, Sunny; Meslin, François-Xavier; Abela-Ridder, Bernadette; Ngeleja, Chanasa; Changalucha, Joel; Mtema, Zacharia; Sambo, Maganga; Mchau, Geofrey; Rysava, Kristyna; Nanai, Alphoncina; Kazwala, Rudovick; Cleaveland, Sarah; Hampson, Katie

    2017-01-01

    A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project. Bite exposures declined, particularly in the southernmost districts with the smallest dog populations, and health workers successfully transitioned from primarily intramuscular administration of PEP to intradermal administration, resulting in major cost savings. However, even with improved PEP provision, vaccine shortages still occurred in some districts. In laboratory diagnosis, there were several logistical challenges in sample handling and submission but compared to the situation before the project started, there was a moderate increase in the number of laboratory samples submitted and tested for rabies in the project areas with a decrease in the proportion of rabies-positive samples over time. The project had a major impact on public health policy and practice with the formation of a One Health Coordination Unit at the Prime Minister’s Office and development of the Tanzania National Rabies Control Strategy, which lays a roadmap for elimination of rabies in Tanzania by 2030 by following the Stepwise Approach towards Rabies Elimination (SARE). Overall, the project generated many important lessons relevant to rabies prevention and control in particular and disease surveillance in general. Lessons include the need for (1) a specific unit in the

  19. Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans

    PubMed Central

    Uhl, M.Andrew; Biery, Matt; Craig, Nancy; Johnson, Alexander D.

    2003-01-01

    Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large-scale loss-of-function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single-cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approxim ately one-third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens. PMID:12773383

  20. Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans.

    PubMed

    Uhl, M Andrew; Biery, Matt; Craig, Nancy; Johnson, Alexander D

    2003-06-02

    Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large-scale loss-of-function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single-cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approximately one-third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens.

  1. Large-scale identification of proteins in human salivary proteome by liquid chromatography/mass spectrometry and two-dimensional gel electrophoresis-mass spectrometry.

    PubMed

    Hu, Shen; Xie, Yongming; Ramachandran, Prasanna; Ogorzalek Loo, Rachel R; Li, Yang; Loo, Joseph A; Wong, David T

    2005-04-01

    Human saliva contains a large number of proteins and peptides (salivary proteome) that help maintain homeostasis in the oral cavity. Global analysis of human salivary proteome is important for understanding oral health and disease pathogenesis. In this study, large-scale identification of salivary proteins was demonstrated by using shotgun proteomics and two-dimensinal gel electrophoresis-mass spectrometry (2-DE-MS). For the shotgun approach, whole saliva proteins were prefractionated according to molecular weight. The smallest fraction, presumably containing salivary peptides, was directly separated by capillary liquid chromatography (LC). However, the large protein fractions were digested into peptides for subsequent LC separation. Separated peptides were analyzed by on-line electrospray tandem mass spectrometry (MS/MS) using a quadrupole-time of flight mass spectrometer, and the obtained spectra were automatically processed to search human protein sequence database for protein identification. Additionally, 2-DE was used to map out the proteins in whole saliva. Protein spots 105 in number were excised and in-gel digested; and the resulting peptide fragments were measured by matrix-assisted laser desorption/ionization-mass spectrometry and sequenced by LC-MS/MS for protein identification. In total, we cataloged 309 proteins from human whole saliva by using these two proteomic approaches.

  2. 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

  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. 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

  5. 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?

  6. Large-scale cortical networks and cognition.

    PubMed

    Bressler, S L

    1995-03-01

    The well-known parcellation of the mammalian cerebral cortex into a large number of functionally distinct cytoarchitectonic areas presents a problem for understanding the complex cortical integrative functions that underlie cognition. How do cortical areas having unique individual functional properties cooperate to accomplish these complex operations? Do neurons distributed throughout the cerebral cortex act together in large-scale functional assemblages? This review examines the substantial body of evidence supporting the view that complex integrative functions are carried out by large-scale networks of cortical areas. Pathway tracing studies in non-human primates have revealed widely distributed networks of interconnected cortical areas, providing an anatomical substrate for large-scale parallel processing of information in the cerebral cortex. Functional coactivation of multiple cortical areas has been demonstrated by neurophysiological studies in non-human primates and several different cognitive functions have been shown to depend on multiple distributed areas by human neuropsychological studies. Electrophysiological studies on interareal synchronization have provided evidence that active neurons in different cortical areas may become not only coactive, but also functionally interdependent. The computational advantages of synchronization between cortical areas in large-scale networks have been elucidated by studies using artificial neural network models. Recent observations of time-varying multi-areal cortical synchronization suggest that the functional topology of a large-scale cortical network is dynamically reorganized during visuomotor behavior.

  7. Validation of a fast method for quantification of intra-abdominal and subcutaneous adipose tissue for large-scale human studies.

    PubMed

    Borga, Magnus; Thomas, E Louise; Romu, Thobias; Rosander, Johannes; Fitzpatrick, Julie; Dahlqvist Leinhard, Olof; Bell, Jimmy D

    2015-12-01

    Central obesity is the hallmark of a number of non-inheritable disorders. The advent of imaging techniques such as MRI has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles to the use of MRI in large-scale studies. In this study we assess the validity of the recently proposed fat-muscle quantitation system (AMRA(TM) Profiler) for the quantification of intra-abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using sliceOmatic, the current gold-standard, and the AMRA(TM) Profiler based on a non-rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by the two analysis methods, (Pearson correlation r = 0.97, p < 0.001), with the AMRA(TM) Profiler analysis being significantly faster (~3 min) than the conventional sliceOmatic approach (~40 min). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 versus sliceOmatic 4.73 ± 1.75 l, p = 0.97). For the AMRA(TM) Profiler analysis, the intra-observer coefficient of variation was 1.6% for IAAT and 1.1% for ASAT, the inter-observer coefficient of variation was 1.4% for IAAT and 1.2% for ASAT, the intra-observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter-observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRA(TM) Profiler, opening up the possibility of large-scale human phenotypic studies.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Base composition at mtDNA boundaries suggests a DNA triple helix model for human mitochondrial DNA large-scale rearrangements.

    PubMed

    Rocher, Christophe; Letellier, Thierry; Copeland, William C; Lestienne, Patrick

    2002-06-01

    Different mechanisms have been proposed to account for mitochondrial DNA (mtDNA) instability based on the presence of short homologous sequences (direct repeats, DR) at the potential boundaries of mtDNA rearrangements. Among them, slippage-mispairing of the replication complex during the asymmetric replication cycle of the mammalian mitochondrial DNA has been proposed to account for the preferential localization of deletions. This mechanism involves a transfer of the replication complex from the first neo-synthesized heavy (H) strand of the DR1, to the DR2, thus bypassing the intervening sequence and producing a deleted molecule. Nevertheless, the nature of the bonds between the DNA strands remains unknown as the forward sequence of DR2, beyond the replication complex, stays double-stranded. Here, we have analyzed the base composition of the DR at the boundaries of mtDNA deletions and duplications and found a skewed pyrimidine content of about 75% in the light-strand DNA template. This suggests the possible building of a DNA triple helix between the G-rich neo-synthesized DR1 and the base-paired homologous G.C-rich DR2. In vitro experiments with the purified human DNA polymerase gamma subunits enabled us to show that the third DNA strand may be used as a primer for DNA replication, using a template with the direct repeat forming a hairpin, with which the primer could initiate DNA replication. These data suggest a novel molecular basis for mitochondrial DNA rearrangements through the distributive nature of the DNA polymerase gamma, at the level of the direct repeats. A general model accounting for large-scale mitochondrial DNA deletion and duplication is proposed. These experiments extend to a DNA polymerase from an eucaryote source the use of a DNA triple helix strand as a primer, like other DNA polymerases from phage and bacterial origins.

  13. 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.

  14. Large-scale structural optimization

    NASA Technical Reports Server (NTRS)

    Sobieszczanski-Sobieski, J.

    1983-01-01

    Problems encountered by aerospace designers in attempting to optimize whole aircraft are discussed, along with possible solutions. Large scale optimization, as opposed to component-by-component optimization, is hindered by computational costs, software inflexibility, concentration on a single, rather than trade-off, design methodology and the incompatibility of large-scale optimization with single program, single computer methods. The software problem can be approached by placing the full analysis outside of the optimization loop. Full analysis is then performed only periodically. Problem-dependent software can be removed from the generic code using a systems programming technique, and then embody the definitions of design variables, objective function and design constraints. Trade-off algorithms can be used at the design points to obtain quantitative answers. Finally, decomposing the large-scale problem into independent subproblems allows systematic optimization of the problems by an organization of people and machines.

  15. Large-scale neuromorphic computing systems

    NASA Astrophysics Data System (ADS)

    Furber, Steve

    2016-10-01

    Neuromorphic computing covers a diverse range of approaches to information processing all of which demonstrate some degree of neurobiological inspiration that differentiates them from mainstream conventional computing systems. The philosophy behind neuromorphic computing has its origins in the seminal work carried out by Carver Mead at Caltech in the late 1980s. This early work influenced others to carry developments forward, and advances in VLSI technology supported steady growth in the scale and capability of neuromorphic devices. Recently, a number of large-scale neuromorphic projects have emerged, taking the approach to unprecedented scales and capabilities. These large-scale projects are associated with major new funding initiatives for brain-related research, creating a sense that the time and circumstances are right for progress in our understanding of information processing in the brain. In this review we present a brief history of neuromorphic engineering then focus on some of the principal current large-scale projects, their main features, how their approaches are complementary and distinct, their advantages and drawbacks, and highlight the sorts of capabilities that each can deliver to neural modellers.

  16. Galaxy clustering on large scales.

    PubMed Central

    Efstathiou, G

    1993-01-01

    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

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

    PubMed

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

    2011-06-15

    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 (>60Hz) 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 mapping

  18. Large-Scale Aerosol Modeling and Analysis

    DTIC Science & Technology

    2008-09-30

    aerosol species up to six days in advance anywhere on the globe. NAAPS and COAMPS are particularly useful for forecasts of dust storms in areas...impact cloud processes globally. With increasing dust storms due to climate change and land use changes in desert regions, the impact of the...bacteria in large-scale dust storms is expected to significantly impact warm ice cloud formation, human health, and ecosystems globally. In Niemi et al

  19. In vitro large scale production of human mature red blood cells from hematopoietic stem cells by coculturing with human fetal liver stromal cells.

    PubMed

    Xi, Jiafei; Li, Yanhua; Wang, Ruoyong; Wang, Yunfang; Nan, Xue; He, Lijuan; Zhang, Peng; Chen, Lin; Yue, Wen; Pei, Xuetao

    2013-01-01

    In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs). HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 10(9)-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive β -globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs) are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.

  20. Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

    PubMed Central

    D’Aiuto, Leonardo; Zhi, Yun; Kumar Das, Dhanjit; Wilcox, Madeleine R; Johnson, Jon W; McClain, Lora; MacDonald, Matthew L; Di Maio, Roberto; Schurdak, Mark E; Piazza, Paolo; Viggiano, Luigi; Sweet, Robert; Kinchington, Paul R; Bhattacharjee, Ayantika G; Yolken, Robert; Nimgaonka, Vishwajit L

    2014-01-01

    Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented opportunity to perform high-throughput screening of novel drugs for neurological and neurodegenerative diseases. Such screenings require a robust and scalable method for generating large numbers of mature, differentiated neuronal cells. Currently available methods based on differentiation of embryoid bodies (EBs) or directed differentiation of adherent culture systems are either expensive or are not scalable. We developed a protocol for large-scale generation of neuronal stem cells (NSCs)/early neural progenitor cells (eNPCs) and their differentiation into neurons. Our scalable protocol allows robust and cost-effective generation of NSCs/eNPCs from iPSCs. Following culture in neurobasal medium supplemented with B27 and BDNF, NSCs/eNPCs differentiate predominantly into vesicular glutamate transporter 1 (VGLUT1) positive neurons. Targeted mass spectrometry analysis demonstrates that iPSC-derived neurons express ligand-gated channels and other synaptic proteins and whole-cell patch-clamp experiments indicate that these channels are functional. The robust and cost-effective differentiation protocol described here for large-scale generation of NSCs/eNPCs and their differentiation into neurons paves the way for automated high-throughput screening of drugs for neurological and neurodegenerative diseases. PMID:25629202

  1. Large-Scale Visual Data Analysis

    NASA Astrophysics Data System (ADS)

    Johnson, Chris

    2014-04-01

    Modern high performance computers have speeds measured in petaflops and handle data set sizes measured in terabytes and petabytes. Although these machines offer enormous potential for solving very large-scale realistic computational problems, their effectiveness will hinge upon the ability of human experts to interact with their simulation results and extract useful information. One of the greatest scientific challenges of the 21st century is to effectively understand and make use of the vast amount of information being produced. Visual data analysis will be among our most most important tools in helping to understand such large-scale information. Our research at the Scientific Computing and Imaging (SCI) Institute at the University of Utah has focused on innovative, scalable techniques for large-scale 3D visual data analysis. In this talk, I will present state- of-the-art visualization techniques, including scalable visualization algorithms and software, cluster-based visualization methods and innovate visualization techniques applied to problems in computational science, engineering, and medicine. I will conclude with an outline for a future high performance visualization research challenges and opportunities.

  2. 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…

  3. The Human Brain Uses Noise

    NASA Astrophysics Data System (ADS)

    Mori, Toshio; Kai, Shoichi

    2003-05-01

    We present the first observation of stochastic resonance (SR) in the human brain's visual processing area. The novel experimental protocol is to stimulate the right eye with a sub-threshold periodic optical signal and the left eye with a noisy one. The stimuli bypass sensory organs and are mixed in the visual cortex. With many noise sources present in the brain, higher brain functions, e.g. perception and cognition, may exploit SR.

  4. Large-scale PACS implementation.

    PubMed

    Carrino, J A; Unkel, P J; Miller, I D; Bowser, C L; Freckleton, M W; Johnson, T G

    1998-08-01

    The transition to filmless radiology is a much more formidable task than making the request for proposal to purchase a (Picture Archiving and Communications System) PACS. The Department of Defense and the Veterans Administration have been pioneers in the transformation of medical diagnostic imaging to the electronic environment. Many civilian sites are expected to implement large-scale PACS in the next five to ten years. This presentation will related the empirical insights gleaned at our institution from a large-scale PACS implementation. Our PACS integration was introduced into a fully operational department (not a new hospital) in which work flow had to continue with minimal impact. Impediments to user acceptance will be addressed. The critical components of this enormous task will be discussed. The topics covered during this session will include issues such as phased implementation, DICOM (digital imaging and communications in medicine) standard-based interaction of devices, hospital information system (HIS)/radiology information system (RIS) interface, user approval, networking, workstation deployment and backup procedures. The presentation will make specific suggestions regarding the implementation team, operating instructions, quality control (QC), training and education. The concept of identifying key functional areas is relevant to transitioning the facility to be entirely on line. Special attention must be paid to specific functional areas such as the operating rooms and trauma rooms where the clinical requirements may not match the PACS capabilities. The printing of films may be necessary for certain circumstances. The integration of teleradiology and remote clinics into a PACS is a salient topic with respect to the overall role of the radiologists providing rapid consultation. A Web-based server allows a clinician to review images and reports on a desk-top (personal) computer and thus reduce the number of dedicated PACS review workstations. This session

  5. Large-Scale Sequence Comparison.

    PubMed

    Lal, Devi; Verma, Mansi

    2017-01-01

    There are millions of sequences deposited in genomic databases, and it is an important task to categorize them according to their structural and functional roles. Sequence comparison is a prerequisite for proper categorization of both DNA and protein sequences, and helps in assigning a putative or hypothetical structure and function to a given sequence. There are various methods available for comparing sequences, alignment being first and foremost for sequences with a small number of base pairs as well as for large-scale genome comparison. Various tools are available for performing pairwise large sequence comparison. The best known tools either perform global alignment or generate local alignments between the two sequences. In this chapter we first provide basic information regarding sequence comparison. This is followed by the description of the PAM and BLOSUM matrices that form the basis of sequence comparison. We also give a practical overview of currently available methods such as BLAST and FASTA, followed by a description and overview of tools available for genome comparison including LAGAN, MumMER, BLASTZ, and AVID.

  6. Large Scale Magnetostrictive Valve Actuator

    NASA Technical Reports Server (NTRS)

    Richard, James A.; Holleman, Elizabeth; Eddleman, David

    2008-01-01

    Marshall Space Flight Center's Valves, Actuators and Ducts Design and Development Branch developed a large scale magnetostrictive valve actuator. The potential advantages of this technology are faster, more efficient valve actuators that consume less power and provide precise position control and deliver higher flow rates than conventional solenoid valves. Magnetostrictive materials change dimensions when a magnetic field is applied; this property is referred to as magnetostriction. Magnetostriction is caused by the alignment of the magnetic domains in the material s crystalline structure and the applied magnetic field lines. Typically, the material changes shape by elongating in the axial direction and constricting in the radial direction, resulting in no net change in volume. All hardware and testing is complete. This paper will discuss: the potential applications of the technology; overview of the as built actuator design; discuss problems that were uncovered during the development testing; review test data and evaluate weaknesses of the design; and discuss areas for improvement for future work. This actuator holds promises of a low power, high load, proportionally controlled actuator for valves requiring 440 to 1500 newtons load.

  7. Large scale cluster computing workshop

    SciTech Connect

    Dane Skow; Alan Silverman

    2002-12-23

    Recent revolutions in computer hardware and software technologies have paved the way for the large-scale deployment of clusters of commodity computers to address problems heretofore the domain of tightly coupled SMP processors. Near term projects within High Energy Physics and other computing communities will deploy clusters of scale 1000s of processors and be used by 100s to 1000s of independent users. This will expand the reach in both dimensions by an order of magnitude from the current successful production facilities. The goals of this workshop were: (1) to determine what tools exist which can scale up to the cluster sizes foreseen for the next generation of HENP experiments (several thousand nodes) and by implication to identify areas where some investment of money or effort is likely to be needed. (2) To compare and record experimences gained with such tools. (3) To produce a practical guide to all stages of planning, installing, building and operating a large computing cluster in HENP. (4) To identify and connect groups with similar interest within HENP and the larger clustering community.

  8. 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.

  9. 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.

  10. Large scale study of tooth enamel

    SciTech Connect

    Bodart, F.; Deconninck, G.; Martin, M.Th.

    1981-04-01

    Human tooth enamel contains traces of foreign elements. The presence of these elements is related to the history and the environment of the human body and can be considered as the signature of perturbations which occur during the growth of a tooth. A map of the distribution of these traces on a large scale sample of the population will constitute a reference for further investigations of environmental effects. One hundred eighty samples of teeth were first analysed using PIXE, backscattering and nuclear reaction techniques. The results were analysed using statistical methods. Correlations between O, F, Na, P, Ca, Mn, Fe, Cu, Zn, Pb and Sr were observed and cluster analysis was in progress. The techniques described in the present work have been developed in order to establish a method for the exploration of very large samples of the Belgian population.

