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

Jacques Hugo

Traditional engineering methods do not make provision for the integration of human considerations, while traditional human factors methods do not scale well to the complexity of large-scale nuclear power plant projects. Although the need for up-to-date human factors engineering processes and tools is recognised widely in industry, so far no formal guidance has been developed. This article proposes such a framework.

Balancing selfishness and norm conformity can explain human behavior in large-scale prisoner's dilemma games and can poise human groups near criticality

NASA Astrophysics Data System (ADS)

Realpe-Gómez, John; Andrighetto, Giulia; Nardin, Luis Gustavo; Montoya, Javier Antonio

2018-04-01

Cooperation is central to the success of human societies as it is crucial for overcoming some of the most pressing social challenges of our time; still, how human cooperation is achieved and may persist is a main puzzle in the social and biological sciences. Recently, scholars have recognized the importance of social norms as solutions to major local and large-scale collective action problems, from the management of water resources to the reduction of smoking in public places to the change in fertility practices. Yet a well-founded model of the effect of social norms on human cooperation is still lacking. Using statistical-physics techniques and integrating findings from cognitive and behavioral sciences, we present an analytically tractable model in which individuals base their decisions to cooperate both on the economic rewards they obtain and on the degree to which their action complies with social norms. Results from this parsimonious model are in agreement with observations in recent large-scale experiments with humans. We also find the phase diagram of the model and show that the experimental human group is poised near a critical point, a regime where recent work suggests living systems respond to changing external conditions in an efficient and coordinated manner.

The micro-environmental impact of volatile organic compound emissions from large-scale assemblies of people in a confined space

USDA-ARS?s Scientific Manuscript database

Large-scale assemblies of people in a con'ned space can exert signi'cant impacts on the local air chemistry due to human emissions of volatile organics. Variations of air-quality in such small scale can be studied by quantifying 'ngerprint volatile organic compounds (VOCs) such as acetone, toluene, ...

Translating chimpanzee personality to humans: Investigating the transportability of chimpanzee-derived personality scales to humans.

PubMed

Latzman, Robert D; Sauvigné, Katheryn C; Hopkins, William D

2016-06-01

There is a growing interest in the study of personality in chimpanzees with repeated findings of a similar structure of personality in apes to that found in humans. To date, however, the direct translational value of instruments used to assess chimpanzee personality to humans has yet to be explicitly tested. As such, in the current study we sought to determine the transportability of factor analytically-derived chimpanzee personality scales to humans in a large human sample (N = 301). Human informants reporting on target individuals they knew well completed chimpanzee-derived and human-derived measures of personality from the two most widely studied models of human personality: Big Five and Big Three. The correspondence between informant-reported chimpanzee- and human-derived personality scales was then investigated. Results indicated high convergence for corresponding scales across most chimpanzee- and human-derived personality scales. Findings from the current study provide evidence that chimpanzee-derived scales translate well to humans and operate quite similarly to the established human-derived personality scales in a human sample. This evidence of transportability lends support to the translational nature of chimpanzee personality research suggesting clear relevance of this growing literature to humans. Am. J. Primatol. 78:601-609, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

River Networks and Human Activities: Global Fractal Analysis Using Nightlight Data

NASA Astrophysics Data System (ADS)

McCurley, K. 4553; Fang, Y.; Ceola, S.; Paik, K.; McGrath, G. S.; Montanari, A.; Rao, P. S.; Jawitz, J. W.

2016-12-01

River networks hold an important historical role in affecting human population distribution. In this study, we link the geomorphological structure of river networks to the pattern of human activities at a global scale. We use nightlights as a valuable proxy for the presence of human settlements and economic activity, and we employ HydroSHEDS as the main data source on river networks. We test the hypotheses that, analogous to Horton's laws, human activities (magnitude of nightlights) also show scaling relationship with stream order, and that the intensity of human activities decrease as the distance from the basin outlet increase. Our results demonstrate that the distribution of human activities shows a fractal structure, with power-law scaling between human activities and stream order. This relationship is robust among global river basins. Human activities are more concentrated in larger order basins, but show large variation in equivalent order basins, with higher population density emergent in the basins connected with high-order rivers. For all global river basins longer than 400km, the average intensity of human activities decrease as the distance to the outlets increases, albeit with signatures of large cities at varied distances. The power spectrum of human width (area) function is found to exhibit power law scaling, with a scaling exponent that indicates enrichment of low frequency variation. The universal fractal structure of human activities may reflect an optimum arrangement for humans in river basins to better utilize the water resources, ecological assets, and geographic advantages. The generalized patterns of human activities could be applied to better understand hydrologic and biogeochemical responses in river basins, and to advance catchment management.

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...

Space and time scales in human-landscape systems.

PubMed

Kondolf, G Mathias; Podolak, Kristen

2014-01-01

Exploring spatial and temporal scales provides a way to understand human alteration of landscape processes and human responses to these processes. We address three topics relevant to human-landscape systems: (1) scales of human impacts on geomorphic processes, (2) spatial and temporal scales in river restoration, and (3) time scales of natural disasters and behavioral and institutional responses. Studies showing dramatic recent change in sediment yields from uplands to the ocean via rivers illustrate the increasingly vast spatial extent and quick rate of human landscape change in the last two millennia, but especially in the second half of the twentieth century. Recent river restoration efforts are typically small in spatial and temporal scale compared to the historical human changes to ecosystem processes, but the cumulative effectiveness of multiple small restoration projects in achieving large ecosystem goals has yet to be demonstrated. The mismatch between infrequent natural disasters and individual risk perception, media coverage, and institutional response to natural disasters results in un-preparedness and unsustainable land use and building practices.

Exploring Entrainment Patterns of Human Emotion in Social Media

PubMed Central

Luo, Chuan; Zhang, Zhu

2016-01-01

Emotion entrainment, which is generally defined as the synchronous convergence of human emotions, performs many important social functions. However, what the specific mechanisms of emotion entrainment are beyond in-person interactions, and how human emotions evolve under different entrainment patterns in large-scale social communities, are still unknown. In this paper, we aim to examine the massive emotion entrainment patterns and understand the underlying mechanisms in the context of social media. As modeling emotion dynamics on a large scale is often challenging, we elaborate a pragmatic framework to characterize and quantify the entrainment phenomenon. By applying this framework on the datasets from two large-scale social media platforms, we find that the emotions of online users entrain through social networks. We further uncover that online users often form their relations via dual entrainment, while maintain it through single entrainment. Remarkably, the emotions of online users are more convergent in nonreciprocal entrainment. Building on these findings, we develop an entrainment augmented model for emotion prediction. Experimental results suggest that entrainment patterns inform emotion proximity in dyads, and encoding their associations promotes emotion prediction. This work can further help us to understand the underlying dynamic process of large-scale online interactions and make more reasonable decisions regarding emergency situations, epidemic diseases, and political campaigns in cyberspace. PMID:26953692

Exploring Entrainment Patterns of Human Emotion in Social Media.

PubMed

He, Saike; Zheng, Xiaolong; Zeng, Daniel; Luo, Chuan; Zhang, Zhu

2016-01-01

Emotion entrainment, which is generally defined as the synchronous convergence of human emotions, performs many important social functions. However, what the specific mechanisms of emotion entrainment are beyond in-person interactions, and how human emotions evolve under different entrainment patterns in large-scale social communities, are still unknown. In this paper, we aim to examine the massive emotion entrainment patterns and understand the underlying mechanisms in the context of social media. As modeling emotion dynamics on a large scale is often challenging, we elaborate a pragmatic framework to characterize and quantify the entrainment phenomenon. By applying this framework on the datasets from two large-scale social media platforms, we find that the emotions of online users entrain through social networks. We further uncover that online users often form their relations via dual entrainment, while maintain it through single entrainment. Remarkably, the emotions of online users are more convergent in nonreciprocal entrainment. Building on these findings, we develop an entrainment augmented model for emotion prediction. Experimental results suggest that entrainment patterns inform emotion proximity in dyads, and encoding their associations promotes emotion prediction. This work can further help us to understand the underlying dynamic process of large-scale online interactions and make more reasonable decisions regarding emergency situations, epidemic diseases, and political campaigns in cyberspace.

3D Data Acquisition Platform for Human Activity Understanding

DTIC Science & Technology

2016-03-02

address fundamental research problems of representation and invariant description of3D data, human motion modeling and applications of human activity analysis, and computational optimization of large-scale 3D data.

3D Data Acquisition Platform for Human Activity Understanding

DTIC Science & Technology

2016-03-02

address fundamental research problems of representation and invariant description of 3D data, human motion modeling and applications of human activity analysis, and computational optimization of large-scale 3D data.

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

Genetics of Resistant Hypertension: the Missing Heritability and Opportunities.

PubMed

Teixeira, Samantha K; Pereira, Alexandre C; Krieger, Jose E

2018-05-19

Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use. Here, we propose the combined use of resistant hypertension as a trait for mapping genetic determinants in humans and the integration of new large-scale technologies to approach in model systems the multidimensional nature of the problem. New large-scale efforts in the genetic and genomic arenas are paving the way for an increased and granular understanding of genetic determinants of hypertension. New technologies for whole genome sequence and large-scale forward genetic screens can help prioritize gene and gene-pathways for downstream characterization and large-scale population studies, and guided pharmacological design can be used to drive discoveries to the translational application through better risk stratification and new therapeutic approaches. Although significant challenges remain in the mapping and identification of genetic determinants of hypertension, new large-scale technological approaches have been proposed to surpass some of the shortcomings that have limited progress in the area for the last three decades. The incorporation of these technologies to hypertension research may significantly help in the understanding of inter-individual blood pressure variation and the deployment of new phenotyping and treatment approaches for the condition.

Functional Topography of Human Auditory Cortex

PubMed Central

Rauschecker, Josef P.

2016-01-01

Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior–posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or “periodotopy,” are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale “periodotopic” organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex. SIGNIFICANCE STATEMENT In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds. PMID:26818527

Multiscale factors affecting human attitudes toward snow leopards and wolves.

PubMed

Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

2014-12-01

The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at appropriate scales. Our results reiterate the need for conflict management programs to be multipronged. © 2014 Society for Conservation Biology.

The micro-environmental impact of volatile organic compound emissions from large-scale assemblies of people in a confined space

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

Dutta, Tanushree

Large-scale assemblies of people in a confined space can exert significant impacts on the local air chemistry due to human emissions of volatile organics. Variations of air-quality in such small scale can be studied by quantifying fingerprint volatile organic compounds (VOCs) such as acetone, toluene, and isoprene produced during concerts, movie screenings, and sport events (like the Olympics and the World Cup). This review summarizes the extent of VOC accumulation resulting from a large population in a confined area or in a small open area during sporting and other recreational activities. Apart from VOCs emitted directly from human bodies (e.g.,more » perspiration and exhaled breath), those released indirectly from other related sources (e.g., smoking, waste disposal, discharge of food-waste, and use of personal-care products) are also discussed. Although direct and indirect emissions of VOCs from human may constitute <1% of the global atmospheric VOCs budget, unique spatiotemporal variations in VOCs species within a confined space can have unforeseen impacts on the local atmosphere to lead to acute human exposure to harmful pollutants.« less

Punishment sustains large-scale cooperation in prestate warfare

PubMed Central

Mathew, Sarah; Boyd, Robert

2011-01-01

Understanding cooperation and punishment in small-scale societies is crucial for explaining the origins of human cooperation. We studied warfare among the Turkana, a politically uncentralized, egalitarian, nomadic pastoral society in East Africa. Based on a representative sample of 88 recent raids, we show that the Turkana sustain costly cooperation in combat at a remarkably large scale, at least in part, through punishment of free-riders. Raiding parties comprised several hundred warriors and participants are not kin or day-to-day interactants. Warriors incur substantial risk of death and produce collective benefits. Cowardice and desertions occur, and are punished by community-imposed sanctions, including collective corporal punishment and fines. Furthermore, Turkana norms governing warfare benefit the ethnolinguistic group, a population of a half-million people, at the expense of smaller social groupings. These results challenge current views that punishment is unimportant in small-scale societies and that human cooperation evolved in small groups of kin and familiar individuals. Instead, these results suggest that cooperation at the larger scale of ethnolinguistic units enforced by third-party sanctions could have a deep evolutionary history in the human species. PMID:21670285

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.

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

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

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

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. PMID:23352202

TOXICOGENOMICS AND HUMAN DISEASE RISK ASSESSMENT

EPA Science Inventory

Toxicogenomics and Human Disease Risk Assessment.

Complete sequencing of human and other genomes, availability of large-scale gene
expression arrays with ever-increasing numbers of genes displayed, and steady
improvements in protein expression technology can hav...

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 bioenergy cropping systems. Published by Elsevier B.V.

Incorporating human-water dynamics in a hyper-resolution land surface model

NASA Astrophysics Data System (ADS)

Vergopolan, N.; Chaney, N.; Wanders, N.; Sheffield, J.; Wood, E. F.

2017-12-01

The increasing demand for water, energy, and food is leading to unsustainable groundwater and surface water exploitation. As a result, the human interactions with the environment, through alteration of land and water resources dynamics, need to be reflected in hydrologic and land surface models (LSMs). Advancements in representing human-water dynamics still leave challenges related to the lack of water use data, water allocation algorithms, and modeling scales. This leads to an over-simplistic representation of human water use in large-scale models; this is in turn leads to an inability to capture extreme events signatures and to provide reliable information at stakeholder-level spatial scales. The emergence of hyper-resolution models allows one to address these challenges by simulating the hydrological processes and interactions with the human impacts at field scales. We integrated human-water dynamics into HydroBlocks - a hyper-resolution, field-scale resolving LSM. HydroBlocks explicitly solves the field-scale spatial heterogeneity of land surface processes through interacting hydrologic response units (HRUs); and its HRU-based model parallelization allows computationally efficient long-term simulations as well as ensemble predictions. The implemented human-water dynamics include groundwater and surface water abstraction to meet agricultural, domestic and industrial water demands. Furthermore, a supply-demand water allocation scheme based on relative costs helps to determine sectoral water use requirements and tradeoffs. A set of HydroBlocks simulations over the Midwest United States (daily, at 30-m spatial resolution for 30 years) are used to quantify the irrigation impacts on water availability. The model captures large reductions in total soil moisture and water table levels, as well as spatiotemporal changes in evapotranspiration and runoff peaks, with their intensity related to the adopted water management strategy. By incorporating human-water dynamics in a hyper-resolution LSM this work allows for progress on hydrological monitoring and predictions, as well as drought preparedness and water impact assessments at relevant decision-making scales.

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

Using Big Data to Understand the Human Condition: The Kavli HUMAN Project.

PubMed

Azmak, Okan; Bayer, Hannah; Caplin, Andrew; Chun, Miyoung; Glimcher, Paul; Koonin, Steven; Patrinos, Aristides

2015-09-01

Until now, most large-scale studies of humans have either focused on very specific domains of inquiry or have relied on between-subjects approaches. While these previous studies have been invaluable for revealing important biological factors in cardiac health or social factors in retirement choices, no single repository contains anything like a complete record of the health, education, genetics, environmental, and lifestyle profiles of a large group of individuals at the within-subject level. This seems critical today because emerging evidence about the dynamic interplay between biology, behavior, and the environment point to a pressing need for just the kind of large-scale, long-term synoptic dataset that does not yet exist at the within-subject level. At the same time that the need for such a dataset is becoming clear, there is also growing evidence that just such a synoptic dataset may now be obtainable-at least at moderate scale-using contemporary big data approaches. To this end, we introduce the Kavli HUMAN Project (KHP), an effort to aggregate data from 2,500 New York City households in all five boroughs (roughly 10,000 individuals) whose biology and behavior will be measured using an unprecedented array of modalities over 20 years. It will also richly measure environmental conditions and events that KHP members experience using a geographic information system database of unparalleled scale, currently under construction in New York. In this manner, KHP will offer both synoptic and granular views of how human health and behavior coevolve over the life cycle and why they evolve differently for different people. In turn, we argue that this will allow for new discovery-based scientific approaches, rooted in big data analytics, to improving the health and quality of human life, particularly in urban contexts.

Heritability maps of human face morphology through large-scale automated three-dimensional phenotyping

NASA Astrophysics Data System (ADS)

Tsagkrasoulis, Dimosthenis; Hysi, Pirro; Spector, Tim; Montana, Giovanni

2017-04-01

The human face is a complex trait under strong genetic control, as evidenced by the striking visual similarity between twins. Nevertheless, heritability estimates of facial traits have often been surprisingly low or difficult to replicate. Furthermore, the construction of facial phenotypes that correspond to naturally perceived facial features remains largely a mystery. We present here a large-scale heritability study of face geometry that aims to address these issues. High-resolution, three-dimensional facial models have been acquired on a cohort of 952 twins recruited from the TwinsUK registry, and processed through a novel landmarking workflow, GESSA (Geodesic Ensemble Surface Sampling Algorithm). The algorithm places thousands of landmarks throughout the facial surface and automatically establishes point-wise correspondence across faces. These landmarks enabled us to intuitively characterize facial geometry at a fine level of detail through curvature measurements, yielding accurate heritability maps of the human face (www.heritabilitymaps.info).

Large-Scale Analysis of Network Bistability for Human Cancers

PubMed Central

Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

2010-01-01

Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

Expansion of Human Induced Pluripotent Stem Cells in Stirred Suspension Bioreactors.

PubMed

Almutawaa, Walaa; Rohani, Leili; Rancourt, Derrick E

2016-01-01

Human induced pluripotent stem cells (hiPSCs) hold great promise as a cell source for therapeutic applications and regenerative medicine. Traditionally, hiPSCs are expanded in two-dimensional static culture as colonies in the presence or absence of feeder cells. However, this expansion procedure is associated with lack of reproducibility and low cell yields. To fulfill the large cell number demand for clinical use, robust large-scale production of these cells under defined conditions is needed. Herein, we describe a scalable, low-cost protocol for expanding hiPSCs as aggregates in a lab-scale bioreactor.

Large Scale Generation and Characterization of Anti-Human CD34 Monoclonal Antibody in Ascetic Fluid of Balb/c Mice

PubMed Central

Aghebati Maleki, Leili; Majidi, Jafar; Baradaran, Behzad; Abdolalizadeh, Jalal; Kazemi, Tohid; Aghebati Maleki, Ali; Sineh sepehr, Koushan

2013-01-01

Purpose: Monoclonal antibodies or specific antibodies are now an essential tool of biomedical research and are of great commercial and medical value. The purpose of this study was to produce large scale of monoclonal antibody against CD34 in order to diagnostic application in leukemia and purification of human hematopoietic stem/progenitor cells. Methods: For large scale production of monoclonal antibody, hybridoma cells that produce monoclonal antibody against human CD34 were injected into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. 5 ml ascitic fluid was harvested from each mouse in two times. Evaluation of mAb titration was assessed by ELISA method. The ascitic fluid was examined for class and subclasses by ELISA mouse mAb isotyping Kit. mAb was purified from ascitic fluid by affinity chromatography on Protein A-Sepharose. Purity of monoclonal antibody was monitored by SDS -PAGE and the purified monoclonal antibody was conjugated with FITC. Results: Monoclonal antibodies with high specificity and sensitivity against human CD34 by hybridoma technology were prepared. The subclass of antibody was IgG1 and its light chain was kappa. Conclusion: The conjugated monoclonal antibody could be a useful tool for isolation, purification and characterization of human hematopoietic stem cells. PMID:24312838

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

Highly Efficient Large-Scale Lentiviral Vector Concentration by Tandem Tangential Flow Filtration

PubMed Central

Cooper, Aaron R.; Patel, Sanjeet; Senadheera, Shantha; Plath, Kathrin; Kohn, Donald B.; Hollis, Roger P.

2014-01-01

Large-scale lentiviral vector (LV) concentration can be inefficient and time consuming, often involving multiple rounds of filtration and centrifugation. This report describes a simpler method using two tangential flow filtration (TFF) steps to concentrate liter-scale volumes of LV supernatant, achieving in excess of 2000-fold concentration in less than 3 hours with very high recovery (>97%). Large volumes of LV supernatant can be produced easily through the use of multi-layer flasks, each having 1720 cm2 surface area and producing ~560 mL of supernatant per flask. Combining the use of such flasks and TFF greatly simplifies large-scale production of LV. As a demonstration, the method is used to produce a very high titer LV (>1010 TU/mL) and transduce primary human CD34+ hematopoietic stem/progenitor cells at high final vector concentrations with no overt toxicity. A complex LV (STEMCCA) for induced pluripotent stem cell generation is also concentrated from low initial titer and used to transduce and reprogram primary human fibroblasts with no overt toxicity. Additionally, a generalized and simple multiplexed real- time PCR assay is described for lentiviral vector titer and copy number determination. PMID:21784103

Multichannel noninvasive human-machine interface via stretchable µm thick sEMG patches for robot manipulation

NASA Astrophysics Data System (ADS)

Zhou, Ying; Wang, Youhua; Liu, Runfeng; Xiao, Lin; Zhang, Qin; Huang, YongAn

2018-01-01

Epidermal electronics (e-skin) emerging in recent years offer the opportunity to noninvasively and wearably extract biosignals from human bodies. The conventional processes of e-skin based on standard microelectronic fabrication processes and a variety of transfer printing methods, nevertheless, unquestionably constrains the size of the devices, posing a serious challenge to collecting signals via skin, the largest organ in the human body. Herein we propose a multichannel noninvasive human-machine interface (HMI) using stretchable surface electromyography (sEMG) patches to realize a robot hand mimicking human gestures. Time-efficient processes are first developed to manufacture µm thick large-scale stretchable devices. With micron thickness, the stretchable µm thick sEMG patches show excellent conformability with human skin and consequently comparable electrical performance with conventional gel electrodes. Combined with the large-scale size, the multichannel noninvasive HMI via stretchable µm thick sEMG patches successfully manipulates the robot hand with eight different gestures, whose precision is as high as conventional gel electrodes array.

Estimating large carnivore populations at global scale based on spatial predictions of density and distribution – Application to the jaguar (Panthera onca)

PubMed Central

Robinson, Hugh S.; Abarca, Maria; Zeller, Katherine A.; Velasquez, Grisel; Paemelaere, Evi A. D.; Goldberg, Joshua F.; Payan, Esteban; Hoogesteijn, Rafael; Boede, Ernesto O.; Schmidt, Krzysztof; Lampo, Margarita; Viloria, Ángel L.; Carreño, Rafael; Robinson, Nathaniel; Lukacs, Paul M.; Nowak, J. Joshua; Salom-Pérez, Roberto; Castañeda, Franklin; Boron, Valeria; Quigley, Howard

2018-01-01

Broad scale population estimates of declining species are desired for conservation efforts. However, for many secretive species including large carnivores, such estimates are often difficult. Based on published density estimates obtained through camera trapping, presence/absence data, and globally available predictive variables derived from satellite imagery, we modelled density and occurrence of a large carnivore, the jaguar, across the species’ entire range. We then combined these models in a hierarchical framework to estimate the total population. Our models indicate that potential jaguar density is best predicted by measures of primary productivity, with the highest densities in the most productive tropical habitats and a clear declining gradient with distance from the equator. Jaguar distribution, in contrast, is determined by the combined effects of human impacts and environmental factors: probability of jaguar occurrence increased with forest cover, mean temperature, and annual precipitation and declined with increases in human foot print index and human density. Probability of occurrence was also significantly higher for protected areas than outside of them. We estimated the world’s jaguar population at 173,000 (95% CI: 138,000–208,000) individuals, mostly concentrated in the Amazon Basin; elsewhere, populations tend to be small and fragmented. The high number of jaguars results from the large total area still occupied (almost 9 million km2) and low human densities (< 1 person/km2) coinciding with high primary productivity in the core area of jaguar range. Our results show the importance of protected areas for jaguar persistence. We conclude that combining modelling of density and distribution can reveal ecological patterns and processes at global scales, can provide robust estimates for use in species assessments, and can guide broad-scale conservation actions. PMID:29579129

Patterns of resting state connectivity in human primary visual cortical areas: a 7T fMRI study.

PubMed

Raemaekers, Mathijs; Schellekens, Wouter; van Wezel, Richard J A; Petridou, Natalia; Kristo, Gert; Ramsey, Nick F

2014-01-01

The nature and origin of fMRI resting state fluctuations and connectivity are still not fully known. More detailed knowledge on the relationship between resting state patterns and brain function may help to elucidate this matter. We therefore performed an in depth study of how resting state fluctuations map to the well known architecture of the visual system. We investigated resting state connectivity at both a fine and large scale within and across visual areas V1, V2 and V3 in ten human subjects using a 7Tesla scanner. We found evidence for several coexisting and overlapping connectivity structures at different spatial scales. At the fine-scale level we found enhanced connectivity between the same topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to the contralateral functional homologue, and to a lesser extent enhanced connectivity between iso-eccentric locations within the same visual area. However, by far the largest proportion of the resting state fluctuations occurred within large-scale bilateral networks. These large-scale networks mapped to some extent onto the architecture of the visual system and could thereby obscure fine-scale connectivity. In fact, most of the fine-scale connectivity only became apparent after the large-scale network fluctuations were filtered from the timeseries. We conclude that fMRI resting state fluctuations in the visual cortex may in fact be a composite signal of different overlapping sources. Isolating the different sources could enhance correlations between BOLD and electrophysiological correlates of resting state activity. © 2013 Elsevier Inc. All rights reserved.

Timescales of Massive Human Entrainment

PubMed Central

Fusaroli, Riccardo; Perlman, Marcus; Mislove, Alan; Paxton, Alexandra; Matlock, Teenie; Dale, Rick

2015-01-01

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend the concept of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment—as expressed by the content and patterns of hundreds of thousands of messages on Twitter—during the 2012 US presidential debates. By time-locking these data sources, we quantify the impact of the unfolding debate on human attention at three time scales. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient content during the debates: Across well-known remarks in each debate, mentions in social media start within 5–10 seconds after it occurs; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment. PMID:25880357

Using Relational Reasoning to Learn about Scientific Phenomena at Unfamiliar Scales

ERIC Educational Resources Information Center

Resnick, Ilyse; Davatzes, Alexandra; Newcombe, Nora S.; Shipley, Thomas F.

2016-01-01

Many scientific theories and discoveries involve reasoning about extreme scales, removed from human experience, such as time in geology, size in nanoscience. Thus, understanding scale is central to science, technology, engineering, and mathematics. Unfortunately, novices have trouble understanding and comparing sizes of unfamiliar large and small…

Using Relational Reasoning to Learn about Scientific Phenomena at Unfamiliar Scales

ERIC Educational Resources Information Center

Resnick, Ilyse; Davatzes, Alexandra; Newcombe, Nora S.; Shipley, Thomas F.

2017-01-01

Many scientific theories and discoveries involve reasoning about extreme scales, removed from human experience, such as time in geology and size in nanoscience. Thus, understanding scale is central to science, technology, engineering, and mathematics. Unfortunately, novices have trouble understanding and comparing sizes of unfamiliar large and…

Human Factors in the Large: Experiences from Denmark, Finland and Canada in Moving Towards Regional and National Evaluations of Health Information System Usability. Contribution of the IMIA Human Factors Working Group.

PubMed

Kushniruk, A; Kaipio, J; Nieminen, M; Hyppönen, H; Lääveri, T; Nohr, C; Kanstrup, A M; Berg Christiansen, M; Kuo, M-H; Borycki, E

2014-08-15

The objective of this paper is to explore approaches to understanding the usability of health information systems at regional and national levels. Several different methods are discussed in case studies from Denmark, Finland and Canada. They range from small scale qualitative studies involving usability testing of systems to larger scale national level questionnaire studies aimed at assessing the use and usability of health information systems by entire groups of health professionals. It was found that regional and national usability studies can complement smaller scale usability studies, and that they are needed in order to understand larger trends regarding system usability. Despite adoption of EHRs, many health professionals rate the usability of the systems as low. A range of usability issues have been noted when data is collected on a large scale through use of widely distributed questionnaires and websites designed to monitor user perceptions of usability. As health information systems are deployed on a widespread basis, studies that examine systems used regionally or nationally are required. In addition, collection of large scale data on the usability of specific IT products is needed in order to complement smaller scale studies of specific systems.

Public Health Crisis in War and Conflict - Health Security in Aggregate.

PubMed

Quinn, John; Zelený, Tomáš; Subramaniam, Rammika; Bencko, Vladimír

2017-03-01

Public health status of populations is multifactorial and besides other factors it is linked to war and conflict. Public health crisis can erupt when states go to war or are invaded; health security may be reduced for affected populations. This study reviews in aggregate multiple indices of human security, human development and legitimacy of the state in order to describe a predictable global health portrait. Paradigm shift of large global powers to that non-state actors and proxies impact regional influence through scaled conflict and present major global health challenges for policy makers. Small scale conflict with large scale violence threatens health security for at-risk populations. The paper concludes that health security is directly proportional to state security. Copyright© by the National Institute of Public Health, Prague 2017

Emergent Network Defense

ERIC Educational Resources Information Center

Crane, Earl Newell

2013-01-01

The research problem that inspired this effort is the challenge of managing the security of systems in large-scale heterogeneous networked environments. Human intervention is slow and limited: humans operate at much slower speeds than networked computer communications and there are few humans associated with each network. Enabling each node in the…

Human seizures couple across spatial scales through travelling wave dynamics

NASA Astrophysics Data System (ADS)

Martinet, L.-E.; Fiddyment, G.; Madsen, J. R.; Eskandar, E. N.; Truccolo, W.; Eden, U. T.; Cash, S. S.; Kramer, M. A.

2017-04-01

Epilepsy--the propensity toward recurrent, unprovoked seizures--is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms--namely, the effects of an increased extracellular potassium concentration diffusing in space--that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures--and connecting these dynamics to specific biological mechanisms--promises new insights to treat this devastating disease.

A Multiscale Survival Process for Modeling Human Activity Patterns.

PubMed

Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

2016-01-01

Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

Wearable Wide-Range Strain Sensors Based on Ionic Liquids and Monitoring of Human Activities

PubMed Central

Zhang, Shao-Hui; Wang, Feng-Xia; Li, Jia-Jia; Peng, Hong-Dan; Yan, Jing-Hui; Pan, Ge-Bo

2017-01-01

Wearable sensors for detection of human activities have encouraged the development of highly elastic sensors. In particular, to capture subtle and large-scale body motion, stretchable and wide-range strain sensors are highly desired, but still a challenge. Herein, a highly stretchable and transparent stain sensor based on ionic liquids and elastic polymer has been developed. The as-obtained sensor exhibits impressive stretchability with wide-range strain (from 0.1% to 400%), good bending properties and high sensitivity, whose gauge factor can reach 7.9. Importantly, the sensors show excellent biological compatibility and succeed in monitoring the diverse human activities ranging from the complex large-scale multidimensional motions to subtle signals, including wrist, finger and elbow joint bending, finger touch, breath, speech, swallow behavior and pulse wave. PMID:29135928

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

PubMed Central

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

2014-01-01

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

Characterization and Enhanced Processing of Soluble, Oligomeric gp140 Envelope Glycoproteins Derived from Human Immunodeficiency Virus Type-1 Primary Isolates

DTIC Science & Technology

2001-05-01

isolates could retain gp120 in an oligomer. A large scale purification scheme was developed using lentil lectin affinity and size exclusion...34 e. Western blot analysis……………………………………………… 35 f. Large scale protein expression and purification…………………... 35 g. Metabolic labeling, size...isolate HIV-1 Env………... 60 c. Large scale antigen preparation and analysis……………………… 67 d. Cleaved, soluble crosslinked primary isolate Env binds

PROBLEM OF FORMING IN A MAN-OPERATOR A HABIT OF TRACKING A MOVING TARGET,

DTIC Science & Technology

Cybernetics stimulated the large-scale use of the method of functional analogy which makes it possible to compare technical and human activity systems...interesting and highly efficient human activity because of the psychological control factor involved in its operation. The human tracking system is

Social sciences in Puget Sound recovery

Treesearch

Katharine F. Wellman; Kelly Biedenweg; Kathleen Wolf

2014-01-01

Advancing the recovery of large-scale ecosystems, such as the Puget Sound inWashington State, requires improved knowledge of the interdependencies between nature and humans in that basin region. As Biedenweg et al. (this issue) illustrate, human wellbeing and human behavior do not occur independently of the biophysical environment. Natural environments contribute to...

A fast boosting-based screening method for large-scale association study in complex traits with genetic heterogeneity.

PubMed

Wang, Lu-Yong; Fasulo, D

2006-01-01

Genome-wide association study for complex diseases will generate massive amount of single nucleotide polymorphisms (SNPs) data. Univariate statistical test (i.e. Fisher exact test) was used to single out non-associated SNPs. However, the disease-susceptible SNPs may have little marginal effects in population and are unlikely to retain after the univariate tests. Also, model-based methods are impractical for large-scale dataset. Moreover, genetic heterogeneity makes the traditional methods harder to identify the genetic causes of diseases. A more recent random forest method provides a more robust method for screening the SNPs in thousands scale. However, for more large-scale data, i.e., Affymetrix Human Mapping 100K GeneChip data, a faster screening method is required to screening SNPs in whole-genome large scale association analysis with genetic heterogeneity. We propose a boosting-based method for rapid screening in large-scale analysis of complex traits in the presence of genetic heterogeneity. It provides a relatively fast and fairly good tool for screening and limiting the candidate SNPs for further more complex computational modeling task.

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. © 2013 John Wiley & Sons Ltd/CNRS.

Introduction: demography and cultural macroevolution.

PubMed

Steele, James; Shennan, Stephen

2009-04-01

The papers in this special issue of Human Biology, which derive from a conference sponsored by the Arts and Humanities Research Council (AHRC) Center for the Evolution of Cultural Diversity, lay some of the foundations for an empirical macroevolutionary analysis of cultural dynamics. Our premise here is that cultural dynamics-including the stability of traditions and the rate of origination of new variants-are influenced by independently occurring demographic processes (population size, structure, and distribution as these vary over time as a result of changes in rates of fertility, mortality, and migration). The contributors focus on three sets of problems relevant to empirical studies of cultural macroevolution: large-scale reconstruction of past population dynamics from archaeological and genetic data; juxtaposition of models and evidence of cultural dynamics using large-scale archaeological and historical data sets; and juxtaposition of models and evidence of cultural dynamics from large-scale linguistic data sets. In this introduction we outline some of the theoretical and methodological issues and briefly summarize the individual contributions.

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

PubMed

Ernst, Jason; Kellis, Manolis

2015-04-01

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

Expansion of Human Mesenchymal Stem Cells in a Microcarrier Bioreactor.

PubMed

Tsai, Ang-Chen; Ma, Teng

2016-01-01

Human mesenchymal stem cells (hMSCs) are considered as a primary candidate in cell therapy owing to their self-renewability, high differentiation capabilities, and secretions of trophic factors. In clinical application, a large quantity of therapeutically competent hMSCs is required that cannot be produced in conventional petri dish culture. Bioreactors are scalable and have the capacity to meet the production demand. Microcarrier suspension culture in stirred-tank bioreactors is the most widely used method to expand anchorage dependent cells in a large scale. Stirred-tank bioreactors have the potential to scale up and microcarriers provide the high surface-volume ratio. As a result, a spinner flask bioreactor with microcarriers has been commonly used in large scale expansion of adherent cells. This chapter describes a detailed culture protocol for hMSC expansion in a 125 mL spinner flask using microcarriers, Cytodex I, and a procedure for cell seeding, expansion, metabolic sampling, and quantification and visualization using microculture tetrazolium (MTT) reagent.

Using multitype branching processes to quantify statistics of disease outbreaks in zoonotic epidemics

NASA Astrophysics Data System (ADS)

Singh, Sarabjeet; Schneider, David J.; Myers, Christopher R.

2014-03-01

Branching processes have served as a model for chemical reactions, biological growth processes, and contagion (of disease, information, or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this work we focus on coupled branching processes as a model of infectious diseases spreading from one population to another. An exceedingly important example of such coupled outbreaks are zoonotic infections that spill over from animal populations to humans. We derive several statistical quantities characterizing the first spillover event from animals to humans, including the probability of spillover, the first passage time distribution for human infection, and disease prevalence in the animal population at spillover. Large stochastic fluctuations in those quantities can make inference of the state of the system at the time of spillover difficult. Focusing on outbreaks in the human population, we then characterize the critical threshold for a large outbreak, the distribution of outbreak sizes, and associated scaling laws. These all show a strong dependence on the basic reproduction number in the animal population and indicate the existence of a novel multicritical point with altered scaling behavior. The coupling of animal and human infection dynamics has crucial implications, most importantly allowing for the possibility of large human outbreaks even when human-to-human transmission is subcritical.

Identifying and modeling the structural discontinuities of human interactions

NASA Astrophysics Data System (ADS)

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-04-01

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

Identifying and modeling the structural discontinuities of human interactions

PubMed Central

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-01-01

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales. PMID:28443647

Identifying and modeling the structural discontinuities of human interactions.

PubMed

Grauwin, Sebastian; Szell, Michael; Sobolevsky, Stanislav; Hövel, Philipp; Simini, Filippo; Vanhoof, Maarten; Smoreda, Zbigniew; Barabási, Albert-László; Ratti, Carlo

2017-04-26

The idea of a hierarchical spatial organization of society lies at the core of seminal theories in human geography that have strongly influenced our understanding of social organization. Along the same line, the recent availability of large-scale human mobility and communication data has offered novel quantitative insights hinting at a strong geographical confinement of human interactions within neighboring regions, extending to local levels within countries. However, models of human interaction largely ignore this effect. Here, we analyze several country-wide networks of telephone calls - both, mobile and landline - and in either case uncover a systematic decrease of communication induced by borders which we identify as the missing variable in state-of-the-art models. Using this empirical evidence, we propose an alternative modeling framework that naturally stylizes the damping effect of borders. We show that this new notion substantially improves the predictive power of widely used interaction models. This increases our ability to understand, model and predict social activities and to plan the development of infrastructures across multiple scales.

Large-scale absence of sharks on reefs in the greater-Caribbean: a footprint of human pressures.

PubMed

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

2010-08-05

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. 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. 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.

Control factors and scale analysis of annual river water, sediments and carbon transport in China.

PubMed

Song, Chunlin; Wang, Genxu; Sun, Xiangyang; Chang, Ruiying; Mao, Tianxu

2016-05-11

Under the context of dramatic human disturbances on river system, the processes that control the transport of water, sediment, and carbon from river basins to coastal seas are not completely understood. Here we performed a quantitative synthesis for 121 sites across China to find control factors of annual river exports (Rc: runoff coefficient; TSSC: total suspended sediment concentration; TSSL: total suspended sediment loads; TOCL: total organic carbon loads) at different spatial scales. The results indicated that human activities such as dam construction and vegetation restoration might have a greater influence than climate on the transport of river sediment and carbon, although climate was a major driver of Rc. Multiple spatial scale analyses indicated that Rc increased from the small to medium scale by 20% and then decreased at the sizable scale by 20%. TSSC decreased from the small to sizeable scale but increase from the sizeable to large scales; however, TSSL significantly decreased from small (768 g·m(-2)·a(-1)) to medium spatial scale basins (258 g·m(-2)·a(-1)), and TOCL decreased from the medium to large scale. Our results will improve the understanding of water, sediment and carbon transport processes and contribute better water and land resources management strategies from different spatial scales.

An analytical approach to separate climate and human contributions to basin streamflow variability

NASA Astrophysics Data System (ADS)

Li, Changbin; Wang, Liuming; Wanrui, Wang; Qi, Jiaguo; Linshan, Yang; Zhang, Yuan; Lei, Wu; Cui, Xia; Wang, Peng

2018-04-01

Climate variability and anthropogenic regulations are two interwoven factors in the ecohydrologic system across large basins. Understanding the roles that these two factors play under various hydrologic conditions is of great significance for basin hydrology and sustainable water utilization. In this study, we present an analytical approach based on coupling water balance method and Budyko hypothesis to derive effectiveness coefficients (ECs) of climate change, as a way to disentangle contributions of it and human activities to the variability of river discharges under different hydro-transitional situations. The climate dominated streamflow change (ΔQc) by EC approach was compared with those deduced by the elasticity method and sensitivity index. The results suggest that the EC approach is valid and applicable for hydrologic study at large basin scale. Analyses of various scenarios revealed that contributions of climate change and human activities to river discharge variation differed among the regions of the study area. Over the past several decades, climate change dominated hydro-transitions from dry to wet, while human activities played key roles in the reduction of streamflow during wet to dry periods. Remarkable decline of discharge in upstream was mainly due to human interventions, although climate contributed more to runoff increasing during dry periods in the semi-arid downstream. Induced effectiveness on streamflow changes indicated a contribution ratio of 49% for climate and 51% for human activities at the basin scale from 1956 to 2015. The mathematic derivation based simple approach, together with the case example of temporal segmentation and spatial zoning, could help people understand variation of river discharge with more details at a large basin scale under the background of climate change and human regulations.

A modeling approach to assess coastal management effects on benthic habitat quality: A case study on coastal defense and navigability

NASA Astrophysics Data System (ADS)

Cozzoli, Francesco; Smolders, Sven; Eelkema, Menno; Ysebaert, Tom; Escaravage, Vincent; Temmerman, Stijn; Meire, Patrick; Herman, Peter M. J.; Bouma, Tjeerd J.

2017-01-01

The natural coastal hydrodynamics and morphology worldwide is altered by human interventions such as embankments, shipping and dredging, which may have consequences for ecosystem functionality. To ensure long-term ecological sustainability, requires capability to predict long-term large-scale ecological effects of altered hydromorphology. As empirical data sets at relevant scales are missing, there is need for integrating ecological modeling with physical modeling. This paper presents a case study showing the long-term, large-scale macrozoobenthic community response to two contrasting human alterations of the hydromorphological habitat: deepening of estuarine channels to enhance navigability (Westerschelde) vs. realization of a storm surge barrier to enhance coastal safety (Oosterschelde). A multidisciplinary integration of empirical data and modeling of estuarine morphology, hydrodynamics and benthic ecology was used to reconstruct the hydrological evolution and resulting long-term (50 years) large-scale ecological trends for both estuaries over the last. Our model indicated that hydrodynamic alterations following the deepening of the Westerschelde had negative implications for benthic life, while the realization of the Oosterschelde storm surge barriers had mixed and habitat-dependent responses, that also include unexpected improvement of environmental quality. Our analysis illustrates long-term trends in the natural community caused by opposing management strategies. The divergent human pressures on the Oosterschelde and Westerschelde are examples of what could happen in a near future for many global coastal ecosystems. The comparative analysis of the two basins is a valuable source of information to understand (and communicate) the future ecological consequences of human coastal development.

Decadal opportunities for space architects

NASA Astrophysics Data System (ADS)

Sherwood, Brent

2012-12-01

A significant challenge for the new field of space architecture is the dearth of project opportunities. Yet every year more young professionals express interest to enter the field. This paper derives projections that bound the number, type, and range of global development opportunities that may be reasonably expected over the next few decades for human space flight (HSF) systems so those interested in the field can benchmark their goals. Four categories of HSF activity are described: human Exploration of solar system bodies; human Servicing of space-based assets; large-scale development of space Resources; and Breakout of self-sustaining human societies into the solar system. A progressive sequence of capabilities for each category starts with its earliest feasible missions and leads toward its full expression. The four sequences are compared in scale, distance from Earth, and readiness. Scenarios hybridize the most synergistic features from the four sequences for comparison to status quo, government-funded HSF program plans. Finally qualitative, decadal, order-of-magnitude estimates are derived for system development needs, and hence opportunities for space architects. Government investment towards human planetary exploration is the weakest generator of space architecture work. Conversely, the strongest generator is a combination of three market drivers: (1) commercial passenger travel in low Earth orbit; (2) in parallel, government extension of HSF capability to GEO; both followed by (3) scale-up demonstration of end-to-end solar power satellites in GEO. The rich end of this scale affords space architecture opportunities which are more diverse, complex, large-scale, and sociologically challenging than traditional exploration vehicle cabins and habitats.

Scaling identity connects human mobility and social interactions.

PubMed

Deville, Pierre; Song, Chaoming; Eagle, Nathan; Blondel, Vincent D; Barabási, Albert-László; Wang, Dashun

2016-06-28

Massive datasets that capture human movements and social interactions have catalyzed rapid advances in our quantitative understanding of human behavior during the past years. One important aspect affecting both areas is the critical role space plays. Indeed, growing evidence suggests both our movements and communication patterns are associated with spatial costs that follow reproducible scaling laws, each characterized by its specific critical exponents. Although human mobility and social networks develop concomitantly as two prolific yet largely separated fields, we lack any known relationships between the critical exponents explored by them, despite the fact that they often study the same datasets. Here, by exploiting three different mobile phone datasets that capture simultaneously these two aspects, we discovered a new scaling relationship, mediated by a universal flux distribution, which links the critical exponents characterizing the spatial dependencies in human mobility and social networks. Therefore, the widely studied scaling laws uncovered in these two areas are not independent but connected through a deeper underlying reality.

Scaling identity connects human mobility and social interactions

PubMed Central

Deville, Pierre; Song, Chaoming; Eagle, Nathan; Blondel, Vincent D.; Barabási, Albert-László; Wang, Dashun

2016-01-01

Massive datasets that capture human movements and social interactions have catalyzed rapid advances in our quantitative understanding of human behavior during the past years. One important aspect affecting both areas is the critical role space plays. Indeed, growing evidence suggests both our movements and communication patterns are associated with spatial costs that follow reproducible scaling laws, each characterized by its specific critical exponents. Although human mobility and social networks develop concomitantly as two prolific yet largely separated fields, we lack any known relationships between the critical exponents explored by them, despite the fact that they often study the same datasets. Here, by exploiting three different mobile phone datasets that capture simultaneously these two aspects, we discovered a new scaling relationship, mediated by a universal flux distribution, which links the critical exponents characterizing the spatial dependencies in human mobility and social networks. Therefore, the widely studied scaling laws uncovered in these two areas are not independent but connected through a deeper underlying reality. PMID:27274050

Teaching Real Science with a Microcomputer.

ERIC Educational Resources Information Center

Naiman, Adeline

1983-01-01

Discusses various ways science can be taught using microcomputers, including simulations/games which allow large-scale or historic experiments to be replicated on a manageable scale in a brief time. Examples of several computer programs are also presented, including "Experiments in Human Physiology,""Health Awareness…

War, space, and the evolution of Old World complex societies.

PubMed

Turchin, Peter; Currie, Thomas E; Turner, Edward A L; Gavrilets, Sergey

2013-10-08

How did human societies evolve from small groups, integrated by face-to-face cooperation, to huge anonymous societies of today, typically organized as states? Why is there so much variation in the ability of different human populations to construct viable states? Existing theories are usually formulated as verbal models and, as a result, do not yield sharply defined, quantitative predictions that could be unambiguously tested with data. Here we develop a cultural evolutionary model that predicts where and when the largest-scale complex societies arose in human history. The central premise of the model, which we test, is that costly institutions that enabled large human groups to function without splitting up evolved as a result of intense competition between societies-primarily warfare. Warfare intensity, in turn, depended on the spread of historically attested military technologies (e.g., chariots and cavalry) and on geographic factors (e.g., rugged landscape). The model was simulated within a realistic landscape of the Afroeurasian landmass and its predictions were tested against a large dataset documenting the spatiotemporal distribution of historical large-scale societies in Afroeurasia between 1,500 BCE and 1,500 CE. The model-predicted pattern of spread of large-scale societies was very similar to the observed one. Overall, the model explained 65% of variance in the data. An alternative model, omitting the effect of diffusing military technologies, explained only 16% of variance. Our results support theories that emphasize the role of institutions in state-building and suggest a possible explanation why a long history of statehood is positively correlated with political stability, institutional quality, and income per capita.

War, space, and the evolution of Old World complex societies

PubMed Central

Turchin, Peter; Currie, Thomas E.; Turner, Edward A. L.; Gavrilets, Sergey

2013-01-01

How did human societies evolve from small groups, integrated by face-to-face cooperation, to huge anonymous societies of today, typically organized as states? Why is there so much variation in the ability of different human populations to construct viable states? Existing theories are usually formulated as verbal models and, as a result, do not yield sharply defined, quantitative predictions that could be unambiguously tested with data. Here we develop a cultural evolutionary model that predicts where and when the largest-scale complex societies arose in human history. The central premise of the model, which we test, is that costly institutions that enabled large human groups to function without splitting up evolved as a result of intense competition between societies—primarily warfare. Warfare intensity, in turn, depended on the spread of historically attested military technologies (e.g., chariots and cavalry) and on geographic factors (e.g., rugged landscape). The model was simulated within a realistic landscape of the Afroeurasian landmass and its predictions were tested against a large dataset documenting the spatiotemporal distribution of historical large-scale societies in Afroeurasia between 1,500 BCE and 1,500 CE. The model-predicted pattern of spread of large-scale societies was very similar to the observed one. Overall, the model explained 65% of variance in the data. An alternative model, omitting the effect of diffusing military technologies, explained only 16% of variance. Our results support theories that emphasize the role of institutions in state-building and suggest a possible explanation why a long history of statehood is positively correlated with political stability, institutional quality, and income per capita. PMID:24062433

Family and Human Development across Cultures: A View from the Other Side.

ERIC Educational Resources Information Center

Kagitcibasi, Cigdem

Using a contextual-developmental-functional approach, this book seeks to discover the functional links between family dynamics and socialization within varying sociocultural contexts to human development, and to integrate theory and application in large-scale interventions promoting human well-being and societal development in the Majority World.…

Automated Essay Scoring versus Human Scoring: A Correlational Study

ERIC Educational Resources Information Center

Wang, Jinhao; Brown, Michelle Stallone

2008-01-01

The purpose of the current study was to analyze the relationship between automated essay scoring (AES) and human scoring in order to determine the validity and usefulness of AES for large-scale placement tests. Specifically, a correlational research design was used to examine the correlations between AES performance and human raters' performance.…

Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro

PubMed Central

Murphy, Patricia; Kabir, Md Humayun; Srivastava, Tarini; Mason, Michele E.; Dewi, Chitra U.; Lim, Seakcheng; Yang, Andrian; Djordjevic, Djordje; Killingsworth, Murray C.; Ho, Joshua W. K.; Harman, David G.

2018-01-01

ABSTRACT Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. PMID:29217756

Light-focusing human micro-lenses generated from pluripotent stem cells model lens development and drug-induced cataract in vitro.

PubMed

Murphy, Patricia; Kabir, Md Humayun; Srivastava, Tarini; Mason, Michele E; Dewi, Chitra U; Lim, Seakcheng; Yang, Andrian; Djordjevic, Djordje; Killingsworth, Murray C; Ho, Joshua W K; Harman, David G; O'Connor, Michael D

2018-01-09

Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified, including drug treatments, age, smoking and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here, we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells. The purified lens cells and micro-lenses display similar morphology, cellular arrangement, mRNA expression and protein expression to human lens cells and lenses. Exposing the micro-lenses to the emergent cystic fibrosis drug Vx-770 reduces micro-lens transparency and focusing ability. These human micro-lenses provide a powerful and large-scale platform for defining molecular disease mechanisms caused by cataract risk factors, for anti-cataract drug screening and for clinically relevant toxicity assays. © 2018. Published by The Company of Biologists Ltd.

(New hosts and vectors for genome cloning)

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

Not Available

The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

[New hosts and vectors for genome cloning]. Progress report

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

Not Available

The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

Frequent global transmission of H1N1pdm09 influenza viruses from humans to swine, 2009-2011

USDA-ARS?s Scientific Manuscript database

Using a large-scale phylogenetic approach we identify at least 52 human-to-swine transmission events of pandemic A/H1N1/09 influenza virus. These results highlight the global frequency of swine exposure to human influenza viruses and the permeability of the human-swine species barrier, even followin...

Universality of accelerating change

NASA Astrophysics Data System (ADS)

Eliazar, Iddo; Shlesinger, Michael F.

2018-03-01

On large time scales the progress of human technology follows an exponential growth trend that is termed accelerating change. The exponential growth trend is commonly considered to be the amalgamated effect of consecutive technology revolutions - where the progress carried in by each technology revolution follows an S-curve, and where the aging of each technology revolution drives humanity to push for the next technology revolution. Thus, as a collective, mankind is the 'intelligent designer' of accelerating change. In this paper we establish that the exponential growth trend - and only this trend - emerges universally, on large time scales, from systems that combine together two elements: randomness and amalgamation. Hence, the universal generation of accelerating change can be attained by systems with no 'intelligent designer'.

Scale dependent behavioral responses to human development by a large predator, the puma.

PubMed

Wilmers, Christopher C; Wang, Yiwei; Nickel, Barry; Houghtaling, Paul; Shakeri, Yasaman; Allen, Maximilian L; Kermish-Wells, Joe; Yovovich, Veronica; Williams, Terrie

2013-01-01

The spatial scale at which organisms respond to human activity can affect both ecological function and conservation planning. Yet little is known regarding the spatial scale at which distinct behaviors related to reproduction and survival are impacted by human interference. Here we provide a novel approach to estimating the spatial scale at which a top predator, the puma (Puma concolor), responds to human development when it is moving, feeding, communicating, and denning. We find that reproductive behaviors (communication and denning) require at least a 4× larger buffer from human development than non-reproductive behaviors (movement and feeding). In addition, pumas give a wider berth to types of human development that provide a more consistent source of human interference (neighborhoods) than they do to those in which human presence is more intermittent (arterial roads with speeds >35 mph). Neighborhoods were a deterrent to pumas regardless of behavior, while arterial roads only deterred pumas when they were communicating and denning. Female pumas were less deterred by human development than males, but they showed larger variation in their responses overall. Our behaviorally explicit approach to modeling animal response to human activity can be used as a novel tool to assess habitat quality, identify wildlife corridors, and mitigate human-wildlife conflict.

Understanding metropolitan patterns of daily encounters.

PubMed

Sun, Lijun; Axhausen, Kay W; Lee, Der-Horng; Huang, Xianfeng

2013-08-20

Understanding of the mechanisms driving our daily face-to-face encounters is still limited; the field lacks large-scale datasets describing both individual behaviors and their collective interactions. However, here, with the help of travel smart card data, we uncover such encounter mechanisms and structures by constructing a time-resolved in-vehicle social encounter network on public buses in a city (about 5 million residents). Using a population scale dataset, we find physical encounters display reproducible temporal patterns, indicating that repeated encounters are regular and identical. On an individual scale, we find that collective regularities dominate distinct encounters' bounded nature. An individual's encounter capability is rooted in his/her daily behavioral regularity, explaining the emergence of "familiar strangers" in daily life. Strikingly, we find individuals with repeated encounters are not grouped into small communities, but become strongly connected over time, resulting in a large, but imperceptible, small-world contact network or "structure of co-presence" across the whole metropolitan area. Revealing the encounter pattern and identifying this large-scale contact network are crucial to understanding the dynamics in patterns of social acquaintances, collective human behaviors, and--particularly--disclosing the impact of human behavior on various diffusion/spreading processes.

Understanding metropolitan patterns of daily encounters

PubMed Central

Sun, Lijun; Axhausen, Kay W.; Lee, Der-Horng; Huang, Xianfeng

2013-01-01

Understanding of the mechanisms driving our daily face-to-face encounters is still limited; the field lacks large-scale datasets describing both individual behaviors and their collective interactions. However, here, with the help of travel smart card data, we uncover such encounter mechanisms and structures by constructing a time-resolved in-vehicle social encounter network on public buses in a city (about 5 million residents). Using a population scale dataset, we find physical encounters display reproducible temporal patterns, indicating that repeated encounters are regular and identical. On an individual scale, we find that collective regularities dominate distinct encounters’ bounded nature. An individual’s encounter capability is rooted in his/her daily behavioral regularity, explaining the emergence of “familiar strangers” in daily life. Strikingly, we find individuals with repeated encounters are not grouped into small communities, but become strongly connected over time, resulting in a large, but imperceptible, small-world contact network or “structure of co-presence” across the whole metropolitan area. Revealing the encounter pattern and identifying this large-scale contact network are crucial to understanding the dynamics in patterns of social acquaintances, collective human behaviors, and—particularly—disclosing the impact of human behavior on various diffusion/spreading processes. PMID:23918373

Coexistence between wildlife and humans at fine spatial scales.

PubMed

Carter, Neil H; Shrestha, Binoj K; Karki, Jhamak B; Pradhan, Narendra Man Babu; Liu, Jianguo

2012-09-18

Many wildlife species face imminent extinction because of human impacts, and therefore, a prevailing belief is that some wildlife species, particularly large carnivores and ungulates, cannot coexist with people at fine spatial scales (i.e., cannot regularly use the exact same point locations). This belief provides rationale for various conservation programs, such as resettling human communities outside protected areas. However, quantitative information on the capacity and mechanisms for wildlife to coexist with humans at fine spatial scales is scarce. Such information is vital, because the world is becoming increasingly crowded. Here, we provide empirical information about the capacity and mechanisms for tigers (a globally endangered species) to coexist with humans at fine spatial scales inside and outside Nepal's Chitwan National Park, a flagship protected area for imperiled wildlife. Information obtained from field cameras in 2010 and 2011 indicated that human presence (i.e., people on foot and vehicles) was ubiquitous and abundant throughout the study site; however, tiger density was also high. Surprisingly, even at a fine spatial scale (i.e., camera locations), tigers spatially overlapped with people on foot and vehicles in both years. However, in both years, tigers offset their temporal activity patterns to be much less active during the day when human activity peaked. In addition to temporal displacement, tiger-human coexistence was likely enhanced by abundant tiger prey and low levels of tiger poaching. Incorporating fine-scale spatial and temporal activity patterns into conservation plans can help address a major global challenge-meeting human needs while sustaining wildlife.

Superior Red Blood Cell Generation from Human Pluripotent Stem Cells Through a Novel Microcarrier-Based Embryoid Body Platform.

PubMed

Sivalingam, Jaichandran; Lam, Alan Tin-Lun; Chen, Hong Yu; Yang, Bin Xia; Chen, Allen Kuan-Liang; Reuveny, Shaul; Loh, Yuin-Han; Oh, Steve Kah-Weng

2016-08-01

In vitro generation of red blood cells (RBCs) from human embryonic stem cells and human induced pluripotent stem cells appears to be a promising alternate approach to circumvent shortages in donor-derived blood supplies for clinical applications. Conventional methods for hematopoietic differentiation of human pluripotent stem cells (hPSC) rely on embryoid body (EB) formation and/or coculture with xenogeneic cell lines. However, most current methods for hPSC expansion and EB formation are not amenable for scale-up to levels required for large-scale RBC generation. Moreover, differentiation methods that rely on xenogenic cell lines would face obstacles for future clinical translation. In this study, we report the development of a serum-free and chemically defined microcarrier-based suspension culture platform for scalable hPSC expansion and EB formation. Improved survival and better quality EBs generated with the microcarrier-based method resulted in significantly improved mesoderm induction and, when combined with hematopoietic differentiation, resulted in at least a 6-fold improvement in hematopoietic precursor expansion, potentially culminating in a 80-fold improvement in the yield of RBC generation compared to a conventional EB-based differentiation method. In addition, we report efficient terminal maturation and generation of mature enucleated RBCs using a coculture system that comprised primary human mesenchymal stromal cells. The microcarrier-based platform could prove to be an appealing strategy for future scale-up of hPSC culture, EB generation, and large-scale generation of RBCs under defined and xeno-free conditions.

Validating Bayesian truth serum in large-scale online human experiments.

PubMed

Frank, Morgan R; Cebrian, Manuel; Pickard, Galen; Rahwan, Iyad

2017-01-01

Bayesian truth serum (BTS) is an exciting new method for improving honesty and information quality in multiple-choice survey, but, despite the method's mathematical reliance on large sample sizes, existing literature about BTS only focuses on small experiments. Combined with the prevalence of online survey platforms, such as Amazon's Mechanical Turk, which facilitate surveys with hundreds or thousands of participants, BTS must be effective in large-scale experiments for BTS to become a readily accepted tool in real-world applications. We demonstrate that BTS quantifiably improves honesty in large-scale online surveys where the "honest" distribution of answers is known in expectation on aggregate. Furthermore, we explore a marketing application where "honest" answers cannot be known, but find that BTS treatment impacts the resulting distributions of answers.

Validating Bayesian truth serum in large-scale online human experiments

PubMed Central

Frank, Morgan R.; Cebrian, Manuel; Pickard, Galen; Rahwan, Iyad

2017-01-01

Bayesian truth serum (BTS) is an exciting new method for improving honesty and information quality in multiple-choice survey, but, despite the method’s mathematical reliance on large sample sizes, existing literature about BTS only focuses on small experiments. Combined with the prevalence of online survey platforms, such as Amazon’s Mechanical Turk, which facilitate surveys with hundreds or thousands of participants, BTS must be effective in large-scale experiments for BTS to become a readily accepted tool in real-world applications. We demonstrate that BTS quantifiably improves honesty in large-scale online surveys where the “honest” distribution of answers is known in expectation on aggregate. Furthermore, we explore a marketing application where “honest” answers cannot be known, but find that BTS treatment impacts the resulting distributions of answers. PMID:28494000

Large-scale model quality assessment for improving protein tertiary structure prediction.