  11. 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

  12. 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.

  13. Large-scale Intelligent Transporation Systems simulation

    SciTech Connect

    Ewing, T.; Canfield, T.; Hannebutte, U.; Levine, D.; Tentner, A.

    1995-06-01

    A prototype computer system has been developed which defines a high-level architecture for a large-scale, comprehensive, scalable simulation of an Intelligent Transportation System (ITS) capable of running on massively parallel computers and distributed (networked) computer systems. The prototype includes the modelling of instrumented ``smart`` vehicles with in-vehicle navigation units capable of optimal route planning and Traffic Management Centers (TMC). The TMC has probe vehicle tracking capabilities (display position and attributes of instrumented vehicles), and can provide 2-way interaction with traffic to provide advisories and link times. Both the in-vehicle navigation module and the TMC feature detailed graphical user interfaces to support human-factors studies. The prototype has been developed on a distributed system of networked UNIX computers but is designed to run on ANL`s IBM SP-X parallel computer system for large scale problems. A novel feature of our design is that vehicles will be represented by autonomus computer processes, each with a behavior model which performs independent route selection and reacts to external traffic events much like real vehicles. With this approach, one will be able to take advantage of emerging massively parallel processor (MPP) systems.

  14. Long term and large-scale cultivation of human hepatoma Hep G2 cells in hollow fiber bioreactor. Cultivation of human hepatoma Hep G2 in hollow fiber bioreactor.

    PubMed

    Liu, J J; Chen, B S; Tsai, T F; Wu, Y J; Pang, V F; Hsieh, A; Hsieh, J H; Chang, T H

    1991-02-01

    Long-term and large scale cultivation of an anchorage-dependent cell line using an industrial scale hollow fiber perfusion bioreactor is described. Hep G2 cells (a human hepatoma cell line) were cultivated in an Acusyst-P (Endotronic) with a total fiber surface area of 7.2 m2 6 x 1.2m2) to produce Hep G2 crude conditioned medium (CCM). Pretreatment of the cellulose acetate hollow fibers with collagen enhances the attachment of the anchorage-dependent cells. We have succeeded in growing the Hep G2 cells in an antibiotics- and serum-free IMDM medium, supplemented with 50 micrograms/ml of Hep G2 CCM protein at inoculation. The Hep G2 cells replicate and secrete CCM protein in quantities comparable to those produced in DMEM containing 10% fetal calf serum (FCS). The highest CCM protein productivity during the 80-day cultivation was 1.1 g/day with a total of 30 g of protein accumulated. Hep G2 CCM (20-40 micrograms protein/ml) was comparable to or even better than 10% FCS in supporting the growth of Molt-4 (a human T leukemia cell line) and FO (a mouse myeloma cell line) cells in vitro. The availability of this large amount of Hep G2 CCM will aid the further purification and characterization of growth factor(s) which could be used as serum substituents.

  15. 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.

  16. 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

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

    PubMed

    Liu, J; Stanton, V P; Fujiwara, T M; Wang, J X; Rezonzew, R; Crumley, M J; Morgan, K; Gros, P; Housman, D; Schurr, E

    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.

  18. Cloning, large scale over-expression in E. coli and purification of the components of the human LAT 1 (SLC7A5) amino acid transporter.

    PubMed

    Galluccio, Michele; Pingitore, Piero; Scalise, Mariafrancesca; Indiveri, Cesare

    2013-08-01

    The high yield expression of the human LAT1 transporter has been obtained for the first time using E. coli. The hLAT1 cDNA was amplified from HEK293 cells and cloned in pH6EX3 vector. The construct pH6EX3-6His-hLAT1 was used to express the 6His-hLAT1 protein in the Rosetta(DE3)pLysS strain of E. coli. The highest level of expression was detected 8 h after induction by IPTG at 28 °C. The expressed protein was collected in the insoluble fraction of cell lysate. On SDS-PAGE the apparent molecular mass of the polypeptide was 40 kDa. After solubilization with sarkosyl and denaturation with urea the protein carrying a 6His N-terminal tag was purified by Ni(2+)-chelating affinity chromatography and identified by anti-His antibody. The yield of the over-expressed protein after purification was 3.5 mg/L (cell culture). The human CD98 cDNA amplified from Imagene plasmid was cloned in pGEX-4T1. The construct pGEX-4T1-hCD98 was used to express the GST-hCD98 protein in the Rosetta(DE3)pLysS strain of E. coli. The highest level of expression was detected in this case 4 h after induction by IPTG at 28 °C. The expressed protein was accumulated in the soluble fraction of cell lysate. The molecular mass was determined on the basis of marker proteins on SDS-PAGE; it was about 110 kDa. GST was cleaved from the protein construct by incubation with thrombin for 12 h and the hCD98 was separated by Sephadex G-200 chromatography (size exclusion). hCD98 showed a 62 kDa apparent molecular mass, as determined on the basis of molecular mass markers using SDS-PAGE. The yield of CD98 was 2 mg/L of cell culture.

  19. 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

  20. Large scale production of the active human ASCT2 (SLC1A5) transporter in Pichia pastoris--functional and kinetic asymmetry revealed in proteoliposomes.

    PubMed

    Pingitore, Piero; Pochini, Lorena; Scalise, Mariafrancesca; Galluccio, Michele; Hedfalk, Kristina; Indiveri, Cesare

    2013-09-01

    The human glutamine/neutral amino acid transporter ASCT2 (hASCT2) was over-expressed in Pichia pastoris and purified by Ni(2+)-chelating and gel filtration chromatography. The purified protein was reconstituted in liposomes by detergent removal with a batch-wise procedure. Time dependent [(3)H]glutamine/glutamine antiport was measured in proteoliposomes which was active only in the presence of external Na(+). Internal Na(+) slightly stimulated the antiport. Optimal activity was found at pH7.0. A substantial inhibition of the transport was observed by Cys, Thr, Ser, Ala, Asn and Met (≥70%) and by mercurials and methanethiosulfonates (≥80%). Heterologous antiport of [(3)H]glutamine with other neutral amino acids was also studied. The transporter showed asymmetric specificity for amino acids: Ala, Cys, Val, Met were only inwardly transported, while Gln, Ser, Asn, and Thr were transported bi-directionally. From kinetic analysis of [(3)H]glutamine/glutamine antiport Km values of 0.097 and 1.8mM were measured on the external and internal sides of proteoliposomes, respectively. The Km for Na(+) on the external side was 32mM. The homology structural model of the hASCT2 protein was built using the GltPh of Pyrococcus horikoshii as template. Cys395 was the only Cys residue externally exposed, thus being the potential target of SH reagents inhibition and, hence, potentially involved in the transport mechanism.

  1. Large scale production and purification of human IL-2 from buffy coat lymphocytes stimulated with 12-O-tetradecanoylphorbol 13-acetate and calcium ionophore A23187.

    PubMed

    Grote, W; Klaar, J; Mühlradt, P F; Monner, D A

    1987-10-23

    Methods for the production of high titers of interleukin-2 (IL-2) from human buffy coat lymphocytes, and subsequent purification of the IL-2 are described. 50 buffy coats containing 1 X 10(11) leukocytes were first depleted of erythrocytes by batchwise leukapheresis using a Haemonetics model 15 blood wash centrifuge. Further lymphocyte enrichment was achieved using a one-step sedimentation in the presence of hydroxyethyl starch, which produced suspensions of more than 90% lymphocytes. This degree of lymphocyte purity was important since phagocytes were inhibitory to 12-O-tetradecanoylphorbol 13-acetate/calcium ionophore (TPA/A23187)-induced IL-2 production when their concentration exceeded 15% of the total cells. Cell culture was performed in stirred fermenters. Using TPA/A23187 induction, up to 500 micrograms of IL-2 per liter were produced. The IL-2 was purified by absorption from the supernatants onto controlled pore glass and elution with 50% ethylene glycol, followed by Fractogel chromatography, and then preparative high-performance liquid chromatography (HPLC) using an RP-6 column and elution with a gradient of n-propanol. A final HPLC rechromatography step using an analytical RP-6 column gave a homogeneous preparation with specific activity of 1.2 X 10(7) U/mg and a recovery from the starting supernatant of 22%.

  2. Expression and large-scale production of the biochemically active human tissue-plasminogen activator in hairy roots of Oriental melon (Cucumis melo).

    PubMed

    Kim, Sung-Ryong; Sim, Joon-Soo; Ajjappala, Hemavathi; Kim, Yong-Hwan; Hahn, Bum-Soo

    2012-01-01

    Human tissue-plasminogen activator (t-PA) is a thrombolytic protein that plays an active role in dissolving fibrin clots by fibrinolysis and in activating plasminogen to plasmin in blood vessels. t-PA and synthetic t-PA (st-PA) genes were expressed as enzymatically active form in hairy roots of Oriental melon (Cucumis melo L. cv. Geumssaragi-euncheon) infected by Agrobacterium rhizogenes. The insertion of the t-PA genes in genomic DNA of transgenic hairy roots was verified by PCR. The presence and expression of t-PA-specific transcripts in the total RNAs of transgenic hairy roots were confirmed by RT-PCR. Western blot analysis of the transgenic hairy roots showed a single major band of 59-kDa recombinant t-PAs. ELISA demonstrated that the highest level of recombinant t-PA (798 ng mg⁻¹) was detected in hairy roots expressing t-PA. Similarly, the maximum fibrinolysis of recombinant t-PAs was observed in hairy roots transformed with t-PA. WPM medium was found to be more suitable for rapid growth of hairy roots among all the seven media types tested. The hairy root production was 5.8 times higher than that of White medium. The total yield of hairy roots grown on WPM medium was 621.8±8.7 g L⁻¹ at pH 7.0. These studies demonstrate that the hairy roots could be employed for the mass production of enzymatically active t-PA.

  3. 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

    2014-10-05

    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.

  4. 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

  5. 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.

  6. 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…

  7. Mindboggling morphometry of human brains

    PubMed Central

    Bao, Forrest S.; Giard, Joachim; Stavsky, Eliezer; Lee, Noah; Rossa, Brian; Reuter, Martin; Chaibub Neto, Elias

    2017-01-01

    Mindboggle (http://mindboggle.info) is an open source brain morphometry platform that takes in preprocessed T1-weighted MRI data and outputs volume, surface, and tabular data containing label, feature, and shape information for further analysis. In this article, we document the software and demonstrate its use in studies of shape variation in healthy and diseased humans. The number of different shape measures and the size of the populations make this the largest and most detailed shape analysis of human brains ever conducted. Brain image morphometry shows great potential for providing much-needed biological markers for diagnosing, tracking, and predicting progression of mental health disorders. Very few software algorithms provide more than measures of volume and cortical thickness, while more subtle shape measures may provide more sensitive and specific biomarkers. Mindboggle computes a variety of (primarily surface-based) shapes: area, volume, thickness, curvature, depth, Laplace-Beltrami spectra, Zernike moments, etc. We evaluate Mindboggle’s algorithms using the largest set of manually labeled, publicly available brain images in the world and compare them against state-of-the-art algorithms where they exist. All data, code, and results of these evaluations are publicly available. PMID:28231282

  8. Modeling Human Behavior at a Large Scale

    DTIC Science & Technology

    2012-01-01

    features (day of week and holiday), our models can handle arbitrary number of additional features, such as season , predicted weather, social and... allergies , that people discuss on Twitter. In a follow-up work (Paul and Dredze, 2011b) begin to consider the geographical patterns in the prevalence...preventative care, focusing specifically on suicide. Twitter has also been used to monitor the seasonal variation in affect around the globe (Golder and Macy

  9. 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

  10. 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.

  11. Chromosome conformation elucidates regulatory relationships in developing human brain.

    PubMed

    Won, Hyejung; de la Torre-Ubieta, Luis; Stein, Jason L; Parikshak, Neelroop N; Huang, Jerry; Opland, Carli K; Gandal, Michael J; Sutton, Gavin J; Hormozdiari, Farhad; Lu, Daning; Lee, Changhoon; Eskin, Eleazar; Voineagu, Irina; Ernst, Jason; Geschwind, Daniel H

    2016-10-27

    Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with enhancers gained on the human lineage, many of which are under purifying selection and associated with human cognitive function. We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), highlighting multiple candidate schizophrenia risk genes and pathways, including transcription factors involved in neurogenesis, and cholinergic signalling molecules, several of which are supported by independent expression quantitative trait loci and gene expression analyses. Genome editing in human neural progenitors suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, supporting its potential role as a schizophrenia risk gene. This work provides a framework for understanding the effect of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel mechanisms underlying neuropsychiatric disorders.

  12. Chromosome conformation elucidates regulatory relationships in developing human brain

    PubMed Central

    Won, Hyejung; de la Torre-Ubieta, Luis; Stein, Jason L.; Parikshak, Neelroop N.; Huang, Jerry; Opland, Carli K.; Gandal, Michael; Sutton, Gavin J.; Hormozdiari, Farhad; Lu, Daning; Lee, Changhoon; Eskin, Eleazar; Voineagu, Irina; Ernst, Jason; Geschwind, Daniel H.

    2016-01-01

    Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner1–3. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia4–6, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease. Our analyses identify hundreds of genes that physically interact with enhancers gained on the human, many of which are under purifying selection and associated with human cognitive function. We integrate chromatin contacts with non-coding variants identified in schizophrenia genome-wide association studies (GWAS), highlighting multiple new candidate schizophrenia risk genes and pathways, including transcription factors involved in neurogenesis, as well as cholinergic signalling, several of which are supported by independent expression quantitative trait loci and gene expression analyses. Genome editing in human neural progenitors suggests that one of these distal schizophrenia GWAS loci regulates FOXG1 expression, supporting its potential role as a novel schizophrenia risk gene. This work provides a framework for understanding the impact of non-coding regulatory elements on human brain development and the evolution of cognition, and highlights novel mechanisms underlying neuropsychiatric disorders. PMID:27760116

  13. Large Scale Metal Additive Techniques Review

    SciTech Connect

    Nycz, Andrzej; Adediran, Adeola I; Noakes, Mark W; Love, Lonnie J

    2016-01-01

    In recent years additive manufacturing made long strides toward becoming a main stream production technology. Particularly strong progress has been made in large-scale polymer deposition. However, large scale metal additive has not yet reached parity with large scale polymer. This paper is a review study of the metal additive techniques in the context of building large structures. Current commercial devices are capable of printing metal parts on the order of several cubic feet compared to hundreds of cubic feet for the polymer side. In order to follow the polymer progress path several factors are considered: potential to scale, economy, environment friendliness, material properties, feedstock availability, robustness of the process, quality and accuracy, potential for defects, and post processing as well as potential applications. This paper focuses on current state of art of large scale metal additive technology with a focus on expanding the geometric limits.

  14. 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.

  15. 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...

  16. Large-scale screening by the automated Wassermann reaction

    PubMed Central

    Wagstaff, W.; Firth, R.; Booth, J. R.; Bowley, C. C.

    1969-01-01

    In view of the drawbacks in the use of the Kahn test for large-scale screening of blood donors, mainly those of human error through work overload and fatiguability, an attempt was made to adapt an existing automated complement-fixation technique for this purpose. This paper reports the successful results of that adaptation. PMID:5776559

  17. 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

  18. A direct brain-to-brain interface in humans.

    PubMed

    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.

  19. Large-scale multiplex absolute protein quantification of drug-metabolizing enzymes and transporters in human intestine, liver, and kidney microsomes by SWATH-MS: Comparison with MRM/SRM and HR-MRM/PRM.

    PubMed

    Nakamura, Kenji; Hirayama-Kurogi, Mio; Ito, Shingo; Kuno, Takuya; Yoneyama, Toshihiro; Obuchi, Wataru; Terasaki, Tetsuya; Ohtsuki, Sumio

    2016-08-01

    The purpose of the present study was to examine simultaneously the absolute protein amounts of 152 membrane and membrane-associated proteins, including 30 metabolizing enzymes and 107 transporters, in pooled microsomal fractions of human liver, kidney, and intestine by means of SWATH-MS with stable isotope-labeled internal standard peptides, and to compare the results with those obtained by MRM/SRM and high resolution (HR)-MRM/PRM. The protein expression levels of 27 metabolizing enzymes, 54 transporters, and six other membrane proteins were quantitated by SWATH-MS; other targets were below the lower limits of quantitation. Most of the values determined by SWATH-MS differed by less than 50% from those obtained by MRM/SRM or HR-MRM/PRM. Various metabolizing enzymes were expressed in liver microsomes more abundantly than in other microsomes. Ten, 13, and eight transporters listed as important for drugs by International Transporter Consortium were quantified in liver, kidney, and intestinal microsomes, respectively. Our results indicate that SWATH-MS enables large-scale multiplex absolute protein quantification while retaining similar quantitative capability to MRM/SRM or HR-MRM/PRM. SWATH-MS is expected to be useful methodology in the context of drug development for elucidating the molecular mechanisms of drug absorption, metabolism, and excretion in the human body based on protein profile information.

  20. Recursive architecture for large-scale adaptive system

    NASA Astrophysics Data System (ADS)

    Hanahara, Kazuyuki; Sugiyama, Yoshihiko

    1994-09-01

    'Large scale' is one of major trends in the research and development of recent engineering, especially in the field of aerospace structural system. This term expresses the large scale of an artifact in general, however, it also implies the large number of the components which make up the artifact in usual. Considering a large scale system which is especially used in remote space or deep-sea, such a system should be adaptive as well as robust by itself, because its control as well as maintenance by human operators are not easy due to the remoteness. An approach to realizing this large scale, adaptive and robust system is to build the system as an assemblage of components which are respectively adaptive by themselves. In this case, the robustness of the system can be achieved by using a large number of such components and suitable adaptation as well as maintenance strategies. Such a system gathers many research's interest and their studies such as decentralized motion control, configurating algorithm and characteristics of structural elements are reported. In this article, a recursive architecture concept is developed and discussed towards the realization of large scale system which consists of a number of uniform adaptive components. We propose an adaptation strategy based on the architecture and its implementation by means of hierarchically connected processing units. The robustness and the restoration from degeneration of the processing unit are also discussed. Two- and three-dimensional adaptive truss structures are conceptually designed based on the recursive architecture.