PubMed

Cao, Renzhi; Bhattacharya, Debswapna; Adhikari, Badri; Li, Jilong; Cheng, Jianlin

2015-06-15

Sampling structural models and ranking them are the two major challenges of protein structure prediction. Traditional protein structure prediction methods generally use one or a few quality assessment (QA) methods to select the best-predicted models, which cannot consistently select relatively better models and rank a large number of models well. Here, we develop a novel large-scale model QA method in conjunction with model clustering to rank and select protein structural models. It unprecedentedly applied 14 model QA methods to generate consensus model rankings, followed by model refinement based on model combination (i.e. averaging). Our experiment demonstrates that the large-scale model QA approach is more consistent and robust in selecting models of better quality than any individual QA method. Our method was blindly tested during the 11th Critical Assessment of Techniques for Protein Structure Prediction (CASP11) as MULTICOM group. It was officially ranked third out of all 143 human and server predictors according to the total scores of the first models predicted for 78 CASP11 protein domains and second according to the total scores of the best of the five models predicted for these domains. MULTICOM's outstanding performance in the extremely competitive 2014 CASP11 experiment proves that our large-scale QA approach together with model clustering is a promising solution to one of the two major problems in protein structure modeling. The web server is available at: http://sysbio.rnet.missouri.edu/multicom_cluster/human/. © The Author 2015. Published by Oxford University Press.

LARGE SCALE DISASTER ANALYSIS AND MANAGEMENT: SYSTEM LEVEL STUDY ON AN INTEGRATED MODEL

EPA Science Inventory

The increasing intensity and scale of human activity across the globe leading to severe depletion and deterioration of the Earth's natural resources has meant that sustainability has emerged as a new paradigm of analysis and management. Sustainability, conceptually defined by the...

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

DOE PAGES

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.; ...

2018-02-06

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Domain-Adapted Convolutional Networks for Satellite Image Classification: A Large-Scale Interactive Learning Workflow

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

Lunga, Dalton D.; Yang, Hsiuhan Lexie; Reith, Andrew E.

Satellite imagery often exhibits large spatial extent areas that encompass object classes with considerable variability. This often limits large-scale model generalization with machine learning algorithms. Notably, acquisition conditions, including dates, sensor position, lighting condition, and sensor types, often translate into class distribution shifts introducing complex nonlinear factors and hamper the potential impact of machine learning classifiers. Here, this article investigates the challenge of exploiting satellite images using convolutional neural networks (CNN) for settlement classification where the class distribution shifts are significant. We present a large-scale human settlement mapping workflow based-off multiple modules to adapt a pretrained CNN to address themore » negative impact of distribution shift on classification performance. To extend a locally trained classifier onto large spatial extents areas we introduce several submodules: First, a human-in-the-loop element for relabeling of misclassified target domain samples to generate representative examples for model adaptation; second, an efficient hashing module to minimize redundancy and noisy samples from the mass-selected examples; and third, a novel relevance ranking module to minimize the dominance of source example on the target domain. The workflow presents a novel and practical approach to achieve large-scale domain adaptation with binary classifiers that are based-off CNN features. Experimental evaluations are conducted on areas of interest that encompass various image characteristics, including multisensors, multitemporal, and multiangular conditions. Domain adaptation is assessed on source–target pairs through the transfer loss and transfer ratio metrics to illustrate the utility of the workflow.« less

Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

PubMed

Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

2011-10-07

Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes.

Perceptions of Human Services Students about Social Change Education

ERIC Educational Resources Information Center

Herzberg, Judith T.

2010-01-01

Human services educators and scholars maintain that they are teaching social change theory and skills that will allow students to engage in large-scale social change. A review of the literature, from a critical theory perspective, offered little evidence that social change is being taught in human services programs. In this collective case study,…

The evolution of reciprocity in sizable human groups.

PubMed

Rothschild, Casey G

2009-04-21

The scale and complexity of human cooperation is an important and unresolved evolutionary puzzle. This article uses the finitely repeated n person Prisoners' Dilemma game to illustrate how sapience can greatly enhance group-selection effects and lead to the evolutionary stability of cooperation in large groups. This affords a simple and direct explanation of the human "exception".

Measuring happiness in large population

NASA Astrophysics Data System (ADS)

Wenas, Annabelle; Sjahputri, Smita; Takwin, Bagus; Primaldhi, Alfindra; Muhamad, Roby

2016-01-01

The ability to know emotional states for large number of people is important, for example, to ensure the effectiveness of public policies. In this study, we propose a measure of happiness that can be used in large scale population that is based on the analysis of Indonesian language lexicons. Here, we incorporate human assessment of Indonesian words, then quantify happiness on large-scale of texts gathered from twitter conversations. We used two psychological constructs to measure happiness: valence and arousal. We found that Indonesian words have tendency towards positive emotions. We also identified several happiness patterns during days of the week, hours of the day, and selected conversation topics.

New strategy for drug discovery by large-scale association analysis of molecular networks of different species.

PubMed

Zhang, Bo; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Wu, Ziyin; Zhang, Wenjuan; Yang, Xiaoyan; Gong, Fukai; Li, Yuerong; Chen, Xiaoyu; Gao, Shuo; Chen, Xuetong; Li, Yan; Lu, Aiping; Wang, Yonghua

2016-02-25

The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.

A conditional approach to determining the effect of anthropogenic climate change on very rare events.

NASA Astrophysics Data System (ADS)

Wehner, Michael; Pall, Pardeep; Zarzycki, Colin; Stone, Daithi

2016-04-01

Probabilistic extreme event attribution is especially difficult for weather events that are caused by extremely rare large-scale meteorological patterns. Traditional modeling techniques have involved using ensembles of climate models, either fully coupled or with prescribed ocean and sea ice. Ensemble sizes for the latter case ranges from several 100 to tens of thousand. However, even if the simulations are constrained by the observed ocean state, the requisite large-scale meteorological pattern may not occur frequently enough or even at all in free running climate model simulations. We present a method to ensure that simulated events similar to the observed event are modeled with enough fidelity that robust statistics can be determined given the large scale meteorological conditions. By initializing suitably constrained short term ensemble hindcasts of both the actual weather system and a counterfactual weather system where the human interference in the climate system is removed, the human contribution to the magnitude of the event can be determined. However, the change (if any) in the probability of an event of the observed magnitude is conditional not only on the state of the ocean/sea ice system but also on the prescribed initial conditions determined by the causal large scale meteorological pattern. We will discuss the implications of this technique through two examples; the 2013 Colorado flood and the 2014 Typhoon Haiyan.

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

PubMed Central

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

2015-01-01

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

Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

PubMed

Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

2003-01-01

An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma-derived FVIIa concentrate with a high yield, making it possible to provide sufficient FVIIa concentrate for use in haemophiliacs with inhibitory antibodies.

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

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.

[New hosts and vectors for genome cloning]. Progress report, 1990--1991

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

Not Available

The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

Representation matters: quantitative behavioral variation in wild worm strains

NASA Astrophysics Data System (ADS)

Brown, Andre

Natural genetic variation in populations is the basis of genome-wide association studies, an approach that has been applied in large studies of humans to study the genetic architecture of complex traits including disease risk. Of course, the traits you choose to measure determine which associated genes you discover (or miss). In large-scale human studies, the measured traits are usually taken as a given during the association step because they are expensive to collect and standardize. Working with the nematode worm C. elegans, we do not have the same constraints. In this talk I will describe how large-scale imaging of worm behavior allows us to develop alternative representations of behavior that vary differently across wild populations. The alternative representations yield novel traits that can be used for genome-wide association studies and may reveal basic properties of the genotype-phenotype map that are obscured if only a small set of fixed traits are used.

High-resolution Continental Scale Land Surface Model incorporating Land-water Management in United States

NASA Astrophysics Data System (ADS)

Shin, S.; Pokhrel, Y. N.

2016-12-01

Land surface models have been used to assess water resources sustainability under changing Earth environment and increasing human water needs. Overwhelming observational records indicate that human activities have ubiquitous and pertinent effects on the hydrologic cycle; however, they have been crudely represented in large scale land surface models. In this study, we enhance an integrated continental-scale land hydrology model named Leaf-Hydro-Flood to better represent land-water management. The model is implemented at high resolution (5km grids) over the continental US. Surface water and groundwater are withdrawn based on actual practices. Newly added irrigation, water diversion, and dam operation schemes allow better simulations of stream flows, evapotranspiration, and infiltration. Results of various hydrologic fluxes and stores from two sets of simulation (one with and the other without human activities) are compared over a range of river basin and aquifer scales. The improved simulations of land hydrology have potential to build consistent modeling framework for human-water-climate interactions.

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

NASA Astrophysics Data System (ADS)

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

1997-01-01

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

Using stroboscopic flow imaging to validate large-scale computational fluid dynamics simulations

NASA Astrophysics Data System (ADS)

Laurence, Ted A.; Ly, Sonny; Fong, Erika; Shusteff, Maxim; Randles, Amanda; Gounley, John; Draeger, Erik

2017-02-01

The utility and accuracy of computational modeling often requires direct validation against experimental measurements. The work presented here is motivated by taking a combined experimental and computational approach to determine the ability of large-scale computational fluid dynamics (CFD) simulations to understand and predict the dynamics of circulating tumor cells in clinically relevant environments. We use stroboscopic light sheet fluorescence imaging to track the paths and measure the velocities of fluorescent microspheres throughout a human aorta model. Performed over complex physiologicallyrealistic 3D geometries, large data sets are acquired with microscopic resolution over macroscopic distances.

Coexistence between wildlife and humans at fine spatial scales

PubMed Central

Carter, Neil H.; Shrestha, Binoj K.; Karki, Jhamak B.; Pradhan, Narendra Man Babu; Liu, Jianguo

2012-01-01

Many wildlife species face imminent extinction because of human impacts, and therefore, a prevailing belief is that some wildlife species, particularly large carnivores and ungulates, cannot coexist with people at fine spatial scales (i.e., cannot regularly use the exact same point locations). This belief provides rationale for various conservation programs, such as resettling human communities outside protected areas. However, quantitative information on the capacity and mechanisms for wildlife to coexist with humans at fine spatial scales is scarce. Such information is vital, because the world is becoming increasingly crowded. Here, we provide empirical information about the capacity and mechanisms for tigers (a globally endangered species) to coexist with humans at fine spatial scales inside and outside Nepal’s Chitwan National Park, a flagship protected area for imperiled wildlife. Information obtained from field cameras in 2010 and 2011 indicated that human presence (i.e., people on foot and vehicles) was ubiquitous and abundant throughout the study site; however, tiger density was also high. Surprisingly, even at a fine spatial scale (i.e., camera locations), tigers spatially overlapped with people on foot and vehicles in both years. However, in both years, tigers offset their temporal activity patterns to be much less active during the day when human activity peaked. In addition to temporal displacement, tiger–human coexistence was likely enhanced by abundant tiger prey and low levels of tiger poaching. Incorporating fine-scale spatial and temporal activity patterns into conservation plans can help address a major global challenge—meeting human needs while sustaining wildlife. PMID:22949642

Integrating an agent-based model into a large-scale hydrological model for evaluating drought management in California

NASA Astrophysics Data System (ADS)

Sheffield, J.; He, X.; Wada, Y.; Burek, P.; Kahil, M.; Wood, E. F.; Oppenheimer, M.

2017-12-01

California has endured record-breaking drought since winter 2011 and will likely experience more severe and persistent drought in the coming decades under changing climate. At the same time, human water management practices can also affect drought frequency and intensity, which underscores the importance of human behaviour in effective drought adaptation and mitigation. Currently, although a few large-scale hydrological and water resources models (e.g., PCR-GLOBWB) consider human water use and management practices (e.g., irrigation, reservoir operation, groundwater pumping), none of them includes the dynamic feedback between local human behaviors/decisions and the natural hydrological system. It is, therefore, vital to integrate social and behavioral dimensions into current hydrological modeling frameworks. This study applies the agent-based modeling (ABM) approach and couples it with a large-scale hydrological model (i.e., Community Water Model, CWatM) in order to have a balanced representation of social, environmental and economic factors and a more realistic representation of the bi-directional interactions and feedbacks in coupled human and natural systems. In this study, we focus on drought management in California and considers two types of agents, which are (groups of) farmers and state management authorities, and assumed that their corresponding objectives are to maximize the net crop profit and to maintain sufficient water supply, respectively. Farmers' behaviors are linked with local agricultural practices such as cropping patterns and deficit irrigation. More precisely, farmers' decisions are incorporated into CWatM across different time scales in terms of daily irrigation amount, seasonal/annual decisions on crop types and irrigated area as well as the long-term investment of irrigation infrastructure. This simulation-based optimization framework is further applied by performing different sets of scenarios to investigate and evaluate the effectiveness of different water management strategies and how policy interventions will facilitate drought adaptation in California.

Emergence of scaling in human-interest dynamics.

PubMed

Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

2013-12-11

Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical "Big Data" sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction.

Emergence of scaling in human-interest dynamics

NASA Astrophysics Data System (ADS)

Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

2013-12-01

Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical ``Big Data'' sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction.

Fractal multi-level organisation of human groups in a virtual world.

PubMed

Fuchs, Benedikt; Sornette, Didier; Thurner, Stefan

2014-10-06

Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology.

Fractal multi-level organisation of human groups in a virtual world

PubMed Central

Fuchs, Benedikt; Sornette, Didier; Thurner, Stefan

2014-01-01

Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology. PMID:25283998

Fractal multi-level organisation of human groups in a virtual world

NASA Astrophysics Data System (ADS)

Fuchs, Benedikt; Sornette, Didier; Thurner, Stefan

2014-10-01

Humans are fundamentally social. They form societies which consist of hierarchically layered nested groups of various quality, size, and structure. The anthropologic literature has classified these groups as support cliques, sympathy groups, bands, cognitive groups, tribes, linguistic groups, and so on. Anthropologic data show that, on average, each group consists of approximately three subgroups. However, a general understanding of the structural dependence of groups at different layers is largely missing. We extend these early findings to a very large high-precision large-scale internet-based social network data. We analyse the organisational structure of a complete, multi-relational, large social multiplex network of a human society consisting of about 400,000 odd players of an open-ended massive multiplayer online game for which we know all about their various group memberships at different layers. Remarkably, the online players' society exhibits the same type of structured hierarchical layers as found in hunter-gatherer societies. Our findings suggest that the hierarchical organisation of human society is deeply nested in human psychology.

Influence of land use on water quality in a tropical landscape: a multi-scale analysis

PubMed Central

Yackulic, Charles B.; Lim, Yili; Arce-Nazario, Javier A.

2015-01-01

There is a pressing need to understand the consequences of human activities, such as land transformations, on watershed ecosystem services. This is a challenging task because different indicators of water quality and yield are expected to vary in their responsiveness to large versus local-scale heterogeneity in land use and land cover (LUC). Here we rely on water quality data collected between 1977 and 2000 from dozens of gauge stations in Puerto Rico together with precipitation data and land cover maps to (1) quantify impacts of spatial heterogeneity in LUC on several water quality indicators; (2) determine the spatial scale at which this heterogeneity influences water quality; and (3) examine how antecedent precipitation modulates these impacts. Our models explained 30–58% of observed variance in water quality metrics. Temporal variation in antecedent precipitation and changes in LUC between measurements periods rather than spatial variation in LUC accounted for the majority of variation in water quality. Urbanization and pasture development generally degraded water quality while agriculture and secondary forest re-growth had mixed impacts. The spatial scale over which LUC influenced water quality differed across indicators. Turbidity and dissolved oxygen (DO) responded to LUC in large-scale watersheds, in-stream nitrogen concentrations to LUC in riparian buffers of large watersheds, and fecal matter content and in-stream phosphorus concentration to LUC at the sub-watershed scale. Stream discharge modulated impacts of LUC on water quality for most of the metrics. Our findings highlight the importance of considering multiple spatial scales for understanding the impacts of human activities on watershed ecosystem services. PMID:26146455

The Human Ecology of the American Educational Research Association. Report No. 261.

ERIC Educational Resources Information Center

Richards, James M., Jr.

The concepts and methods of human ecology are applied to the geographic distribution of members of the American Educational Research Association. State characteristics are measured by five factors: (1) large-scale agriculture; (2) population size; (3) affluence-urbanization; (4) white predominance; (5) emphasis on specialized agriculture. City…

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

Remote Imaging Applied to Schistosomiasis Control: The Anning River Project

NASA Technical Reports Server (NTRS)

Seto, Edmund Y. W.; Maszle, Don R.; Spear, Robert C.; Gong, Peng

1997-01-01

The use of satellite imaging to remotely detect areas of high risk for transmission of infectious disease is an appealing prospect for large-scale monitoring of these diseases. The detection of large-scale environmental determinants of disease risk, often called landscape epidemiology, has been motivated by several authors (Pavlovsky 1966; Meade et al. 1988). The basic notion is that large-scale factors such as population density, air temperature, hydrological conditions, soil type, and vegetation can determine in a coarse fashion the local conditions contributing to disease vector abundance and human contact with disease agents. These large-scale factors can often be remotely detected by sensors or cameras mounted on satellite or aircraft platforms and can thus be used in a predictive model to mark high risk areas of transmission and to target control or monitoring efforts. A review of satellite technologies for this purpose was recently presented by Washino and Wood (1994) and Hay (1997) and Hay et al. (1997).

Automatic Selection of Order Parameters in the Analysis of Large Scale Molecular Dynamics Simulations.

PubMed

Sultan, Mohammad M; Kiss, Gert; Shukla, Diwakar; Pande, Vijay S

2014-12-09

Given the large number of crystal structures and NMR ensembles that have been solved to date, classical molecular dynamics (MD) simulations have become powerful tools in the atomistic study of the kinetics and thermodynamics of biomolecular systems on ever increasing time scales. By virtue of the high-dimensional conformational state space that is explored, the interpretation of large-scale simulations faces difficulties not unlike those in the big data community. We address this challenge by introducing a method called clustering based feature selection (CB-FS) that employs a posterior analysis approach. It combines supervised machine learning (SML) and feature selection with Markov state models to automatically identify the relevant degrees of freedom that separate conformational states. We highlight the utility of the method in the evaluation of large-scale simulations and show that it can be used for the rapid and automated identification of relevant order parameters involved in the functional transitions of two exemplary cell-signaling proteins central to human disease states.

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

PubMed Central

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

2014-01-01

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

A biological rationale for musical scales.

PubMed

Gill, Kamraan Z; Purves, Dale

2009-12-03

Scales are collections of tones that divide octaves into specific intervals used to create music. Since humans can distinguish about 240 different pitches over an octave in the mid-range of hearing, in principle a very large number of tone combinations could have been used for this purpose. Nonetheless, compositions in Western classical, folk and popular music as well as in many other musical traditions are based on a relatively small number of scales that typically comprise only five to seven tones. Why humans employ only a few of the enormous number of possible tone combinations to create music is not known. Here we show that the component intervals of the most widely used scales throughout history and across cultures are those with the greatest overall spectral similarity to a harmonic series. These findings suggest that humans prefer tone combinations that reflect the spectral characteristics of conspecific vocalizations. The analysis also highlights the spectral similarity among the scales used by different cultures.

Scale and the representation of human agency in the modeling of agroecosystems

DOE PAGES

Preston, Benjamin L.; King, Anthony W.; Ernst, Kathleen M.; ...

2015-07-17

Human agency is an essential determinant of the dynamics of agroecosystems. However, the manner in which agency is represented within different approaches to agroecosystem modeling is largely contingent on the scales of analysis and the conceptualization of the system of interest. While appropriate at times, narrow conceptualizations of agroecosystems can preclude consideration for how agency manifests at different scales, thereby marginalizing processes, feedbacks, and constraints that would otherwise affect model results. Modifications to the existing modeling toolkit may therefore enable more holistic representations of human agency. Model integration can assist with the development of multi-scale agroecosystem modeling frameworks that capturemore » different aspects of agency. In addition, expanding the use of socioeconomic scenarios and stakeholder participation can assist in explicitly defining context-dependent elements of scale and agency. Finally, such approaches, however, should be accompanied by greater recognition of the meta agency of model users and the need for more critical evaluation of model selection and application.« less

A Biological Rationale for Musical Scales

PubMed Central

Gill, Kamraan Z.; Purves, Dale

2009-01-01

Scales are collections of tones that divide octaves into specific intervals used to create music. Since humans can distinguish about 240 different pitches over an octave in the mid-range of hearing [1], in principle a very large number of tone combinations could have been used for this purpose. Nonetheless, compositions in Western classical, folk and popular music as well as in many other musical traditions are based on a relatively small number of scales that typically comprise only five to seven tones [2]–[6]. Why humans employ only a few of the enormous number of possible tone combinations to create music is not known. Here we show that the component intervals of the most widely used scales throughout history and across cultures are those with the greatest overall spectral similarity to a harmonic series. These findings suggest that humans prefer tone combinations that reflect the spectral characteristics of conspecific vocalizations. The analysis also highlights the spectral similarity among the scales used by different cultures. PMID:19997506

Large-scale machine learning and evaluation platform for real-time traffic surveillance

NASA Astrophysics Data System (ADS)

Eichel, Justin A.; Mishra, Akshaya; Miller, Nicholas; Jankovic, Nicholas; Thomas, Mohan A.; Abbott, Tyler; Swanson, Douglas; Keller, Joel

2016-09-01

In traffic engineering, vehicle detectors are trained on limited datasets, resulting in poor accuracy when deployed in real-world surveillance applications. Annotating large-scale high-quality datasets is challenging. Typically, these datasets have limited diversity; they do not reflect the real-world operating environment. There is a need for a large-scale, cloud-based positive and negative mining process and a large-scale learning and evaluation system for the application of automatic traffic measurements and classification. The proposed positive and negative mining process addresses the quality of crowd sourced ground truth data through machine learning review and human feedback mechanisms. The proposed learning and evaluation system uses a distributed cloud computing framework to handle data-scaling issues associated with large numbers of samples and a high-dimensional feature space. The system is trained using AdaBoost on 1,000,000 Haar-like features extracted from 70,000 annotated video frames. The trained real-time vehicle detector achieves an accuracy of at least 95% for 1/2 and about 78% for 19/20 of the time when tested on ˜7,500,000 video frames. At the end of 2016, the dataset is expected to have over 1 billion annotated video frames.

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review

PubMed Central

Huang, Eileen; Pillai, Satish K.; Bower, William A.; Hendricks, Katherine A.; Guarnizo, Julie T.; Hoyle, Jamechia D.; Gorman, Susan E.; Boyer, Anne E.; Quinn, Conrad P.; Meaney-Delman, Dana

2016-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident. PMID:26690378

Antitoxin Treatment of Inhalation Anthrax: A Systematic Review.

PubMed

Huang, Eileen; Pillai, Satish K; Bower, William A; Hendricks, Katherine A; Guarnizo, Julie T; Hoyle, Jamechia D; Gorman, Susan E; Boyer, Anne E; Quinn, Conrad P; Meaney-Delman, Dana

2015-01-01

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.

Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

PubMed

Takayama, Kazuo; Mizuguchi, Hiroyuki

2017-02-01

Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Plague and Climate: Scales Matter

PubMed Central

Ben Ari, Tamara; Neerinckx, Simon; Gage, Kenneth L.; Kreppel, Katharina; Laudisoit, Anne; Leirs, Herwig; Stenseth, Nils Chr.

2011-01-01

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations. PMID:21949648

Die-off rates of Cryptosporidium parvum oocysts in a swine lagoon and in a spray field

USDA-ARS?s Scientific Manuscript database

Background: Because of several large-scale outbreaks of cryptosporidiosis in humans, Cryptosporidium has become a public health concern. Commercial swine operations apply large volumes of effluent from lagoons to spray fields as a waste management practice. This effluent is a source of Cryptosporidi...

Quantitative Missense Variant Effect Prediction Using Large-Scale Mutagenesis Data.

PubMed

Gray, Vanessa E; Hause, Ronald J; Luebeck, Jens; Shendure, Jay; Fowler, Douglas M

2018-01-24

Large datasets describing the quantitative effects of mutations on protein function are becoming increasingly available. Here, we leverage these datasets to develop Envision, which predicts the magnitude of a missense variant's molecular effect. Envision combines 21,026 variant effect measurements from nine large-scale experimental mutagenesis datasets, a hitherto untapped training resource, with a supervised, stochastic gradient boosting learning algorithm. Envision outperforms other missense variant effect predictors both on large-scale mutagenesis data and on an independent test dataset comprising 2,312 TP53 variants whose effects were measured using a low-throughput approach. This dataset was never used for hyperparameter tuning or model training and thus serves as an independent validation set. Envision prediction accuracy is also more consistent across amino acids than other predictors. Finally, we demonstrate that Envision's performance improves as more large-scale mutagenesis data are incorporated. We precompute Envision predictions for every possible single amino acid variant in human, mouse, frog, zebrafish, fruit fly, worm, and yeast proteomes (https://envision.gs.washington.edu/). Copyright © 2017 Elsevier Inc. All rights reserved.

Is environmental legislation conserving tropical stream faunas? A large-scale assessment of local, riparian and catchment-scale influences on Amazonian fishes

EPA Science Inventory

Tropical agricultural is a major threat to biodiversity worldwide. In addition to the direct impacts of converting native vegetation to agriculture this process is accompanied by a wider set of human-induced disturbances, many of which are poorly addressed by existing environment...

Voting contagion: Modeling and analysis of a century of U.S. presidential elections

PubMed Central

de Aguiar, Marcus A. M.

2017-01-01

Social influence plays an important role in human behavior and decisions. Sources of influence can be divided as external, which are independent of social context, or as originating from peers, such as family and friends. An important question is how to disentangle the social contagion by peers from external influences. While a variety of experimental and observational studies provided insight into this problem, identifying the extent of contagion based on large-scale observational data with an unknown network structure remains largely unexplored. By bridging the gap between the large-scale complex systems perspective of collective human dynamics and the detailed approach of social sciences, we present a parsimonious model of social influence, and apply it to a central topic in political science—elections and voting behavior. We provide an analytical expression of the county vote-share distribution, which is in excellent agreement with almost a century of observed U.S. presidential election data. Analyzing the social influence topography over this period reveals an abrupt phase transition from low to high levels of social contagion, and robust differences among regions. These results suggest that social contagion effects are becoming more instrumental in shaping large-scale collective political behavior, with implications on democratic electoral processes and policies. PMID:28542409

Toward exascale production of recombinant adeno-associated virus for gene transfer applications.

PubMed

Cecchini, S; Negrete, A; Kotin, R M

2008-06-01

To gain acceptance as a medical treatment, adeno-associated virus (AAV) vectors require a scalable and economical production method. Recent developments indicate that recombinant AAV (rAAV) production in insect cells is compatible with current good manufacturing practice production on an industrial scale. This platform can fully support development of rAAV therapeutics from tissue culture to small animal models, to large animal models, to toxicology studies, to Phase I clinical trials and beyond. Efforts to characterize, optimize and develop insect cell-based rAAV production have culminated in successful bioreactor-scale production of rAAV, with total yields potentially capable of approaching the exa-(10(18)) scale. These advances in large-scale AAV production will allow us to address specific catastrophic, intractable human diseases such as Duchenne muscular dystrophy, for which large amounts of recombinant vector are essential for successful outcome.

Intact mass detection, interpretation, and visualization to automate Top-Down proteomics on a large scale

PubMed Central

Durbin, Kenneth R.; Tran, John C.; Zamdborg, Leonid; Sweet, Steve M. M.; Catherman, Adam D.; Lee, Ji Eun; Li, Mingxi; Kellie, John F.; Kelleher, Neil L.

2011-01-01

Applying high-throughput Top-Down MS to an entire proteome requires a yet-to-be-established model for data processing. Since Top-Down is becoming possible on a large scale, we report our latest software pipeline dedicated to capturing the full value of intact protein data in automated fashion. For intact mass detection, we combine algorithms for processing MS1 data from both isotopically resolved (FT) and charge-state resolved (ion trap) LC-MS data, which are then linked to their fragment ions for database searching using ProSight. Automated determination of human keratin and tubulin isoforms is one result. Optimized for the intricacies of whole proteins, new software modules visualize proteome-scale data based on the LC retention time and intensity of intact masses and enable selective detection of PTMs to automatically screen for acetylation, phosphorylation, and methylation. Software functionality was demonstrated using comparative LC-MS data from yeast strains in addition to human cells undergoing chemical stress. We further these advances as a key aspect of realizing Top-Down MS on a proteomic scale. PMID:20848673

Social and environmental sustainability in large-scale coastal zones: Taking an issue-based approach to the implementation of the Prince William Sound sustainable human use framework

Treesearch

Dale J. Blahna; Aaron Poe; Courtney Brown; Clare M. Ryan; H. Randy Gimblett

2017-01-01

Following the grounding of the Exxon Valdez in 1989, a sustainable human use framework (human use framework) for Prince William Sound (PWS), AK was developed by the Chugach National Forest after concerns emerged about the social and environmental impacts of expanding human use due to cleanup activities and increased recreation visitation. A practical, issue-based...

A human factors approach to range scheduling for satellite control

NASA Technical Reports Server (NTRS)

Wright, Cameron H. G.; Aitken, Donald J.

1991-01-01

Range scheduling for satellite control presents a classical problem: supervisory control of a large-scale dynamic system, with unwieldy amounts of interrelated data used as inputs to the decision process. Increased automation of the task, with the appropriate human-computer interface, is highly desirable. The development and user evaluation of a semi-automated network range scheduling system is described. The system incorporates a synergistic human-computer interface consisting of a large screen color display, voice input/output, a 'sonic pen' pointing device, a touchscreen color CRT, and a standard keyboard. From a human factors standpoint, this development represents the first major improvement in almost 30 years to the satellite control network scheduling task.

Large-Scale Atmospheric Teleconnection Patterns Associated with the Interannual Variability of Heatwaves in East Asia and Its Decadal Changes

NASA Astrophysics Data System (ADS)

Choi, N.; Lee, M. I.; Lim, Y. K.; Kim, K. M.

2017-12-01

Heatwave is an extreme hot weather event which accompanies fatal damage to human health. The heatwave has a strong relationship with the large-scale atmospheric teleconnection patterns. In this study, we examine the spatial pattern of heatwave in East Asia by using the EOF analysis and the relationship between heatwave frequency and large-scale atmospheric teleconnection patterns. We also separate the time scale of heatwave frequency as the time scale longer than a decade and the interannual time scale. The long-term variation of heatwave frequency in East Asia shows a linkage with the sea surface temperature (SST) variability over the North Atlantic with a decadal time scale (a.k.a. the Atlantic Multidecadal Oscillation; AMO). On the other hands, the interannual variation of heatwave frequency is linked with the two dominant spatial patterns associated with the large-scale teleconnection patterns mimicking the Scandinavian teleconnection (SCAND-like) pattern and the circumglobal teleconnection (CGT-like) pattern, respectively. It is highlighted that the interannual variation of heatwave frequency in East Asia shows a remarkable change after mid-1990s. While the heatwave frequency was mainly associated with the CGT-like pattern before mid-1990s, the SCAND-like pattern becomes the most dominant one after mid-1990s, making the CGT-like pattern as the second. This study implies that the large-scale atmospheric teleconnection patterns play a key role in developing heatwave events in East Asia. This study further discusses possible mechanisms for the decadal change in the linkage between heatwave frequency and the large-scale teleconnection patterns in East Asia such as early melting of snow cover and/or weakening of East Asian jet stream due to global warming.

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

Cyclic avian mass mortality in the northeastern United States is associated with a novel orthomyxovirus

USGS Publications Warehouse

Allison, Andrew B.; Ballard, Jennifer R.; Tesh, Robert B.; Brown, Justin D.; Ruder, Mark G.; Keel, M. Kevin; Munk, Brandon A.; Mickley, Randall M.; Gibbs, Samantha E.J.; Ellis, Julie C.; Travassos da Rosac, Amelia P.A.; Ip, Hon S.; Shearn-Bochsler, Valerie I.; Rogers, Matthew B.; Gheldin, Elodie; Holmes, Edward C.; Parrish, Colin R.; Dwyer, Chris P.

2015-01-01

Importance The emergence or reemergence of viral pathogens resulting in large-scale outbreaks of disease in humans and/or animals is one of the most important challenges facing biomedicine. For example, understanding how orthomyxoviruses such as novel influenza A virus reassortants and/or mutants emerge to cause epidemic or pandemic disease is at the forefront of current global health concerns. Here we describe the emergence of a novel orthomyxovirus, Wellfleet Bay virus (WFBV), which has been associated with cyclic large-scale bird die-offs in the northeastern United States. This initial characterization study provides a foundation for further research into the evolution, epidemiology, and ecology of newly emerging orthomyxoviruses, such as WFBV, and their potential impacts on animal and/or human health.

Klamath Basin: A Watershed Approach to Support Habitat Restoration, Species Recovery, and Water Resource Planning

USGS Publications Warehouse

VanderKooi, S.P.; Thorsteinson, L.

2007-01-01

Water allocation among human and natural resource uses in the American West is challenging. Western rivers have been largely managed for hydropower, irrigation, drinking water, and navigation. Today land and water use practices have gained importance, particularly as aging dams are faced with re-licensing requirements and provisions of the Endangered Species and Clean Water Acts. Rising demand for scarce water heightens the need for scientific research to predict consequences of management actions on habitats, human resource use, and fish and wildlife. Climate change, introduction of invasive species, or restoration of fish passage can have large, landscape-scaled consequences - research must expand to encompass the appropriate scale and by applying multiple scientific disciplines to complex ecosystem challenges improve the adaptive management framework for decision-making.

Large Scale Anthropogenic Reduction of Forest Cover in Last Glacial Maximum Europe

PubMed Central

Pfeiffer, Mirjam; Kolen, Jan C. A.; Davis, Basil A. S.

2016-01-01

Reconstructions of the vegetation of Europe during the Last Glacial Maximum (LGM) are an enigma. Pollen-based analyses have suggested that Europe was largely covered by steppe and tundra, and forests persisted only in small refugia. Climate-vegetation model simulations on the other hand have consistently suggested that broad areas of Europe would have been suitable for forest, even in the depths of the last glaciation. Here we reconcile models with data by demonstrating that the highly mobile groups of hunter-gatherers that inhabited Europe at the LGM could have substantially reduced forest cover through the ignition of wildfires. Similar to hunter-gatherers of the more recent past, Upper Paleolithic humans were masters of the use of fire, and preferred inhabiting semi-open landscapes to facilitate foraging, hunting and travel. Incorporating human agency into a dynamic vegetation-fire model and simulating forest cover shows that even small increases in wildfire frequency over natural background levels resulted in large changes in the forested area of Europe, in part because trees were already stressed by low atmospheric CO2 concentrations and the cold, dry, and highly variable climate. Our results suggest that the impact of humans on the glacial landscape of Europe may be one of the earliest large-scale anthropogenic modifications of the earth system. PMID:27902716

When is bigger better? The effects of group size on the evolution of helping behaviours.

PubMed

Powers, Simon T; Lehmann, Laurent

2017-05-01

Understanding the evolution of sociality in humans and other species requires understanding how selection on social behaviour varies with group size. However, the effects of group size are frequently obscured in the theoretical literature, which often makes assumptions that are at odds with empirical findings. In particular, mechanisms are suggested as supporting large-scale cooperation when they would in fact rapidly become ineffective with increasing group size. Here we review the literature on the evolution of helping behaviours (cooperation and altruism), and frame it using a simple synthetic model that allows us to delineate how the three main components of the selection pressure on helping must vary with increasing group size. The first component is the marginal benefit of helping to group members, which determines both direct fitness benefits to the actor and indirect fitness benefits to recipients. While this is often assumed to be independent of group size, marginal benefits are in practice likely to be maximal at intermediate group sizes for many types of collective action problems, and will eventually become very small in large groups due to the law of decreasing marginal returns. The second component is the response of social partners on the past play of an actor, which underlies conditional behaviour under repeated social interactions. We argue that under realistic conditions on the transmission of information in a population, this response on past play decreases rapidly with increasing group size so that reciprocity alone (whether direct, indirect, or generalised) cannot sustain cooperation in very large groups. The final component is the relatedness between actor and recipient, which, according to the rules of inheritance, again decreases rapidly with increasing group size. These results explain why helping behaviours in very large social groups are limited to cases where the number of reproducing individuals is small, as in social insects, or where there are social institutions that can promote (possibly through sanctioning) large-scale cooperation, as in human societies. Finally, we discuss how individually devised institutions can foster the transition from small-scale to large-scale cooperative groups in human evolution. © 2016 Cambridge Philosophical Society.

Zebrafish Whole-Adult-Organism Chemogenomics for Large-Scale Predictive and Discovery Chemical Biology

PubMed Central

Lam, Siew Hong; Mathavan, Sinnakarupan; Tong, Yan; Li, Haixia; Karuturi, R. Krishna Murthy; Wu, Yilian; Vega, Vinsensius B.; Liu, Edison T.; Gong, Zhiyuan

2008-01-01

The ability to perform large-scale, expression-based chemogenomics on whole adult organisms, as in invertebrate models (worm and fly), is highly desirable for a vertebrate model but its feasibility and potential has not been demonstrated. We performed expression-based chemogenomics on the whole adult organism of a vertebrate model, the zebrafish, and demonstrated its potential for large-scale predictive and discovery chemical biology. Focusing on two classes of compounds with wide implications to human health, polycyclic (halogenated) aromatic hydrocarbons [P(H)AHs] and estrogenic compounds (ECs), we generated robust prediction models that can discriminate compounds of the same class from those of different classes in two large independent experiments. The robust expression signatures led to the identification of biomarkers for potent aryl hydrocarbon receptor (AHR) and estrogen receptor (ER) agonists, respectively, and were validated in multiple targeted tissues. Knowledge-based data mining of human homologs of zebrafish genes revealed highly conserved chemical-induced biological responses/effects, health risks, and novel biological insights associated with AHR and ER that could be inferred to humans. Thus, our study presents an effective, high-throughput strategy of capturing molecular snapshots of chemical-induced biological states of a whole adult vertebrate that provides information on biomarkers of effects, deregulated signaling pathways, and possible affected biological functions, perturbed physiological systems, and increased health risks. These findings place zebrafish in a strategic position to bridge the wide gap between cell-based and rodent models in chemogenomics research and applications, especially in preclinical drug discovery and toxicology. PMID:18618001

Cis-regulatory Elements and Human Evolution

PubMed Central

Siepel, Adam

2014-01-01

Modification of gene regulation has long been considered an important force in human evolution, particularly through changes to cis-regulatory elements (CREs) that function in transcriptional regulation. For decades, however, the study of cis-regulatory evolution was severely limited by the available data. New data sets describing the locations of CREs and genetic variation within and between species have now made it possible to study CRE evolution much more directly on a genome-wide scale. Here, we review recent research on the evolution of CREs in humans based on large-scale genomic data sets. We consider inferences based on primate divergence, human polymorphism, and combinations of divergence and polymorphism. We then consider “new frontiers” in this field stemming from recent research on transcriptional regulation. PMID:25218861

Differences in rocky reef habitats related to human disturbances across a latitudinal gradient.

PubMed

Glasby, Tim M; Gibson, Peter T; Cruz-Motta, Juan J

2017-08-01

This study tested for differences in the composition of intertidal and shallow subtidal rocky reef habitats subjected to a range of human pressures across ∼1000 km of coastline in New South Wales, Australia over 5 years. Percentage covers of habitats were sampled using aerial photography and a large grain size (20 m 2 intertidal; 800 m 2 subtidal) in a nested hierarchical design. Results were consistent with anthropogenic impacts on habitat structure only around estuaries with the most heavily urbanised or agriculturally-intense catchments. The most convincing relationships documented here related to environmental variables such as SST, latitude, reef width and proximity to large estuaries irrespective of human disturbance levels. Moreover, there were suggestions that any influences of estuarine waters (be they anthropogenic or natural) on reef assemblages could potentially extend 10s of kilometres from major estuaries. In general, our results supported those of studies that utilised smaller grain sizes (greatest variability often at smallest spatial scales), but we found that variability over scales of 100s of km can be similar to or greater than variability over scales of 10s of metres. Copyright © 2017 Elsevier Ltd. All rights reserved.

Collaboration in the Humanities, Arts and Social Sciences in Australia

ERIC Educational Resources Information Center

Haddow, Gaby; Xia, Jianhong; Willson, Michele

2017-01-01

This paper reports on the first large-scale quantitative investigation into collaboration, demonstrated in co-authorship, by Australian humanities, arts and social sciences (HASS) researchers. Web of Science data were extracted for Australian HASS publications, with a focus on the softer social sciences, over the period 2004-2013. The findings…

COMPARABLE MEASURES OF COGNITIVE FUNCTION IN HUMAN INFANTS AND LABORATORY ANIMALS TO IDENTIFY ENVIRONMENTAL HEALTH RISKS TO CHILDREN

EPA Science Inventory

The importance of including neurodevelopmental end points in environmental studies is clear. A validated measure of cognitive function in human infants that also has a homologous or parallel test in laboratory animal studies will provide a valuable approach for large-scale studie...

Fishery-independent data reveal negative effect of human population density on Caribbean predatory fish communities.

PubMed

Stallings, Christopher D

2009-01-01

Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable.

Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

PubMed Central

Stallings, Christopher D.

2009-01-01

Background Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. Methodology/Principal Findings Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. Conclusions/Significance Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable. PMID:19421312

Viral Organization of Human Proteins

PubMed Central

Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

2010-01-01

Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

Scalable cultivation of human pluripotent stem cells on chemically-defined surfaces

NASA Astrophysics Data System (ADS)

Hsiung, Michael Chi-Wei

Human stem cells (SCs) are classified as self-renewing cells possessing great ability in therapeutic applications due of their ability to differentiate along any major cell lineage in the human body. Despite their restorative potential, widespread use of SCs is hampered by strenuous control issues. Along with the need for strict xeno-free environments to sustain growth in culture, current methods for growing human pluripotent stem cells (hPSCs) rely on platforms which impede large-scale cultivation and therapeutic delivery. Hence, any progress towards development of large-scale culture systems is severely hindered. In a concentrated effort to develop a scheme that can serve as a model precursor for large scale SC propagation in clinical use, we have explored methods for cultivating hPSCs on completely defined surfaces. We discuss novel approaches with the potential to go beyond the limitations presented by current methods. In particular, we studied the cultivation of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) on surface which underwent synthetic or chemical modification. Current methods for hPSCs rely on animal-based extracellular matrices (ECMs) such as mouse embryonic fibroblasts (MEFs) or feeders and murine sacoma cell-derived substrates to facilitate their growth. While these layers or coatings can be used to maximize the output of hPSC production, they cannot be considered for clinical use because they risk introducing foreign pathogens into culture. We have identified and developed conditions for a completely defined xeno-free substrate used for culturing hPSCs. By utilizing coupling chemistry, we can functionalize ester groups on a given surface and conjugate synthetic peptides containing the arginine-glycine-aspartic acid (RGD) motif, known for their role in cell adhesion. This method offers advantages over traditional hPSC culture by keeping the modified substrata free of xenogenic response and can be scaled up in adherent microcarrier culture. To treat a major organ such as the heart or kidney, producing large quantities of clinical-grade pluripotent cells is a necessity for cell-based therapy. Here we apply our approach to spherical beads or microcarriers for large-scale cultivation of hPSCs in a stirred-suspension bioreactor. Stem cells seeded on microcarriers and cultivated for multiple six day passages in a stirred-suspension bioreactors remained viable (≥90%) and increased by an average of 25.0+/-7.2-fold in concentration. The cells maintained their expression of pluripotency markers POU5F1 and NANOG as assessed by RT-PCR and quantitative PCR. These findings aim at the development of a flexible cost-effect method for the generation of pluripotent cells which can be repurposed and utilized for cell therapies. This work also aims to promote exploration into different methods of surface modification to develop new tactics for culturing hPSCs that can achieve higher fold growth while maintaining overall therapeutic potential.

Shift of large-scale atmospheric systems over Europe during late MIS 3 and implications for Modern Human dispersal.

PubMed

Obreht, Igor; Hambach, Ulrich; Veres, Daniel; Zeeden, Christian; Bösken, Janina; Stevens, Thomas; Marković, Slobodan B; Klasen, Nicole; Brill, Dominik; Burow, Christoph; Lehmkuhl, Frank

2017-07-19

Understanding the past dynamics of large-scale atmospheric systems is crucial for our knowledge of the palaeoclimate conditions in Europe. Southeastern Europe currently lies at the border between Atlantic, Mediterranean, and continental climate zones. Past changes in the relative influence of associated atmospheric systems must have been recorded in the region's palaeoarchives. By comparing high-resolution grain-size, environmental magnetic and geochemical data from two loess-palaeosol sequences in the Lower Danube Basin with other Eurasian palaeorecords, we reconstructed past climatic patterns over Southeastern Europe and the related interaction of the prevailing large-scale circulation modes over Europe, especially during late Marine Isotope Stage 3 (40,000-27,000 years ago). We demonstrate that during this time interval, the intensification of the Siberian High had a crucial influence on European climate causing the more continental conditions over major parts of Europe, and a southwards shift of the Westerlies. Such a climatic and environmental change, combined with the Campanian Ignimbrite/Y-5 volcanic eruption, may have driven the Anatomically Modern Human dispersal towards Central and Western Europe, pointing to a corridor over the Eastern European Plain as an important pathway in their dispersal.

Orthographic and Phonological Neighborhood Databases across Multiple Languages.

PubMed

Marian, Viorica

2017-01-01

The increased globalization of science and technology and the growing number of bilinguals and multilinguals in the world have made research with multiple languages a mainstay for scholars who study human function and especially those who focus on language, cognition, and the brain. Such research can benefit from large-scale databases and online resources that describe and measure lexical, phonological, orthographic, and semantic information. The present paper discusses currently-available resources and underscores the need for tools that enable measurements both within and across multiple languages. A general review of language databases is followed by a targeted introduction to databases of orthographic and phonological neighborhoods. A specific focus on CLEARPOND illustrates how databases can be used to assess and compare neighborhood information across languages, to develop research materials, and to provide insight into broad questions about language. As an example of how using large-scale databases can answer questions about language, a closer look at neighborhood effects on lexical access reveals that not only orthographic, but also phonological neighborhoods can influence visual lexical access both within and across languages. We conclude that capitalizing upon large-scale linguistic databases can advance, refine, and accelerate scientific discoveries about the human linguistic capacity.

Human factors engineering verification and validation for APR1400 computerized control room

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

Shin, Y. C.; Moon, H. K.; Kim, J. H.

2006-07-01

This paper introduces the Advanced Power Reactor 1400 (APR1400) HFE V and V activities the Korea Hydro Nuclear Plant Co. LTD. (KHNP) has performed for the last 10 years and some of the lessons learned through these activities. The features of APR1400 main control room include large display panel, redundant compact workstations, computer-based procedure, and safety console. Several iterations of human factors evaluations have been performed from small scale proof of concept tests to large scale integrated system tests for identifying human engineering deficiencies in the human system interface design. Evaluations in the proof of concept test were focused onmore » checking the presence of any show stopper problems in the design concept. Later evaluations were mostly for finding design problems and for assuring the resolution of human factors issues of advanced control room. The results of design evaluations were useful not only for refining the control room design, but also for licensing the standard design. Several versions of APR1400 mock-ups with dynamic simulation models of currently operating Korea Standard Nuclear Plant (KSNP) have been used for the evaluations with the participation of operators from KSNP plants. (authors)« less

Emergence of scaling in human-interest dynamics

PubMed Central

Zhao, Zhi-Dan; Yang, Zimo; Zhang, Zike; Zhou, Tao; Huang, Zi-Gang; Lai, Ying-Cheng

2013-01-01

Human behaviors are often driven by human interests. Despite intense recent efforts in exploring the dynamics of human behaviors, little is known about human-interest dynamics, partly due to the extreme difficulty in accessing the human mind from observations. However, the availability of large-scale data, such as those from e-commerce and smart-phone communications, makes it possible to probe into and quantify the dynamics of human interest. Using three prototypical “Big Data” sets, we investigate the scaling behaviors associated with human-interest dynamics. In particular, from the data sets we uncover fat-tailed (possibly power-law) distributions associated with the three basic quantities: (1) the length of continuous interest, (2) the return time of visiting certain interest, and (3) interest ranking and transition. We argue that there are three basic ingredients underlying human-interest dynamics: preferential return to previously visited interests, inertial effect, and exploration of new interests. We develop a biased random-walk model, incorporating the three ingredients, to account for the observed fat-tailed distributions. Our study represents the first attempt to understand the dynamical processes underlying human interest, which has significant applications in science and engineering, commerce, as well as defense, in terms of specific tasks such as recommendation and human-behavior prediction. PMID:24326949

Banana production systems: identification of alternative systems for more sustainable production.

PubMed

Bellamy, Angelina Sanderson

2013-04-01

Large-scale, monoculture production systems dependent on synthetic fertilizers and pesticides, increase yields, but are costly and have deleterious impacts on human health and the environment. This research investigates variations in banana production practices in Costa Rica, to identify alternative systems that combine high productivity and profitability, with reduced reliance on agrochemicals. Farm workers were observed during daily production activities; 39 banana producers and 8 extension workers/researchers were interviewed; and a review of field experiments conducted by the National Banana Corporation between 1997 and 2002 was made. Correspondence analysis showed that there is no structured variation in large-scale banana producers' practices, but two other banana production systems were identified: a small-scale organic system and a small-scale conventional coffee-banana intercropped system. Field-scale research may reveal ways that these practices can be scaled up to achieve a productive and profitable system producing high-quality export bananas with fewer or no pesticides.

Atomic scale chemical tomography of human bone

NASA Astrophysics Data System (ADS)

Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

2017-01-01

Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale - the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

Managing landscapes at multiple scales for sustainability of ecosystem functions (Preface)

Treesearch

R.A. Birdsey; R. Lucas; Y. Pan; G. Sun; E.J. Gustafson; A.H.  Perera

2010-01-01

The science of landscape ecology is a rapidly evolving academic field with an emphasis on studying large-scale spatial heterogeneity created by natural influences and human activities. These advances have important implications for managing and conserving natural resources. At a September 2008 IUFRO conference in Chengdu, Sichuan, P.R. China, we highlighted both the...

Academic-industrial partnerships in drug discovery in the age of genomics.

PubMed

Harris, Tim; Papadopoulos, Stelios; Goldstein, David B

2015-06-01

Many US FDA-approved drugs have been developed through productive interactions between the biotechnology industry and academia. Technological breakthroughs in genomics, in particular large-scale sequencing of human genomes, is creating new opportunities to understand the biology of disease and to identify high-value targets relevant to a broad range of disorders. However, the scale of the work required to appropriately analyze large genomic and clinical data sets is challenging industry to develop a broader view of what areas of work constitute precompetitive research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Collaborative mining and interpretation of large-scale data for biomedical research insights.

PubMed

Tsiliki, Georgia; Karacapilidis, Nikos; Christodoulou, Spyros; Tzagarakis, Manolis

2014-01-01

Biomedical research becomes increasingly interdisciplinary and collaborative in nature. Researchers need to efficiently and effectively collaborate and make decisions by meaningfully assembling, mining and analyzing available large-scale volumes of complex multi-faceted data residing in different sources. In line with related research directives revealing that, in spite of the recent advances in data mining and computational analysis, humans can easily detect patterns which computer algorithms may have difficulty in finding, this paper reports on the practical use of an innovative web-based collaboration support platform in a biomedical research context. Arguing that dealing with data-intensive and cognitively complex settings is not a technical problem alone, the proposed platform adopts a hybrid approach that builds on the synergy between machine and human intelligence to facilitate the underlying sense-making and decision making processes. User experience shows that the platform enables more informed and quicker decisions, by displaying the aggregated information according to their needs, while also exploiting the associated human intelligence.

Collaborative Mining and Interpretation of Large-Scale Data for Biomedical Research Insights

PubMed Central

Tsiliki, Georgia; Karacapilidis, Nikos; Christodoulou, Spyros; Tzagarakis, Manolis

2014-01-01

Biomedical research becomes increasingly interdisciplinary and collaborative in nature. Researchers need to efficiently and effectively collaborate and make decisions by meaningfully assembling, mining and analyzing available large-scale volumes of complex multi-faceted data residing in different sources. In line with related research directives revealing that, in spite of the recent advances in data mining and computational analysis, humans can easily detect patterns which computer algorithms may have difficulty in finding, this paper reports on the practical use of an innovative web-based collaboration support platform in a biomedical research context. Arguing that dealing with data-intensive and cognitively complex settings is not a technical problem alone, the proposed platform adopts a hybrid approach that builds on the synergy between machine and human intelligence to facilitate the underlying sense-making and decision making processes. User experience shows that the platform enables more informed and quicker decisions, by displaying the aggregated information according to their needs, while also exploiting the associated human intelligence. PMID:25268270

Human cardiomyocyte generation from pluripotent stem cells: A state-of-art.

PubMed

Talkhabi, Mahmood; Aghdami, Nasser; Baharvand, Hossein

2016-01-15

The human heart is considered a non-regenerative organ. Worldwide, cardiovascular diseases continue to be the leading cause of death. Despite advances in cardiac treatment, myocardial repair remains severely limited by the lack of an appropriate source of viable cardiomyocytes (CMs) to replace damaged tissue. Human pluripotent stem cells (hPSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can efficiently be differentiated into functional CMs necessary for cell replacement therapy and other potential applications. The number of protocols that derive CMs from hPSCs has increased exponentially over the past decade following observation of the first human beating CMs. A number of highly efficient, chemical based protocols have been developed to generate human CMs (hCMs) in small-scale and large-scale suspension systems. To reduce the heterogeneity of hPSC-derived CMs, the differentiation protocols were modulated to exclusively generate atrial-, ventricular-, and nodal-like CM subtypes. Recently, remarkable advances have been achieved in hCM generation including chemical-based cardiac differentiation, cardiac subtype specification, large-scale suspension culture differentiation, and development of chemically defined culture conditions. These hCMs could be useful particularly in the context of in vitro disease modeling, pharmaceutical screening and in cellular replacement therapies once the safety issues are overcome. Herein we review recent progress in the in vitro generation of CMs and cardiac subtypes from hPSCs and discuss their potential applications and current limitations. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-scale approaches to the epigenetics of common human disease

PubMed Central

2011-01-01

Traditionally, the pathology of human disease has been focused on microscopic examination of affected tissues, chemical and biochemical analysis of biopsy samples, other available samples of convenience, such as blood, and noninvasive or invasive imaging of varying complexity, in order to classify disease and illuminate its mechanistic basis. The molecular age has complemented this armamentarium with gene expression arrays and selective analysis of individual genes. However, we are entering a new era of epigenomic profiling, i.e., genome-scale analysis of cell-heritable nonsequence genetic change, such as DNA methylation. The epigenome offers access to stable measurements of cellular state and to biobanked material for large-scale epidemiological studies. Some of these genome-scale technologies are beginning to be applied to create the new field of epigenetic epidemiology. PMID:19844740

Billion-scale production of hepatocyte-like cells from human induced pluripotent stem cells.

PubMed

Yamashita, Tomoki; Takayama, Kazuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki

2018-02-19

Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells are expected to be utilized in drug screening and regenerative medicine. However, hepatocyte-like cells have not been fully used in such applications because it is difficult to produce such cells on a large scale. In this study, we tried to establish a method to mass produce hepatocyte-like cells using a three-dimensional (3D) cell culture bioreactor called the Rotary Cell Culture System (RCCS). RCCS enabled us to obtain homogenous hepatocyte-like cells on a billion scale (>10 9  cells). The gene expression levels of some hepatocyte markers (alpha-1 antitrypsin, cytochrome (CYP) 1A2, CYP2D6, and hepatocyte nuclear factor 4alpha) were higher in 3D-cultured hepatocyte-like cells than in 2D-cultured hepatocyte-like cells. This result suggests that RCCS could provide more suitable conditions for hepatocyte maturation than the conventional 2D cell culture conditions. In addition, more than 90% of hepatocyte-like cells were positive for albumin and could uptake low-density lipoprotein in the culture medium. We succeeded in the large-scale production of homogenous and functional hepatocyte-like cells from human iPS cells. This technology will be useful in drug screening and regenerative medicine, which require enormous numbers of hepatocyte-like cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of human response to blasting vibration from excavation of a large scale rock slope: A case study

NASA Astrophysics Data System (ADS)

Yan, Peng; Lu, Wenbo; Zhang, Jing; Zou, Yujun; Chen, Ming

2017-04-01

Ground vibration, as the most critical public hazard of blasting, has received much attention from the community. Many countries established national standards to suppress vibration impact on structures, but a world-accepted blasting vibration criterion on human safety is still missing. In order to evaluate human response to the vibration from blasting excavation of a large-scale rock slope in China, this study aims to suggest a revised criterion. The vibration frequency was introduced to improve the existing single-factor (peak particle velocity) standard recommended by the United States Bureau of Mines (USBM). The feasibility of the new criterion was checked based on field vibration monitoring and investigation of human reactions. Moreover, the air overpressure or blast effects on human beings have also been discussed. The result indicates that the entire zone of influence can be divided into three subzones: severe-annoyance, light-annoyance and perception zone according to the revised safety standard. Both the construction company and local residents have provided positive comments on this influence degree assessment, which indicates that the presented criterion is suitable for evaluating human response to nearby blasts. Nevertheless, this specific criterion needs more field tests and verifications before it can be

Cooperation, collective action, and the archeology of large-scale societies.

PubMed

Carballo, David M; Feinman, Gary M

2016-11-01

Archeologists investigating the emergence of large-scale societies in the past have renewed interest in examining the dynamics of cooperation as a means of understanding societal change and organizational variability within human groups over time. Unlike earlier approaches to these issues, which used models designated voluntaristic or managerial, contemporary research articulates more explicitly with frameworks for cooperation and collective action used in other fields, thereby facilitating empirical testing through better definition of the costs, benefits, and social mechanisms associated with success or failure in coordinated group action. Current scholarship is nevertheless bifurcated along lines of epistemology and scale, which is understandable but problematic for forging a broader, more transdisciplinary field of cooperation studies. Here, we point to some areas of potential overlap by reviewing archeological research that places the dynamics of social cooperation and competition in the foreground of the emergence of large-scale societies, which we define as those having larger populations, greater concentrations of political power, and higher degrees of social inequality. We focus on key issues involving the communal-resource management of subsistence and other economic goods, as well as the revenue flows that undergird political institutions. Drawing on archeological cases from across the globe, with greater detail from our area of expertise in Mesoamerica, we offer suggestions for strengthening analytical methods and generating more transdisciplinary research programs that address human societies across scalar and temporal spectra. © 2016 Wiley Periodicals, Inc.

Large-scale quarantine following biological terrorism in the United States: scientific examination, logistic and legal limits, and possible consequences.

PubMed

Barbera, J; Macintyre, A; Gostin, L; Inglesby, T; O'Toole, T; DeAtley, C; Tonat, K; Layton, M

2001-12-05

Concern for potential bioterrorist attacks causing mass casualties has increased recently. Particular attention has been paid to scenarios in which a biological agent capable of person-to-person transmission, such as smallpox, is intentionally released among civilians. Multiple public health interventions are possible to effect disease containment in this context. One disease control measure that has been regularly proposed in various settings is the imposition of large-scale or geographic quarantine on the potentially exposed population. Although large-scale quarantine has not been implemented in recent US history, it has been used on a small scale in biological hoaxes, and it has been invoked in federally sponsored bioterrorism exercises. This article reviews the scientific principles that are relevant to the likely effectiveness of quarantine, the logistic barriers to its implementation, legal issues that a large-scale quarantine raises, and possible adverse consequences that might result from quarantine action. Imposition of large-scale quarantine-compulsory sequestration of groups of possibly exposed persons or human confinement within certain geographic areas to prevent spread of contagious disease-should not be considered a primary public health strategy in most imaginable circumstances. In the majority of contexts, other less extreme public health actions are likely to be more effective and create fewer unintended adverse consequences than quarantine. Actions and areas for future research, policy development, and response planning efforts are provided.

Single-trabecula building block for large-scale finite element models of cancellous bone.

PubMed

Dagan, D; Be'ery, M; Gefen, A

2004-07-01

Recent development of high-resolution imaging of cancellous bone allows finite element (FE) analysis of bone tissue stresses and strains in individual trabeculae. However, specimen-specific stress/strain analyses can include effects of anatomical variations and local damage that can bias the interpretation of the results from individual specimens with respect to large populations. This study developed a standard (generic) 'building-block' of a trabecula for large-scale FE models. Being parametric and based on statistics of dimensions of ovine trabeculae, this building block can be scaled for trabecular thickness and length and be used in commercial or custom-made FE codes to construct generic, large-scale FE models of bone, using less computer power than that currently required to reproduce the accurate micro-architecture of trabecular bone. Orthogonal lattices constructed with this building block, after it was scaled to trabeculae of the human proximal femur, provided apparent elastic moduli of approximately 150 MPa, in good agreement with experimental data for the stiffness of cancellous bone from this site. Likewise, lattices with thinner, osteoporotic-like trabeculae could predict a reduction of approximately 30% in the apparent elastic modulus, as reported in experimental studies of osteoporotic femora. Based on these comparisons, it is concluded that the single-trabecula element developed in the present study is well-suited for representing cancellous bone in large-scale generic FE simulations.