  1. Stress-related noradrenergic activity prompts large-scale neural network reconfiguration.

    PubMed

    Hermans, Erno J; van Marle, Hein J F; Ossewaarde, Lindsey; Henckens, Marloes J A G; Qin, Shaozheng; van Kesteren, Marlieke T R; Schoots, Vincent C; Cousijn, Helena; Rijpkema, Mark; Oostenveld, Robert; Fernández, Guillén

    2011-11-25

    Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

  2. Toward defining the anatomo-proteomic puzzle of the human brain: An integrative analysis.

    PubMed

    Fernandez-Irigoyen, Joaquín; Labarga, Alberto; Zabaleta, Aintzane; de Morentin, Xabier Martínez; Perez-Valderrama, Estela; Zelaya, María Victoria; Santamaria, Enrique

    2015-10-01

    The human brain is exceedingly complex, constituted by billions of neurons and trillions of synaptic connections that, in turn, define ∼900 neuroanatomical subdivisions in the adult brain (Hawrylycz et al. An anatomically comprehensive atlas of the human brain transcriptome. Nature 2012, 489, 391-399). The human brain transcriptome has revealed specific regional transcriptional signatures that are regulated in a spatiotemporal manner, increasing the complexity of the structural and molecular organization of this organ (Kang et al. Spatio-temporal transcriptome of the human brain. Nature 2011, 478, 483-489). During the last decade, neuroproteomics has emerged as a powerful approach to profile neural proteomes using shotgun-based MS, providing complementary information about protein content and function at a global level. Here, we revise recent proteome profiling studies performed in human brain, with special emphasis on proteome mapping of anatomical macrostructures, specific subcellular compartments, and cerebrospinal fluid. Moreover, we have performed an integrative functional analysis of the protein compilation derived from these large-scale human brain proteomic studies in order to obtain a comprehensive view of human brain biology. Finally, we also discuss the potential contribution of our meta-analysis to the Chromosome-centric Human Proteome Project initiative.

  3. Brain mechanisms underlying human communication.

    PubMed

    Noordzij, Matthijs L; Newman-Norlund, Sarah E; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

  4. Brain Mechanisms Underlying Human Communication

    PubMed Central

    Noordzij, Matthijs L.; Newman-Norlund, Sarah E.; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C.; Toni, Ivan

    2009-01-01

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities. PMID:19668699

  5. Integration of visual and motor functional streams in the human brain.

    PubMed

    Sepulcre, Jorge

    2014-05-01

    A long-standing difficulty in brain research has been to disentangle how information flows across circuits composed by multiple local and distant cerebral areas. At the large-scale level, several brain imaging methods have contributed to the understanding of those circuits by capturing the covariance or coupling patterns of blood oxygen level-dependent (BOLD) activity between distributed brain regions. The hypothesis is that underlying information processes are closely associated to synchronized brain activity, and therefore to the functional connectivity structure of the human brain. In this study, we have used a recently developed method called stepwise functional connectivity analysis. Our results show that motor and visual connectivity merge in a multimodal integration network that links together perception, action and cognition in the human functional connectome.

  6. Resting-state fMRI: a window into human brain plasticity.

    PubMed

    Guerra-Carrillo, Belén; Mackey, Allyson P; Bunge, Silvia A

    2014-10-01

    Although brain plasticity is greatest in the first few years of life, the brain continues to be shaped by experience throughout adulthood. Advances in fMRI have enabled us to examine the plasticity of large-scale networks using blood oxygen level-dependent (BOLD) correlations measured at rest. Resting-state functional connectivity analysis makes it possible to measure task-independent changes in brain function and therefore could provide unique insights into experience-dependent brain plasticity in humans. Here, we evaluate the hypothesis that resting-state functional connectivity reflects the repeated history of co-activation between brain regions. To this end, we review resting-state fMRI studies in the sensory, motor, and cognitive learning literature. This body of research provides evidence that the brain's resting-state functional architecture displays dynamic properties in young adulthood.

  7. 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.

  8. 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.

  9. Brain evolution and human neuropsychology: the inferential brain hypothesis.

    PubMed

    Koscik, Timothy R; Tranel, Daniel

    2012-05-01

    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. (JINS, 2012, 18, 394-401).

  10. Large-scale nanophotonic phased array.

    PubMed

    Sun, Jie; Timurdogan, Erman; Yaacobi, Ami; Hosseini, Ehsan Shah; Watts, Michael R

    2013-01-10

    Electromagnetic phased arrays at radio frequencies are well known and have enabled applications ranging from communications to radar, broadcasting and astronomy. The ability to generate arbitrary radiation patterns with large-scale phased arrays has long been pursued. Although it is extremely expensive and cumbersome to deploy large-scale radiofrequency phased arrays, optical phased arrays have a unique advantage in that the much shorter optical wavelength holds promise for large-scale integration. However, the short optical wavelength also imposes stringent requirements on fabrication. As a consequence, although optical phased arrays have been studied with various platforms and recently with chip-scale nanophotonics, all of the demonstrations so far are restricted to one-dimensional or small-scale two-dimensional arrays. Here we report the demonstration of a large-scale two-dimensional nanophotonic phased array (NPA), in which 64 × 64 (4,096) optical nanoantennas are densely integrated on a silicon chip within a footprint of 576 μm × 576 μm with all of the nanoantennas precisely balanced in power and aligned in phase to generate a designed, sophisticated radiation pattern in the far field. We also show that active phase tunability can be realized in the proposed NPA by demonstrating dynamic beam steering and shaping with an 8 × 8 array. This work demonstrates that a robust design, together with state-of-the-art complementary metal-oxide-semiconductor technology, allows large-scale NPAs to be implemented on compact and inexpensive nanophotonic chips. In turn, this enables arbitrary radiation pattern generation using NPAs and therefore extends the functionalities of phased arrays beyond conventional beam focusing and steering, opening up possibilities for large-scale deployment in applications such as communication, laser detection and ranging, three-dimensional holography and biomedical sciences, to name just a few.

  11. 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.

  12. Lipid transport and human brain development.

    PubMed

    Betsholtz, Christer

    2015-07-01

    How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.

  13. Towards multimodal atlases of the human brain

    PubMed Central

    Toga, Arthur W.; Thompson, Paul M.; Mori, Susumu; Amunts, Katrin; Zilles, Karl

    2010-01-01

    Atlases of the human brain have an important impact on neuroscience. The emergence of ever more sophisticated imaging techniques, brain mapping methods and analytical strategies has the potential to revolutionize the concept of the brain atlas. Atlases can now combine data describing multiple aspects of brain structure or function at different scales from different subjects, yielding a truly integrative and comprehensive description of this organ. These integrative approaches have provided significant impetus for the human brain mapping initiatives, and have important applications in health and disease. PMID:17115077

  14. Small-world anatomical networks in the human brain revealed by cortical thickness from MRI.

    PubMed

    He, Yong; Chen, Zhang J; Evans, Alan C

    2007-10-01

    An important issue in neuroscience is the characterization for the underlying architectures of complex brain networks. However, little is known about the network of anatomical connections in the human brain. Here, we investigated large-scale anatomical connection patterns of the human cerebral cortex using cortical thickness measurements from magnetic resonance images. Two areas were considered anatomically connected if they showed statistically significant correlations in cortical thickness and we constructed the network of such connections using 124 brains from the International Consortium for Brain Mapping database. Significant short- and long-range connections were found in both intra- and interhemispheric regions, many of which were consistent with known neuroanatomical pathways measured by human diffusion imaging. More importantly, we showed that the human brain anatomical network had robust small-world properties with cohesive neighborhoods and short mean distances between regions that were insensitive to the selection of correlation thresholds. Additionally, we also found that this network and the probability of finding a connection between 2 regions for a given anatomical distance had both exponentially truncated power-law distributions. Our results demonstrated the basic organizational principles for the anatomical network in the human brain compatible with previous functional networks studies, which provides important implications of how functional brain states originate from their structural underpinnings. To our knowledge, this study provides the first report of small-world properties and degree distribution of anatomical networks in the human brain using cortical thickness measurements.

  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. 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…

  17. Large-scale Advanced Propfan (LAP) program

    NASA Technical Reports Server (NTRS)

    Sagerser, D. A.; Ludemann, S. G.

    1985-01-01

    The propfan is an advanced propeller concept which maintains the high efficiencies traditionally associated with conventional propellers at the higher aircraft cruise speeds associated with jet transports. The large-scale advanced propfan (LAP) program extends the research done on 2 ft diameter propfan models to a 9 ft diameter article. The program includes design, fabrication, and testing of both an eight bladed, 9 ft diameter propfan, designated SR-7L, and a 2 ft diameter aeroelastically scaled model, SR-7A. The LAP program is complemented by the propfan test assessment (PTA) program, which takes the large-scale propfan and mates it with a gas generator and gearbox to form a propfan propulsion system and then flight tests this system on the wing of a Gulfstream 2 testbed aircraft.

  18. 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.

  19. Large-scale instabilities of helical flows

    NASA Astrophysics Data System (ADS)

    Cameron, Alexandre; Alexakis, Alexandros; Brachet, Marc-Étienne

    2016-10-01

    Large-scale hydrodynamic instabilities of periodic helical flows of a given wave number K are investigated using three-dimensional Floquet numerical computations. In the Floquet formalism the unstable field is expanded in modes of different spacial periodicity. This allows us (i) to clearly distinguish large from small scale instabilities and (ii) to study modes of wave number q of arbitrarily large-scale separation q ≪K . Different flows are examined including flows that exhibit small-scale turbulence. The growth rate σ of the most unstable mode is measured as a function of the scale separation q /K ≪1 and the Reynolds number Re. It is shown that the growth rate follows the scaling σ ∝q if an AKA effect [Frisch et al., Physica D: Nonlinear Phenomena 28, 382 (1987), 10.1016/0167-2789(87)90026-1] is present or a negative eddy viscosity scaling σ ∝q2 in its absence. This holds both for the Re≪1 regime where previously derived asymptotic results are verified but also for Re=O (1 ) that is beyond their range of validity. Furthermore, for values of Re above a critical value ReSc beyond which small-scale instabilities are present, the growth rate becomes independent of q and the energy of the perturbation at large scales decreases with scale separation. The nonlinear behavior of these large-scale instabilities is also examined in the nonlinear regime where the largest scales of the system are found to be the most dominant energetically. These results are interpreted by low-order models.

  20. Economically viable large-scale hydrogen liquefaction

    NASA Astrophysics Data System (ADS)

    Cardella, U.; Decker, L.; Klein, H.

    2017-02-01

    The liquid hydrogen demand, particularly driven by clean energy applications, will rise in the near future. As industrial large scale liquefiers will play a major role within the hydrogen supply chain, production capacity will have to increase by a multiple of today’s typical sizes. The main goal is to reduce the total cost of ownership for these plants by increasing energy efficiency with innovative and simple process designs, optimized in capital expenditure. New concepts must ensure a manageable plant complexity and flexible operability. In the phase of process development and selection, a dimensioning of key equipment for large scale liquefiers, such as turbines and compressors as well as heat exchangers, must be performed iteratively to ensure technological feasibility and maturity. Further critical aspects related to hydrogen liquefaction, e.g. fluid properties, ortho-para hydrogen conversion, and coldbox configuration, must be analysed in detail. This paper provides an overview on the approach, challenges and preliminary results in the development of efficient as well as economically viable concepts for large-scale hydrogen liquefaction.

  1. Assessment of the two Helicobacter pylori alpha-1,3-fucosyltransferase ortholog genes for the large-scale synthesis of LewisX human milk oligosaccharides by metabolically engineered Escherichia coli.

    PubMed

    Dumon, Claire; Samain, Eric; Priem, Bernard

    2004-01-01

    We previously described a bacterial fermentation process for the in vivo conversion of lactose into fucosylated derivatives of lacto-N-neotetraose Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc (LNnT). The major product obtained was lacto-N-neofucopentaose-V Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc, carrying fucose on the glucosyl residue of LNnT. Only a small amount of oligosaccharides fucosylated on N-acetylglucosaminyl residues and thus carrying the LewisX group (Le(X)) was also produced. We report here a fermentation process for the large-scale production of Le(X) oligosaccharides. The two fucosyltransferase genes futA and futB of Helicobacter pylori (strain 26695) were compared in order to optimize fucosylation in vivo. futA was found to provide the best activity on the LNnT acceptor, whereas futB expressed a better Le(X) activity in vitro. Both genes were expressed to produce oligosaccharides in engineered Escherichia coli (E. coli) cells. The fucosylation pattern of the recombinant oligosaccharides was closely correlated with the specificity observed in vitro, FutB favoring the formation of Le(X) carrying oligosaccharides. Lacto-N-neodifucohexaose-II Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc represented 70% of the total oligosaccharide amount of futA-on-driven fermentation and was produced at a concentration of 1.7 g/L. Fermentation driven by futB led to equal amounts of both lacto-N-neofucopentaose-V and lacto-N-neofucopentaose-II Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc, produced at 280 and 260 mg/L, respectively. Unexpectedly, a noticeable proportion (0.5 g/L) of the human milk oligosaccharide 3-fucosyllactose Gal(beta1-4)[Fuc(alpha1-3)]Glc was produced in futA-on-driven fermentation, underlining the activity of fucosyltransferase FutA in E. coli and leading to a reassessment of its activity on lactose. All oligosaccharides produced by the products of both fut genes were natural compounds of

  2. Inside SMP proteomics: six years German Human Brain Proteome Project (HBPP) - a summary.

    PubMed

    Hamacher, Michael; Hardt, Tanja; van Hall, Andre; Stephan, Christian; Marcus, Katrin; Meyer, Helmut E

    2008-03-01

    In 2001, the German Federal Ministry of Education and Research (BMBF) initiated the National Genome Research Network (NGFN; www.ngfn.de) as a nation-wide multidisciplinary networking platform aiming at the analysis of common human diseases and aging. Within the NGFN the Human Brain Proteome Project (HBPP; www.smp-proteomics.de) focuses on the analysis of the human brain in health and disease. The concept is based on two consecutive steps: (i) Elaborating and establishing the necessary technology platforms. (ii) Application of the established technologies for research in Alzheimer's disease and Parkinson's disease. In the first funding period, HBPP1, running from 2001 to 2004, necessary technologies were established and optimized. In HBPP2, which started 2004 and will end in May 2008, the developed technologies are used for large-scale experiments, offering new links for disease related research and therapies. The following overview describes structure, aims and outcome of this unique German Brain Proteome Project.

  3. 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

    2016-04-05

    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.

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

    PubMed Central

    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.

    2016-01-01

    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

  5. Transcranial magnetic stimulation and the human brain

    NASA Astrophysics Data System (ADS)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  6. Human brain slices for epilepsy research: Pitfalls, solutions and future challenges.

    PubMed

    Jones, Roland S G; da Silva, Anderson Brito; Whittaker, Roger G; Woodhall, Gavin L; Cunningham, Mark O

    2016-02-15

    Increasingly, neuroscientists are taking the opportunity to use live human tissue obtained from elective neurosurgical procedures for electrophysiological studies in vitro. Access to this valuable resource permits unique studies into the network dynamics that contribute to the generation of pathological electrical activity in the human epileptic brain. Whilst this approach has provided insights into the mechanistic features of electrophysiological patterns associated with human epilepsy, it is not without technical and methodological challenges. This review outlines the main difficulties associated with working with epileptic human brain slices from the point of collection, through the stages of preparation, storage and recording. Moreover, it outlines the limitations, in terms of the nature of epileptic activity that can be observed in such tissue, in particular, the rarity of spontaneous ictal discharges, we discuss manipulations that can be utilised to induce such activity. In addition to discussing conventional electrophysiological techniques that are routinely employed in epileptic human brain slices, we review how imaging and multielectrode array recordings could provide novel insights into the network dynamics of human epileptogenesis. Acute studies in human brain slices are ultimately limited by the lifetime of the tissue so overcoming this issue provides increased opportunity for information gain. We review the literature with respect to organotypic culture techniques that may hold the key to prolonging the viability of this material. A combination of long-term culture techniques, viral transduction approaches and electrophysiology in human brain slices promotes the possibility of large scale monitoring and manipulation of neuronal activity in epileptic microcircuits.

  7. 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.

  8. 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.

  9. What is a large-scale dynamo?

    NASA Astrophysics Data System (ADS)

    Nigro, G.; Pongkitiwanichakul, P.; Cattaneo, F.; Tobias, S. M.

    2017-01-01

    We consider kinematic dynamo action in a sheared helical flow at moderate to high values of the magnetic Reynolds number (Rm). We find exponentially growing solutions which, for large enough shear, take the form of a coherent part embedded in incoherent fluctuations. We argue that at large Rm large-scale dynamo action should be identified by the presence of structures coherent in time, rather than those at large spatial scales. We further argue that although the growth rate is determined by small-scale processes, the period of the coherent structures is set by mean-field considerations.

  10. 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.

  11. 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.

  12. 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.

  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. Large-scale Heterogeneous Network Data Analysis

    DTIC Science & Technology

    2012-07-31

    Data for Multi-Player Influence Maximization on Social Networks.” KDD 2012 (Demo).  Po-Tzu Chang , Yen-Chieh Huang, Cheng-Lun Yang, Shou-De Lin, Pu...Jen Cheng. “Learning-Based Time-Sensitive Re-Ranking for Web Search.” SIGIR 2012 (poster)  Hung -Che Lai, Cheng-Te Li, Yi-Chen Lo, and Shou-De Lin...Exploiting and Evaluating MapReduce for Large-Scale Graph Mining.” ASONAM 2012 (Full, 16% acceptance ratio).  Hsun-Ping Hsieh , Cheng-Te Li, and Shou

  15. Discovering Cortical Folding Patterns in Neonatal Cortical Surfaces Using Large-Scale Dataset

    PubMed Central

    Meng, Yu; Li, Gang; Wang, Li; Lin, Weili; Gilmore, John H.

    2017-01-01

    The cortical folding of the human brain is highly complex and variable across individuals. Mining the major patterns of cortical folding from modern large-scale neuroimaging datasets is of great importance in advancing techniques for neuroimaging analysis and understanding the inter-individual variations of cortical folding and its relationship with cognitive function and disorders. As the primary cortical folding is genetically influenced and has been established at term birth, neonates with the minimal exposure to the complicated postnatal environmental influence are the ideal candidates for understanding the major patterns of cortical folding. In this paper, for the first time, we propose a novel method for discovering the major patterns of cortical folding in a large-scale dataset of neonatal brain MR images (N = 677). In our method, first, cortical folding is characterized by the distribution of sulcal pits, which are the locally deepest points in cortical sulci. Because deep sulcal pits are genetically related, relatively consistent across individuals, and also stable during brain development, they are well suitable for representing and characterizing cortical folding. Then, the similarities between sulcal pit distributions of any two subjects are measured from spatial, geometrical, and topological points of view. Next, these different measurements are adaptively fused together using a similarity network fusion technique, to preserve their common information and also catch their complementary information. Finally, leveraging the fused similarity measurements, a hierarchical affinity propagation algorithm is used to group similar sulcal folding patterns together. The proposed method has been applied to 677 neonatal brains (the largest neonatal dataset to our knowledge) in the central sulcus, superior temporal sulcus, and cingulate sulcus, and revealed multiple distinct and meaningful folding patterns in each region. PMID:28229131

  16. Interoperable atlases of the human brain.

    PubMed

    Amunts, K; Hawrylycz, M J; Van Essen, D C; Van Horn, J D; Harel, N; Poline, J-B; De Martino, F; Bjaalie, J G; Dehaene-Lambertz, G; Dehaene, S; Valdes-Sosa, P; Thirion, B; Zilles, K; Hill, S L; Abrams, M B; Tass, P A; Vanduffel, W; Evans, A C; Eickhoff, S B

    2014-10-01

    The last two decades have seen an unprecedented development of human brain mapping approaches at various spatial and temporal scales. Together, these have provided a large fundus of information on many different aspects of the human brain including micro- and macrostructural segregation, regional specialization of function, connectivity, and temporal dynamics. Atlases are central in order to integrate such diverse information in a topographically meaningful way. It is noteworthy, that the brain mapping field has been developed along several major lines such as structure vs. function, postmortem vs. in vivo, individual features of the brain vs. population-based aspects, or slow vs. fast dynamics. In order to understand human brain organization, however, it seems inevitable that these different lines are integrated and combined into a multimodal human brain model. To this aim, we held a workshop to determine the constraints of a multi-modal human brain model that are needed to enable (i) an integration of different spatial and temporal scales and data modalities into a common reference system, and (ii) efficient data exchange and analysis. As detailed in this report, to arrive at fully interoperable atlases of the human brain will still require much work at the frontiers of data acquisition, analysis, and representation. Among them, the latter may provide the most challenging task, in particular when it comes to representing features of vastly different scales of space, time and abstraction. The potential benefits of such endeavor, however, clearly outweigh the problems, as only such kind of multi-modal human brain atlas may provide a starting point from which the complex relationships between structure, function, and connectivity may be explored.

  17. 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.

  18. Computerized Anatomy Atlas Of The Human Brain

    NASA Astrophysics Data System (ADS)

    Adair, Taylor; Bajcsy, Ruzena; Karp, Peter; Stein, Alan

    1981-10-01

    A software for developing, editing and displaying a 3-D computerized anatomic atlas of a human brain is described. The objective of this atlas is to serve as a reference in identifying various structures in CT scans.

  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. Large-scale Globally Propagating Coronal Waves.

    PubMed

    Warmuth, Alexander

    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.

  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. Alteration of Large-Scale Chromatin Structure by Estrogen Receptor

    PubMed Central

    Nye, Anne C.; Rajendran, Ramji R.; Stenoien, David L.; Mancini, Michael A.; Katzenellenbogen, Benita S.; Belmont, Andrew S.

    2002-01-01

    The estrogen receptor (ER), a member of the nuclear hormone receptor superfamily important in human physiology and disease, recruits coactivators which modify local chromatin structure. Here we describe effects of ER on large-scale chromatin structure as visualized in live cells. We targeted ER to gene-amplified chromosome arms containing large numbers of lac operator sites either directly, through a lac repressor-ER fusion protein (lac rep-ER), or indirectly, by fusing lac repressor with the ER interaction domain of the coactivator steroid receptor coactivator 1. Significant decondensation of large-scale chromatin structure, comparable to that produced by the ∼150-fold-stronger viral protein 16 (VP16) transcriptional activator, was produced by ER in the absence of estradiol using both approaches. Addition of estradiol induced a partial reversal of this unfolding by green fluorescent protein-lac rep-ER but not by wild-type ER recruited by a lac repressor-SRC570-780 fusion protein. The chromatin decondensation activity did not require transcriptional activation by ER nor did it require ligand-induced coactivator interactions, and unfolding did not correlate with histone hyperacetylation. Ligand-induced coactivator interactions with helix 12 of ER were necessary for the partial refolding of chromatin in response to estradiol using the lac rep-ER tethering system. This work demonstrates that when tethered or recruited to DNA, ER possesses a novel large-scale chromatin unfolding activity. PMID:11971975

  3. The human parental brain: in vivo neuroimaging.

    PubMed

    Swain, James E

    2011-07-01

    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.

  4. A comparative study of theoretical graph models for characterizing structural networks of human brain.

    PubMed

    Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

    2013-01-01

    Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

  5. 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

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

    PubMed

    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.

  7. Large-scale parametric survival analysis.

    PubMed

    Mittal, Sushil; Madigan, David; Cheng, Jerry Q; Burd, Randall S

    2013-10-15

    Survival analysis has been a topic of active statistical research in the past few decades with applications spread across several areas. Traditional applications usually consider data with only a small numbers of predictors with a few hundreds or thousands of observations. Recent advances in data acquisition techniques and computation power have led to considerable interest in analyzing very-high-dimensional data where the number of predictor variables and the number of observations range between 10(4) and 10(6). In this paper, we present a tool for performing large-scale regularized parametric survival analysis using a variant of the cyclic coordinate descent method. Through our experiments on two real data sets, we show that application of regularized models to high-dimensional data avoids overfitting and can provide improved predictive performance and calibration over corresponding low-dimensional models.

  8. Primer design for large scale sequencing.

    PubMed

    Haas, S; Vingron, M; Poustka, A; Wiemann, S

    1998-06-15

    We have developed PRIDE, a primer design program that automatically designs primers in single contigs or whole sequencing projects to extend the already known sequence and to double strand single-stranded regions. The program is fully integrated into the Staden package (GAP4) and accessible with a graphical user interface. PRIDE uses a fuzzy logic-based system to calculate primer qualities. The computational performance of PRIDE is enhanced by using suffix trees to store the huge amount of data being produced. A test set of 110 sequencing primers and 11 PCR primer pairs has been designed on genomic templates, cDNAs and sequences containing repetitive elements to analyze PRIDE's success rate. The high performance of PRIDE, combined with its minimal requirement of user interaction and its fast algorithm, make this program useful for the large scale design of primers, especially in large sequencing projects.

  9. Large scale preparation of pure phycobiliproteins.

    PubMed

    Padgett, M P; Krogmann, D W

    1987-01-01

    This paper describes simple procedures for the purification of large amounts of phycocyanin and allophycocyanin from the cyanobacterium Microcystis aeruginosa. A homogeneous natural bloom of this organism provided hundreds of kilograms of cells. Large samples of cells were broken by freezing and thawing. Repeated extraction of the broken cells with distilled water released phycocyanin first, then allophycocyanin, and provides supporting evidence for the current models of phycobilisome structure. The very low ionic strength of the aqueous extracts allowed allophycocyanin release in a particulate form so that this protein could be easily concentrated by centrifugation. Other proteins in the extract were enriched and concentrated by large scale membrane filtration. The biliproteins were purified to homogeneity by chromatography on DEAE cellulose. Purity was established by HPLC and by N-terminal amino acid sequence analysis. The proteins were examined for stability at various pHs and exposures to visible light.

  10. 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.

  11. Efficient, large scale separation of coal macerals

    SciTech Connect

    Dyrkacz, G.R.; Bloomquist, C.A.A.

    1988-01-01

    The authors believe that the separation of macerals by continuous flow centrifugation offers a simple technique for the large scale separation of macerals. With relatively little cost (/approximately/ $10K), it provides an opportunity for obtaining quite pure maceral fractions. Although they have not completely worked out all the nuances of this separation system, they believe that the problems they have indicated can be minimized to pose only minor inconvenience. It cannot be said that this system completely bypasses the disagreeable tedium or time involved in separating macerals, nor will it by itself overcome the mental inertia required to make maceral separation an accepted necessary fact in fundamental coal science. However, they find their particular brand of continuous flow centrifugation is considerably faster than sink/float separation, can provide a good quality product with even one separation cycle, and permits the handling of more material than a conventional sink/float centrifuge separation.

  12. 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.

  13. Large-scale optimization of neuron arbors

    NASA Astrophysics Data System (ADS)

    Cherniak, Christopher; Changizi, Mark; Won Kang, Du

    1999-05-01

    At the global as well as local scales, some of the geometry of types of neuron arbors-both dendrites and axons-appears to be self-organizing: Their morphogenesis behaves like flowing water, that is, fluid dynamically; waterflow in branching networks in turn acts like a tree composed of cords under tension, that is, vector mechanically. Branch diameters and angles and junction sites conform significantly to this model. The result is that such neuron tree samples globally minimize their total volume-rather than, for example, surface area or branch length. In addition, the arbors perform well at generating the cheapest topology interconnecting their terminals: their large-scale layouts are among the best of all such possible connecting patterns, approaching 5% of optimum. This model also applies comparably to arterial and river networks.

  14. 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.

  15. 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

  16. Primer design for large scale sequencing.

    PubMed Central

    Haas, S; Vingron, M; Poustka, A; Wiemann, S

    1998-01-01

    We have developed PRIDE, a primer design program that automatically designs primers in single contigs or whole sequencing projects to extend the already known sequence and to double strand single-stranded regions. The program is fully integrated into the Staden package (GAP4) and accessible with a graphical user interface. PRIDE uses a fuzzy logic-based system to calculate primer qualities. The computational performance of PRIDE is enhanced by using suffix trees to store the huge amount of data being produced. A test set of 110 sequencing primers and 11 PCR primer pairs has been designed on genomic templates, cDNAs and sequences containing repetitive elements to analyze PRIDE's success rate. The high performance of PRIDE, combined with its minimal requirement of user interaction and its fast algorithm, make this program useful for the large scale design of primers, especially in large sequencing projects. PMID:9611248

  17. Modeling the Internet's large-scale topology

    PubMed Central

    Yook, Soon-Hyung; Jeong, Hawoong; Barabási, Albert-László

    2002-01-01

    Network generators that capture the Internet's large-scale topology are crucial for the development of efficient routing protocols and modeling Internet traffic. Our ability to design realistic generators is limited by the incomplete understanding of the fundamental driving forces that affect the Internet's evolution. By combining several independent databases capturing the time evolution, topology, and physical layout of the Internet, we identify the universal mechanisms that shape the Internet's router and autonomous system level topology. We find that the physical layout of nodes form a fractal set, determined by population density patterns around the globe. The placement of links is driven by competition between preferential attachment and linear distance dependence, a marked departure from the currently used exponential laws. The universal parameters that we extract significantly restrict the class of potentially correct Internet models and indicate that the networks created by all available topology generators are fundamentally different from the current Internet. PMID:12368484

  18. 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

  19. Voids in the Large-Scale Structure

    NASA Astrophysics Data System (ADS)

    El-Ad, Hagai; Piran, Tsvi

    1997-12-01

    Voids are the most prominent feature of the large-scale structure of the universe. Still, their incorporation into quantitative analysis of it has been relatively recent, owing essentially to the lack of an objective tool to identify the voids and to quantify them. To overcome this, we present here the VOID FINDER algorithm, a novel tool for objectively quantifying voids in the galaxy distribution. The algorithm first classifies galaxies as either wall galaxies or field galaxies. Then, it identifies voids in the wall-galaxy distribution. Voids are defined as continuous volumes that do not contain any wall galaxies. The voids must be thicker than an adjustable limit, which is refined in successive iterations. In this way, we identify the same regions that would be recognized as voids by the eye. Small breaches in the walls are ignored, avoiding artificial connections between neighboring voids. We test the algorithm using Voronoi tesselations. By appropriate scaling of the parameters with the selection function, we apply it to two redshift surveys, the dense SSRS2 and the full-sky IRAS 1.2 Jy. Both surveys show similar properties: ~50% of the volume is filled by voids. The voids have a scale of at least 40 h-1 Mpc and an average -0.9 underdensity. Faint galaxies do not fill the voids, but they do populate them more than bright ones. These results suggest that both optically and IRAS-selected galaxies delineate the same large-scale structure. Comparison with the recovered mass distribution further suggests that the observed voids in the galaxy distribution correspond well to underdense regions in the mass distribution. This confirms the gravitational origin of the voids.

  20. Improving Recent Large-Scale Pulsar Surveys

    NASA Astrophysics Data System (ADS)

    Cardoso, Rogerio Fernando; Ransom, S.

    2011-01-01

    Pulsars are unique in that they act as celestial laboratories for precise tests of gravity and other extreme physics (Kramer 2004). There are approximately 2000 known pulsars today, which is less than ten percent of pulsars in the Milky Way according to theoretical models (Lorimer 2004). Out of these 2000 known pulsars, approximately ten percent are known millisecond pulsars, objects used for their period stability for detailed physics tests and searches for gravitational radiation (Lorimer 2008). As the field and instrumentation progress, pulsar astronomers attempt to overcome observational biases and detect new pulsars, consequently discovering new millisecond pulsars. We attempt to improve large scale pulsar surveys by examining three recent pulsar surveys. The first, the Green Bank Telescope 350MHz Drift Scan, a low frequency isotropic survey of the northern sky, has yielded a large number of candidates that were visually inspected and identified, resulting in over 34.000 thousands candidates viewed, dozens of detections of known pulsars, and the discovery of a new low-flux pulsar, PSRJ1911+22. The second, the PALFA survey, is a high frequency survey of the galactic plane with the Arecibo telescope. We created a processing pipeline for the PALFA survey at the National Radio Astronomy Observatory in Charlottesville- VA, in addition to making needed modifications upon advice from the PALFA consortium. The third survey examined is a new GBT 820MHz survey devoted to find new millisecond pulsars by observing the target-rich environment of unidentified sources in the FERMI LAT catalogue. By approaching these three pulsar surveys at different stages, we seek to improve the success rates of large scale surveys, and hence the possibility for ground-breaking work in both basic physics and astrophysics.

  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. 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.

  4. Statistical analysis of large-scale neuronal recording data

    PubMed Central

    Reed, Jamie L.; Kaas, Jon H.

    2010-01-01

    Relating stimulus properties to the response properties of individual neurons and neuronal networks is a major goal of sensory research. Many investigators implant electrode arrays in multiple brain areas and record from chronically implanted electrodes over time to answer a variety of questions. Technical challenges related to analyzing large-scale neuronal recording data are not trivial. Several analysis methods traditionally used by neurophysiologists do not account for dependencies in the data that are inherent in multi-electrode recordings. In addition, when neurophysiological data are not best modeled by the normal distribution and when the variables of interest may not be linearly related, extensions of the linear modeling techniques are recommended. A variety of methods exist to analyze correlated data, even when data are not normally distributed and the relationships are nonlinear. Here we review expansions of the Generalized Linear Model designed to address these data properties. Such methods are used in other research fields, and the application to large-scale neuronal recording data will enable investigators to determine the variable properties that convincingly contribute to the variances in the observed neuronal measures. Standard measures of neuron properties such as response magnitudes can be analyzed using these methods, and measures of neuronal network activity such as spike timing correlations can be analyzed as well. We have done just that in recordings from 100-electrode arrays implanted in the primary somatosensory cortex of owl monkeys. Here we illustrate how one example method, Generalized Estimating Equations analysis, is a useful method to apply to large-scale neuronal recordings. PMID:20472395

  5. Computational Methods and Challenges for Large-Scale Circuit Mapping

    PubMed Central

    Helmstaedter, Moritz; Mitra, Partha

    2012-01-01

    Summary The connectivity architecture of neuronal circuits is essential to understand how brains work, yet our knowledge about the neuronal wiring diagrams remains limited and partial. Technical breakthroughs in labeling and imaging methods starting more than a century ago have advanced knowledge in the field. However, the volume of data associated with imaging a whole brain or a significant fraction thereof, with electron or light microscopy, has only recently become amenable to digital storage and analysis. A mouse brain imaged at light microscopic resolution is about a terabyte of data, and 1 mm3 of the brain at EM resolution is about half a petabyte. This has given rise to a new field of research, computational analysis of large scale neuroanatomical data sets, with goals that include reconstructions of the morphology of individual neurons as well as entire circuits. The problems encountered include large data management, segmentation and 3D reconstruction, computational geometry and workflow management allowing for hybrid approaches combining manual and algorithmic processing. Here we review this growing field of neuronal data analysis with emphasis on reconstructing neurons from EM data cubes. PMID:22221862

  6. Inferential stereomorphology of human brain lesions

    NASA Astrophysics Data System (ADS)

    Gedye, John L.

    1980-07-01

    I very much appreciated the invitation to contribute a paper to this Symposium on Applications of Human Biostereometrics, as it provides a valuable opportunity for me to take a fresh look at a problemâ€""the cerebral localisation of psychological function"â€"in which I have been interested for many years. This interest grew out of considerations of the clinically important problem of how we should go about the task of relating the form of the changes in human behavior consequent upon damage to the human brain following, say, head injury, to the form of the changes in brain morphology which constitute that damage, and related issues.

  7. 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.

  8. Large-Scale Measurement of Absolute Protein Glycosylation Stoichiometry.

    PubMed

    Sun, Shisheng; Zhang, Hui

    2015-07-07

    Protein glycosylation is one of the most important protein modifications. Glycosylation site occupancy alteration has been implicated in human diseases and cancers. However, current glycoproteomic methods focus on the identification and quantification of glycosylated peptides and glycosylation sites but not glycosylation occupancy or glycoform stoichiometry. Here we describe a method for large-scale determination of the absolute glycosylation stoichiometry using three independent relative ratios. Using this method, we determined 117 absolute N-glycosylation occupancies in OVCAR-3 cells. Finally, we investigated the possible functions and the determinants for partial glycosylation.

  9. Individual Variability of the System-Level Organization of the Human Brain.

    PubMed

    Gordon, Evan M; Laumann, Timothy O; Adeyemo, Babatunde; Petersen, Steven E

    2015-10-13

    Recent functional magnetic resonance imaging-based resting-state functional connectivity analyses of group average data have characterized large-scale systems that represent a high level in the organizational hierarchy of the human brain. These systems are likely to vary spatially across individuals, even after anatomical alignment, but the characteristics of this variance are unknown. Here, we characterized large-scale brain systems across two independent datasets of young adults. In these individuals, we were able to identify brain systems that were similar to those described in the group average, and we observed that individuals had consistent topological arrangement of the system features present in the group average. However, the size of system features varied across individuals in systematic ways, such that expansion of one feature of a given system predicted expansion of other parts of the system. Individual-specific systems also contained unique topological features not present in group average systems; some of these features were consistent across a minority of individuals. These effects were observed even after controlling for data quality and for the accuracy of anatomical registration. The variability characterized here has important implications for cognitive neuroscience investigations, which often assume the functional equivalence of aligned brain regions across individuals.

  10. 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.

  11. 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.

  12. Noise-induced sensitization of human brain

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yoshiharu; Hidaka, Ichiro; Nozaki, Daichi; Iso-o, Noriko; Soma, Rika; Kwak, Shin

    2002-11-01

    In the past decade, it has been recognized that noise can enhance the response of nonlinear systems to weak signals, via a mechanism known as stochastic resonance (SR). Particularly, the concept of SR has generated considerable interest in sensory biology, because it has been shown in several experimental studies that noise can assist neural systems in detecting weak signals which could not be detected in its absence. Recently, we have shown a similar type of noise-induced sensitization of human brain; externally added noise to the brain stem baroreflex centers sensitized their responses in maintaining adequate blood perfusion to the brain itself. Furthermore, the addition of noise has also shown to be useful in compensating for dysfunctions of the baroreflex centers in certain neurological diseases. It is concluded that the statistical physics concept of SR could be useful in sensitizing human brain in health and disease.