Delay effects in the human sensory system during balancing.

PubMed

Stepan, Gabor

2009-03-28

Mechanical models of human self-balancing often use the Newtonian equations of inverted pendula. While these mathematical models are precise enough on the mechanical side, the ways humans balance themselves are still quite unexplored on the control side. Time delays in the sensory and motoric neural pathways give essential limitations to the stabilization of the human body as a multiple inverted pendulum. The sensory systems supporting each other provide the necessary signals for these control tasks; but the more complicated the system is, the larger delay is introduced. Human ageing as well as our actual physical and mental state affects the time delays in the neural system, and the mechanical structure of the human body also changes in a large range during our lives. The human balancing organ, the labyrinth, and the vision system essentially adapted to these relatively large time delays and parameter regions occurring during balancing. The analytical study of the simplified large-scale time-delayed models of balancing provides a Newtonian insight into the functioning of these organs that may also serve as a basis to support theories and hypotheses on balancing and vision.

Human Gut Microbiome: Function Matters.

PubMed

Heintz-Buschart, Anna; Wilmes, Paul

2017-11-22

The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dealing with Big Numbers: Representation and Understanding of Magnitudes outside of Human Experience

ERIC Educational Resources Information Center

Resnick, Ilyse; Newcombe, Nora S.; Shipley, Thomas F.

2017-01-01

Being able to estimate quantity is important in everyday life and for success in the STEM disciplines. However, people have difficulty reasoning about magnitudes outside of human perception (e.g., nanoseconds, geologic time). This study examines patterns of estimation errors across temporal and spatial magnitudes at large scales. We evaluated the…

Global change in wilderness areas: disentangling natural and anthropogenic changes

Treesearch

Lisa J. Graumlich

2000-01-01

Human impacts on the Earth’s ecosystems are globally pervasive. Wilderness areas, although largely protected from direct human impact at local scales, nevertheless are subject to global changes in atmospheric composition, climate and biodiversity. Research in wilderness areas plays a critical role in disentangling natural and anthropogenic changes in ecosystems by...

Promoting the Reading Culture Towards Human Capital and Global Development

ERIC Educational Resources Information Center

Olasehinde, M. O.; Akanmode, O. A.; Alaiyemola, A. T.; Babatunde, O. T.

2015-01-01

It is commonly agreed that a country cannot be fully developed without large-scale investment in her educational scheme since the breakthrough of a country is directly proportional to her educational level. Since the acquisition of effective reading skills has a positive effect on all school subjects, then reading is sine-qua-non for human capital…

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.

Globalization and human cooperation

PubMed Central

Buchan, Nancy R.; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

2009-01-01

Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, “globalized” individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods. PMID:19255433

Globalization and human cooperation.

PubMed

Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

2009-03-17

Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods.

Automation of large scale transient protein expression in mammalian cells

PubMed Central

Zhao, Yuguang; Bishop, Benjamin; Clay, Jordan E.; Lu, Weixian; Jones, Margaret; Daenke, Susan; Siebold, Christian; Stuart, David I.; Yvonne Jones, E.; Radu Aricescu, A.

2011-01-01

Traditional mammalian expression systems rely on the time-consuming generation of stable cell lines; this is difficult to accommodate within a modern structural biology pipeline. Transient transfections are a fast, cost-effective solution, but require skilled cell culture scientists, making man-power a limiting factor in a setting where numerous samples are processed in parallel. Here we report a strategy employing a customised CompacT SelecT cell culture robot allowing the large-scale expression of multiple protein constructs in a transient format. Successful protocols have been designed for automated transient transfection of human embryonic kidney (HEK) 293T and 293S GnTI− cells in various flask formats. Protein yields obtained by this method were similar to those produced manually, with the added benefit of reproducibility, regardless of user. Automation of cell maintenance and transient transfection allows the expression of high quality recombinant protein in a completely sterile environment with limited support from a cell culture scientist. The reduction in human input has the added benefit of enabling continuous cell maintenance and protein production, features of particular importance to structural biology laboratories, which typically use large quantities of pure recombinant proteins, and often require rapid characterisation of a series of modified constructs. This automated method for large scale transient transfection is now offered as a Europe-wide service via the P-cube initiative. PMID:21571074

Co-evolutionary dynamics of the human-environment system in the Heihe River basin in the past 2000years.

PubMed

Lu, Zhixiang; Wei, Yongping; Feng, Qi; Xie, Jiali; Xiao, Honglang; Cheng, Guodong

2018-09-01

There is limited quantitative understanding of interactions between human and environmental systems over the millennial scale. We aim to reveal the co-evolutionary dynamics of the human-environment system in a river basin by simulating the water use and net primary production (NPP) allocation for human and environmental systems over the last 2000years in Heihe River basin (HRB) in northwest China. We partition the catchment total evapotranspiration (ET) into ET for human and environmental systems with a social-hydrological framework and estimate the NPP for human and environmental systems using the Box-Lieth model, then classify the co-evolutionary processes of the human-environment system into distinct phases using the rate of changes of NPP over time, and discover the trade-offs or synergies relationships between them based on the elasticity of change of the NPP for humans to the change of NPP for environment. The co-evolutionary dynamics of human-environment system in the HRB can be divided into four periods, including: Phase I (Han Dynasty-Yuan Dynasty): predevelopment characterized by nearly no trade-offs between human and environment; Phase II (Yuan Dynasty-RC): slow agricultural development: characterized by a small human win due to small trade-offs between human and environment; Phase III (RC-2000): rapid agricultural development: characterized by a large human win due to large trade-offs between human and environment, and Phase IV (2000-2010): a rebalance characterized by large human wins with a small-environment win due to synergies, although these occurred very occasionally. This study provides a quantitative approach to describe the co-evolution of the human-environment system from the perspective of trade-offs and synergies in the millennial scale for the first time. The relationships between humans and environment changed from trade-off to synergy with the implementation of the water reallocation scheme in 2000. These findings improve the understanding of how humans influence environmental systems and responses to environmental stresses. Copyright © 2018 Elsevier B.V. All rights reserved.

An effective and simple procedure to isolate abundant quantities of biologically active chemopreventive lunasin-protease inhibitor concentrate (LPIC) from soybean

USDA-ARS?s Scientific Manuscript database

Lunasin is a 5-kDa soybean bioactive peptide with demonstrated anti-cancer and anti-inflammatory properties. The use of lunasin as a chemopreventive agent in large-scale animal studies and human clinical trials is hampered by the paucity of large quantities of lunasin. Recently, purification methods...

High Schools on a Human Scale: How Small Schools Can Transform American Education.

ERIC Educational Resources Information Center

Toch, Thomas

This book argues that large American high schools have become obsolete and uses case studies of four new or restructured schools to show why smallness and distinctiveness are prerequisites for school reform. The large comprehensive high school developed as an economical means of providing a range of "tracks," from practical subjects for future…

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury.

PubMed

Sindhurakar, Anil; Butensky, Samuel D; Meyers, Eric; Santos, Joshua; Bethea, Thelma; Khalili, Ashley; Sloan, Andrew P; Rennaker, Robert L; Carmel, Jason B

2017-02-01

Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.

Effectiveness of Government's Occupational Skills Development Strategies for Small- and Medium-Scale Enterprises: A Case Study of Korea

ERIC Educational Resources Information Center

Lee, Kye Woo

2006-01-01

In many developing countries, small- and medium-scale enterprises (SMEs) account for a large part of national employment and income. Therefore, governments have used various strategies/policy instruments to develop human resources for SMEs and improve their productivity and national welfare. In the literature, however, there has been little effort…

A Policy-Driven Large Scale Ecological Restoration: Quantifying Ecosystem Services Changes in the Loess Plateau of China

Treesearch

Yihe Lu; Bojie Fu; Xiaoming Feng; Yuan Zeng; Yu Liu; Ruiying Chang; Ge Sun; Bingfang Wu

2012-01-01

As one of the key tools for regulating human-ecosystem relations, environmental conservation policies can promote ecological rehabilitation across a variety of spatiotemporal scales. However, quantifying the ecological effects of such policies at the regional level is difficult. A case study was conducted at the regional level in the ecologically vulnerable region of...

Human impacts on bear habitat use

USGS Publications Warehouse

Mattson, David J.

1990-01-01

: Human effects on bear habitat use are mediated through food biomass changes, bear tolerance of humans and their impacts, and human tolerance of bears. Large-scale changes in bear food biomass have been caused by conversion of wildlands and waterways to intensive human use, and by the introduction of exotic pathogens. Bears consume virtually all human foods that have been established in former wildlands, but bear use has been limited by access. Air pollution has also affected bear food biomass on a small scale and is likely to have major future impacts on bear habitat through climatic warming. Major changes in disturbance cycles and landscape mosaics wrought by humans have further altered temporal and spatial pulses of bear food production. These changes have brought short-term benefits in places, but have also added long-term stresses to most bear populations. Although bears tend to avoid humans, they will also use exotic and native foods in close proximity to humans. Subadult males and adult females are more often impelled to forage closer to humans because of their energetic predicament and because more secure sites are often preempted by adult males. Although male bears are typically responsible for most livestock predation, adult females and subadult males are more likely to be habituated to humans because they tend to forage closer to humans. Elimination of human-habituated bears predictably reduces effective carrying capacity and is more likely to be a factor in preserving bear populations where humans are present in moderate-to-high densities. If humans desire to preserve viable bear populations, they will either have to accept increased risk of injury associated with preserving habituated animals, or continue to crop habituated bears while at the same time preserving large tracts of wildlands free from significant human intrusion.

Task-Related Edge Density (TED)—A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain

PubMed Central

Lohmann, Gabriele; Stelzer, Johannes; Zuber, Verena; Buschmann, Tilo; Margulies, Daniel; Bartels, Andreas; Scheffler, Klaus

2016-01-01

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach “Task-related Edge Density” (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function. PMID:27341204

Task-Related Edge Density (TED)-A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain.

PubMed

Lohmann, Gabriele; Stelzer, Johannes; Zuber, Verena; Buschmann, Tilo; Margulies, Daniel; Bartels, Andreas; Scheffler, Klaus

2016-01-01

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.

An interactive web application for the dissemination of human systems immunology data.

PubMed

Speake, Cate; Presnell, Scott; Domico, Kelly; Zeitner, Brad; Bjork, Anna; Anderson, David; Mason, Michael J; Whalen, Elizabeth; Vargas, Olivia; Popov, Dimitry; Rinchai, Darawan; Jourde-Chiche, Noemie; Chiche, Laurent; Quinn, Charlie; Chaussabel, Damien

2015-06-19

Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

Scaling behavior of online human activity

NASA Astrophysics Data System (ADS)

Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

2012-11-01

The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

Theoretical and Practical Issues That Are Relevant When Scaling Up hMSC Microcarrier Production Processes

PubMed Central

Jossen, Valentin; Schirmer, Cedric; Mostafa Sindi, Dolman; Eibl, Regine; Kraume, Matthias; Pörtner, Ralf; Eibl, Dieter

2016-01-01

The potential of human mesenchymal stem cells (hMSCs) for allogeneic cell therapies has created a large amount of interest. However, this presupposes the availability of efficient scale-up procedures. Promising results have been reported for stirred bioreactors that operate with microcarriers. Recent publications focusing on microcarrier-based stirred bioreactors have demonstrated the successful use of Computational Fluid Dynamics (CFD) and suspension criteria (N S1u, N S1) for rapidly scaling up hMSC expansions from mL- to pilot scale. Nevertheless, one obstacle may be the formation of large microcarrier-cell-aggregates, which may result in mass transfer limitations and inhomogeneous distributions of stem cells in the culture broth. The dependence of microcarrier-cell-aggregate formation on impeller speed and shear stress levels was investigated for human adipose derived stromal/stem cells (hASCs) at the spinner scale by recording the Sauter mean diameter (d 32) versus time. Cultivation at the suspension criteria provided d 32 values between 0.2 and 0.7 mm, the highest cell densities (1.25 × 106 cells mL−1 hASCs), and the highest expansion factors (117.0 ± 4.7 on day 7), while maintaining the expression of specific surface markers. Furthermore, suitability of the suspension criterion N S1u was investigated for scaling up microcarrier-based processes in wave-mixed bioreactors for the first time. PMID:26981131

Millennial-scale faunal record reveals differential resilience of European large mammals to human impacts across the Holocene.

PubMed

Crees, Jennifer J; Carbone, Chris; Sommer, Robert S; Benecke, Norbert; Turvey, Samuel T

2016-03-30

The use of short-term indicators for understanding patterns and processes of biodiversity loss can mask longer-term faunal responses to human pressures. We use an extensive database of approximately 18,700 mammalian zooarchaeological records for the last 11,700 years across Europe to reconstruct spatio-temporal dynamics of Holocene range change for 15 large-bodied mammal species. European mammals experienced protracted, non-congruent range losses, with significant declines starting in some species approximately 3000 years ago and continuing to the present, and with the timing, duration and magnitude of declines varying individually between species. Some European mammals became globally extinct during the Holocene, whereas others experienced limited or no significant range change. These findings demonstrate the relatively early onset of prehistoric human impacts on postglacial biodiversity, and mirror species-specific patterns of mammalian extinction during the Late Pleistocene. Herbivores experienced significantly greater declines than carnivores, revealing an important historical extinction filter that informs our understanding of relative resilience and vulnerability to human pressures for different taxa. We highlight the importance of large-scale, long-term datasets for understanding complex protracted extinction processes, although the dynamic pattern of progressive faunal depletion of European mammal assemblages across the Holocene challenges easy identification of 'static' past baselines to inform current-day environmental management and restoration. © 2016 The Author(s).

An investigation of human body model morphing for the assessment of abdomen responses to impact against a population of test subjects.

PubMed

Beillas, Philippe; Berthet, Fabien

2017-05-29

Human body models have the potential to better describe the human anatomy and variability than dummies. However, data sets available to verify the human response to impact are typically limited in numbers, and they are not size or gender specific. The objective of this study was to investigate the use of model morphing methodologies within that context. In this study, a simple human model scaling methodology was developed to morph two detailed human models (Global Human Body Model Consortium models 50th male, M50, and 5th female, F05) to the dimensions of post mortem human surrogates (PMHS) used in published literature. The methodology was then successfully applied to 52 PMHS tested in 14 impact conditions loading the abdomen. The corresponding 104 simulations were compared to the responses of the PMHS and to the responses of the baseline models without scaling (28 simulations). The responses were analysed using the CORA method and peak values. The results suggest that model scaling leads to an improvement of the predicted force and deflection but has more marginal effects on the predicted abdominal compressions. M50 and F05 models scaled to the same PMHS were also found to have similar external responses, but large differences were found between the two sets of models for the strain energy densities in the liver and the spleen for mid-abdomen impact simulations. These differences, which were attributed to the anatomical differences in the abdomen of the baseline models, highlight the importance of the selection of the impact condition for simulation studies, especially if the organ location is not known in the test. While the methodology could be further improved, it shows the feasibility of using model scaling methodologies to compare human models of different sizes and to evaluate scaling approaches within the context of human model validation.

Large-scale functional models of visual cortex for remote sensing

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

Brumby, Steven P; Kenyon, Garrett; Rasmussen, Craig E

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 simplemore » 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.« less

Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation.

PubMed

Pesaran, Bijan; Vinck, Martin; Einevoll, Gaute T; Sirota, Anton; Fries, Pascal; Siegel, Markus; Truccolo, Wilson; Schroeder, Charles E; Srinivasan, Ramesh

2018-06-25

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (electroencephalograms, magnetoencephalograms, electrocorticograms and local field potentials) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide recommendations for interpreting the data using forward and inverse models. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems.

Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

PubMed

de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

2018-01-23

High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

A multi-scale framework to link remotely sensed metrics with socioeconomic data

NASA Astrophysics Data System (ADS)

Watmough, Gary; Svenning, Jens-Christian; Palm, Cheryl; Sullivan, Clare; Danylo, Olha; McCallum, Ian

2017-04-01

There is increasing interest in the use of remotely sensed satellite data for estimating human poverty as it can bridge data gaps that prevent fine scale monitoring of development goals across large areas. The ways in which metrics derived from satellite imagery are linked with socioeconomic data are crucial for accurate estimation of poverty. Yet, to date, approaches in the literature linking satellite metrics with socioeconomic data are poorly characterized. Typically, approaches use a GIS approach such as circular buffer zones around a village or household or an administrative boundary such as a district or census enumeration area. These polygons are then used to extract environmental data from satellite imagery and related to the socioeconomic data in statistical analyses. The use of a single polygon to link environment and socioeconomic data is inappropriate in coupled human-natural systems as processes operate over multiple scales. Human interactions with the environment occur at multiple levels from individual (household) access to agricultural plots adjacent to homes, to communal access to common pool resources (CPR) such as forests at the village level. Here, we present a multi-scale framework that explicitly considers how people use the landscape. The framework is presented along with a case study example in Kenya. The multi-scale approach could enhance the modelling of human-environment interactions which will have important consequences for monitoring the sustainable development goals for human livelihoods and biodiversity conservation.

Micron-scale coherence in interphase chromatin dynamics

PubMed Central

Zidovska, Alexandra; Weitz, David A.; Mitchison, Timothy J.

2013-01-01

Chromatin structure and dynamics control all aspects of DNA biology yet are poorly understood, especially at large length scales. We developed an approach, displacement correlation spectroscopy based on time-resolved image correlation analysis, to map chromatin dynamics simultaneously across the whole nucleus in cultured human cells. This method revealed that chromatin movement was coherent across large regions (4–5 µm) for several seconds. Regions of coherent motion extended beyond the boundaries of single-chromosome territories, suggesting elastic coupling of motion over length scales much larger than those of genes. These large-scale, coupled motions were ATP dependent and unidirectional for several seconds, perhaps accounting for ATP-dependent directed movement of single genes. Perturbation of major nuclear ATPases such as DNA polymerase, RNA polymerase II, and topoisomerase II eliminated micron-scale coherence, while causing rapid, local movement to increase; i.e., local motions accelerated but became uncoupled from their neighbors. We observe similar trends in chromatin dynamics upon inducing a direct DNA damage; thus we hypothesize that this may be due to DNA damage responses that physically relax chromatin and block long-distance communication of forces. PMID:24019504

Fabrication of the HIAD Large-Scale Demonstration Assembly and Upcoming Mission Applications

NASA Technical Reports Server (NTRS)

Swanson, G. T.; Johnson, R. K.; Hughes, S. J.; Dinonno, J. M.; Cheatwood, F M.

2017-01-01

Over a decade of work has been conducted in the development of NASAs Hypersonic Inflatable Aerodynamic Decelerator (HIAD) technology. This effort has included multiple ground test campaigns and flight tests culminating in the HIAD projects second generation (Gen-2) deployable aeroshell system and associated analytical tools. NASAs HIAD project team has developed, fabricated, and tested inflatable structures (IS) integrated with flexible thermal protection system (F-TPS), ranging in diameters from 3-6m, with cone angles of 60 and 70 deg.In 2015, United Launch Alliance (ULA) announced that they will use a HIAD (10-12m) as part of their Sensible, Modular, Autonomous Return Technology (SMART) for their upcoming Vulcan rocket. ULA expects SMART reusability, coupled with other advancements for Vulcan, will substantially reduce the cost of access to space. The first booster engine recovery via HIAD is scheduled for 2024. To meet this near-term need, as well as future NASA applications, the HIAD team is investigating taking the technology to the 10-15m diameter scale.In the last year, many significant development and fabrication efforts have been accomplished, culminating in the construction of a large-scale inflatable structure demonstration assembly. This assembly incorporated the first three tori for a 12m Mars Human-Scale Pathfinder HIAD conceptual design that was constructed with the current state of the art material set. Numerous design trades and torus fabrication demonstrations preceded this effort. In 2016, three large-scale tori (0.61m cross-section) and six subscale tori (0.25m cross-section) were manufactured to demonstrate fabrication techniques using the newest candidate material sets. These tori were tested to evaluate durability and load capacity. This work led to the selection of the inflatable structures third generation (Gen-3) structural liner. In late 2016, the three tori required for the large-scale demonstration assembly were fabricated, and then integrated in early 2017. The design includes provisions to add the remaining four tori necessary to complete the assembly of the 12m Human-Scale Pathfinder HIAD in the event future project funding becomes available.This presentation will discuss the HIAD large-scale demonstration assembly design and fabrication per-formed in the last year including the precursor tori development and the partial-stack fabrication. Potential near-term and future 10-15m HIAD applications will also be discussed.

Fabrication of the HIAD Large-Scale Demonstration Assembly

NASA Technical Reports Server (NTRS)

Swanson, G. T.; Johnson, R. K.; Hughes, S. J.; DiNonno, J. M.; Cheatwood, F. M.

2017-01-01

Over a decade of work has been conducted in the development of NASA's Hypersonic Inflatable Aerodynamic Decelerator (HIAD) technology. This effort has included multiple ground test campaigns and flight tests culminating in the HIAD projects second generation (Gen-2) deployable aeroshell system and associated analytical tools. NASAs HIAD project team has developed, fabricated, and tested inflatable structures (IS) integrated with flexible thermal protection system (F-TPS), ranging in diameters from 3-6m, with cone angles of 60 and 70 deg.In 2015, United Launch Alliance (ULA) announced that they will use a HIAD (10-12m) as part of their Sensible, Modular, Autonomous Return Technology (SMART) for their upcoming Vulcan rocket. ULA expects SMART reusability, coupled with other advancements for Vulcan, will substantially reduce the cost of access to space. The first booster engine recovery via HIAD is scheduled for 2024. To meet this near-term need, as well as future NASA applications, the HIAD team is investigating taking the technology to the 10-15m diameter scale. In the last year, many significant development and fabrication efforts have been accomplished, culminating in the construction of a large-scale inflatable structure demonstration assembly. This assembly incorporated the first three tori for a 12m Mars Human-Scale Pathfinder HIAD conceptual design that was constructed with the current state of the art material set. Numerous design trades and torus fabrication demonstrations preceded this effort. In 2016, three large-scale tori (0.61m cross-section) and six subscale tori (0.25m cross-section) were manufactured to demonstrate fabrication techniques using the newest candidate material sets. These tori were tested to evaluate durability and load capacity. This work led to the selection of the inflatable structures third generation (Gen-3) structural liner. In late 2016, the three tori required for the large-scale demonstration assembly were fabricated, and then integrated in early 2017. The design includes provisions to add the remaining four tori necessary to complete the assembly of the 12m Human-Scale Pathfinder HIAD in the event future project funding becomes available.This presentation will discuss the HIAD large-scale demonstration assembly design and fabrication per-formed in the last year including the precursor tori development and the partial-stack fabrication. Potential near-term and future 10-15m HIAD applications will also be discussed.

Management applications of discontinuity theory

EPA Science Inventory

1.Human impacts on the environment are multifaceted and can occur across distinct spatiotemporal scales. Ecological responses to environmental change are therefore difficult to predict, and entail large degrees of uncertainty. Such uncertainty requires robust tools for management...

The Plant Phenology Ontology: A New Informatics Resource for Large-Scale Integration of Plant Phenology Data.

PubMed

Stucky, Brian J; Guralnick, Rob; Deck, John; Denny, Ellen G; Bolmgren, Kjell; Walls, Ramona

2018-01-01

Plant phenology - the timing of plant life-cycle events, such as flowering or leafing out - plays a fundamental role in the functioning of terrestrial ecosystems, including human agricultural systems. Because plant phenology is often linked with climatic variables, there is widespread interest in developing a deeper understanding of global plant phenology patterns and trends. Although phenology data from around the world are currently available, truly global analyses of plant phenology have so far been difficult because the organizations producing large-scale phenology data are using non-standardized terminologies and metrics during data collection and data processing. To address this problem, we have developed the Plant Phenology Ontology (PPO). The PPO provides the standardized vocabulary and semantic framework that is needed for large-scale integration of heterogeneous plant phenology data. Here, we describe the PPO, and we also report preliminary results of using the PPO and a new data processing pipeline to build a large dataset of phenology information from North America and Europe.

Large-scale Meteorological Patterns Associated with Extreme Precipitation Events over Portland, OR

NASA Astrophysics Data System (ADS)

Aragon, C.; Loikith, P. C.; Lintner, B. R.; Pike, M.

2017-12-01

Extreme precipitation events can have profound impacts on human life and infrastructure, with broad implications across a range of stakeholders. Changes to extreme precipitation events are a projected outcome of climate change that warrants further study, especially at regional- to local-scales. While global climate models are generally capable of simulating mean climate at global-to-regional scales with reasonable skill, resiliency and adaptation decisions are made at local-scales where most state-of-the-art climate models are limited by coarse resolution. Characterization of large-scale meteorological patterns associated with extreme precipitation events at local-scales can provide climatic information without this scale limitation, thus facilitating stakeholder decision-making. This research will use synoptic climatology as a tool by which to characterize the key large-scale meteorological patterns associated with extreme precipitation events in the Portland, Oregon metro region. Composite analysis of meteorological patterns associated with extreme precipitation days, and associated watershed-specific flooding, is employed to enhance understanding of the climatic drivers behind such events. The self-organizing maps approach is then used to characterize the within-composite variability of the large-scale meteorological patterns associated with extreme precipitation events, allowing us to better understand the different types of meteorological conditions that lead to high-impact precipitation events and associated hydrologic impacts. A more comprehensive understanding of the meteorological drivers of extremes will aid in evaluation of the ability of climate models to capture key patterns associated with extreme precipitation over Portland and to better interpret projections of future climate at impact-relevant scales.

Large Scale Expansion of Human Umbilical Cord Cells in a Rotating Bed System Bioreactor for Cardiovascular Tissue Engineering Applications

PubMed Central

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 108 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. PMID:23847691

A Chimpanzee (Pan troglodytes) Model of Triarchic Psychopathy Constructs: Development and Initial Validation

PubMed Central

Latzman, Robert D.; Drislane, Laura E.; Hecht, Lisa K.; Brislin, Sarah J.; Patrick, Christopher J.; Lilienfeld, Scott O.; Freeman, Hani J.; Schapiro, Steven J.; Hopkins, William D.

2015-01-01

The current work sought to operationalize constructs of the triarchic model of psychopathy in chimpanzees (Pan troglodytes), a species well-suited for investigations of basic biobehavioral dispositions relevant to psychopathology. Across three studies, we generated validity evidence for scale measures of the triarchic model constructs in a large sample (N=238) of socially-housed chimpanzees. Using a consensus-based rating approach, we first identified candidate items for the chimpanzee triarchic (CHMP-Tri) scales from an existing primate personality instrument and refined these into scales. In Study 2, we collected data for these scales from human informants (N=301), and examined their convergent and divergent relations with scales from another triarchic inventory developed for human use. In Study 3, we undertook validation work examining associations between CHMP-Tri scales and task measures of approach-avoidance behavior (N=73) and ability to delay gratification (N=55). Current findings provide support for a chimpanzee model of core dispositions relevant to psychopathy and other forms of psychopathology. PMID:26779396

Solar Power in Space?

DTIC Science & Technology

2012-01-01

orbit stupendously large orbital power plants—kilometers across—which collect the sun’s raw energy and beam it down to where it is needed on the earth...24-hour, large -scale power to the urban centers where the majority of humanity lives. A network of thousands of solar-power satellites (SPS) could...provide all the power required for an Earth-based population as large as 10 billion people, even for a fully developed “first world” lifestyle but

Beetles among us: Social and economic impacts of the MPB epidemic [Chapter 6

Treesearch

Krista Gebert; Greg Jones; Patty Champ; Mike Czaja; Chuck Oliver; Paul E. Cruz; Jessica Clement

2014-01-01

Healthy forest ecosystems provide many goods and services that are vital to human well-being. When forest ecosystems are impacted by disturbances, such as the widespread mountain pine beetle (MPB) epidemic, the services provided by these ecosystems are also affected. Likewise, management in response to large-scale forest disturbances impacts both the natural and human...

New Ratings of Humanities Journals Do More than Rank--They Rankle

ERIC Educational Resources Information Center

Howard, Jennifer

2008-01-01

This paper reports that a large-scale, multinational attempt in Europe to rank humanities journals has set off a revolt. In a protest letter, some journal editors have called it "a dangerous and misguided exercise." The project has also started a drumbeat of alarm in this country, as U.S.-based scholars begin to grasp the implications…

Effects of an Informational Brochure, Lottery-Based Financial Incentive, and Public Posting on Absenteeism of Direct-Care Human Services Employees

ERIC Educational Resources Information Center

Luiselli, James K.; DiGennaro Reed, Florence D.; Christian, Walter P.; Markowski, Andrea; Rue, Hanna C.; St. Amand, CarrieAnne; Ryan, Chad J.

2009-01-01

Chronic absenteeism is a problem encountered by many human services organizations. Large-scale intervention projects to reduce staff absences have incorporated applied behavior analysis methods but there are few studies in the extant literature. In the present study, the authors record staff absenteeism at a specialized school for students with…

Large-scale evidence of dependency length minimization in 37 languages

PubMed Central

Futrell, Richard; Mahowald, Kyle; Gibson, Edward

2015-01-01

Explaining the variation between human languages and the constraints on that variation is a core goal of linguistics. In the last 20 y, it has been claimed that many striking universals of cross-linguistic variation follow from a hypothetical principle that dependency length—the distance between syntactically related words in a sentence—is minimized. Various models of human sentence production and comprehension predict that long dependencies are difficult or inefficient to process; minimizing dependency length thus enables effective communication without incurring processing difficulty. However, despite widespread application of this idea in theoretical, empirical, and practical work, there is not yet large-scale evidence that dependency length is actually minimized in real utterances across many languages; previous work has focused either on a small number of languages or on limited kinds of data about each language. Here, using parsed corpora of 37 diverse languages, we show that overall dependency lengths for all languages are shorter than conservative random baselines. The results strongly suggest that dependency length minimization is a universal quantitative property of human languages and support explanations of linguistic variation in terms of general properties of human information processing. PMID:26240370

Infraslow Electroencephalographic and Dynamic Resting State Network Activity.

PubMed

Grooms, Joshua K; Thompson, Garth J; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H; Epstein, Charles M; Keilholz, Shella D

2017-06-01

A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies.

Infraslow Electroencephalographic and Dynamic Resting State Network Activity

PubMed Central

Grooms, Joshua K.; Thompson, Garth J.; Pan, Wen-Ju; Billings, Jacob; Schumacher, Eric H.; Epstein, Charles M.

2017-01-01

Abstract A number of studies have linked the blood oxygenation level dependent (BOLD) signal to electroencephalographic (EEG) signals in traditional frequency bands (δ, θ, α, β, and γ), but the relationship between BOLD and its direct frequency correlates in the infraslow band (<1 Hz) has been little studied. Previously, work in rodents showed that infraslow local field potentials play a role in functional connectivity, particularly in the dynamic organization of large-scale networks. To examine the relationship between infraslow activity and network dynamics in humans, direct current (DC) EEG and resting state magnetic resonance imaging data were acquired simultaneously. The DC EEG signals were correlated with the BOLD signal in patterns that resembled resting state networks. Subsequent dynamic analysis showed that the correlation between DC EEG and the BOLD signal varied substantially over time, even within individual subjects. The variation in DC EEG appears to reflect the time-varying contribution of different resting state networks. Furthermore, some of the patterns of DC EEG and BOLD correlation are consistent with previous work demonstrating quasiperiodic spatiotemporal patterns of large-scale network activity in resting state. These findings demonstrate that infraslow electrical activity is linked to BOLD fluctuations in humans and that it may provide a basis for large-scale organization comparable to that observed in animal studies. PMID:28462586

Simulation research on the process of large scale ship plane segmentation intelligent workshop

NASA Astrophysics Data System (ADS)

Xu, Peng; Liao, Liangchuang; Zhou, Chao; Xue, Rui; Fu, Wei

2017-04-01

Large scale ship plane segmentation intelligent workshop is a new thing, and there is no research work in related fields at home and abroad. The mode of production should be transformed by the existing industry 2.0 or part of industry 3.0, also transformed from "human brain analysis and judgment + machine manufacturing" to "machine analysis and judgment + machine manufacturing". In this transforming process, there are a great deal of tasks need to be determined on the aspects of management and technology, such as workshop structure evolution, development of intelligent equipment and changes in business model. Along with them is the reformation of the whole workshop. Process simulation in this project would verify general layout and process flow of large scale ship plane section intelligent workshop, also would analyze intelligent workshop working efficiency, which is significant to the next step of the transformation of plane segmentation intelligent workshop.

A review of sensing technologies for small and large-scale touch panels

NASA Astrophysics Data System (ADS)

Akhtar, Humza; Kemao, Qian; Kakarala, Ramakrishna

2017-06-01

A touch panel is an input device for human computer interaction. It consists of a network of sensors, a sampling circuit and a micro controller for detecting and locating a touch input. Touch input can come from either finger or stylus depending upon the type of touch technology. These touch panels provide an intuitive and collaborative workspace so that people can perform various tasks with the use of their fingers instead of traditional input devices like keyboard and mouse. Touch sensing technology is not new. At the time of this writing, various technologies are available in the market and this paper reviews the most common ones. We review traditional designs and sensing algorithms for touch technology. We also observe that due to its various strengths, capacitive touch will dominate the large-scale touch panel industry in years to come. In the end, we discuss the motivation for doing academic research on large-scale panels.

Rare variation facilitates inferences of fine-scale population structure in humans.

PubMed

O'Connor, Timothy D; Fu, Wenqing; Mychaleckyj, Josyf C; Logsdon, Benjamin; Auer, Paul; Carlson, Christopher S; Leal, Suzanne M; Smith, Joshua D; Rieder, Mark J; Bamshad, Michael J; Nickerson, Deborah A; Akey, Joshua M

2015-03-01

Understanding the genetic structure of human populations has important implications for the design and interpretation of disease mapping studies and reconstructing human evolutionary history. To date, inferences of human population structure have primarily been made with common variants. However, recent large-scale resequencing studies have shown an abundance of rare variation in humans, which may be particularly useful for making inferences of fine-scale population structure. To this end, we used an information theory framework and extensive coalescent simulations to rigorously quantify the informativeness of rare and common variation to detect signatures of fine-scale population structure. We show that rare variation affords unique insights into patterns of recent population structure. Furthermore, to empirically assess our theoretical findings, we analyzed high-coverage exome sequences in 6,515 European and African American individuals. As predicted, rare variants are more informative than common polymorphisms in revealing a distinct cluster of European-American individuals, and subsequent analyses demonstrate that these individuals are likely of Ashkenazi Jewish ancestry. Our results provide new insights into the population structure using rare variation, which will be an important factor to account for in rare variant association studies. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Constraining free riding in public goods games: designated solitary punishers can sustain human cooperation

PubMed Central

O'Gorman, Rick; Henrich, Joseph; Van Vugt, Mark

2008-01-01

Much of human cooperation remains an evolutionary riddle. Unlike other animals, people frequently cooperate with non-relatives in large groups. Evolutionary models of large-scale cooperation require not just incentives for cooperation, but also a credible disincentive for free riding. Various theoretical solutions have been proposed and experimentally explored, including reputation monitoring and diffuse punishment. Here, we empirically examine an alternative theoretical proposal: responsibility for punishment can be borne by one specific individual. This experiment shows that allowing a single individual to punish increases cooperation to the same level as allowing each group member to punish and results in greater group profits. These results suggest a potential key function of leadership in human groups and provides further evidence supporting that humans will readily and knowingly behave altruistically. PMID:18812292

PHENOstruct: Prediction of human phenotype ontology terms using heterogeneous data sources.

PubMed

Kahanda, Indika; Funk, Christopher; Verspoor, Karin; Ben-Hur, Asa

2015-01-01

The human phenotype ontology (HPO) was recently developed as a standardized vocabulary for describing the phenotype abnormalities associated with human diseases. At present, only a small fraction of human protein coding genes have HPO annotations. But, researchers believe that a large portion of currently unannotated genes are related to disease phenotypes. Therefore, it is important to predict gene-HPO term associations using accurate computational methods. In this work we demonstrate the performance advantage of the structured SVM approach which was shown to be highly effective for Gene Ontology term prediction in comparison to several baseline methods. Furthermore, we highlight a collection of informative data sources suitable for the problem of predicting gene-HPO associations, including large scale literature mining data.

Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?

PubMed

Büscher, Philippe; Bart, Jean-Mathieu; Boelaert, Marleen; Bucheton, Bruno; Cecchi, Giuliano; Chitnis, Nakul; Courtin, David; Figueiredo, Luisa M; Franco, José-Ramon; Grébaut, Pascal; Hasker, Epco; Ilboudo, Hamidou; Jamonneau, Vincent; Koffi, Mathurin; Lejon, Veerle; MacLeod, Annette; Masumu, Justin; Matovu, Enock; Mattioli, Raffaele; Noyes, Harry; Picado, Albert; Rock, Kat S; Rotureau, Brice; Simo, Gustave; Thévenon, Sophie; Trindade, Sandra; Truc, Philippe; Van Reet, Nick

2018-03-01

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent Progresses in Incorporating Human Land-Water Management into Global Land Surface Models Toward Their Integration into Earth System Models

NASA Technical Reports Server (NTRS)

Pokhrel, Yadu N.; Hanasaki, Naota; Wada, Yoshihide; Kim, Hyungjun

2016-01-01

The global water cycle has been profoundly affected by human land-water management. As the changes in the water cycle on land can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to represent human land-water management in Earth system models (ESMs). During the recent past, noteworthy progress has been made in large-scale modeling of human impacts on the water cycle but sufficient advancements have not yet been made in integrating the newly developed schemes into ESMs. This study reviews the progresses made in incorporating human factors in large-scale hydrological models and their integration into ESMs. The study focuses primarily on the recent advancements and existing challenges in incorporating human impacts in global land surface models (LSMs) as a way forward to the development of ESMs with humans as integral components, but a brief review of global hydrological models (GHMs) is also provided. The study begins with the general overview of human impacts on the water cycle. Then, the algorithms currently employed to represent irrigation, reservoir operation, and groundwater pumping are discussed. Next, methodological deficiencies in current modeling approaches and existing challenges are identified. Furthermore, light is shed on the sources of uncertainties associated with model parameterizations, grid resolution, and datasets used for forcing and validation. Finally, representing human land-water management in LSMs is highlighted as an important research direction toward developing integrated models using ESM frameworks for the holistic study of human-water interactions within the Earths system.

XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing.

PubMed

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

2013-08-08

Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Emergency response health physics.

PubMed

Mena, Rajah; Pemberton, Wendy; Beal, William

2012-05-01

Health physics is an important discipline with regard to understanding the effects of radiation on human health. This paper aims to illustrate the unique challenges presented to the health physicist or analyst of radiological data in a large-scale emergency.

Distant storms as drivers of environmental change at Pacific atolls.

PubMed

Gardner, Jonathan P A; Garton, David W; Collen, John D; Zwartz, Daniel

2014-01-01

The central Pacific Ocean with its many low lying islands and atolls is under threat from sea level rise and increased storm activity. Here, we illustrate how increasing frequency and severity of large scale storm events associated with global climate change may be particularly profound at the local scale for human populations that rely on lagoon systems for provision of a variety of goods and services. In August 2011 a storm originating in the Southern Ocean caused a large amplitude ocean swell to move northward through the Pacific Ocean. Its arrival at Palmyra Atoll coincided with transient elevated sea surface height and triggered turnover of the lagoon water column. This storm-induced change to the lagoon reflects long distance connectivity with propagated wave energy from the Southern Ocean and illustrates the increasing threats generated by climate change that are faced by human populations on most low-lying Pacific islands and atolls.

Distant Storms as Drivers of Environmental Change at Pacific Atolls

PubMed Central

Gardner, Jonathan P. A.; Garton, David W.; Collen, John D.; Zwartz, Daniel

2014-01-01

The central Pacific Ocean with its many low lying islands and atolls is under threat from sea level rise and increased storm activity. Here, we illustrate how increasing frequency and severity of large scale storm events associated with global climate change may be particularly profound at the local scale for human populations that rely on lagoon systems for provision of a variety of goods and services. In August 2011 a storm originating in the Southern Ocean caused a large amplitude ocean swell to move northward through the Pacific Ocean. Its arrival at Palmyra Atoll coincided with transient elevated sea surface height and triggered turnover of the lagoon water column. This storm-induced change to the lagoon reflects long distance connectivity with propagated wave energy from the Southern Ocean and illustrates the increasing threats generated by climate change that are faced by human populations on most low-lying Pacific islands and atolls. PMID:24498232

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.

Allometric scaling for predicting human clearance of bisphenol A

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

Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr

The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady statemore » volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.« less

Ecosystem transformation by emerging infectious disease: loss of large tanoak from California forests

Treesearch

Richard C. Cobb; Joao A.N. Filipe; Ross K. Meentemeyer; Christopher A. Gilligan; David M. Rizzo

2012-01-01

1. Few pathogens are the sole or primary cause of species extinctions, but forest disease has caused spectacular declines in North American overstorey trees and restructured forest ecosystems at large spatial scales over the past 100 years. These events threaten biodiversity associated with impacted host trees and other resources valued by human societies even when...

Comparing Human and Automated Essay Scoring for Prospective Graduate Students with Learning Disabilities and/or ADHD

ERIC Educational Resources Information Center

Buzick, Heather; Oliveri, Maria Elena; Attali, Yigal; Flor, Michael

2016-01-01

Automated essay scoring is a developing technology that can provide efficient scoring of large numbers of written responses. Its use in higher education admissions testing provides an opportunity to collect validity and fairness evidence to support current uses and inform its emergence in other areas such as K-12 large-scale assessment. In this…

Pharmacogenomic agreement between two cancer cell line data sets.

PubMed

2015-12-03

Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases.

Computational Framework for Analysis of Prey–Prey Associations in Interaction Proteomics Identifies Novel Human Protein–Protein Interactions and Networks

PubMed Central

Saha, Sudipto; Dazard, Jean-Eudes; Xu, Hua; Ewing, Rob M.

2013-01-01

Large-scale protein–protein interaction data sets have been generated for several species including yeast and human and have enabled the identification, quantification, and prediction of cellular molecular networks. Affinity purification-mass spectrometry (AP-MS) is the preeminent methodology for large-scale analysis of protein complexes, performed by immunopurifying a specific “bait” protein and its associated “prey” proteins. The analysis and interpretation of AP-MS data sets is, however, not straightforward. In addition, although yeast AP-MS data sets are relatively comprehensive, current human AP-MS data sets only sparsely cover the human interactome. Here we develop a framework for analysis of AP-MS data sets that addresses the issues of noise, missing data, and sparsity of coverage in the context of a current, real world human AP-MS data set. Our goal is to extend and increase the density of the known human interactome by integrating bait–prey and cocomplexed preys (prey–prey associations) into networks. Our framework incorporates a score for each identified protein, as well as elements of signal processing to improve the confidence of identified protein–protein interactions. We identify many protein networks enriched in known biological processes and functions. In addition, we show that integrated bait–prey and prey–prey interactions can be used to refine network topology and extend known protein networks. PMID:22845868

Livestock-associated methicillin-resistant Staphylococcus aureus ST9 in pigs and related personnel in Taiwan.

PubMed

Fang, Hsin-Wei; Chiang, Po-Hsing; Huang, Yhu-Chering

2014-01-01

A livestock-associated (LA) methicillin-resistant Staphylococcus aureus (MRSA) strain sequence type 398 (ST398) is found related to animals and humans in Europe and North America. To evaluate the nasal carriage of MRSA among pigs and related workers in Taiwan, we conducted this study. From June 25 to October 1 2012, a total of 641 and 100 nasal swabs were obtained from pigs and related workers, respectively, from 22 pig farms nationwide and 2 pig auction markets in Taiwan. All MRSA isolates were molecularly characterized. Overall, the nasal carriage rate of MRSA was 14.4% for pigs and 13% for humans. The carriage rate for pigs younger than 3 months was significantly higher than those older than 3 months (25.4% vs. 5.8%, p<.001). Percentage of MRSA-positive pig farms was 59.1% (13/22). The carriage rate for pigs in large-scale herds (≥ 10000 pigs) was significantly higher than that in small-scale (34.3% vs. 7.0%, p<.001) and that in auction markets (3.8%). The carriage rate was 19.2% (10/52) for pig farm workers, and the rate in large-scale farms was significantly higher than that in small-scale (36.8% vs. 9.1%, p = .014). Except for 3 isolates from humans, the other 99 isolates belonged to sequence type (ST) 9. 83 of 89 isolates from pigs shared a common pulsotype, which was also shared by 6 isolates from humans. More than 10% of pigs and related workers in Taiwan carried LA-MRSA ST9 in nares and cross-species transmission of LA-MRSA was documented by molecular methods.

Large-scale prediction of ADAR-mediated effective human A-to-I RNA editing.

PubMed

Yao, Li; Wang, Heming; Song, Yuanyuan; Dai, Zhen; Yu, Hao; Yin, Ming; Wang, Dongxu; Yang, Xin; Wang, Jinlin; Wang, Tiedong; Cao, Nan; Zhu, Jimin; Shen, Xizhong; Song, Guangqi; Zhao, Yicheng

2017-08-10

Adenosine-to-inosine (A-to-I) editing by adenosine deaminase acting on the RNA (ADAR) proteins is one of the most frequent modifications during post- and co-transcription. To facilitate the assignment of biological functions to specific editing sites, we designed an automatic online platform to annotate A-to-I RNA editing sites in pre-mRNA splicing signals, microRNAs (miRNAs) and miRNA target untranslated regions (3' UTRs) from human (Homo sapiens) high-throughput sequencing data and predict their effects based on large-scale bioinformatic analysis. After analysing plenty of previously reported RNA editing events and human normal tissues RNA high-seq data, >60 000 potentially effective RNA editing events on functional genes were found. The RNA Editing Plus platform is available for free at https://www.rnaeditplus.org/, and we believe our platform governing multiple optimized methods will improve further studies of A-to-I-induced editing post-transcriptional regulation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk

PubMed Central

Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong

2015-01-01

β-Lactoglobulin (BLG) is a major goat’s milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable targeted genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale production of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential targeting, respectively, by using targeting vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated targeting events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene targeting via TALEN-induced HR may expedite the production of genetically engineered livestock for agriculture and biomedicine. PMID:25994151

Gene targeting by TALEN-induced homologous recombination in goats directs production of β-lactoglobulin-free, high-human lactoferrin milk.

PubMed

Cui, Chenchen; Song, Yujie; Liu, Jun; Ge, Hengtao; Li, Qian; Huang, Hui; Hu, Linyong; Zhu, Hongmei; Jin, Yaping; Zhang, Yong

2015-05-21

β-Lactoglobulin (BLG) is a major goat's milk allergen that is absent in human milk. Engineered endonucleases, including transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases, enable targeted genetic modification in livestock. In this study, TALEN-mediated gene knockout followed by gene knock-in were used to generate BLG knockout goats as mammary gland bioreactors for large-scale production of human lactoferrin (hLF). We introduced precise genetic modifications in the goat genome at frequencies of approximately 13.6% and 6.09% for the first and second sequential targeting, respectively, by using targeting vectors that underwent TALEN-induced homologous recombination (HR). Analysis of milk from the cloned goats revealed large-scale hLF expression or/and decreased BLG levels in milk from heterozygous goats as well as the absence of BLG in milk from homozygous goats. Furthermore, the TALEN-mediated targeting events in somatic cells can be transmitted through the germline after SCNT. Our result suggests that gene targeting via TALEN-induced HR may expedite the production of genetically engineered livestock for agriculture and biomedicine.

Human Mars EDL Pathfinder Study: Assessment of Technology Development Gaps and Mitigations

NASA Technical Reports Server (NTRS)

Lillard, Randolph; Olejniczak, Joe; Polsgrove, Tara; Cianciolo, Alice Dwyer; Munk, Michelle; Whetsel, Charles; Drake, Bret

2017-01-01

This paper presents the results of a NASA initiated Agency-wide assessment to better characterize the risks and potential mitigation approaches associated with landing human class Entry, Descent, and Landing (EDL) systems on Mars. Due to the criticality and long-lead nature of advancing EDL techniques, it is necessary to determine an appropriate strategy to improve the capability to land large payloads. A key focus of this study was to understand the key EDL risks and with a focus on determining what "must" be tested at Mars. This process identified the various risks and potential risk mitigation strategies along with the key near term technology development efforts required and in what environment those technology demonstrations were best suited. The study identified key risks along with advantages to each entry technology. In addition, it was identified that provided the EDL concept of operations (con ops) minimized large scale transition events, there was no technology requirement for a Mars pre-cursor demonstration. Instead, NASA should take a direct path to a human-scale lander.

Humans and Deep Networks Largely Agree on Which Kinds of Variation Make Object Recognition Harder.

PubMed

Kheradpisheh, Saeed R; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

2016-01-01

View-invariant object recognition is a challenging problem that has attracted much attention among the psychology, neuroscience, and computer vision communities. Humans are notoriously good at it, even if some variations are presumably more difficult to handle than others (e.g., 3D rotations). Humans are thought to solve the problem through hierarchical processing along the ventral stream, which progressively extracts more and more invariant visual features. This feed-forward architecture has inspired a new generation of bio-inspired computer vision systems called deep convolutional neural networks (DCNN), which are currently the best models for object recognition in natural images. Here, for the first time, we systematically compared human feed-forward vision and DCNNs at view-invariant object recognition task using the same set of images and controlling the kinds of transformation (position, scale, rotation in plane, and rotation in depth) as well as their magnitude, which we call "variation level." We used four object categories: car, ship, motorcycle, and animal. In total, 89 human subjects participated in 10 experiments in which they had to discriminate between two or four categories after rapid presentation with backward masking. We also tested two recent DCNNs (proposed respectively by Hinton's group and Zisserman's group) on the same tasks. We found that humans and DCNNs largely agreed on the relative difficulties of each kind of variation: rotation in depth is by far the hardest transformation to handle, followed by scale, then rotation in plane, and finally position (much easier). This suggests that DCNNs would be reasonable models of human feed-forward vision. In addition, our results show that the variation levels in rotation in depth and scale strongly modulate both humans' and DCNNs' recognition performances. We thus argue that these variations should be controlled in the image datasets used in vision research.

Small molecule screening with laser cytometry can be used to identify pro-survival molecules in human embryonic stem cells.

PubMed

Sherman, Sean P; Pyle, April D

2013-01-01

Differentiated cells from human embryonic stem cells (hESCs) provide an unlimited source of cells for use in regenerative medicine. The recent derivation of human induced pluripotent cells (hiPSCs) provides a potential supply of pluripotent cells that avoid immune rejection and could provide patient-tailored therapy. In addition, the use of pluripotent cells for drug screening could enable routine toxicity testing and evaluation of underlying disease mechanisms. However, prior to establishment of patient specific cells for cell therapy it is important to understand the basic regulation of cell fate decisions in hESCs. One critical issue that hinders the use of these cells is the fact that hESCs survive poorly upon dissociation, which limits genetic manipulation because of poor cloning efficiency of individual hESCs, and hampers production of large-scale culture of hESCs. To address the problems associated with poor growth in culture and our lack of understanding of what regulates hESC signaling, we successfully developed a screening platform that allows for large scale screening for small molecules that regulate survival. In this work we developed the first large scale platform for hESC screening using laser scanning cytometry and were able to validate this platform by identifying the pro-survival molecule HA-1077. These small molecules provide targets for both improving our basic understanding of hESC survival as well as a tool to improve our ability to expand and genetically manipulate hESCs for use in regenerative applications.

Environmental impacts of a large-scale incinerator with mixed MSW of high water content from a LCA perspective.

PubMed

Lou, Ziyang; Bilitewski, Bernd; Zhu, Nanwen; Chai, Xiaoli; Li, Bing; Zhao, Youcai

2015-04-01

Large-scale incinerators are applied widely as a result of the heavy burden of municipal solid waste (MSW) generated, while strong opposition is arising from the public living nearby. A large-scale working incineration plant of 1500 ton/day was chosen for evaluation using life cycle assessment. It was found that the corresponding human toxicity impacts via soil (HTs), human toxicity impacts via water (HTw) and human toxicity impacts via air (HTa) categories are 0.213, 2.171, and 0.012 personal equivalents (PE), and global warming (GW100) and nutrient enrichment (NE) impacts are 0.002 and 0.001 PE per ton of waste burned for this plant. Heavy metals in flue gas, such as Hg and Pb, are the two dominant contributors to the toxicity impact categories, and energy recovery could reduce the GW100 and NE greatly. The corresponding HTs, HTw and HTa decrease to 0.087, 0.911 and 0.008 PE, and GW100 turns into savings of -0.007 PE due to the increase of the heating value from 3935 to 5811 kJ/kg, if a trommel screener of 40 mm mesh size is used to pre-separate MSW. MSW sorting and the reduction of water content by physical pressure might be two promising pre-treatment methods to improve the combustion performance, and the application of stricter standards for leachate discharge and the flue gas purification process are two critical factors for improvement of the environmental profile identified in this work. Copyright © 2015. Published by Elsevier B.V.

Physical and human dimensions of deforestation in Amazonia

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

Skole, D.L.; Chomentowski, W.H.; Salas W.A.

1994-05-01

In the Brazilian Amazon, regional trends are influenced by large scale external forces but mediated by local conditions. Tropical deforestation has a large influence on global hydrology, climate and biogeochemical cycles, but understanding is inadequate because of a lack of accurate measurements of rate, geographic extent and spatial patterns and lack of insight into its causes including interrelated social, economic and environmental factors. This article proposes an interdisciplinary approach for analyzing tropical deforestation in the Brazilian Amazon. The first part shows how deforestation can be measured from satellite remote sensing and sociodemographic and economic data. The second part proposes anmore » explanatory model, considering the relationship among deforestation and large scale social, economic, and institutional factors. 43 refs., 8 figs.« less

Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

PubMed Central

Cook, Brian L.; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P.; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

2009-01-01

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be ≈50% α-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices. PMID:19581598

Large-scale production and study of a synthetic G protein-coupled receptor: human olfactory receptor 17-4.

PubMed

Cook, Brian L; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

2009-07-21

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be approximately 50% alpha-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.

Connecting Humans and Water: The Case for Coordinated Data Collection

NASA Astrophysics Data System (ADS)

Braden, J. B.; Brown, D. G.; Jolejole-Foreman, C.; Maidment, D. R.; Marquart-Pyatt, S. T.; Schneider, D. W.

2012-12-01

"Water problems" are fundamentally human problems -- aligning water quality and quantity with human aspirations. In the U.S., however, the few ongoing efforts to repeatedly observe humans in relation to water at large scale are disjointed both with each other and with observing systems for water quality and quantity. This presentation argues for the systematic, coordinated, and on-going collection of primary data on humans, spanning beliefs, perceptions, behaviors, and institutions, alongside the water environments in which they are embedded. Such an enterprise would advance not only water science and related policy and management decisions, but also generate basic insights into human cognition, decision making, and institutional development as they relate to the science of sustainability. In support of this argument, two types of original analyses are presented. First, two case studies using existing data sets illustrate methodological issues involved in integrating natural system data with social data at large scale: one concerns the influence of water quality conditions on personal efforts to conserve water and contribute financially to environmental protection; the other explores relationships between recreation behavior and water quality. Both case studies show how methodological differences between data programs seriously undercut the potential to draw inference about human responses to water quality while also illustrating the scientific potential that could be realized from linking human and scientific surveys of the water environment. Second, the results of a survey of water scientists concerning important scientific and policy questions around humans and water provide insight into data collection priorities for a coordinated program of observation.

Microcarrier-based platforms for in vitro expansion and differentiation of human pluripotent stem cells in bioreactor culture systems.

PubMed

Badenes, Sara M; Fernandes, Tiago G; Rodrigues, Carlos A V; Diogo, Maria Margarida; Cabral, Joaquim M S

2016-09-20

Human pluripotent stem cells (hPSC) have attracted a great attention as an unlimited source of cells for cell therapies and other in vitro biomedical applications such as drug screening, toxicology assays and disease modeling. The implementation of scalable culture platforms for the large-scale production of hPSC and their derivatives is mandatory to fulfill the requirement of obtaining large numbers of cells for these applications. Microcarrier technology has been emerging as an effective approach for the large scale ex vivo hPSC expansion and differentiation. This review presents recent achievements in hPSC microcarrier-based culture systems and discusses the crucial aspects that influence the performance of these culture platforms. Recent progress includes addressing chemically-defined culture conditions for manufacturing of hPSC and their derivatives, with the development of xeno-free media and microcarrier coatings to meet good manufacturing practice (GMP) quality requirements. Finally, examples of integrated platforms including hPSC expansion and directed differentiation to specific lineages are also presented in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

Single-domain monoclonal antibodies for the treatment of hepatocellular carcinoma | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models.

Hydropower and sustainability: resilience and vulnerability in China's powersheds.

PubMed

McNally, Amy; Magee, Darrin; Wolf, Aaron T

2009-07-01

Large dams represent a whole complex of social, economic and ecological processes, perhaps more than any other large infrastructure project. Today, countries with rapidly developing economies are constructing new dams to provide energy and flood control to growing populations in riparian and distant urban communities. If the system is lacking institutional capacity to absorb these physical and institutional changes there is potential for conflict, thereby threatening human security. In this paper, we propose analyzing sustainability (political, socioeconomic, and ecological) in terms of resilience versus vulnerability, framed within the spatial abstraction of a powershed. The powershed framework facilitates multi-scalar and transboundary analysis while remaining focused on the questions of resilience and vulnerability relating to hydropower dams. Focusing on examples from China, this paper describes the complex nature of dams using the sustainability and powershed frameworks. We then analyze the roles of institutions in China to understand the relationships between power, human security and the socio-ecological system. To inform the study of conflicts over dams China is a particularly useful case study because we can examine what happens at the international, national and local scales. The powershed perspective allows us to examine resilience and vulnerability across political boundaries from a dynamic, process-defined analytical scale while remaining focused on a host of questions relating to hydro-development that invoke drivers and impacts on national and sub-national scales. The ability to disaggregate the affects of hydropower dam construction from political boundaries allows for a deeper analysis of resilience and vulnerability. From our analysis we find that reforms in China's hydropower sector since 1996 have been motivated by the need to create stability at the national scale rather than resilient solutions to China's growing demand for energy and water resource control at the local and international scales. Some measures that improved economic development through the market economy and a combination of dam construction and institutional reform may indeed improve hydro-political resilience at a single scale. However, if China does address large-scale hydropower construction's potential to create multi-scale geopolitical tensions, they may be vulnerable to conflict - though not necessarily violent - in domestic and international political arenas. We conclude with a look toward a resilient basin institution for the Nu/Salween River, the site of a proposed large-scale hydropower development effort in China and Myanmar.

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

Preston, Benjamin L.; King, Anthony W.; Ernst, Kathleen M.

Human agency is an essential determinant of the dynamics of agroecosystems. However, the manner in which agency is represented within different approaches to agroecosystem modeling is largely contingent on the scales of analysis and the conceptualization of the system of interest. While appropriate at times, narrow conceptualizations of agroecosystems can preclude consideration for how agency manifests at different scales, thereby marginalizing processes, feedbacks, and constraints that would otherwise affect model results. Modifications to the existing modeling toolkit may therefore enable more holistic representations of human agency. Model integration can assist with the development of multi-scale agroecosystem modeling frameworks that capturemore » different aspects of agency. In addition, expanding the use of socioeconomic scenarios and stakeholder participation can assist in explicitly defining context-dependent elements of scale and agency. Finally, such approaches, however, should be accompanied by greater recognition of the meta agency of model users and the need for more critical evaluation of model selection and application.« less

Extreme reaction times determine fluctuation scaling in human color vision

NASA Astrophysics Data System (ADS)

Medina, José M.; Díaz, José A.

2016-11-01

In modern mental chronometry, human reaction time defines the time elapsed from stimulus presentation until a response occurs and represents a reference paradigm for investigating stochastic latency mechanisms in color vision. Here we examine the statistical properties of extreme reaction times and whether they support fluctuation scaling in the skewness-kurtosis plane. Reaction times were measured for visual stimuli across the cardinal directions of the color space. For all subjects, the results show that very large reaction times deviate from the right tail of reaction time distributions suggesting the existence of dragon-kings events. The results also indicate that extreme reaction times are correlated and shape fluctuation scaling over a wide range of stimulus conditions. The scaling exponent was higher for achromatic than isoluminant stimuli, suggesting distinct generative mechanisms. Our findings open a new perspective for studying failure modes in sensory-motor communications and in complex networks.