  13. 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.

  14. 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.

  15. 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

  16. Transcriptional landscape of the prenatal human brain.

    PubMed

    Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; 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; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; 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

    2014-04-10

    The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the 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 post-mitotic 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 outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the 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.

  17. Age-dependent changes in task-based modular organization of the human brain.

    PubMed

    Schlesinger, Kimberly J; Turner, Benjamin O; Lopez, Brian A; Miller, Michael B; Carlson, Jean M

    2017-02-01

    As humans age, cognition and behavior change significantly, along with associated brain function and organization. Aging has been shown to decrease variability in functional magnetic resonance imaging (fMRI) signals, and to affect the modular organization of human brain function. In this work, we use complex network analysis to investigate the dynamic community structure of large-scale brain function, asking how evolving communities interact with known brain systems, and how the dynamics of communities and brain systems are affected by age. We analyze dynamic networks derived from fMRI scans of 104 human subjects performing a word memory task, and determine the time-evolving modular structure of these networks by maximizing the multislice modularity, thereby identifying distinct communities, or sets of brain regions with strong intra-set functional coherence. To understand how community structure changes over time, we examine the number of communities as well as the flexibility, or the likelihood that brain regions will switch between communities. We find a significant positive correlation between age and both these measures: younger subjects tend to have less fragmented and more coherent communities, and their brain regions tend to change communities less often during the memory task. We characterize the relationship of community structure to known brain systems by the recruitment coefficient, or the probability of a brain region being grouped in the same community as other regions in the same system. We find that regions associated with cingulo-opercular, somatosensory, ventral attention, and subcortical circuits have a significantly higher recruitment coefficient in younger subjects. This indicates that the within-system functional coherence of these specific systems during the memory task declines with age. Such a correspondence does not exist for other systems (e.g. visual and default mode), whose recruitment coefficients remain relatively uniform across ages

  18. The Brain Prize 2014: complex human functions.

    PubMed

    Grigaityte, Kristina; Iacoboni, Marco

    2014-11-01

    Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research?

  19. Human blood-brain barrier insulin receptor.

    PubMed

    Pardridge, W M; Eisenberg, J; Yang, J

    1985-06-01

    A new model system for characterizing the human brain capillary, which makes up the blood-brain barrier (BBB) in vivo, is described in these studies and is applied initially to the investigation of the human BBB insulin receptor. Autopsy brains were obtained from the pathologist between 22-36 h postmortem and were used to isolate human brain microvessels which appeared intact on both light and phase microscopy. The microvessels were positive for human factor 8 and for a BBB-specific enzyme marker, gamma-glutamyl transpeptidase. The microvessels avidly bound insulin with a high-affinity dissociation constant, KD = 1.2 +/- 0.5 nM. The human brain microvessels internalized insulin based on acid-wash assay, and 75% of insulin was internalized at 37 degrees C. The microvessels transported insulin to the medium at 37 degrees C with a t1/2 = approximately 70 min. Little of the 125I-insulin was metabolized by the microvessels under these conditions based on the elution profile of the medium extract over a Sephadex G-50 column. Plasma membranes were obtained from the human brain microvessels and these membranes were enriched in membrane markers such as gamma-glutamyl transpeptidase or alkaline phosphatase. The plasma membranes bound 125I-insulin with and ED50 = 10 ng/ml, which was identical to the 50% binding point in intact microvessels. The human BBB plasma membranes were solubilized in Triton X-100 and were adsorbed to a wheat germ agglutinin Sepharose affinity column, indicating the BBB insulin receptor is a glycoprotein. Affinity cross-linking of insulin to the plasma membranes revealed a 127K protein that specifically binds insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Seasonality in human cognitive brain responses

    PubMed Central

    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

    2016-01-01

    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

  1. 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.

  2. 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.

  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 tides in general relativity

    NASA Astrophysics Data System (ADS)

    Ip, Hiu Yan; Schmidt, Fabian

    2017-02-01

    Density perturbations in cosmology, i.e. spherically symmetric adiabatic perturbations of a Friedmann-Lemaȋtre-Robertson-Walker (FLRW) spacetime, are locally exactly equivalent to a different FLRW solution, as long as their wavelength is much larger than the sound horizon of all fluid components. This fact is known as the "separate universe" paradigm. However, no such relation is known for anisotropic adiabatic perturbations, which correspond to an FLRW spacetime with large-scale tidal fields. Here, we provide a closed, fully relativistic set of evolutionary equations for the nonlinear evolution of such modes, based on the conformal Fermi (CFC) frame. We show explicitly that the tidal effects are encoded by the Weyl tensor, and are hence entirely different from an anisotropic Bianchi I spacetime, where the anisotropy is sourced by the Ricci tensor. In order to close the system, certain higher derivative terms have to be dropped. We show that this approximation is equivalent to the local tidal approximation of Hui and Bertschinger [1]. We also show that this very simple set of equations matches the exact evolution of the density field at second order, but fails at third and higher order. This provides a useful, easy-to-use framework for computing the fully relativistic growth of structure at second order.

  5. Large-scale autostereoscopic outdoor display

    NASA Astrophysics Data System (ADS)

    Reitterer, Jörg; Fidler, Franz; Saint Julien-Wallsee, Ferdinand; Schmid, Gerhard; Gartner, Wolfgang; Leeb, Walter; Schmid, Ulrich

    2013-03-01

    State-of-the-art autostereoscopic displays are often limited in size, effective brightness, number of 3D viewing zones, and maximum 3D viewing distances, all of which are mandatory requirements for large-scale outdoor displays. Conventional autostereoscopic indoor concepts like lenticular lenses or parallax barriers cannot simply be adapted for these screens due to the inherent loss of effective resolution and brightness, which would reduce both image quality and sunlight readability. We have developed a modular autostereoscopic multi-view laser display concept with sunlight readable effective brightness, theoretically up to several thousand 3D viewing zones, and maximum 3D viewing distances of up to 60 meters. For proof-of-concept purposes a prototype display with two pixels was realized. Due to various manufacturing tolerances each individual pixel has slightly different optical properties, and hence the 3D image quality of the display has to be calculated stochastically. In this paper we present the corresponding stochastic model, we evaluate the simulation and measurement results of the prototype display, and we calculate the achievable autostereoscopic image quality to be expected for our concept.

  6. 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.

  7. Large scale mechanical metamaterials as seismic shields

    NASA Astrophysics Data System (ADS)

    Miniaci, Marco; Krushynska, Anastasiia; Bosia, Federico; Pugno, Nicola M.

    2016-08-01

    Earthquakes represent one of the most catastrophic natural events affecting mankind. At present, a universally accepted risk mitigation strategy for seismic events remains to be proposed. Most approaches are based on vibration isolation of structures rather than on the remote shielding of incoming waves. In this work, we propose a novel approach to the problem and discuss the feasibility of a passive isolation strategy for seismic waves based on large-scale mechanical metamaterials, including for the first time numerical analysis of both surface and guided waves, soil dissipation effects, and adopting a full 3D simulations. The study focuses on realistic structures that can be effective in frequency ranges of interest for seismic waves, and optimal design criteria are provided, exploring different metamaterial configurations, combining phononic crystals and locally resonant structures and different ranges of mechanical properties. Dispersion analysis and full-scale 3D transient wave transmission simulations are carried out on finite size systems to assess the seismic wave amplitude attenuation in realistic conditions. Results reveal that both surface and bulk seismic waves can be considerably attenuated, making this strategy viable for the protection of civil structures against seismic risk. The proposed remote shielding approach could open up new perspectives in the field of seismology and in related areas of low-frequency vibration damping or blast protection.

  8. 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.

  9. 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

  10. REVISITING GLYCOGEN CONTENT IN THE HUMAN BRAIN

    PubMed Central

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

    2015-01-01

    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 13C magnetic resonance spectroscopy (MRS) in conjunction with [1-13C]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 13C labeling in glycogen, here we administered [1-13C]glucose to healthy volunteers for 80 hours. 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 [1-13C]glucose administration and 13C-glycogen levels in the occipital lobe were measured by 13C MRS approximately every 12 hours. 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 13C-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

  11. 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.

  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. Magnetite pollution nanoparticles in the human brain

    NASA Astrophysics Data System (ADS)

    Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <˜200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  14. Magnetite pollution nanoparticles in the human brain

    PubMed Central

    Maher, Barbara A.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-01-01

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683–7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health. PMID:27601646

  15. Magnetite pollution nanoparticles in the human brain.

    PubMed

    Maher, Barbara A; Ahmed, Imad A M; Karloukovski, Vassil; MacLaren, Donald A; Foulds, Penelope G; Allsop, David; Mann, David M A; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

    2016-09-27

    Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

  16. 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

  17. Synchronization of coupled large-scale Boolean networks

    NASA Astrophysics Data System (ADS)

    Li, Fangfei

    2014-03-01

    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.

  18. 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.

  19. Hemispherical map for the human brain cortex

    NASA Astrophysics Data System (ADS)

    Tosun, Duygu; Prince, Jerry L.

    2001-07-01

    Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

  20. 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.

  1. Intergenerational Neuroimaging of Human Brain Circuitry.

    PubMed

    Ho, Tiffany C; Sanders, Stephan J; Gotlib, Ian H; Hoeft, Fumiko

    2016-10-01

    Neuroscientists are increasingly using advanced neuroimaging methods to elucidate the intergenerational transmission of human brain circuitry. This new line of work promises to shed light on the ontogeny of complex behavioral traits, including psychiatric disorders, and possible mechanisms of transmission. Here we highlight recent intergenerational neuroimaging studies and provide recommendations for future work.

  2. MRI Technologies in Recent Human Brain Mapping

    NASA Astrophysics Data System (ADS)

    Sasaki, Yuka

    The recent magnetic resonance imaging (MRI) technology and techniques used in human brain mapping are remarkable. They are getting, faster, stronger and better. The advanced MRI technologies and techniques include, but not to limited to, the magnetic resonance imaging at higher magnetic field strengths, diffusion tensor imaging, multimodal neuroimaging, and monkey functional MRI. In this article, these advanced MRI techniques are briefly overviewed.

  3. Neurosteroid metabolism in the human brain.

    PubMed

    Stoffel-Wagner, B

    2001-12-01

    This review summarizes the current knowledge of the biosynthesis of neurosteroids in the human brain, the enzymes mediating these reactions, their localization and the putative effects of neurosteroids. Molecular biological and biochemical studies have now firmly established the presence of the steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC), aromatase, 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in human brain. The functions attributed to specific neurosteroids include modulation of gamma-aminobutyric acid A (GABAA), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection and induction of neurite outgrowth, dendritic spines and synaptogenesis. The first clinical investigations in humans produced evidence for an involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, post partum depression, catamenial epilepsy, depressive disorders and dementia disorders. Better knowledge of the biochemical pathways of neurosteroidogenesis and their actions on the brain seems to open new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.

  4. '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.

  5. 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

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

    PubMed

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

    2014-08-28

    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.

  7. 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.

  8. Extending SME to Handle Large-Scale Cognitive Modeling.

    PubMed

    Forbus, Kenneth D; Ferguson, Ronald W; Lovett, Andrew; Gentner, Dedre

    2016-06-20

    Analogy and similarity are central phenomena in human cognition, involved in processes ranging from visual perception to conceptual change. To capture this centrality requires that a model of comparison must be able to integrate with other processes and handle the size and complexity of the representations required by the tasks being modeled. This paper describes extensions to Structure-Mapping Engine (SME) since its inception in 1986 that have increased its scope of operation. We first review the basic SME algorithm, describe psychological evidence for SME as a process model, and summarize its role in simulating similarity-based retrieval and generalization. Then we describe five techniques now incorporated into the SME that have enabled it to tackle large-scale modeling tasks: (a) Greedy merging rapidly constructs one or more best interpretations of a match in polynomial time: O(n(2) log(n)); (b) Incremental operation enables mappings to be extended as new information is retrieved or derived about the base or target, to model situations where information in a task is updated over time; (c) Ubiquitous predicates model the varying degrees to which items may suggest alignment; (d) Structural evaluation of analogical inferences models aspects of plausibility judgments; (e) Match filters enable large-scale task models to communicate constraints to SME to influence the mapping process. We illustrate via examples from published studies how these enable it to capture a broader range of psychological phenomena than before.

  9. Evolution and genomics of the human brain.

    PubMed

    Rosales-Reynoso, M A; Juárez-Vázquez, C I; Barros-Núñez, P

    2015-08-21

    Most living beings are able to perform actions that can be considered intelligent or, at the very least, the result of an appropriate reaction to changing circumstances in their environment. However, the intelligence or intellectual processes of humans are vastly superior to those achieved by all other species. The adult human brain is a highly complex organ weighing approximately 1500g, which accounts for only 2% of the total body weight but consumes an amount of energy equal to that required by all skeletal muscle at rest. Although the human brain displays a typical primate structure, it can be identified by its specific distinguishing features. The process of evolution and humanisation of the Homo sapiens brain resulted in a unique and distinct organ with the largest relative volume of any animal species. It also permitted structural reorganization of tissues and circuits in specific segments and regions. These steps explain the remarkable cognitive abilities of modern humans compared not only with other species in our genus, but also with older members of our own species. Brain evolution required the coexistence of two adaptation mechanisms. The first involves genetic changes that occur at the species level, and the second occurs at the individual level and involves changes in chromatin organisation or epigenetic changes. The genetic mechanisms include: a) genetic changes in coding regions that lead to changes in the sequence and activity of existing proteins; b) duplication and deletion of previously existing genes; c) changes in gene expression through changes in the regulatory sequences of different genes; and d) synthesis of non-coding RNAs. Lastly, this review describes some of the main documented chromosomal differences between humans and great apes. These differences have also contributed to the evolution and humanisation process of the H. sapiens brain.

  10. Imaging visual function of the human brain

    SciTech Connect

    Marg, E.

    1988-10-01

    Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references.

  11. Human astrocytes in the diseased brain.

    PubMed

    Dossi, Elena; Vasile, Flora; Rouach, Nathalie

    2017-02-13

    Astrocytes are key active elements of the brain that contribute to information processing. They not only provide neurons with metabolic and structural support, but also regulate neurogenesis and brain wiring. Furthermore, astrocytes modulate synaptic activity and plasticity in part by controlling the extracellular space volume, as well as ion and neurotransmitter homeostasis. These findings, together with the discovery that human astrocytes display contrasting characteristics with their rodent counterparts, point to a role for astrocytes in higher cognitive functions. Dysfunction of astrocytes can thereby induce major alterations in neuronal functions, contributing to the pathogenesis of several brain disorders. In this review we summarize the current knowledge on the structural and functional alterations occurring in astrocytes from the human brain in pathological conditions such as epilepsy, primary tumours, Alzheimer's disease, major depressive disorder and Down syndrome. Compelling evidence thus shows that dysregulations of astrocyte functions and interplay with neurons contribute to the development and progression of various neurological diseases. Targeting astrocytes is thus a promising alternative approach that could contribute to the development of novel and effective therapies to treat brain disorders.

  12. 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.

  13. [Evolution of human brain and intelligence].

    PubMed

    Lakatos, László; Janka, Zoltán

    2008-07-30

    The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

  14. 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.

  15. Sense of agency in the human brain.

    PubMed

    Haggard, Patrick

    2017-04-01

    In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cognitive and behavioural experiments, and a growing understanding of the brain circuits that generate this distinctive but elusive experience. The sense of agency is a mental and neural state of cardinal importance in human civilization, because it is frequently altered in psychopathology and because it underpins the concept of responsibility in human societies.

  16. 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

  17. 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

  18. 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

  19. Magnetic source imaging of the human brain

    NASA Astrophysics Data System (ADS)

    Lu, Zhong L.; Williamson, Samuel J.; Kaufman, Lloyd

    1993-08-01

    The importance of neuromagnetic studies in basic research on sensory and cognitive functions is well recognized. Researchers are now exploiting more sophisticated paradigms as well as more sophisticated data analysis techniques to achieve new knowledge about the human brain. Our recent identification of characteristic time constants in human auditory cortex that well predict the behavioral lifetime of human auditory sensory memory, and developments and application of various procedures for the magnetic inverse problem have opened new areas of investigation and advanced the technical capability of MSI. With multi-disciplinary efforts from physicists, neural scientists, psychologists and physiologists, MSI is being established as an important modality for functional images.

  20. Phospholipid biosynthetic enzymes in human brain.

    PubMed

    Ross, B M; Moszczynska, A; Blusztajn, J K; Sherwin, A; Lozano, A; Kish, S J

    1997-04-01

    Growing evidence suggests an involvement of brain membrane phospholipid metabolism in a variety of neurodegenerative and psychiatric conditions. This has prompted the use of drugs (e.g., CDPcholine) aimed at elevating the rate of neural membrane synthesis. However, no information is available regarding the human brain enzymes of phospholipid synthesis which these drugs affect. Thus, the objective of our study was to characterize the enzymes involved, in particular, whether differences existed in the relative affinity of substrates for the enzymes of phosphatidylethanolamine (PE) compared to those of phosphatidylcholine (PC) synthesis. The concentration of choline in rapidly frozen human brain biopsies ranged from 32-186 nmol/g tissue, a concentration similar to that determined previously for ethanolamine. Since human brain ethanolamine kinase possessed a much lower affinity for ethanolamine (Km = 460 microM) than choline kinase did for choline (Km = 17 microM), the activity of ethanolamine kinase in vivo may be more dependent on substrate availability than that of choline kinase. In addition, whereas ethanolamine kinase was inhibited by choline, and to a lesser extent by phosphocholine, choline kinase activity was unaffected by the presence of ethanolamine, or phosphoethanolamine, and only weakly inhibited by phosphocholine. Phosphoethanolamine cytidylyltransferase (PECT) and phosphocholine cytidylyltransferase (PCCT) also displayed dissimilar characteristics, with PECT and PCCT being located predominantly in the cytosolic and particulate fractions, respectively. Both PECT and PCCT exhibited a low affinity for CTP (Km approximately 1.2 mM), suggesting that the activities of these enzymes, and by implication, the rate of phospholipid synthesis, are highly dependent upon the cellular concentration of CTP. In conclusion our data indicate different regulatory properties of PE and PC synthesis in human brain, and suggest that the rate of PE synthesis may be more

  1. Disentangling the dynamic core: a research program for a neurodynamics at the large-scale.

    PubMed

    Le Van Quyen, Michel

    2003-01-01

    My purpose in this paper is to sketch a research direction based on Francisco Varela's pioneering work in neurodynamics (see also Rudrauf et al. 2003, in this issue). Very early on he argued that the internal coherence of every mental-cognitive state lies in the global self-organization of the brain activities at the large-scale, constituting a fundamental pole of integration called here a "dynamic core". Recent neuroimaging evidence appears to broadly support this hypothesis and suggests that a global brain dynamics emerges at the large scale level from the cooperative interactions among widely distributed neuronal populations. Despite a growing body of evidence supporting this view, our understanding of these large-scale brain processes remains hampered by the lack of a theoretical language for expressing these complex behaviors in dynamical terms. In this paper, I propose a rough cartography of a comprehensive approach that offers a conceptual and mathematical framework to analyze spatio-temporal large-scale brain phenomena. I emphasize how these nonlinear methods can be applied, what property might be inferred from neuronal signals, and where one might productively proceed for the future. This paper is dedicated, with respect and affection, to the memory of Francisco Varela.