Fine-Scale Cartography of Human Impacts along French Mediterranean Coasts: A Relevant Map for the Management of Marine Ecosystems

PubMed Central

Holon, Florian; Mouquet, Nicolas; Boissery, Pierre; Bouchoucha, Marc; Delaruelle, Gwenaelle; Tribot, Anne-Sophie; Deter, Julie

2015-01-01

Ecosystem services provided by oceans and seas support most human needs but are threatened by human activities. Despite existing maps illustrating human impacts on marine ecosystems, information remains either large-scale but rough and insufficient for stakeholders (1 km² grid, lack of data along the coast) or fine-scale but fragmentary and heterogeneous in methodology. The objectives of this study are to map and quantify the main pressures exerted on near-coast marine ecosystems, at a large spatial scale though in fine and relevant resolution for managers (one pixel = 20 x 20 m). It focuses on the French Mediterranean coast (1,700 km of coastline including Corsica) at a depth of 0 to 80 m. After completing and homogenizing data presently available under GIS on the bathymetry and anthropogenic pressures but also on the seabed nature and ecosystem vulnerability, we provide a fine modeling of the extent and impacts of 10 anthropogenic pressures on marine habitats. The considered pressures are man-made coastline, boat anchoring, aquaculture, urban effluents, industrial effluents, urbanization, agriculture, coastline erosion, coastal population and fishing. A 1:10 000 continuous habitat map is provided considering 11 habitat classes. The marine bottom is mostly covered by three habitats: infralittoral soft bottom, Posidonia oceanica meadows and circalittoral soft bottom. Around two thirds of the bottoms are found within medium and medium high cumulative impact categories. Seagrass meadows are the most impacted habitats. The most important pressures (in area and intensity) are urbanization, coastal population, coastal erosion and man-made coastline. We also identified areas in need of a special management interest. This work should contribute to prioritize environmental needs, as well as enhance the development of indicators for the assessment of the ecological status of coastal systems. It could also help better apply and coordinate management measures at a relevant scale for biodiversity conservation. PMID:26266542

Fine-Scale Cartography of Human Impacts along French Mediterranean Coasts: A Relevant Map for the Management of Marine Ecosystems.

PubMed

Holon, Florian; Mouquet, Nicolas; Boissery, Pierre; Bouchoucha, Marc; Delaruelle, Gwenaelle; Tribot, Anne-Sophie; Deter, Julie

2015-01-01

Ecosystem services provided by oceans and seas support most human needs but are threatened by human activities. Despite existing maps illustrating human impacts on marine ecosystems, information remains either large-scale but rough and insufficient for stakeholders (1 km² grid, lack of data along the coast) or fine-scale but fragmentary and heterogeneous in methodology. The objectives of this study are to map and quantify the main pressures exerted on near-coast marine ecosystems, at a large spatial scale though in fine and relevant resolution for managers (one pixel = 20 x 20 m). It focuses on the French Mediterranean coast (1,700 km of coastline including Corsica) at a depth of 0 to 80 m. After completing and homogenizing data presently available under GIS on the bathymetry and anthropogenic pressures but also on the seabed nature and ecosystem vulnerability, we provide a fine modeling of the extent and impacts of 10 anthropogenic pressures on marine habitats. The considered pressures are man-made coastline, boat anchoring, aquaculture, urban effluents, industrial effluents, urbanization, agriculture, coastline erosion, coastal population and fishing. A 1:10 000 continuous habitat map is provided considering 11 habitat classes. The marine bottom is mostly covered by three habitats: infralittoral soft bottom, Posidonia oceanica meadows and circalittoral soft bottom. Around two thirds of the bottoms are found within medium and medium high cumulative impact categories. Seagrass meadows are the most impacted habitats. The most important pressures (in area and intensity) are urbanization, coastal population, coastal erosion and man-made coastline. We also identified areas in need of a special management interest. This work should contribute to prioritize environmental needs, as well as enhance the development of indicators for the assessment of the ecological status of coastal systems. It could also help better apply and coordinate management measures at a relevant scale for biodiversity conservation.

Ten Minutes Wide: Human Walking Capacities and the Experiential Quality of Campus Design

ERIC Educational Resources Information Center

Spooner, David

2011-01-01

Whether a campus is large or small, the idea of a 10-minute walk is an important human-scaled design standard that affects an institution in significant ways beyond just getting students to class on time. Designing a 10-minute walk seems like a simple exercise. Based on earlier information, all one needs to do is provide a walking surface and make…

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…

Experimental design and quantitative analysis of microbial community multiomics.

PubMed

Mallick, Himel; Ma, Siyuan; Franzosa, Eric A; Vatanen, Tommi; Morgan, Xochitl C; Huttenhower, Curtis

2017-11-30

Studies of the microbiome have become increasingly sophisticated, and multiple sequence-based, molecular methods as well as culture-based methods exist for population-scale microbiome profiles. To link the resulting host and microbial data types to human health, several experimental design considerations, data analysis challenges, and statistical epidemiological approaches must be addressed. Here, we survey current best practices for experimental design in microbiome molecular epidemiology, including technologies for generating, analyzing, and integrating microbiome multiomics data. We highlight studies that have identified molecular bioactives that influence human health, and we suggest steps for scaling translational microbiome research to high-throughput target discovery across large populations.

The social brain: scale-invariant layering of Erdős-Rényi networks in small-scale human societies.

PubMed

Harré, Michael S; Prokopenko, Mikhail

2016-05-01

The cognitive ability to form social links that can bind individuals together into large cooperative groups for safety and resource sharing was a key development in human evolutionary and social history. The 'social brain hypothesis' argues that the size of these social groups is based on a neurologically constrained capacity for maintaining long-term stable relationships. No model to date has been able to combine a specific socio-cognitive mechanism with the discrete scale invariance observed in ethnographic studies. We show that these properties result in nested layers of self-organizing Erdős-Rényi networks formed by each individual's ability to maintain only a small number of social links. Each set of links plays a specific role in the formation of different social groups. The scale invariance in our model is distinct from previous 'scale-free networks' studied using much larger social groups; here, the scale invariance is in the relationship between group sizes, rather than in the link degree distribution. We also compare our model with a dominance-based hierarchy and conclude that humans were probably egalitarian in hunter-gatherer-like societies, maintaining an average maximum of four or five social links connecting all members in a largest social network of around 132 people. © 2016 The Author(s).

Increasing returns to scale: The solution to the second-order social dilemma

PubMed Central

Ye, Hang; Chen, Shu; Luo, Jun; Tan, Fei; Jia, Yongmin; Chen, Yefeng

2016-01-01

Humans benefit from extensive cooperation; however, the existence of free-riders may cause cooperation to collapse. This is called the social dilemma. It has been shown that punishing free-riders is an effective way of resolving this problem. Because punishment is costly, this gives rise to the second-order social dilemma. Without exception, existing solutions rely on some stringent assumptions. This paper proposes, under very mild conditions, a simple model of a public goods game featuring increasing returns to scale. We find that punishers stand out and even dominate the population provided that the degree of increasing returns to scale is large enough; consequently, the second-order social dilemma dissipates. Historical evidence shows that people are more willing to cooperate with others and punish defectors when they suffer from either internal or external menaces. During the prehistoric age, the abundance of contributors was decisive in joint endeavours such as fighting floods, defending territory, and hunting. These situations serve as favourable examples of public goods games in which the degrees of increasing returns to scale are undoubtedly very large. Our findings show that natural selection has endowed human kind with a tendency to pursue justice and punish defection that deviates from social norms. PMID:27535087

Social welfare as small-scale help: evolutionary psychology and the deservingness heuristic.

PubMed

Petersen, Michael Bang

2012-01-01

Public opinion concerning social welfare is largely driven by perceptions of recipient deservingness. Extant research has argued that this heuristic is learned from a variety of cultural, institutional, and ideological sources. The present article provides evidence supporting a different view: that the deservingness heuristic is rooted in psychological categories that evolved over the course of human evolution to regulate small-scale exchanges of help. To test predictions made on the basis of this view, a method designed to measure social categorization is embedded in nationally representative surveys conducted in different countries. Across the national- and individual-level differences that extant research has used to explain the heuristic, people categorize welfare recipients on the basis of whether they are lazy or unlucky. This mode of categorization furthermore induces people to think about large-scale welfare politics as its presumed ancestral equivalent: small-scale help giving. The general implications for research on heuristics are discussed.

From plot to regional scales: Interactions of slope and catchment hydrological and geomorphic processes in the Spanish Pyrenees

NASA Astrophysics Data System (ADS)

García-Ruiz, José M.; Lana-Renault, Noemí; Beguería, Santiago; Lasanta, Teodoro; Regüés, David; Nadal-Romero, Estela; Serrano-Muela, Pilar; López-Moreno, Juan I.; Alvera, Bernardo; Martí-Bono, Carlos; Alatorre, Luis C.

2010-08-01

The hydrological and geomorphic effects of land use/land cover changes, particularly those associated with vegetation regrowth after farmland abandonment were investigated in the Central Spanish Pyrenees. The main focus was to assess the interactions among slope, catchment, basin, and fluvial channel processes over a range of spatial scales. In recent centuries most Mediterranean mountain areas have been subjected to significant human pressure through deforestation, cultivation of steep slopes, fires, and overgrazing. Depopulation commencing at the beginning of the 20th century, and particularly since the 1960s, has resulted in farmland abandonment and a reduction in livestock numbers, and this has led to an expansion of shrubs and forests. Studies in the Central Spanish Pyrenees, based on experimental plots and catchments, in large basins and fluvial channels, have confirmed that these land use changes have had hydrological and geomorphic consequences regardless of the spatial scale considered, and that processes occurring at any particular scale can be explained by such processes acting on other scales. Studies using experimental plots have demonstrated that during the period of greatest human pressure (mainly the 18th and 19th centuries), cultivation of steep slopes caused high runoff rates and extreme soil loss. Large parts of the small catchments behaved as runoff and sediment source areas, whereas the fluvial channels of large basins showed signs of high torrentiality (braided morphology, bare sedimentary bars, instability, and prevalence of bedload transport). Depopulation has concentrated most human pressure on the valley bottoms and specific locations such as resorts, whereas the remainder of the area has been affected by an almost generalized abandonment. Subsequent plant recolonization has resulted in a reduction of overland flow and declining soil erosion. At a catchment scale this has caused a reduction in sediment sources, and channel incision in the secondary streams. At the regional scale, the most important consequences include a reduction in the frequency of floods, reduced sediment yields, increasing stabilization of fluvial channels (colonization of sedimentary bars by riparian vegetation and a reduction in the braiding index), and stabilization of alluvial fans. These results demonstrate the complexity and multiscalar nature of the interactions among land use and runoff generation, soil erosion, sediment transport, and fluvial channel dynamics, and highlight the need to adopt a multiscale approach in other mountain areas of the world.

Human Finger-Prick Induced Pluripotent Stem Cells Facilitate the Development of Stem Cell Banking

PubMed Central

Tan, Hong-Kee; Toh, Cheng-Xu Delon; Ma, Dongrui; Yang, Binxia; Liu, Tong Ming; Lu, Jun; Wong, Chee-Wai; Tan, Tze-Kai; Li, Hu; Syn, Christopher; Tan, Eng-Lee; Lim, Bing; Lim, Yoon-Pin; Cook, Stuart A.

2014-01-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients can be a good model for studying human diseases and for future therapeutic regenerative medicine. Current initiatives to establish human iPSC (hiPSC) banking face challenges in recruiting large numbers of donors with diverse diseased, genetic, and phenotypic representations. In this study, we describe the efficient derivation of transgene-free hiPSCs from human finger-prick blood. Finger-prick sample collection can be performed on a “do-it-yourself” basis by donors and sent to the hiPSC facility for reprogramming. We show that single-drop volumes of finger-prick samples are sufficient for performing cellular reprogramming, DNA sequencing, and blood serotyping in parallel. Our novel strategy has the potential to facilitate the development of large-scale hiPSC banking worldwide. PMID:24646489

Carbohydrates and the human gut microbiota.

PubMed

Chassard, Christophe; Lacroix, Christophe

2013-07-01

Due to its scale and its important role in maintaining health, the gut microbiota can be considered as a 'new organ' inside the human body. Many complex carbohydrates are degraded and fermented by the human gut microbiota in the large intestine to both yield basic energy salvage and impact gut health through produced metabolites. This review will focus on the gut microbes and microbial mechanisms responsible for polysaccharides degradation and fermentation in the large intestine. Gut microbes and bacterial metabolites impact the host at many levels, including modulation of inflammation, and glucose and lipid metabolisms. A complex relationship occurs in the intestine between the human gut microbiota, diet and the host. Research on carbohydrates and gut microbiota composition and functionality is fast developing and will open opportunities for prevention and treatment of obesity, diabetes and other related metabolic disorders through manipulation of the gut ecosystem.

Local-Scale Air Quality Modeling in Support of Human Health and Exposure Research (Invited)

NASA Astrophysics Data System (ADS)

Isakov, V.

2010-12-01

Spatially- and temporally-sparse information on air quality is a key concern for air-pollution-related environmental health studies. Monitor networks are sparse in both space and time, are costly to maintain, and are often designed purposely to avoid detecting highly localized sources. Recent studies have shown that more narrowly defining the geographic domain of the study populations and improvements in the measured/estimated ambient concentrations can lead to stronger associations between air pollution and hospital admissions and mortality records. Traditionally, ambient air quality measurements have been used as a primary input to support human health and exposure research. However, there is increasing evidence that the current ambient monitoring network is not capturing sharp gradients in exposure due to the presence of high concentration levels near, for example, major roadways. Many air pollutants exhibit large concentration gradients near large emitters such as major roadways, factories, ports, etc. To overcome these limitations, researchers are now beginning to use air quality models to support air pollution exposure and health studies. There are many advantages to using air quality models over traditional approaches based on existing ambient measurements alone. First, models can provide spatially- and temporally-resolved concentrations as direct input to exposure and health studies and thus better defining the concentration levels for the population in the geographic domain. Air quality models have a long history of use in air pollution regulations, and supported by regulatory agencies and a large user community. Also, models can provide bidirectional linkages between sources of emissions and ambient concentrations, thus allowing exploration of various mitigation strategies to reduce risk to exposure. In order to provide best estimates of air concentrations to support human health and exposure studies, model estimates should consider local-scale features, regional-scale transport, and photochemical transformations. Since these needs are currently not met by a single model, hybrid air quality modeling has recently been developed to combine these capabilities. In this paper, we present the results of two studies where we applied the hybrid modeling approach to provide spatial and temporal details in air quality concentrations to support exposure and health studies: a) an urban-scale air quality accountability study involving near-source exposures to multiple ambient air pollutants, and b) an urban-scale epidemiological study involving human health data based on emergency department visits.

Human Factors: Tenerife Revisited

DOT National Transportation Integrated Search

1998-01-01

A collision between two 747 jumbo jets occurred at the Los Rodeos airport in Tenerife, on the Canary Islands cost the lives of 583 people. This case study of that collision shows how large scale disasters result from errors made by people in crucial ...

Human and biophysical influences on fire occurrence in the United States

USGS Publications Warehouse

Hawbaker, Todd J.; Radeloff, Volker C.; Stewart, Susan I.; Hammer, Roger B.; Keuler, Nicholas S.; Clayton, Murray K.

2013-01-01

National-scale analyses of fire occurrence are needed to prioritize fire policy and management activities across the United States. However, the drivers of national-scale patterns of fire occurrence are not well understood, and how the relative importance of human or biophysical factors varies across the country is unclear. Our research goal was to model the drivers of fire occurrence within ecoregions across the conterminous United States. We used generalized linear models to compare the relative influence of human, vegetation, climate, and topographic variables on fire occurrence in the United States, as measured by MODIS active fire detections collected between 2000 and 2006. We constructed models for all fires and for large fires only and generated predictive maps to quantify fire occurrence probabilities. Areas with high fire occurrence probabilities were widespread in the Southeast, and localized in the Mountain West, particularly in southern California, Arizona, and New Mexico. Probabilities for large-fire occurrence were generally lower, but hot spots existed in the western and south-central United States The probability of fire occurrence is a critical component of fire risk assessments, in addition to vegetation type, fire behavior, and the values at risk. Many of the hot spots we identified have extensive development in the wildland–urban interface and are near large metropolitan areas. Our results demonstrated that human variables were important predictors of both all fires and large fires and frequently exhibited nonlinear relationships. However, vegetation, climate, and topography were also significant variables in most ecoregions. If recent housing growth trends and fire occurrence patterns continue, these areas will continue to challenge policies and management efforts seeking to balance the risks generated by wildfires with the ecological benefits of fire.

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. © 2015 Wiley Periodicals, Inc.

Human cells: new platform for recombinant therapeutic protein production.

PubMed

Swiech, Kamilla; Picanço-Castro, Virgínia; Covas, Dimas Tadeu

2012-07-01

The demand for recombinant therapeutic proteins is significantly increasing. There is a constant need to improve the existing expression systems, and also developing novel approaches to face the therapeutic proteins demands. Human cell lines have emerged as a new and powerful alternative for the production of human therapeutic proteins because this expression system is expected to produce recombinant proteins with post translation modifications more similar to their natural counterpart and reduce the potential immunogenic reactions against nonhuman epitopes. Currently, little information about the cultivation of human cells for the production of biopharmaceuticals is available. These cells have shown efficient production in laboratory scale and represent an important tool for the pharmaceutical industry. This review presents the cell lines available for large-scale recombinant proteins production and evaluates critically the advantages of this expression system in comparison with other expression systems for recombinant therapeutic protein production. Copyright © 2012 Elsevier Inc. All rights reserved.

Polar ocean ecosystems in a changing world.

PubMed

Smetacek, Victor; Nicol, Stephen

2005-09-15

Polar organisms have adapted their seasonal cycles to the dynamic interface between ice and water. This interface ranges from the micrometre-sized brine channels within sea ice to the planetary-scale advance and retreat of sea ice. Polar marine ecosystems are particularly sensitive to climate change because small temperature differences can have large effects on the extent and thickness of sea ice. Little is known about the interactions between large, long-lived organisms and their planktonic food supply. Disentangling the effects of human exploitation of upper trophic levels from basin-wide, decade-scale climate cycles to identify long-term, global trends is a daunting challenge facing polar bio-oceanography.

In silico identification and comparative analysis of differentially expressed genes in human and mouse tissues

PubMed Central

Pao, Sheng-Ying; Lin, Win-Li; Hwang, Ming-Jing

2006-01-01

Background Screening for differentially expressed genes on the genomic scale and comparative analysis of the expression profiles of orthologous genes between species to study gene function and regulation are becoming increasingly feasible. Expressed sequence tags (ESTs) are an excellent source of data for such studies using bioinformatic approaches because of the rich libraries and tremendous amount of data now available in the public domain. However, any large-scale EST-based bioinformatics analysis must deal with the heterogeneous, and often ambiguous, tissue and organ terms used to describe EST libraries. Results To deal with the issue of tissue source, in this work, we carefully screened and organized more than 8 million human and mouse ESTs into 157 human and 108 mouse tissue/organ categories, to which we applied an established statistic test using different thresholds of the p value to identify genes differentially expressed in different tissues. Further analysis of the tissue distribution and level of expression of human and mouse orthologous genes showed that tissue-specific orthologs tended to have more similar expression patterns than those lacking significant tissue specificity. On the other hand, a number of orthologs were found to have significant disparity in their expression profiles, hinting at novel functions, divergent regulation, or new ortholog relationships. Conclusion Comprehensive statistics on the tissue-specific expression of human and mouse genes were obtained in this very large-scale, EST-based analysis. These statistical results have been organized into a database, freely accessible at our website , for easy searching of human and mouse tissue-specific genes and for investigating gene expression profiles in the context of comparative genomics. Comparative analysis showed that, although highly tissue-specific genes tend to exhibit similar expression profiles in human and mouse, there are significant exceptions, indicating that orthologous genes, while sharing basic genomic properties, could result in distinct phenotypes. PMID:16626500

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.

Serial grouping of 2D-image regions with object-based attention in humans.

PubMed

Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R

2016-06-13

After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas.

Human Factors in the Large: Experiences from Denmark, Finland and Canada in Moving Towards Regional and National Evaluations of Health Information System Usability

PubMed Central

Kaipio, J.; Nieminen, M.; Hyppönen, H.; Lääveri, T.; Nohr, C.; Kanstrup, A. M.; Berg Christiansen, M.; Kuo, M.-H.; Borycki, E.

2014-01-01

Summary Objectives The objective of this paper is to explore approaches to understanding the usability of health information systems at regional and national levels. Methods Several different methods are discussed in case studies from Denmark, Finland and Canada. They range from small scale qualitative studies involving usability testing of systems to larger scale national level questionnaire studies aimed at assessing the use and usability of health information systems by entire groups of health professionals. Results It was found that regional and national usability studies can complement smaller scale usability studies, and that they are needed in order to understand larger trends regarding system usability. Despite adoption of EHRs, many health professionals rate the usability of the systems as low. A range of usability issues have been noted when data is collected on a large scale through use of widely distributed questionnaires and websites designed to monitor user perceptions of usability. Conclusion As health information systems are deployed on a widespread basis, studies that examine systems used regionally or nationally are required. In addition, collection of large scale data on the usability of specific IT products is needed in order to complement smaller scale studies of specific systems. PMID:25123725

Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

PubMed Central

2012-01-01

Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

Human, Oceanographic and Habitat Drivers of Central and Western Pacific Coral Reef Fish Assemblages

PubMed Central

Williams, Ivor D.; Baum, Julia K.; Heenan, Adel; Hanson, Katharine M.; Nadon, Marc O.; Brainard, Russell E.

2015-01-01

Coral reefs around US- and US-affiliated Pacific islands and atolls span wide oceanographic gradients and levels of human impact. Here we examine the relative influence of these factors on coral reef fish biomass, using data from a consistent large-scale ecosystem monitoring program conducted by scientific divers over the course of >2,000 hours of underwater observation at 1,934 sites, across ~40 islands and atolls. Consistent with previous smaller-scale studies, our results show sharp declines in reef fish biomass at relatively low human population density, followed by more gradual declines as human population density increased further. Adjusting for other factors, the highest levels of oceanic productivity among our study locations were associated with more than double the biomass of reef fishes (including ~4 times the biomass of planktivores and piscivores) compared to islands with lowest oceanic productivity. Our results emphasize that coral reef areas do not all have equal ability to sustain large reef fish stocks, and that what is natural varies significantly amongst locations. Comparisons of biomass estimates derived from visual surveys with predicted biomass in the absence of humans indicated that total reef fish biomass was depleted by 61% to 69% at populated islands in the Mariana Archipelago; by 20% to 78% in the Main Hawaiian islands; and by 21% to 56% in American Samoa. PMID:25831196

Twitter web-service for soft agent reporting in persistent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2010-04-01

Persistent surveillance is an intricate process requiring monitoring, gathering, processing, tracking, and characterization of many spatiotemporal events occurring concurrently. Data associated with events can be readily attained by networking of hard (physical) sensors. Sensors may have homogeneous or heterogeneous (hybrid) sensing modalities with different communication bandwidth requirements. Complimentary to hard sensors are human observers or "soft sensors" that can report occurrences of evolving events via different communication devices (e.g., texting, cell phones, emails, instant messaging, etc.) to the command control center. However, networking of human observers in ad-hoc way is rather a difficult task. In this paper, we present a Twitter web-service for soft agent reporting in persistent surveillance systems (called Web-STARS). The objective of this web-service is to aggregate multi-source human observations in hybrid sensor networks rapidly. With availability of Twitter social network, such a human networking concept can not only be realized for large scale persistent surveillance systems (PSS), but also, it can be employed with proper interfaces to expedite rapid events reporting by human observers. The proposed technique is particularly suitable for large-scale persistent surveillance systems with distributed soft and hard sensor networks. The efficiency and effectiveness of the proposed technique is measured experimentally by conducting several simulated persistent surveillance scenarios. It is demonstrated that by fusion of information from hard and soft agents improves understanding of common operating picture and enhances situational awareness.

Spatial scale and distribution of neurovascular signals underlying decoding of orientation and eye of origin from fMRI data

PubMed Central

Harrison, Charlotte; Jackson, Jade; Oh, Seung-Mock; Zeringyte, Vaida

2016-01-01

Multivariate pattern analysis of functional magnetic resonance imaging (fMRI) data is widely used, yet the spatial scales and origin of neurovascular signals underlying such analyses remain unclear. We compared decoding performance for stimulus orientation and eye of origin from fMRI measurements in human visual cortex with predictions based on the columnar organization of each feature and estimated the spatial scales of patterns driving decoding. Both orientation and eye of origin could be decoded significantly above chance in early visual areas (V1–V3). Contrary to predictions based on a columnar origin of response biases, decoding performance for eye of origin in V2 and V3 was not significantly lower than that in V1, nor did decoding performance for orientation and eye of origin differ significantly. Instead, response biases for both features showed large-scale organization, evident as a radial bias for orientation, and a nasotemporal bias for eye preference. To determine whether these patterns could drive classification, we quantified the effect on classification performance of binning voxels according to visual field position. Consistent with large-scale biases driving classification, binning by polar angle yielded significantly better decoding performance for orientation than random binning in V1–V3. Similarly, binning by hemifield significantly improved decoding performance for eye of origin. Patterns of orientation and eye preference bias in V2 and V3 showed a substantial degree of spatial correlation with the corresponding patterns in V1, suggesting that response biases in these areas originate in V1. Together, these findings indicate that multivariate classification results need not reflect the underlying columnar organization of neuronal response selectivities in early visual areas. NEW & NOTEWORTHY Large-scale response biases can account for decoding of orientation and eye of origin in human early visual areas V1–V3. For eye of origin this pattern is a nasotemporal bias; for orientation it is a radial bias. Differences in decoding performance across areas and stimulus features are not well predicted by differences in columnar-scale organization of each feature. Large-scale biases in extrastriate areas are spatially correlated with those in V1, suggesting biases originate in primary visual cortex. PMID:27903637

Improved technique that allows the performance of large-scale SNP genotyping on DNA immobilized by FTA technology.

PubMed

He, Hongbin; Argiro, Laurent; Dessein, Helia; Chevillard, Christophe

2007-01-01

FTA technology is a novel method designed to simplify the collection, shipment, archiving and purification of nucleic acids from a wide variety of biological sources. The number of punches that can normally be obtained from a single specimen card are often however, insufficient for the testing of the large numbers of loci required to identify genetic factors that control human susceptibility or resistance to multifactorial diseases. In this study, we propose an improved technique to perform large-scale SNP genotyping. We applied a whole genome amplification method to amplify DNA from buccal cell samples stabilized using FTA technology. The results show that using the improved technique it is possible to perform up to 15,000 genotypes from one buccal cell sample. Furthermore, the procedure is simple. We consider this improved technique to be a promising methods for performing large-scale SNP genotyping because the FTA technology simplifies the collection, shipment, archiving and purification of DNA, while whole genome amplification of FTA card bound DNA produces sufficient material for the determination of thousands of SNP genotypes.

Evaluation of nucleus segmentation in digital pathology images through large scale image synthesis

NASA Astrophysics Data System (ADS)

Zhou, Naiyun; Yu, Xiaxia; Zhao, Tianhao; Wen, Si; Wang, Fusheng; Zhu, Wei; Kurc, Tahsin; Tannenbaum, Allen; Saltz, Joel; Gao, Yi

2017-03-01

Digital histopathology images with more than 1 Gigapixel are drawing more and more attention in clinical, biomedical research, and computer vision fields. Among the multiple observable features spanning multiple scales in the pathology images, the nuclear morphology is one of the central criteria for diagnosis and grading. As a result it is also the mostly studied target in image computing. Large amount of research papers have devoted to the problem of extracting nuclei from digital pathology images, which is the foundation of any further correlation study. However, the validation and evaluation of nucleus extraction have yet been formulated rigorously and systematically. Some researches report a human verified segmentation with thousands of nuclei, whereas a single whole slide image may contain up to million. The main obstacle lies in the difficulty of obtaining such a large number of validated nuclei, which is essentially an impossible task for pathologist. We propose a systematic validation and evaluation approach based on large scale image synthesis. This could facilitate a more quantitatively validated study for current and future histopathology image analysis field.

Development of large-scale manufacturing of adipose-derived stromal cells for clinical applications using bioreactors and human platelet lysate.

PubMed

Haack-Sørensen, Mandana; Juhl, Morten; Follin, Bjarke; Harary Søndergaard, Rebekka; Kirchhoff, Maria; Kastrup, Jens; Ekblond, Annette

2018-04-17

In vitro expanded adipose-derived stromal cells (ASCs) are a useful resource for tissue regeneration. Translation of small-scale autologous cell production into a large-scale, allogeneic production process for clinical applications necessitates well-chosen raw materials and cell culture platform. We compare the use of clinical-grade human platelet lysate (hPL) and fetal bovine serum (FBS) as growth supplements for ASC expansion in the automated, closed hollow fibre quantum cell expansion system (bioreactor). Stromal vascular fractions were isolated from human subcutaneous abdominal fat. In average, 95 × 10 6 cells were suspended in 10% FBS or 5% hPL medium, and loaded into a bioreactor coated with cryoprecipitate. ASCs (P0) were harvested, and 30 × 10 6 ASCs were reloaded for continued expansion (P1). Feeding rate and time of harvest was guided by metabolic monitoring. Viability, sterility, purity, differentiation capacity, and genomic stability of ASCs P1 were determined. Cultivation of SVF in hPL medium for in average nine days, yielded 546 × 10 6 ASCs compared to 111 × 10 6 ASCs, after 17 days in FBS medium. ASCs P1 yields were in average 605 × 10 6 ASCs (PD [population doublings]: 4.65) after six days in hPL medium, compared to 119 × 10 6 ASCs (PD: 2.45) in FBS medium, after 21 days. ASCs fulfilled ISCT criteria and demonstrated genomic stability and sterility. The use of hPL as a growth supplement for ASCs expansion in the quantum cell expansion system provides an efficient expansion process compared to the use of FBS, while maintaining cell quality appropriate for clinical use. The described process is an obvious choice for manufacturing of large-scale allogeneic ASC products.

Applications and Methods for Continuous Monitoring of Physiological Chemistry

DTIC Science & Technology

2016-02-04

product and test platform to verify the performance characteristics of the enzymes when used in diagnostic device fabrication. 1.3 Results This...project had three primary objectives: 1. Engineer a cortisol oxidase enzyme suitable for use in diagnostic devices 2. Large scale production and...for both animal and human use , and for direct sale to other entities to manufacture biosensors and other products for human monitoring. The enzymes

Functional annotation of HOT regions in the human genome: implications for human disease and cancer

PubMed Central

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-01-01

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy. PMID:26113264

Functional annotation of HOT regions in the human genome: implications for human disease and cancer.