  2. 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.

  3. Histidine-tryptophan-ketoglutarate and University of Wisconsin solution demonstrate equal effectiveness in the preservation of human pancreata intended for islet isolation: a large-scale, single-center experience.

    PubMed

    Paushter, Daniel H; Qi, Meirigeng; Danielson, Kirstie K; Harvat, Tricia A; Kinzer, Katie; Barbaro, Barbara; Patel, Sonny; Hassan, Sarah Z; Oberholzer, Jose; Wang, Yong

    2013-01-01

    We previously reported a small-scale study on the efficacy of histidine-tryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution on pancreas preservation for islet isolation. In this large-scale, retrospective analysis (n = 252), we extend our initial description of the impact of HTK on islet isolation outcomes and include pancreatic digestion efficacy, purification outcomes, and islet size distribution. Multivariable linear regression analysis, adjusted for donor age, sex, BMI, cold ischemia time, and enzyme, demonstrated similar results for the HTK group (n = 95) and the UW group (n = 157), including postpurification islet yields (HTK: 289,702 IEQ vs. UW: 283,036 IEQ; p = 0.76), percentage of digested pancreatic tissue (HTK: 66.9% vs. UW: 64.1%; p = 0.18), and islet loss from postdigestion to postpurification (HTK: 24,972 IEQ vs. UW: 39,551 IEQ; p = 0.38). Changes in islet size between the postdigestion and postpurification stages were comparable within each islet size category for HTK and UW (p = 0.14-0.99). Tissue volume distribution across purification fractions and islet purity in the top fractions were similar between the groups; however, the HTK group had significantly higher islet purity in the middle fractions (p = 0.003-0.008). Islet viability and stimulation indices were also similar between the HTK and the UW groups. In addition, we analyzed a small sample of patients transplanted either with HTK (n = 7) or UW (n = 8) preserved islets and found no significant differences in posttransplant HbA1c, β-score, and frequency of insulin independence. This study demonstrates that HTK and UW solutions offer comparable pancreas preservation for islet transplantation. More in vivo islet outcome data are needed for a complete analysis of the effects of HTK on islet transplantation.

  4. Rapid large-scale oligonucleotide selection for microarrays.

    PubMed

    Rahmann, Sven

    2002-01-01

    We present the first algorithm that selects oligonucleotide probes (e.g. 25-mers) for microarray experiments on a large scale. For example, oligos for human genes can be found within 50 hours. This becomes possible by using the longest common substring as a specificity measure for candidate oligos. We present an algorithm based on a suffix array with additional information that is efficient both in terms of memory usage and running time to rank all candidate oligos according to their specificity. We also introduce the concept of master sequences to describe the sequences from which oligos are to be selected. Constraints such as oligo length, melting temperature, and self-complementarity are incorporated in the master sequence at a preprocessing stage and thus kept separate from the main selection problem. As a result, custom oligos can now be designed for any sequenced genome, just as the technology for on-site chip synthesis is becoming increasingly mature.

  5. 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.

  6. 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

  7. A large-scale crop protection bioassay data set

    NASA Astrophysics Data System (ADS)

    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.

    2015-07-01

    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.

  8. A large-scale crop protection bioassay data set

    PubMed Central

    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

  9. 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.

  10. Large-scale multielectrode recording and stimulation of neural activity

    NASA Astrophysics Data System (ADS)

    Sher, A.; Chichilnisky, E. J.; Dabrowski, W.; Grillo, A. A.; Grivich, M.; Gunning, D.; Hottowy, P.; Kachiguine, S.; Litke, A. M.; Mathieson, K.; Petrusca, D.

    2007-09-01

    Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions.

  11. Aging-associated changes in human brain.

    PubMed

    Mrak, R E; Griffin, S T; Graham, D I

    1997-12-01

    A wide variety of anatomic and histological alterations are common in brains of aged individuals. However, identification of intrinsic aging changes--as distinct from changes resulting from cumulative environmental insult--is problematic. Some degree of neuronal and volume loss would appear to be inevitable, but recent studies have suggested that the magnitudes of such changes are much less than previously thought, and studies of dendritic complexity in cognitively intact individuals suggest continuing neuronal plasticity into the eighth decade. A number of vascular changes become more frequent with age, many attributable to systemic conditions such as hypertension and atherosclerosis. Age-associated vascular changes not clearly linked to such conditions include hyaline arteriosclerotic changes with formation of arterial tortuosities in small intracranial vessels and the radiographic changes in deep cerebral white matter known as "leukoaraiosis." Aging is accompanied by increases in glial cell activation, in oxidative damage to proteins and lipids, in irreversible protein glycation, and in damage to DNA, and such changes may underlie in part the age-associated increasing incidence of "degenerative" conditions such as Alzheimer disease and Parkinson disease. A small number of histological changes appear to be universal in aged human brains. These include increasing numbers of corpora amylacea within astrocytic processes near blood-brain or cerebrospinal fluid-brain interfaces, accumulation of the "aging" pigment lipofuscin in all brain regions, and appearance of Alzheimer-type neurofibrillary tangles (but not necessarily amyloid plaques) in mesial temporal structures.

  12. 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.

  13. 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

  14. 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.

  15. Management Structures and Large-Scale Studies.

    ERIC Educational Resources Information Center

    Welty, Gordon; Lundin, Edward

    The structure of an organization plays a vital role in the evaluation of the organization. Social science researchers often assume that controls inherent in the physical sciences are as applicable to human subjects. Evaluation of Head Start is an example of the social relation of investigator to subject matter and of the variables introduced by…

  16. Imaging retinotopic maps in the human brain

    PubMed Central

    Wandell, Brian A.; Winawer, Jonathan

    2010-01-01

    A quarter-century ago visual neuroscientists had little information about the number and organization of retinotopic maps in human visual cortex. The advent of functional magnetic resonance imaging (MRI), a non-invasive, spatially-resolved technique for measuring brain activity, provided a wealth of data about human retinotopic maps. Just as there are differences amongst nonhuman primate maps, the human maps have their own unique properties. Many human maps can be measured reliably in individual subjects during experimental sessions lasting less than an hour. The efficiency of the measurements and the relatively large amplitude of functional MRI signals in visual cortex make it possible to develop quantitative models of functional responses within specific maps in individual subjects. During this last quarter century, there has also been significant progress in measuring properties of the human brain at a range of length and time scales, including white matter pathways, macroscopic properties of gray and white matter, and cellular and molecular tissue properties. We hope the next twenty-five years will see a great deal of work that aims to integrate these data by modeling the network of visual signals. We don’t know what such theories will look like, but the characterization of human retinotopic maps from the last twenty-five years is likely to be an important part of future ideas about visual computations. PMID:20692278

  17. 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.

  18. Health Terrain: Visualizing Large Scale Health Data

    DTIC Science & Technology

    2015-12-01

    13. SUPPLEMENTARY  NOTES 14.  ABSTRACT The promise of the benefits of fully integrated electronic health care systems can only be realized if the... Language Processing techniques were carried out to process 325791 clinical notes to extract new terms including diseases, symptoms, and mental and...military electronic health record systems by allowing system level integration of the human´s visual capabilities into the overall health data based

  19. Feedforward and feedback frequency-dependent interactions in a large-scale laminar network of the primate cortex

    PubMed Central

    Mejias, Jorge F.; Murray, John D.; Kennedy, Henry; Wang, Xiao-Jing

    2016-01-01

    Interactions between top-down and bottom-up processes in the cerebral cortex hold the key to understanding attentional processes, predictive coding, executive control, and a gamut of other brain functions. However, the underlying circuit mechanism remains poorly understood and represents a major challenge in neuroscience. We approached this problem using a large-scale computational model of the primate cortex constrained by new directed and weighted connectivity data. In our model, the interplay between feedforward and feedback signaling depends on the cortical laminar structure and involves complex dynamics across multiple (intralaminar, interlaminar, interareal, and whole cortex) scales. The model was tested by reproducing, as well as providing insights into, a wide range of neurophysiological findings about frequency-dependent interactions between visual cortical areas, including the observation that feedforward pathways are associated with enhanced gamma (30 to 70 Hz) oscillations, whereas feedback projections selectively modulate alpha/low-beta (8 to 15 Hz) oscillations. Furthermore, the model reproduces a functional hierarchy based on frequency-dependent Granger causality analysis of interareal signaling, as reported in recent monkey and human experiments, and suggests a mechanism for the observed context-dependent hierarchy dynamics. Together, this work highlights the necessity of multiscale approaches and provides a modeling platform for studies of large-scale brain circuit dynamics and functions. PMID:28138530

  20. 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.

  1. 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).

  2. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders.

  3. Metabolism of steroids by human brain tumors.

    PubMed

    Weidenfeld, J; Schiller, H

    1984-01-01

    Hormonal steroids or their precursors can be metabolized in the CNS to products with altered hormonal activity. The importance of the intracerebral transformation of steroids has been demonstrated, particularly with regard to neuroendocrine regulation and sexual behavior. These studies were carried out on normal brain tissues, but the ability of neoplastic tissues of CNS origin to metabolize steroids is unknown. We investigated the in vitro metabolism of tritiated pregnenolone, testosterone, and estradiol-17 beta by homogenates of four brain tumors defined as astrocytomas. In three tumors of cortical origin, removed from adult patients, the only enzymic activity found was the conversion of estradiol to estrone. In one tumor of cerebellar origin removed from an 11-year-old boy, the following conversions were found: pregnenolone to progesterone, testosterone to either androstenedione or estradiol, and estradiol to estrone. These results demonstrate that human astrocytomas can transform steroids to compounds with modified hormonal activity. These compounds formed by the tumorous tissue can affect brain function, which may be of clinical significance. Furthermore, these results may add important parameters for biochemical characterization of neoplastic brain tissues.

  4. Deconstructing Anger in the Human Brain.

    PubMed

    Gilam, Gadi; Hendler, Talma

    2017-01-01

    Anger may be caused by a wide variety of triggers, and though it has negative consequences on health and well-being, it is also crucial in motivating to take action and approach rather than avoid a confrontation. While anger is considered a survival response inherent in all living creatures, humans are endowed with the mental flexibility that enables them to control and regulate their anger, and adapt it to socially accepted norms. Indeed, a profound interpersonal nature is apparent in most events which evoke anger among humans. Since anger consists of physiological, cognitive, subjective, and behavioral components, it is a contextualized multidimensional construct that poses theoretical and operational difficulties in defining it as a single psychobiological phenomenon. Although most neuroimaging studies have neglected the multidimensionality of anger and thus resulted in brain activations dispersed across the entire brain, there seems to be several reoccurring neural circuits subserving the subjective experience of human anger. Nevertheless, to capture the large variety in the forms and fashions in which anger is experienced, expressed, and regulated, and thus to better portray the related underlying neural substrates, neurobehavioral investigations of human anger should aim to further embed realistic social interactions within their anger induction paradigms.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Transcriptional profiles of supragranular-enriched genes associate with corticocortical network architecture in the human brain.

    PubMed

    Krienen, Fenna M; Yeo, B T Thomas; Ge, Tian; Buckner, Randy L; Sherwood, Chet C

    2016-01-26

    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.

  11. Information Tailoring Enhancements for Large-Scale Social Data

    DTIC Science & Technology

    2016-06-15

    Intelligent Automation Incorporated Information Tailoring Enhancements for Large-Scale...Automation Incorporated Progress Report No. 3 Information Tailoring Enhancements for Large-Scale Social Data Submitted in accordance with...also gathers information about entities from all news articles and displays it on over one million entity pages [5][6], and the information is made

  12. Mathematical logic in the human brain: semantics.

    PubMed

    Friedrich, Roland M; Friederici, Angela D

    2013-01-01

    As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge.

  13. 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.

  14. Mathematical Logic in the Human Brain: Semantics

    PubMed Central

    Friedrich, Roland M.; Friederici, Angela D.

    2013-01-01

    As a higher cognitive function in humans, mathematics is supported by parietal and prefrontal brain regions. Here, we give an integrative account of the role of the different brain systems in processing the semantics of mathematical logic from the perspective of macroscopic polysynaptic networks. By comparing algebraic and arithmetic expressions of identical underlying structure, we show how the different subparts of a fronto-parietal network are modulated by the semantic domain, over which the mathematical formulae are interpreted. Within this network, the prefrontal cortex represents a system that hosts three major components, namely, control, arithmetic-logic, and short-term memory. This prefrontal system operates on data fed to it by two other systems: a premotor-parietal top-down system that updates and transforms (external) data into an internal format, and a hippocampal bottom-up system that either detects novel information or serves as an access device to memory for previously acquired knowledge. PMID:23301101

  15. SEGMA: An Automatic SEGMentation Approach for Human Brain MRI Using Sliding Window and Random Forests

    PubMed Central

    Serag, Ahmed; Wilkinson, Alastair G.; Telford, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Anblagan, Devasuda; Macnaught, Gillian; Semple, Scott I.; Boardman, James P.

    2017-01-01

    Quantitative volumes from brain magnetic resonance imaging (MRI) acquired across the life course may be useful for investigating long term effects of risk and resilience factors for brain development and healthy aging, and for understanding early life determinants of adult brain structure. Therefore, there is an increasing need for automated segmentation tools that can be applied to images acquired at different life stages. We developed an automatic segmentation method for human brain MRI, where a sliding window approach and a multi-class random forest classifier were applied to high-dimensional feature vectors for accurate segmentation. The method performed well on brain MRI data acquired from 179 individuals, analyzed in three age groups: newborns (38–42 weeks gestational age), children and adolescents (4–17 years) and adults (35–71 years). As the method can learn from partially labeled datasets, it can be used to segment large-scale datasets efficiently. It could also be applied to different populations and imaging modalities across the life course. PMID:28163680

  16. Effects of brain evolution on human nutrition and metabolism.

    PubMed

    Leonard, William R; Snodgrass, J Josh; Robertson, Marcia L

    2007-01-01

    The evolution of large human brain size has had important implications for the nutritional biology of our species. Large brains are energetically expensive, and humans expend a larger proportion of their energy budget on brain metabolism than other primates. The high costs of large human brains are supported, in part, by our energy- and nutrient-rich diets. Among primates, relative brain size is positively correlated with dietary quality, and humans fall at the positive end of this relationship. Consistent with an adaptation to a high-quality diet, humans have relatively small gastrointestinal tracts. In addition, humans are relatively "undermuscled" and "over fat" compared with other primates, features that help to offset the high energy demands of our brains. Paleontological evidence indicates that rapid brain evolution occurred with the emergence of Homo erectus 1.8 million years ago and was associated with important changes in diet, body size, and foraging behavior.

  17. 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

  18. 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.

  19. For 'Preemies,' Human Touch May Be a Brain Booster

    MedlinePlus

    ... html For 'Preemies,' Human Touch May Be a Brain Booster Diminished response seen in premature infants who ... 16, 2017 (HealthDay News) -- Underscoring the link between brain development and touch, new research suggests premature babies ...

  20. Weighted social networks for a large scale artificial society

    NASA Astrophysics Data System (ADS)

    Fan, Zong Chen; Duan, Wei; Zhang, Peng; Qiu, Xiao Gang

    2016-12-01

    The method of artificial society has provided a powerful way to study and explain how individual behaviors at micro level give rise to the emergence of global social phenomenon. It also creates the need for an appropriate representation of social structure which usually has a significant influence on human behaviors. It has been widely acknowledged that social networks are the main paradigm to describe social structure and reflect social relationships within a population. To generate social networks for a population of interest, considering physical distance and social distance among people, we propose a generation model of social networks for a large-scale artificial society based on human choice behavior theory under the principle of random utility maximization. As a premise, we first build an artificial society through constructing a synthetic population with a series of attributes in line with the statistical (census) data for Beijing. Then the generation model is applied to assign social relationships to each individual in the synthetic population. Compared with previous empirical findings, the results show that our model can reproduce the general characteristics of social networks, such as high clustering coefficient, significant community structure and small-world property. Our model can also be extended to a larger social micro-simulation as an input initial. It will facilitate to research and predict some social phenomenon or issues, for example, epidemic transition and rumor spreading.

  1. 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.

  2. Fast Optical Imaging of Human Brain Function

    PubMed Central

    Gratton, Gabriele; Fabiani, Monica

    2010-01-01

    Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods) emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so) interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years) may provide descriptions of localized (to sub-cm level) brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed. PMID:20631845

  3. 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

  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. Human brain lesion-deficit inference remapped.

    PubMed

    Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

    2014-09-01

    Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

  6. Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes depleted of graft-versus-host reactivity: a new source for graft facilitating cells in bone marrow transplantation.

    PubMed

    Aviner, Shraga; Yao, Xin; Krauthgamer, Rita; Gan, Yehudit; Goren-Arbel, Rinat; Klein, Tirza; Tabilio, Antonio; McMannis, John D; Champlin, Richard; Martelli, Massimo F; Bachar-Lustig, Esther; Reisner, Yair

    2005-06-01

    Induction of donor type chimerism in mildly prepared hosts without graft-versus-host disease (GvHD) is a most desirable goal in bone morrow transplantation. We have recently demonstrated in a mouse model that donor veto cytotoxic T lymphocytes (CTLs) can facilitate the induction of donor type chimerism in sublethally irradiated recipients without causing GvHD if they are effectively depleted of alloreactivity against host cells by means of stimulation against a third party. We extend this approach to human cells, by preparing CTLs in two major steps: primary culture in the absence of interleukin 2, leading to death by neglect of antihost clones, and addition of interleukin 2 and subsequent dilution of antihost clones as a consequence of the expansion of the anti-third-party clones. CTLs prepared in this way specifically suppress host cytotoxic T cells directed against antigens of the donor, but not against fourth-party antigens, as demonstrated in a standard (51)Cr release assay. We conclude that human anti-third-party CTLs afford a new source of veto cells that are depleted of potential graft-versus-host-reactive clones. The cells generated by this approach could potentially be used to facilitate engraftment of allogeneic hematopoietic stem cells.

  7. 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.

  8. Learning networks for sustainable, large-scale improvement.

    PubMed

    McCannon, C Joseph; Perla, Rocco J

    2009-05-01

    Large-scale improvement efforts known as improvement networks offer structured opportunities for exchange of information and insights into the adaptation of clinical protocols to a variety of settings.

  9. Modified gravity and large scale flows, a review

    NASA Astrophysics Data System (ADS)

    Mould, Jeremy

    2017-02-01

    Large scale flows have been a challenging feature of cosmography ever since galaxy scaling relations came on the scene 40 years ago. The next generation of surveys will offer a serious test of the standard cosmology.

  10. 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.

  11. Association between human papillomavirus (HPV) 16, HPV18, and other HR-HPV viral load and the histological classification of cervical lesions: Results from a large-scale cross-sectional study.

    PubMed

    Wu, Zeni; Qin, Yu; Yu, Lulu; Lin, Chunqing; Wang, Hong; Cui, Jianfeng; Liu, Bin; Liao, Yiqun; Warren, De'Andre; Zhang, Xun; Chen, Wen

    2017-03-01

    The relationship between HPV viral load and histological grades in the development of cervical cancer is in argument. It is helpful to better understand the association by quantitatively detecting viral load of HPV16, 18, and a pool of 12 other high-risk HPV type (OT) independently on the samples of precancer and cancer. A cross-sectional study was performed in five medical centers of China. Histological diagnosis made by local pathologists was adjudicated via a pathology expert panel. A fully automated real-time PCR test was used for the measurement of HPV16, 18, OT, and human β-globin gene. A total of 2,513 women [1,341 normal, 209 low grade intraepithelial lesion (LSIL), 392 high grade intraepithelial lesion (HSIL), 520 squamous cell carcinoma (SCC), and 51 adenocarcinoma (ADC)] were included. There is a linear increase in the total 14 HPV viral load with histological grade from normal to SCC. This trend was not observed in HPV18 infection but HPV16. The viral load for OT was low in normal, peaked in LSIL and HSIL, and declined in SCC and ADC. In the co-infection of HPV16 and HPV18, HPV16 viral load was significantly higher than HPV18 in LSIL and HSIL. In co-infection of HPV16 and OT, higher HPV16 viral load was also seen in SCC and ADC. Viral load of HPV16 increases with cervical lesion grade and is predominant in cervical cancer. HPV18 viral load is low in precancer, but going up in cancer. OT viral load shows inverse trend of HPV18. J. Med. Virol. 89:535-541, 2017. © 2016 Wiley Periodicals, Inc.

  12. Analyzing large-scale proteomics projects with latent semantic indexing.

    PubMed

    Klie, Sebastian; Martens, Lennart; Vizcaíno, Juan Antonio; Côté, Richard; Jones, Phil; Apweiler, Rolf; Hinneburg, Alexander; Hermjakob, Henning

    2008-01-01

    Since the advent of public data repositories for proteomics data, readily accessible results from high-throughput experiments have been accumulating steadily. Several large-scale projects in particular have contributed substantially to the amount of identifications available to the community. Despite the considerable body of information amassed, very few successful analyses have been performed and published on this data, leveling off the ultimate value of these projects far below their potential. A prominent reason published proteomics data is seldom reanalyzed lies in the heterogeneous nature of the original sample collection and the subsequent data recording and processing. To illustrate that at least part of this heterogeneity can be compensated for, we here apply a latent semantic analysis to the data contributed by the Human Proteome Organization's Plasma Proteome Project (HUPO PPP). Interestingly, despite the broad spectrum of instruments and methodologies applied in the HUPO PPP, our analysis reveals several obvious patterns that can be used to formulate concrete recommendations for optimizing proteomics project planning as well as the choice of technologies used in future experiments. It is clear from these results that the analysis of large bodies of publicly available proteomics data by noise-tolerant algorithms such as the latent semantic analysis holds great promise and is currently underexploited.

  13. 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.

  14. 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.

  15. Automated workflow for large-scale selected reaction monitoring experiments.

    PubMed

    Malmström, Lars; Malmström, Johan; Selevsek, Nathalie; Rosenberger, George; Aebersold, Ruedi

    2012-03-02

    Targeted proteomics allows researchers to study proteins of interest without being drowned in data from other, less interesting proteins or from redundant or uninformative peptides. While the technique is mostly used for smaller, focused studies, there are several reasons to conduct larger targeted experiments. Automated, highly robust software becomes more important in such experiments. In addition, larger experiments are carried out over longer periods of time, requiring strategies to handle the sometimes large shift in retention time often observed. We present a complete proof-of-principle software stack that automates most aspects of selected reaction monitoring workflows, a targeted proteomics technology. The software allows experiments to be easily designed and carried out. The steps automated are the generation of assays, generation of mass spectrometry driver files and methods files, and the import and analysis of the data. All data are normalized to a common retention time scale, the data are then scored using a novel score model, and the error is subsequently estimated. We also show that selected reaction monitoring can be used for label-free quantification. All data generated are stored in a relational database, and the growing resource further facilitates the design of new experiments. We apply the technology to a large-scale experiment studying how Streptococcus pyogenes remodels its proteome under stimulation of human plasma.

  16. [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.

  17. Bayesian hierarchical model for large-scale covariance matrix estimation.

    PubMed

    Zhu, Dongxiao; Hero, Alfred O

    2007-12-01

    Many bioinformatics problems implicitly depend on estimating large-scale covariance matrix. The traditional approaches tend to give rise to high variance and low accuracy due to "overfitting." We cast the large-scale covariance matrix estimation problem into the Bayesian hierarchical model framework, and introduce dependency between covariance parameters. We demonstrate the advantages of our approaches over the traditional approaches using simulations and OMICS data analysis.

  18. 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

  19. SEARCHING HUMAN BRAIN FOR MECHANISMS OF PSYCHIATRIC DISORDERS

    PubMed Central

    Berretta, Sabina; Heckers, Stephan; Benes, Francine M.

    2014-01-01

    In the past 25 years, research on the human brain has been providing a clear path toward understanding the pathophysiology of psychiatric illnesses. The successes that have been accrued are matched by significant difficulties identifying and controlling a large number of potential confounding variables. By systematically and effectively accounting for unwanted variance in data from imaging and postmortem human brain studies, meaningful and reliable information regarding the pathophysiology of human brain disorders can be obtained. This perspective paper focuses on postmortem investigations to discuss some of the most challenging sources of variance, including diagnosis, comorbidity, substance abuse and pharmacological treatment, which confound investigations of human brain. PMID:25458567

  20. 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.

  1. 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

  2. Large-scale neural networks and the lateralization of motivation and emotion.

    PubMed

    Tops, Mattie; Quirin, Markus; Boksem, Maarten A S; Koole, Sander L

    2017-02-09

    Several lines of research in animals and humans converge on the distinction between two basic large-scale brain networks of self-regulation, giving rise to predictive and reactive control systems (PARCS). Predictive (internally-driven) and reactive (externally-guided) control are supported by dorsal versus ventral corticolimbic systems, respectively. Based on extant empirical evidence, we demonstrate how the PARCS produce frontal laterality effects in emotion and motivation. In addition, we explain how this framework gives rise to individual differences in appraising and coping with challenges. PARCS theory integrates separate fields of research, such as research on the motivational correlates of affect, EEG frontal alpha power asymmetry and implicit affective priming effects on cardiovascular indicators of effort during cognitive task performance. Across these different paradigms, converging evidence points to a qualitative motivational division between, on the one hand, angry and happy emotions, and, on the other hand, sad and fearful emotions. PARCS suggests that those two pairs of emotions are associated with predictive and reactive control, respectively. PARCS theory may thus generate important new insights on the motivational and emotional dynamics that drive autonomic and homeostatic control processes.

  3. 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.

  4. Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes

    PubMed Central

    Glöckner, Gernot; Scherer, Stephen; Schattevoy, Ruben; Boright, Andrew; Weber, Jacqueline; Tsui, Lap-Chee; Rosenthal, André

    1998-01-01

    We have sequenced and annotated two genomic regions located in the Giemsa negative band q22 of human chromosome 7. The first region defined by the erythropoietin (EPO) locus is 228 kb in length and contains 13 genes. Whereas 3 genes (GNB2, EPO, PCOLCE) were known previously on the mRNA level, we have been able to identify 10 novel genes using a newly developed automatic annotation tool RUMMAGE-DP, which comprises >26 different programs mainly for exon prediction, homology searches, and compositional and repeat analysis. For precise annotation we have also resequenced ESTs identified to the region and assembled them to build large cDNAs. In addition, we have investigated the differential splicing of genes. Using these tools we annotated 4 of the 10 genes as a zonadhesin, a transferrin homolog, a nucleoporin-like gene, and an actin gene. Two genes showed weak similarity to an insulin-like receptor and a neuronal protein with a leucine-rich amino-terminal domain. Four predicted genes (CDS1–CDS4) CDS that have been confirmed on the mRNA level showed no similarity to known proteins and a potential function could not be assigned. The second region in 7q22 defined by the CUTL1 (CCAAT displacement protein and its splice variant) locus is 416 kb in length and contains three known genes, including PMSL12, APS, CUTL1, and a novel gene (CDS5). The CUTL1 locus, consisting of two splice variants (CDP and CASP), occupies >300 kb. Based on the G,C profile an isochore switch can be defined between the CUTL1 gene and the APS and PMSL12 genes. [Clones 37G3, 164c7, and 235f8 are deposited in GenBank under accession no. AF053356; clone 123e15, accession no. AF024533; 186d2, accession no. AF024534; 46f6, accession no. AF006752; 50h2, accession no. AF047825; and 76h2, accession no. AF030453] PMID:9799793

  5. A study of MLFMA for large-scale scattering problems

    NASA Astrophysics Data System (ADS)

    Hastriter, Michael Larkin

    This research is centered in computational electromagnetics with a focus on solving large-scale problems accurately in a timely fashion using first principle physics. Error control of the translation operator in 3-D is shown. A parallel implementation of the multilevel fast multipole algorithm (MLFMA) was studied as far as parallel efficiency and scaling. The large-scale scattering program (LSSP), based on the ScaleME library, was used to solve ultra-large-scale problems including a 200lambda sphere with 20 million unknowns. As these large-scale problems were solved, techniques were developed to accurately estimate the memory requirements. Careful memory management is needed in order to solve these massive problems. The study of MLFMA in large-scale problems revealed significant errors that stemmed from inconsistencies in constants used by different parts of the algorithm. These were fixed to produce the most accurate data possible for large-scale surface scattering problems. Data was calculated on a missile-like target using both high frequency methods and MLFMA. This data was compared and analyzed to determine possible strategies to increase data acquisition speed and accuracy through multiple computation method hybridization.

  6. Typical and Atypical Development of Functional Human Brain Networks: Insights from Resting-State fMRI

    PubMed Central

    Uddin, Lucina Q.; Supekar, Kaustubh; Menon, Vinod

    2010-01-01

    Over the past several decades, structural MRI studies have provided remarkable insights into human brain development by revealing the trajectory of gray and white matter maturation from childhood to adolescence and adulthood. In parallel, functional MRI studies have demonstrated changes in brain activation patterns accompanying cognitive development. Despite these advances, studying the maturation of functional brain networks underlying brain development continues to present unique scientific and methodological challenges. Resting-state fMRI (rsfMRI) has emerged as a novel method for investigating the development of large-scale functional brain networks in infants and young children. We review existing rsfMRI developmental studies and discuss how this method has begun to make significant contributions to our understanding of maturing brain organization. In particular, rsfMRI has been used to complement studies in other modalities investigating the emergence of functional segregation and integration across short and long-range connections spanning the entire brain. We show that rsfMRI studies help to clarify and reveal important principles of functional brain development, including a shift from diffuse to focal activation patterns, and simultaneous pruning of local connectivity and strengthening of long-range connectivity with age. The insights gained from these studies also shed light on potentially disrupted functional networks underlying atypical cognitive development associated with neurodevelopmental disorders. We conclude by identifying critical gaps in the current literature, discussing methodological issues, and suggesting avenues for future research. PMID:20577585

  7. 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.

  8. 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

  9. [Sexual differentiation of the human brain].

    PubMed

    Kula, K; Słowikowska-Hilczer, J

    2000-01-01

    Normal human development requires the compatibility between genetic sex (sex chromosomes), sex of gonades (tests or ovaries), genitalia (external and internal sex organs), somatic features (body characteristics) and psychic sex. The psychic sex, called frequently gender, consist of gender identity (self-estimation), gender role (objective estimation) and sexual orientation (hetero- or homosexual). It was believed that the psychic gender depends only on socio-environmental influences such as rearing, learning and individual choice. Although, the process of sexual differentiation of human brain is not completely elucidated, it has became recently evident that endogenous hormones more then socio-environmental factors influence gender differences. Experimental studies on animals revealed that transient action of sex steroids during perinatal period of life is crucial for the dymorphism of sexual behavior (male or female) in adulthood. It seems, that also in the human male neonates testosterone produced by testes perinatally takes the main role in the irreversible masculinization of the brain i.e. creation of the differences vs. female brain. The evaluation of patients with disturbances of sexual differentiation of external genitalia (the lack of the testosterone transformation into 5-alpha dihydrotestosterone in peripheral tissues of men or the inborn excess of androgens in women with the congenital adrenal hyperplasia) has served as a useful clinical model for understanding factors, affecting the formation of gender. In these individuals the formal sex established according to genetic sex and somatic sex may be incompatible with gender identity and role. However, it has been found that the female gender identity is most frequently associated with the presence of ovaries or the lack of gonads (gonadal dysgenesis), while the male gender identity appear most frequently in the presence of testicular tissue irrespective of female or hermaphrodite (intersex) phenotype. In

  10. 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

  11. 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...

  12. The Human Brain Project: social and ethical challenges.

    PubMed

    Rose, Nikolas

    2014-06-18

    Focusing on the Human Brain Project, I discuss some social and ethical challenges raised by such programs of research: the possibility of a unified knowledge of "the brain," balancing privacy and the public good, dilemmas of "dual use," brain-computer interfaces, and "responsible research and innovation" in governance of emerging technologies.

  13. 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

    2016-07-03

    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.

  14. 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...

  15. The human brain produces fructose from glucose

    PubMed Central

    Hwang, Janice J.; Jiang, Lihong; Hamza, Muhammad; Dai, Feng; Cline, Gary; Rothman, Douglas L.; Mason, Graeme; Sherwin, Robert S.

    2017-01-01

    Fructose has been implicated in the pathogenesis of obesity and type 2 diabetes. In contrast to glucose, CNS delivery of fructose in rodents promotes feeding behavior. However, because circulating plasma fructose levels are exceedingly low, it remains unclear to what extent fructose crosses the blood-brain barrier to exert CNS effects. To determine whether fructose can be endogenously generated from glucose via the polyol pathway (glucose → sorbitol → fructose) in human brain, 8 healthy subjects (4 women/4 men; age, 28.8 ± 6.2 years; BMI, 23.4 ± 2.6; HbA1C, 4.9% ± 0.2%) underwent 1H magnetic resonance spectroscopy scanning to measure intracerebral glucose and fructose levels during a 4-hour hyperglycemic clamp (plasma glucose, 220 mg/dl). Using mixed-effects regression model analysis, intracerebral glucose rose significantly over time and differed from baseline at 20 to 230 minutes. Intracerebral fructose levels also rose over time, differing from baseline at 30 to 230 minutes. The changes in intracerebral fructose were related to changes in intracerebral glucose but not to plasma fructose levels. Our findings suggest that the polyol pathway contributes to endogenous CNS production of fructose and that the effects of fructose in the CNS may extend beyond its direct dietary consumption. PMID:28239653

  16. 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

  17. Moment-to-moment brain signal variability: a next frontier in human brain mapping?

    PubMed

    Garrett, Douglas D; Samanez-Larkin, Gregory R; MacDonald, Stuart W S; Lindenberger, Ulman; McIntosh, Anthony R; Grady, Cheryl L

    2013-05-01

    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 lifespan 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.

  18. [Human brain resource--experience at the Brain Research Institute,University of Niigata].

    PubMed

    Kakita, Akiyoshi; Takahashi, Hitoshi

    2010-10-01

    Through 40 years of neuropathological practice,the Brain Research Institute, University of Niigata (BRI-Niigata), Japan has accumulated extensive human brain resource,including fresh-frozen brain slices,for scientific research. Over 30,000 slices obtained from consecutive autopsies have been systematically stored in 25 deep freezers. Establishment of effective networks between brain banks and institutional collections in Japan is essential for promoting scientific activities that require human brain resource. We at the BRI-Niigata are eager to contribute to the establishment of such networks.

  19. Frequency interactions in human epileptic brain.

    PubMed

    Cotic, Marija; Zalay, Osbert; Valiante, Taufik; Carlen, Peter L; Bardakjian, Berj L

    2011-01-01

    We have used two algorithms, wavelet phase coherence (WPC) and modulation index (MI) analysis to study frequency interactions in the human epileptic brain. Quantitative analyses were performed on intracranial electroencephalographic (iEEG) segments from three patients with neocortical epilepsy. Interelectrode coherence was measured using WPC and intraelectrode frequency interactions were analyzed using MI. WPC was performed on electrode pairings and the temporal evolution of phase couplings in the following frequency ranges: 1-4 Hz, 4-8 Hz, 8-13 Hz, 13-30 Hz and 30-100 Hz was studied. WPC was strongest in the 1-4 Hz frequency range during both seizure and non-seizure activities; however, WPC values varied minimally between electrode pairings. The 13-30 Hz band showed the lowest WPC values during seizure activity. MI analysis yielded two prominent patterns of frequency-specific activity, during seizure and non-seizure activities, which were present across all patients.

  20. Diffusion tensor spectroscopy (DTS) of human brain.

    PubMed

    Ellegood, Jacob; Hanstock, Chris C; Beaulieu, Christian

    2006-01-01

    The diffusion tensor of N-acetyl aspartate (NAA), creatine and phosphocreatine (tCr), and choline (Cho) was measured at 3T using a diffusion weighted STEAM (1)H-MRS sequence in the healthy human brain in 6 distinct regions (4 white matter and 2 cortical gray matter). The Trace/3 apparent diffusion coefficient (ADC) of each metabolite was significantly greater in white matter than gray matter. The Trace/3 ADC values of tCr and Cho were found to be significantly greater than NAA in white matter, whereas all 3 metabolites had similar Trace/3 ADC in cortical gray matter. Fractional anisotropy (FA) values for all 3 metabolites were consistent with water FA values in the 4 white matter regions; however, metabolite FA values were found to be higher than expected in the cortical gray matter. The principal diffusion direction derived for NAA was in good agreement with expected anatomic tract directions in the white matter.

  1. Cristobalite and Hematite Particles in Human Brain.

    PubMed

    Kopani, Martin; Kopaniova, A; Trnka, M; Caplovicova, M; Rychly, B; Jakubovsky, J

    2016-11-01

    Foreign substances get into the internal environment of living bodies and accumulate in various organs. Cristobalite and hematite particles in the glial cells of pons cerebri of human brain with diagnosis of Behhet disease with scanning electron microscopy (SEM), energy-dispersive microanalysis (EDX), and transmission electron microscopy (TEM) with diffraction were identified. SEM with EDX revealed the matter of irregular micrometer-sized particles sometimes forming polyhedrons with fibrilar or stratified structure. It was found in some particles Ti, Fe, and Zn. Some particles contained Cu. TEM and electron diffraction showed particles of cristobalite and hematite. The presence of the particles can be a result of environmental effect, disruption of normal metabolism, and transformation of physiologically iron-ferrihydrite into more stable form-hematite. From the size of particles can be drawn the long-term accumulation of elements in glial cells.

  2. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

    PubMed

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

    The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

  3. Human brain glial cells synthesize thrombospondin.

    PubMed Central

    Asch, A S; Leung, L L; Shapiro, J; Nachman, R L

    1986-01-01

    Thrombospondin, a 450-kDa multinodular glycoprotein with lectin-type activity, is found in human platelets, endothelial cells, fibroblasts, smooth muscle cells, monocytes, and granular pneumocytes. Thrombospondin interacts with heparin, fibrinogen, fibronectin, collagen, histidine-rich glycoprotein, and plasminogen. Recently, thrombospondin synthesis by smooth muscle cells has been reported to be augmented by platelet-derived growth factor. We present evidence that thrombospondin is present within and synthesized by astrocytic neuroglial cells. Heparin-Sepharose affinity chromatography of material derived from a human brain homogenate yielded a protein that, when reduced, had an apparent size of 180 kDa and comigrated with reduced platelet thrombospondin on NaDodSO4/PAGE. Immunoblot analysis with monospecific anti-thrombospondin confirmed the presence of immunoreactive thrombospondin. Indirect immunofluorescence of cultured human glial cells indicated the presence of thrombospondin. Metabolic labeling of glial cell cultures with [35S]methionine followed by immunoprecipitation with monospecific anti-thrombospondin revealed synthesis of a 180-kDa polypeptide that comigrated with platelet thrombospondin on NaDodSO4/PAGE. Cultured human glial cells were incubated for 48 hr in serum-free medium with purified platelet-derived growth factor at concentrations up to 50 ng/ml. Aliquots taken at intervals were analyzed by a quantitative double-antibody ELISA. The growth factor stimulated the release of thrombospondin into the culture medium by as much as 10-fold over control cultures. The presence of thrombospondin within glial cells of the central nervous system and the augmentation of its synthesis by platelet-derived growth factor suggest that thrombospondin may play an important role in regulating cell-cell and cell-matrix interactions during periods of cell division and growth. Images PMID:2939460

  4. Lipidomics of human brain aging and Alzheimer's disease pathology.

    PubMed

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.

  5. Sex differences in brain organization: implications for human communication.

    PubMed

    Hanske-Petitpierre, V; Chen, A C

    1985-12-01

    This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

  6. EINSTEIN'S SIGNATURE IN COSMOLOGICAL LARGE-SCALE STRUCTURE

    SciTech Connect

    Bruni, Marco; Hidalgo, Juan Carlos; Wands, David

    2014-10-10

    We show how the nonlinearity of general relativity generates a characteristic nonGaussian signal in cosmological large-scale structure that we calculate at all perturbative orders in a large-scale limit. Newtonian gravity and general relativity provide complementary theoretical frameworks for modeling large-scale structure in ΛCDM cosmology; a relativistic approach is essential to determine initial conditions, which can then be used in Newtonian simulations studying the nonlinear evolution of the matter density. Most inflationary models in the very early universe predict an almost Gaussian distribution for the primordial metric perturbation, ζ. However, we argue that it is the Ricci curvature of comoving-orthogonal spatial hypersurfaces, R, that drives structure formation at large scales. We show how the nonlinear relation between the spatial curvature, R, and the metric perturbation, ζ, translates into a specific nonGaussian contribution to the initial comoving matter density that we calculate for the simple case of an initially Gaussian ζ. Our analysis shows the nonlinear signature of Einstein's gravity in large-scale structure.

  7. Evolutionary origins of human brain and spirituality.

    PubMed

    Henneberg, Maciej; Saniotis, Arthur

    2009-12-01

    Evolving brains produce minds. Minds operate on imaginary entities. Thus they can create what does not exist in the physical world. Spirits can be deified. Perception of spiritual entities is emotional--organic. Spirituality is a part of culture while culture is an adaptive mechanism of human groups as it allows for technology and social organization to support survival and reproduction. Humans are not rational, they are emotional. Most of explanations of the world, offered by various cultures, involve an element of "fiat", a will of a higher spiritual being, or a reference to some ideal. From this the rules of behaviour are deduced. These rules are necessary to maintain social peace and allow a complex unit consisting of individuals of both sexes and all ages to function in a way ensuring their reproductive success and thus survival. There is thus a direct biological benefit of complex ideological superstructure of culture. This complex superstructure most often takes a form of religion in which logic is mixed with appeals to emotions based on images of spiritual beings. God is a consequence of natural evolution. Whether a deity is a cause of this evolution is difficult to discover, but existence of a deity cannot be questioned.

  8. Integrative analyses of RNA editing, alternative splicing, and expression of young genes in human brain transcriptome by deep RNA sequencing.

    PubMed

    Wu, Dong-Dong; Ye, Ling-Qun; Li, Yan; Sun, Yan-Bo; Shao, Yi; Chen, Chunyan; Zhu, Zhu; Zhong, Li; Wang, Lu; Irwin, David M; Zhang, Yong E; Zhang, Ya-Ping

    2015-08-01

    Next-generation RNA sequencing has been successfully used for identification of transcript assembly, evaluation of gene expression levels, and detection of post-transcriptional modifications. Despite these large-scale studies, additional comprehensive RNA-seq data from different subregions of the human brain are required to fully evaluate the evolutionary patterns experienced by the human brain transcriptome. Here, we provide a total of 6.5 billion RNA-seq reads from different subregions of the human brain. A significant correlation was observed between the levels of alternative splicing and RNA editing, which might be explained by a competition between the molecular machineries responsible for the splicing and editing of RNA. Young human protein-coding genes demonstrate biased expression to the neocortical and non-neocortical regions during evolution on the lineage leading to humans. We also found that a significantly greater number of young human protein-coding genes are expressed in the putamen, a tissue that was also observed to have the highest level of RNA-editing activity. The putamen, which previously received little attention, plays an important role in cognitive ability, and our data suggest a potential contribution of the putamen to human evolution.

  9. Modulation analysis of large-scale discrete vortices.

    PubMed

    Cisneros, Luis A; Minzoni, Antonmaria A; Panayotaros, Panayotis; Smyth, Noel F

    2008-09-01

    The behavior of large-scale vortices governed by the discrete nonlinear Schrödinger equation is studied. Using a discrete version of modulation theory, it is shown how vortices are trapped and stabilized by the self-consistent Peierls-Nabarro potential that they generate in the lattice. Large-scale circular and polygonal vortices are studied away from the anticontinuum limit, which is the limit considered in previous studies. In addition numerical studies are performed on large-scale, straight structures, and it is found that they are stabilized by a nonconstant mean level produced by standing waves generated at the ends of the structure. Finally, numerical evidence is produced for long-lived, localized, quasiperiodic structures.

  10. Large-scale simulations of complex physical systems

    NASA Astrophysics Data System (ADS)

    Belić, A.

    2007-04-01

    Scientific computing has become a tool as vital as experimentation and theory for dealing with scientific challenges of the twenty-first century. Large scale simulations and modelling serve as heuristic tools in a broad problem-solving process. High-performance computing facilities make possible the first step in this process - a view of new and previously inaccessible domains in science and the building up of intuition regarding the new phenomenology. The final goal of this process is to translate this newly found intuition into better algorithms and new analytical results. In this presentation we give an outline of the research themes pursued at the Scientific Computing Laboratory of the Institute of Physics in Belgrade regarding large-scale simulations of complex classical and quantum physical systems, and present recent results obtained in the large-scale simulations of granular materials and path integrals.

  11. Large-scale velocity structures in turbulent thermal convection.

    PubMed

    Qiu, X L; Tong, P

    2001-09-01

    A systematic study of large-scale velocity structures in turbulent thermal convection is carried out in three different aspect-ratio cells filled with water. Laser Doppler velocimetry is used to measure the velocity profiles and statistics over varying Rayleigh numbers Ra and at various spatial positions across the whole convection cell. Large velocity fluctuations are found both in the central region and near the cell boundary. Despite the large velocity fluctuations, the flow field still maintains a large-scale quasi-two-dimensional structure, which rotates in a coherent manner. This coherent single-roll structure scales with Ra and can be divided into three regions in the rotation plane: (1) a thin viscous boundary layer, (2) a fully mixed central core region with a constant mean velocity gradient, and (3) an intermediate plume-dominated buffer region. The experiment reveals a unique driving mechanism for the large-scale coherent rotation in turbulent convection.

  12. Acoustic Studies of the Large Scale Ocean Circulation

    NASA Technical Reports Server (NTRS)

    Menemenlis, Dimitris

    1999-01-01

    Detailed knowledge of ocean circulation and its transport properties is prerequisite to an understanding of the earth's climate and of important biological and chemical cycles. Results from two recent experiments, THETIS-2 in the Western Mediterranean and ATOC in the North Pacific, illustrate the use of ocean acoustic tomography for studies of the large scale circulation. The attraction of acoustic tomography is its ability to sample and average the large-scale oceanic thermal structure, synoptically, along several sections, and at regular intervals. In both studies, the acoustic data are compared to, and then combined with, general circulation models, meteorological analyses, satellite altimetry, and direct measurements from ships. Both studies provide complete regional descriptions of the time-evolving, three-dimensional, large scale circulation, albeit with large uncertainties. The studies raise serious issues about existing ocean observing capability and provide guidelines for future efforts.

  13. A relativistic signature in large-scale structure

    NASA Astrophysics Data System (ADS)

    Bartolo, Nicola; Bertacca, Daniele; Bruni, Marco; Koyama, Kazuya; Maartens, Roy; Matarrese, Sabino; Sasaki, Misao; Verde, Licia; Wands, David

    2016-09-01

    In General Relativity, the constraint equation relating metric and density perturbations is inherently nonlinear, leading to an effective non-Gaussianity in the dark matter density field on large scales-even if the primordial metric perturbation is Gaussian. Intrinsic non-Gaussianity in the large-scale dark matter overdensity in GR is real and physical. However, the variance smoothed on a local physical scale is not correlated with the large-scale curvature perturbation, so that there is no relativistic signature in the galaxy bias when using the simplest model of bias. It is an open question whether the observable mass proxies such as luminosity or weak lensing correspond directly to the physical mass in the simple halo bias model. If not, there may be observables that encode this relativistic signature.

  14. Toward Improved Support for Loosely Coupled Large Scale Simulation Workflows

    SciTech Connect

    Boehm, Swen; Elwasif, Wael R; Naughton, III, Thomas J; Vallee, Geoffroy R

    2014-01-01

    High-performance computing (HPC) workloads are increasingly leveraging loosely coupled large scale simula- tions. Unfortunately, most large-scale HPC platforms, including Cray/ALPS environments, are designed for the execution of long-running jobs based on coarse-grained launch capabilities (e.g., one MPI rank per core on all allocated compute nodes). This assumption limits capability-class workload campaigns that require large numbers of discrete or loosely coupled simulations, and where time-to-solution is an untenable pacing issue. This paper describes the challenges related to the support of fine-grained launch capabilities that are necessary for the execution of loosely coupled large scale simulations on Cray/ALPS platforms. More precisely, we present the details of an enhanced runtime system to support this use case, and report on initial results from early testing on systems at Oak Ridge National Laboratory.

  15. PKI security in large-scale healthcare networks.

    PubMed

    Mantas, Georgios; Lymberopoulos, Dimitrios; Komninos, Nikos

    2012-06-01

    During the past few years a lot of PKI (Public Key Infrastructures) infrastructures have been proposed for healthcare networks in order to ensure secure communication services and exchange of data among healthcare professionals. However, there is a plethora of challenges in these healthcare PKI infrastructures. Especially, there are a lot of challenges for PKI infrastructures deployed over large-scale healthcare networks. In this paper, we propose a PKI infrastructure to ensure security in a large-scale Internet-based healthcare network connecting a wide spectrum of healthcare units geographically distributed within a wide region. Furthermore, the proposed PKI infrastructure facilitates the trust issues that arise in a large-scale healthcare network including multi-domain PKI infrastructures.

  16. A Culture-Behavior-Brain Loop Model of Human Development.

    PubMed

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model.

  17. Magnetic Helicity and Large Scale Magnetic Fields: A Primer

    NASA Astrophysics Data System (ADS)

    Blackman, Eric G.

    2015-05-01

    Magnetic fields of laboratory, planetary, stellar, and galactic plasmas commonly exhibit significant order on large temporal or spatial scales compared to the otherwise random motions within the hosting system. Such ordered fields can be measured in the case of planets, stars, and galaxies, or inferred indirectly by the action of their dynamical influence, such as jets. Whether large scale fields are amplified in situ or a remnant from previous stages of an object's history is often debated for objects without a definitive magnetic activity cycle. Magnetic helicity, a measure of twist and linkage of magnetic field lines, is a unifying tool for understanding large scale field evolution for both mechanisms of origin. Its importance stems from its two basic properties: (1) magnetic helicity is typically better conserved than magnetic energy; and (2) the magnetic energy associated with a fixed amount of magnetic helicity is minimized when the system relaxes this helical structure to the largest scale available. Here I discuss how magnetic helicity has come to help us understand the saturation of and sustenance of large scale dynamos, the need for either local or global helicity fluxes to avoid dynamo quenching, and the associated observational consequences. I also discuss how magnetic helicity acts as a hindrance to turbulent diffusion of large scale fields, and thus a helper for fossil remnant large scale field origin models in some contexts. I briefly discuss the connection between large scale fields and accretion disk theory as well. The goal here is to provide a conceptual primer to help the reader efficiently penetrate the literature.

  18. Large scale purification of RNA nanoparticles by preparative ultracentrifugation.

    PubMed

    Jasinski, Daniel L; Schwartz, Chad T; Haque, Farzin; Guo, Peixuan

    2015-01-01

    Purification of large quantities of supramolecular RNA complexes is of paramount importance due to the large quantities of RNA needed and the purity requirements for in vitro and in vivo assays. Purification is generally carried out by liquid chromatography (HPLC), polyacrylamide gel electrophoresis (PAGE), or agarose gel electrophoresis (AGE). Here, we describe an efficient method for the large-scale purification of RNA prepared by in vitro transcription using T7 RNA polymerase by cesium chloride (CsCl) equilibrium density gradient ultracentrifugation and the large-scale purification of RNA nanoparticles by sucrose gradient rate-zonal ultracentrifugation or cushioned sucrose gradient rate-zonal ultracentrifugation.

  19. The Evolution of Baryons in Cosmic Large Scale Structure

    NASA Astrophysics Data System (ADS)

    Snedden, Ali; Arielle Phillips, Lara; Mathews, Grant James; Coughlin, Jared; Suh, In-Saeng; Bhattacharya, Aparna

    2015-01-01

    The environments of galaxies play a critical role in their formation and evolution. We study these environments using cosmological simulations with star formation and supernova feedback included. From these simulations, we parse the large scale structure into clusters, filaments and voids using a segmentation algorithm adapted from medical imaging. We trace the star formation history, gas phase and metal evolution of the baryons in the intergalactic medium as function of structure. We find that our algorithm reproduces the baryon fraction in the intracluster medium and that the majority of star formation occurs in cold, dense filaments. We present the consequences this large scale environment has for galactic halos and galaxy evolution.

  20. [Issues of large scale tissue culture of medicinal plant].

    PubMed

    Lv, Dong-Mei; Yuan, Yuan; Zhan, Zhi-Lai

    2014-09-01

    In order to increase the yield and quality of the medicinal plant and enhance the competitive power of industry of medicinal plant in our country, this paper analyzed the status, problem and countermeasure of the tissue culture of medicinal plant on large scale. Although the biotechnology is one of the most efficient and promising means in production of medicinal plant, it still has problems such as stability of the material, safety of the transgenic medicinal plant and optimization of cultured condition. Establishing perfect evaluation system according to the characteristic of the medicinal plant is the key measures to assure the sustainable development of the tissue culture of medicinal plant on large scale.

  1. Large-Scale Graph Processing Analysis using Supercomputer Cluster

    NASA Astrophysics Data System (ADS)

    Vildario, Alfrido; Fitriyani; Nugraha Nurkahfi, Galih

    2017-01-01

    Graph implementation is widely use in various sector such as automotive, traffic, image processing and many more. They produce graph in large-scale dimension, cause the processing need long computational time and high specification resources. This research addressed the analysis of implementation large-scale graph using supercomputer cluster. We impelemented graph processing by using Breadth-First Search (BFS) algorithm with single destination shortest path problem. Parallel BFS implementation with Message Passing Interface (MPI) used supercomputer cluster at High Performance Computing Laboratory Computational Science Telkom University and Stanford Large Network Dataset Collection. The result showed that the implementation give the speed up averages more than 30 times and eficiency almost 90%.

  2. Corridors Increase Plant Species Richness at Large Scales

    SciTech Connect

    Damschen, Ellen I.; Haddad, Nick M.; Orrock,John L.; Tewksbury, Joshua J.; Levey, Douglas J.

    2006-09-01

    Habitat fragmentation is one of the largest threats to biodiversity. Landscape corridors, which are hypothesized to reduce the negative consequences of fragmentation, have become common features of ecological management plans worldwide. Despite their popularity, there is little evidence documenting the effectiveness of corridors in preserving biodiversity at large scales. Using a large-scale replicated experiment, we showed that habitat patches connected by corridors retain more native plant species than do isolated patches, that this difference increases over time, and that corridors do not promote invasion by exotic species. Our results support the use of corridors in biodiversity conservation.

  3. Clearing and Labeling Techniques for Large-Scale Biological Tissues

    PubMed Central

    Seo, Jinyoung; Choe, Minjin; Kim, Sung-Yon

    2016-01-01

    Clearing and labeling techniques for large-scale biological tissues enable simultaneous extraction of molecular and structural information with minimal disassembly of the sample, facilitating the integration of molecular, cellular and systems biology across different scales. Recent years have witnessed an explosive increase in the number of such methods and their applications, reflecting heightened interest in organ-wide clearing and labeling across many fields of biology and medicine. In this review, we provide an overview and comparison of existing clearing and labeling techniques and discuss challenges and opportunities in the investigations of large-scale biological systems. PMID:27239813

  4. 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

    2014-09-09

    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.

  5. Radial glia cells in the developing human <