PubMed

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-06-26

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy.

Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies

PubMed Central

Sserwadda, Ivan; Amujal, Marion; Namatovu, Norah

2018-01-01

HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers. PMID:29755620

Production of transgenic-cloned pigs expressing large quantities of recombinant human lysozyme in milk.

PubMed

Lu, Dan; Liu, Shen; Shang, Shengzhe; Wu, Fangfang; Wen, Xiao; Li, Zhiyuan; Li, Yan; Hu, Xiaoxiang; Zhao, Yaofeng; Li, Qiuyan; Li, Ning

2015-01-01

Human lysozyme is a natural non-specific immune factor in human milk that plays an important role in the defense of breastfed infants against pathogen infection. Although lysozyme is abundant in human milk, there is only trace quantities in pig milk. Here, we successfully generated transgenic cloned pigs with the expression vector pBAC-hLF-hLZ-Neo and their first generation hybrids (F1). The highest concentration of recombinant human lysozyme (rhLZ) with in vitro bioactivity was 2759.6 ± 265.0 mg/L in the milk of F0 sows. Compared with wild-type milk, rhLZ milk inhibited growth of Escherichia coli K88 during the exponential growth phase. Moreover, rhLZ in milk from transgenic sows was directly absorbed by the intestine of piglets with no observable anaphylactic reaction. Our strategy may provide a powerful tool for large-scale production of this important human protein in pigs to improve resistance to pathogen infection.

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

PubMed Central

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

2013-01-01

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

The atmospheric implications of radiation belt remediation

NASA Astrophysics Data System (ADS)

Rodger, C. J.; Clilverd, M. A.; Ulich, Th.; Verronen, P. T.; Turunen, E.; Thomson, N. R.

2006-08-01

High altitude nuclear explosions (HANEs) and geomagnetic storms can produce large scale injections of relativistic particles into the inner radiation belts. It is recognised that these large increases in >1 MeV trapped electron fluxes can shorten the operational lifetime of low Earth orbiting satellites, threatening a large, valuable population. Therefore, studies are being undertaken to bring about practical human control of the radiation belts, termed "Radiation Belt Remediation" (RBR). Here we consider the upper atmospheric consequences of an RBR system operating over either 1 or 10 days. The RBR-forced neutral chemistry changes, leading to NOx enhancements and Ox depletions, are significant during the timescale of the precipitation but are generally not long-lasting. The magnitudes, time-scales, and altitudes of these changes are no more significant than those observed during large solar proton events. In contrast, RBR-operation will lead to unusually intense HF blackouts for about the first half of the operation time, producing large scale disruptions to radio communication and navigation systems. While the neutral atmosphere changes are not particularly important, HF disruptions could be an important area for policy makers to consider, particularly for the remediation of natural injections.

The scaling of contact rates with population density for the infectious disease models.

PubMed

Hu, Hao; Nigmatulina, Karima; Eckhoff, Philip

2013-08-01

Contact rates and patterns among individuals in a geographic area drive transmission of directly-transmitted pathogens, making it essential to understand and estimate contacts for simulation of disease dynamics. Under the uniform mixing assumption, one of two mechanisms is typically used to describe the relation between contact rate and population density: density-dependent or frequency-dependent. Based on existing evidence of population threshold and human mobility patterns, we formulated a spatial contact model to describe the appropriate form of transmission with initial growth at low density and saturation at higher density. We show that the two mechanisms are extreme cases that do not capture real population movement across all scales. Empirical data of human and wildlife diseases indicate that a nonlinear function may work better when looking at the full spectrum of densities. This estimation can be applied to large areas with population mixing in general activities. For crowds with unusually large densities (e.g., transportation terminals, stadiums, or mass gatherings), the lack of organized social contact structure deviates the physical contacts towards a special case of the spatial contact model - the dynamics of kinetic gas molecule collision. In this case, an ideal gas model with van der Waals correction fits well; existing movement observation data and the contact rate between individuals is estimated using kinetic theory. A complete picture of contact rate scaling with population density may help clarify the definition of transmission rates in heterogeneous, large-scale spatial systems. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

When the globe is your classroom: teaching and learning about large-scale environmental change online

NASA Astrophysics Data System (ADS)

Howard, E. A.; Coleman, K. J.; Barford, C. L.; Kucharik, C.; Foley, J. A.

2005-12-01

Understanding environmental problems that cross physical and disciplinary boundaries requires a more holistic view of the world - a "systems" approach. Yet it is a challenge for many learners to start thinking this way, particularly when the problems are large in scale and not easily visible. We will describe our online university course, "Humans and the Changing Biosphere," which takes a whole-systems perspective for teaching regional to global-scale environmental science concepts, including climate, hydrology, ecology, and human demographics. We will share our syllabus and learning objectives and summarize our efforts to incorporate "best" practices for online teaching. We will describe challenges we have faced, and our efforts to reach different learner types. Our goals for this presentation are: (1) to communicate how a systems approach ties together environmental sciences (including climate, hydrology, ecology, biogeochemistry, and demography) that are often taught as separate disciplines; (2) to generate discussion about challenges of teaching large-scale environmental processes; (3) to share our experiences in teaching these topics online; (4) to receive ideas and feedback on future teaching strategies. We will explain why we developed this course online, and share our experiences about benefits and challenges of teaching over the web - including some suggestions about how to use technology to supplement face-to-face learning experiences (and vice versa). We will summarize assessment data about what students learned during the course, and discuss key misconceptions and barriers to learning. We will highlight the role of an online discussion board in creating classroom community, identifying misconceptions, and engaging different types of learners.

An Extended, Problem-Based Learning Laboratory Exercise on the Diagnosis of Infectious Diseases Suitable for Large Level 1 Undergraduate Biology Classes

ERIC Educational Resources Information Center

Tatner, Mary; Tierney, Anne

2016-01-01

The development and evaluation of a two-week laboratory class, based on the diagnosis of human infectious diseases, is described. It can be easily scaled up or down, to suit class sizes from 50 to 600 and completed in a shorter time scale, and to different audiences as desired. Students employ a range of techniques to solve a real-life and…

Reprint of: Cling film plastic wrap: An innovation for dead body packaging, preservation and transportation by first responders as a replacement for cadaver body bag in large scale disasters.

PubMed

Khoo, Lay See; Lai, Poh Soon; Saidin, Mohd Hilmi; Noor, Zahari; Mahmood, Mohd Shah

2018-07-01

Cadaver body bags are the conventional method to contain a human body or human remains, which includes the use for storage and transportation of the deceased at any crime scene or disaster scene. During disasters, most often than not, the first responders including the police will be equipped with cadaver body bags to do scene processing of human remains and collection of personal belongings at the disaster site. However, in an unanticipated large scale disasters involving hundreds and thousands of fatalities, cadaver body bags supplies may be scarce. The authors have therefore innovated the cling film plastic wrap as an alternative for the cadaver body bag used at the disaster site. The plastic wrap was tested on six different experimental subjects, i.e. both adult and child mannequins; body parts of the mannequin figure (arm and hand); a human adult subject and an unknown dead body. The strengths of the cling film plastic wrap are discussed in comparison with the cadaver body bag in the aspects of costing, weight, duration of the wrap, water and body fluid resistant properties, visibility and other advantages. An average savings of more than 5000% are noted for both adult body wrap and child body wrap compared to the cadaver body wrap. This simply means that the authors can either wrap 25 adult dead bodies or 80 children dead bodies with the cost of 1 cadaver body bag. The cling film plastic wrap has proven to have significant innovation impact for dead body management particularly by the first responders in large scale disasters. With proper handling of dead bodies, first responders can manage the dead with dignity and respect in an overwhelmed situation to facilitate the humanitarian victim identification process later. Copyright © 2018 Elsevier B.V. All rights reserved.

Cling film plastic wrap: An innovation for dead body packaging, preservation and transportation by first responders as a replacement for cadaver body bag in large scale disasters.

PubMed

Khoo, Lay See; Lai, Poh Soon; Saidin, Mohd Hilmi; Noor, Zahari; Mahmood, Mohd Shah

2018-04-01

Cadaver body bags are the conventional method to contain a human body or human remains, which includes the use for storage and transportation of the deceased at any crime scene or disaster scene. During disasters, most often than not, the first responders including the police will be equipped with cadaver body bags to do scene processing of human remains and collection of personal belongings at the disaster site. However, in an unanticipated large scale disasters involving hundreds and thousands of fatalities, cadaver body bags supplies may be scarce. The authors have therefore innovated the cling film plastic wrap as an alternative for the cadaver body bag used at the disaster site. The plastic wrap was tested on six different experimental subjects, i.e. both adult and child mannequins; body parts of the mannequin figure (arm and hand); a human adult subject and an unknown dead body. The strengths of the cling film plastic wrap are discussed in comparison with the cadaver body bag in the aspects of costing, weight, duration of the wrap, water and body fluid resistant properties, visibility and other advantages. An average savings of more than 5000% are noted for both adult body wrap and child body wrap compared to the cadaver body wrap. This simply means that the authors can either wrap 25 adult dead bodies or 80 children dead bodies with the cost of 1 cadaver body bag. The cling film plastic wrap has proven to have significant innovation impact for dead body management particularly by the first responders in large scale disasters. With proper handling of dead bodies, first responders can manage the dead with dignity and respect in an overwhelmed situation to facilitate the humanitarian victim identification process later. Copyright © 2018 Elsevier B.V. All rights reserved.

Studying time of flight imaging through scattering media across multiple size scales (Conference Presentation)

NASA Astrophysics Data System (ADS)

Velten, Andreas

2017-05-01

Light scattering is a primary obstacle to optical imaging in a variety of different environments and across many size and time scales. Scattering complicates imaging on large scales when imaging through the atmosphere when imaging from airborne or space borne platforms, through marine fog, or through fog and dust in vehicle navigation, for example in self driving cars. On smaller scales, scattering is the major obstacle when imaging through human tissue in biomedical applications. Despite the large variety of participating materials and size scales, light transport in all these environments is usually described with very similar scattering models that are defined by the same small set of parameters, including scattering and absorption length and phase function. We attempt a study of scattering and methods of imaging through scattering across different scales and media, particularly with respect to the use of time of flight information. We can show that using time of flight, in addition to spatial information, provides distinct advantages in scattering environments. By performing a comparative study of scattering across scales and media, we are able to suggest scale models for scattering environments to aid lab research. We also can transfer knowledge and methodology between different fields.

Quantification of human responses

NASA Technical Reports Server (NTRS)

Steinlage, R. C.; Gantner, T. E.; Lim, P. Y. W.

1992-01-01

Human perception is a complex phenomenon which is difficult to quantify with instruments. For this reason, large panels of people are often used to elicit and aggregate subjective judgments. Print quality, taste, smell, sound quality of a stereo system, softness, and grading Olympic divers and skaters are some examples of situations where subjective measurements or judgments are paramount. We usually express what is in our mind through language as a medium but languages are limited in available choices of vocabularies, and as a result, our verbalizations are only approximate expressions of what we really have in mind. For lack of better methods to quantify subjective judgments, it is customary to set up a numerical scale such as 1, 2, 3, 4, 5 or 1, 2, 3, ..., 9, 10 for characterizing human responses and subjective judgments with no valid justification except that these scales are easy to understand and convenient to use. But these numerical scales are arbitrary simplifications of the complex human mind; the human mind is not restricted to such simple numerical variations. In fact, human responses and subjective judgments are psychophysical phenomena that are fuzzy entities and therefore difficult to handle by conventional mathematics and probability theory. The fuzzy mathematical approach provides a more realistic insight into understanding and quantifying human responses. This paper presents a method for quantifying human responses and subjective judgments without assuming a pattern of linear or numerical variation for human responses. In particular, quantification and evaluation of linguistic judgments was investigated.

Comparative Study of Seven Commercial Kits for Human DNA Extraction from Urine Samples Suitable for DNA Biomarker-Based Public Health Studies

PubMed Central

El Bali, Latifa; Diman, Aurélie; Bernard, Alfred; Roosens, Nancy H. C.; De Keersmaecker, Sigrid C. J.

2014-01-01

Human genomic DNA extracted from urine could be an interesting tool for large-scale public health studies involving characterization of genetic variations or DNA biomarkers as a result of the simple and noninvasive collection method. These studies, involving many samples, require a rapid, easy, and standardized extraction protocol. Moreover, for practicability, there is a necessity to collect urine at a moment different from the first void and to store it appropriately until analysis. The present study compared seven commercial kits to select the most appropriate urinary human DNA extraction procedure for epidemiological studies. DNA yield has been determined using different quantification methods: two classical, i.e., NanoDrop and PicoGreen, and two species-specific real-time quantitative (q)PCR assays, as DNA extracted from urine contains, besides human, microbial DNA also, which largely contributes to the total DNA yield. In addition, the kits giving a good yield were also tested for the presence of PCR inhibitors. Further comparisons were performed regarding the sampling time and the storage conditions. Finally, as a proof-of-concept, an important gene related to smoking has been genotyped using the developed tools. We could select one well-performing kit for the human DNA extraction from urine suitable for molecular diagnostic real-time qPCR-based assays targeting genetic variations, applicable to large-scale studies. In addition, successful genotyping was possible using DNA extracted from urine stored at −20°C for several months, and an acceptable yield could also be obtained from urine collected at different moments during the day, which is particularly important for public health studies. PMID:25365790

Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients.

PubMed

Siegler, Uwe; Meyer-Monard, Sandrine; Jörger, Simon; Stern, Martin; Tichelli, André; Gratwohl, Alois; Wodnar-Filipowicz, Aleksandra; Kalberer, Christian P

2010-10-01

Alloreactive natural killer (NK) cells are potent effectors of innate anti-tumor defense. The introduction of NK cell-based immunotherapy to current treatment options in acute myeloid leukemia (AML) requires NK cell products with high anti-leukemic efficacy optimized for clinical use. We describe a good manufacturing practice (GMP)-compliant protocol of large-scale ex vivo expansion of alloreactive NK cells suitable for multiple donor lymphocyte infusions (NK-DLI) in AML. CliniMACS-purified NK cells were cultured in closed air-permeable culture bags with certified culture medium and components approved for human use [human serum, interleukin (IL)-2, IL-15 and anti-CD3 antibody] and with autologous irradiated feeder cells. NK cells (6.0 ± 1.2 x 10(8)) were purified from leukaphereses (8.1 ± 0.8 L) of six healthy donors and cultured under GMP conditions. NK cell numbers increased 117.0 ± 20.0-fold in 19 days. To reduce the culture volume associated with expansion of bulk NK cells and to expand selectively the alloreactive NK cell subsets, GMP-certified cell sorting was introduced to obtain cells with single killer immunoglobulin-like receptor (KIR) specificities. The subsequent GMP-compliant expansion of single KIR+ cells was 268.3 ± 66.8-fold, with a contaminating T-cell content of only 0.006 ± 0.002%. The single KIR-expressing NK cells were cytotoxic against HLA-mismatched primary AML blasts in vitro and effectively reduced tumor cell load in vivo in NOD/SCID mice transplanted with human AML. The approach to generating large numbers of GMP-grade alloreactive NK cells described here provides the basis for clinical efficacy trials of NK-DLI to complement and advance therapeutic strategies against human AML.

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

PubMed

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

PubMed Central

Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

2015-01-01

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

PubMed

de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

2016-01-01

Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

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

PubMed Central

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

2015-01-01

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

EvoluCode: Evolutionary Barcodes as a Unifying Framework for Multilevel Evolutionary Data.

PubMed

Linard, Benjamin; Nguyen, Ngoc Hoan; Prosdocimi, Francisco; Poch, Olivier; Thompson, Julie D

2012-01-01

Evolutionary systems biology aims to uncover the general trends and principles governing the evolution of biological networks. An essential part of this process is the reconstruction and analysis of the evolutionary histories of these complex, dynamic networks. Unfortunately, the methodologies for representing and exploiting such complex evolutionary histories in large scale studies are currently limited. Here, we propose a new formalism, called EvoluCode (Evolutionary barCode), which allows the integration of different evolutionary parameters (eg, sequence conservation, orthology, synteny …) in a unifying format and facilitates the multilevel analysis and visualization of complex evolutionary histories at the genome scale. The advantages of the approach are demonstrated by constructing barcodes representing the evolution of the complete human proteome. Two large-scale studies are then described: (i) the mapping and visualization of the barcodes on the human chromosomes and (ii) automatic clustering of the barcodes to highlight protein subsets sharing similar evolutionary histories and their functional analysis. The methodologies developed here open the way to the efficient application of other data mining and knowledge extraction techniques in evolutionary systems biology studies. A database containing all EvoluCode data is available at: http://lbgi.igbmc.fr/barcodes.

Human-Robot Teaming in a Multi-Agent Space Assembly Task

NASA Technical Reports Server (NTRS)

Rehnmark, Fredrik; Currie, Nancy; Ambrose, Robert O.; Culbert, Christopher

2004-01-01

NASA's Human Space Flight program depends heavily on spacewalks performed by pairs of suited human astronauts. These Extra-Vehicular Activities (EVAs) are severely restricted in both duration and scope by consumables and available manpower. An expanded multi-agent EVA team combining the information-gathering and problem-solving skills of humans with the survivability and physical capabilities of robots is proposed and illustrated by example. Such teams are useful for large-scale, complex missions requiring dispersed manipulation, locomotion and sensing capabilities. To study collaboration modalities within a multi-agent EVA team, a 1-g test is conducted with humans and robots working together in various supporting roles.

Parallel human genome analysis: microarray-based expression monitoring of 1000 genes.

PubMed Central

Schena, M; Shalon, D; Heller, R; Chai, A; Brown, P O; Davis, R W

1996-01-01

Microarrays containing 1046 human cDNAs of unknown sequence were printed on glass with high-speed robotics. These 1.0-cm2 DNA "chips" were used to quantitatively monitor differential expression of the cognate human genes using a highly sensitive two-color hybridization assay. Array elements that displayed differential expression patterns under given experimental conditions were characterized by sequencing. The identification of known and novel heat shock and phorbol ester-regulated genes in human T cells demonstrates the sensitivity of the assay. Parallel gene analysis with microarrays provides a rapid and efficient method for large-scale human gene discovery. Images Fig. 1 Fig. 2 Fig. 3 PMID:8855227

Modeling large-scale human alteration of land surface hydrology and climate

NASA Astrophysics Data System (ADS)

Pokhrel, Yadu N.; Felfelani, Farshid; Shin, Sanghoon; Yamada, Tomohito J.; Satoh, Yusuke

2017-12-01

Rapidly expanding human activities have profoundly affected various biophysical and biogeochemical processes of the Earth system over a broad range of scales, and freshwater systems are now amongst the most extensively altered ecosystems. In this study, we examine the human-induced changes in land surface water and energy balances and the associated climate impacts using a coupled hydrological-climate model framework which also simulates the impacts of human activities on the water cycle. We present three sets of analyses using the results from two model versions—one with and the other without considering human activities; both versions are run in offline and coupled mode resulting in a series of four experiments in total. First, we examine climate and human-induced changes in regional water balance focusing on the widely debated issue of the desiccation of the Aral Sea in central Asia. Then, we discuss the changes in surface temperature as a result of changes in land surface energy balance due to irrigation over global and regional scales. Finally, we examine the global and regional climate impacts of increased atmospheric water vapor content due to irrigation. Results indicate that the direct anthropogenic alteration of river flow in the Aral Sea basin resulted in the loss of 510 km3 of water during the latter half of the twentieth century which explains about half of the total loss of water from the sea. Results of irrigation-induced changes in surface energy balance suggest a significant surface cooling of up to 3.3 K over 1° grids in highly irrigated areas but a negligible change in land surface temperature when averaged over sufficiently large global regions. Results from the coupled model indicate a substantial change in 2 m air temperature and outgoing longwave radiation due to irrigation, highlighting the non-local (regional and global) implications of irrigation. These results provide important insights on the direct human alteration of land surface water and energy balances, highlighting the need to incorporate human activities such as irrigation into the framework of global climate models and Earth system models for better prediction of future changes under increasing human influence and continuing global climate change.

Gold nanoparticles for high-throughput genotyping of long-range haplotypes

NASA Astrophysics Data System (ADS)

Chen, Peng; Pan, Dun; Fan, Chunhai; Chen, Jianhua; Huang, Ke; Wang, Dongfang; Zhang, Honglu; Li, You; Feng, Guoyin; Liang, Peiji; He, Lin; Shi, Yongyong

2011-10-01

Completion of the Human Genome Project and the HapMap Project has led to increasing demands for mapping complex traits in humans to understand the aetiology of diseases. Identifying variations in the DNA sequence, which affect how we develop disease and respond to pathogens and drugs, is important for this purpose, but it is difficult to identify these variations in large sample sets. Here we show that through a combination of capillary sequencing and polymerase chain reaction assisted by gold nanoparticles, it is possible to identify several DNA variations that are associated with age-related macular degeneration and psoriasis on significant regions of human genomic DNA. Our method is accurate and promising for large-scale and high-throughput genetic analysis of susceptibility towards disease and drug resistance.

Catastrophic flooding origin of shelf valley systems in the English Channel.

PubMed

Gupta, Sanjeev; Collier, Jenny S; Palmer-Felgate, Andy; Potter, Graeme

2007-07-19

Megaflood events involving sudden discharges of exceptionally large volumes of water are rare, but can significantly affect landscape evolution, continental-scale drainage patterns and climate change. It has been proposed that a significant flood event eroded a network of large ancient valleys on the floor of the English Channel-the narrow seaway between England and France. This hypothesis has remained untested through lack of direct evidence, and alternative non-catastrophist ideas have been entertained for valley formation. Here we analyse a new regional bathymetric map of part of the English Channel derived from high-resolution sonar data, which shows the morphology of the valley in unprecedented detail. We observe a large bedrock-floored valley that contains a distinct assemblage of landforms, including streamlined islands and longitudinal erosional grooves, which are indicative of large-scale subaerial erosion by high-magnitude water discharges. Our observations support the megaflood model, in which breaching of a rock dam at the Dover Strait instigated catastrophic drainage of a large pro-glacial lake in the southern North Sea basin. We suggest that megaflooding provides an explanation for the permanent isolation of Britain from mainland Europe during interglacial high-sea-level stands, and consequently for patterns of early human colonisation of Britain together with the large-scale reorganization of palaeodrainage in northwest Europe.

Natural disturbance production functions

Treesearch

Jeffrey P. Prestemon; D. Evan Mercer; John M. Pye

2008-01-01

Natural disturbances in forests are driven by physical and biological processes. Large, landscape scale disturbances derive primarily from weather (droughts, winds, ice storms, and floods), geophysical activities (earthquakes, volcanic eruptions), fires, insects, and diseases. Humans have invented ways to minimize their negative impacts and reduce their rates of...

Validating a Geographical Image Retrieval System.

ERIC Educational Resources Information Center

Zhu, Bin; Chen, Hsinchun

2000-01-01

Summarizes a prototype geographical image retrieval system that demonstrates how to integrate image processing and information analysis techniques to support large-scale content-based image retrieval. Describes an experiment to validate the performance of this image retrieval system against that of human subjects by examining similarity analysis…

NETWORK DESIGN FOR OZONE MONITORING

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 from air pollution. A major cr...

People and water: Exploring the social-ecological condition of watersheds of the United States

EPA Science Inventory

A recent paradigm shift from purely biophysical towards social-ecological assessment of watersheds has been proposed to understand, monitor, and manipulate the myriad interactions between human well-being and the ecosystem services that watersheds provide. However, large-scale, q...

Large-scale purification and characterization of recombinant human stem cell factor in Escherichia coli.

PubMed

Chen, Liang-Hua; Cai, Feng; Zhang, Dan-Ju; Zhang, Li; Zhu, Peng; Gao, Shun

2017-07-01

The pharmacological importance of recombinant human stem cell factor (rhSCF) has increased the demand to establish effective and large-scale production and purification processes. A good source of bioactive recombinant protein with capability of being scaled-up without losing activity has always been a challenge. The objectives of the study were the rapid and efficient pilot-scale expression and purification of rhSCF. The gene encoding stem cell factor (SCF) was cloned into pBV220 and transformed into Escherichia coli. The recombinant SCF was expressed and isolated using a procedure consisting of isolation of inclusion bodies (IBs), denaturation, and refolding followed by chromatographic steps toward purification. The yield of rhSCF reached 835.6 g/20 L, and the expression levels of rhSCF were about 33.9% of the total E. coli protein content. rhSCF was purified by isolation of IBs, denaturation, and refolding, followed by SP-Sepharose chromatography, Source 30 reversed-phase chromatography, and Q-Sepharose chromatography. This procedure was developed to isolate 5.5 g of rhSCF (99.5% purity) with specific activity at 0.96 × 10 6  IU/mg, endotoxin levels of pyrogen at 1.0 EU/mg, and bacterial DNA at 10 ng/mg. Pilot-scale fermentations and purifications were set up for the production of rhSCF that can be upscaled for industry. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

PubMed

Brannan, Kristopher W; Jin, Wenhao; Huelga, Stephanie C; Banks, Charles A S; Gilmore, Joshua M; Florens, Laurence; Washburn, Michael P; Van Nostrand, Eric L; Pratt, Gabriel A; Schwinn, Marie K; Daniels, Danette L; Yeo, Gene W

2016-10-20

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

PubMed

Keerativittayayut, Ruedeerat; Aoki, Ryuta; Sarabi, Mitra Taghizadeh; Jimura, Koji; Nakahara, Kiyoshi

2018-06-18

Although activation/deactivation of specific brain regions have been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here we investigated time-varying functional connectivity patterns across the human brain in periods of 30-40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding. © 2018, Keerativittayayut et al.

Efficient RNA drug delivery using red blood cell extracellular vesicles.

PubMed

Usman, Waqas Muhammad; Pham, Tin Chanh; Kwok, Yuk Yan; Vu, Luyen Tien; Ma, Victor; Peng, Boya; Chan, Yuen San; Wei, Likun; Chin, Siew Mei; Azad, Ajijur; He, Alex Bai-Liang; Leung, Anskar Y H; Yang, Mengsu; Shyh-Chang, Ng; Cho, William C; Shi, Jiahai; Le, Minh T N

2018-06-15

Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR-Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

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

Assessing large-scale wildlife responses to human infrastructure development.

PubMed

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

2016-07-26

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

Accelerating three-dimensional FDTD calculations on GPU clusters for electromagnetic field simulation.

PubMed

Nagaoka, Tomoaki; Watanabe, Soichi

2012-01-01

Electromagnetic simulation with anatomically realistic computational human model using the finite-difference time domain (FDTD) method has recently been performed in a number of fields in biomedical engineering. To improve the method's calculation speed and realize large-scale computing with the computational human model, we adapt three-dimensional FDTD code to a multi-GPU cluster environment with Compute Unified Device Architecture and Message Passing Interface. Our multi-GPU cluster system consists of three nodes. The seven GPU boards (NVIDIA Tesla C2070) are mounted on each node. We examined the performance of the FDTD calculation on multi-GPU cluster environment. We confirmed that the FDTD calculation on the multi-GPU clusters is faster than that on a multi-GPU (a single workstation), and we also found that the GPU cluster system calculate faster than a vector supercomputer. In addition, our GPU cluster system allowed us to perform the large-scale FDTD calculation because were able to use GPU memory of over 100 GB.

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2016-04-07

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

Large Scale Triboelectric Nanogenerator and Self-Powered Pressure Sensor Array Using Low Cost Roll-to-Roll UV Embossing

PubMed Central

Dhakar, Lokesh; Gudla, Sudeep; Shan, Xuechuan; Wang, Zhiping; Tay, Francis Eng Hock; Heng, Chun-Huat; Lee, Chengkuo

2016-01-01

Triboelectric nanogenerators (TENGs) have emerged as a potential solution for mechanical energy harvesting over conventional mechanisms such as piezoelectric and electromagnetic, due to easy fabrication, high efficiency and wider choice of materials. Traditional fabrication techniques used to realize TENGs involve plasma etching, soft lithography and nanoparticle deposition for higher performance. But lack of truly scalable fabrication processes still remains a critical challenge and bottleneck in the path of bringing TENGs to commercial production. In this paper, we demonstrate fabrication of large scale triboelectric nanogenerator (LS-TENG) using roll-to-roll ultraviolet embossing to pattern polyethylene terephthalate sheets. These LS-TENGs can be used to harvest energy from human motion and vehicle motion from embedded devices in floors and roads, respectively. LS-TENG generated a power density of 62.5 mW m−2. Using roll-to-roll processing technique, we also demonstrate a large scale triboelectric pressure sensor array with pressure detection sensitivity of 1.33 V kPa−1. The large scale pressure sensor array has applications in self-powered motion tracking, posture monitoring and electronic skin applications. This work demonstrates scalable fabrication of TENGs and self-powered pressure sensor arrays, which will lead to extremely low cost and bring them closer to commercial production. PMID:26905285

Cells as advanced therapeutics: State-of-the-art, challenges, and opportunities in large scale biomanufacturing of high-quality cells for adoptive immunotherapies.

PubMed

Dwarshuis, Nate J; Parratt, Kirsten; Santiago-Miranda, Adriana; Roy, Krishnendu

2017-05-15

Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of human mobility on the emergence of dengue epidemics in Pakistan

PubMed Central

Wesolowski, Amy; Qureshi, Taimur; Boni, Maciej F.; Sundsøy, Pål Roe; Johansson, Michael A.; Rasheed, Syed Basit; Engø-Monsen, Kenth; Buckee, Caroline O.

2015-01-01

The recent emergence of dengue viruses into new susceptible human populations throughout Asia and the Middle East, driven in part by human travel on both local and global scales, represents a significant global health risk, particularly in areas with changing climatic suitability for the mosquito vector. In Pakistan, dengue has been endemic for decades in the southern port city of Karachi, but large epidemics in the northeast have emerged only since 2011. Pakistan is therefore representative of many countries on the verge of countrywide endemic dengue transmission, where prevention, surveillance, and preparedness are key priorities in previously dengue-free regions. We analyze spatially explicit dengue case data from a large outbreak in Pakistan in 2013 and compare the dynamics of the epidemic to an epidemiological model of dengue virus transmission based on climate and mobility data from ∼40 million mobile phone subscribers. We find that mobile phone-based mobility estimates predict the geographic spread and timing of epidemics in both recently epidemic and emerging locations. We combine transmission suitability maps with estimates of seasonal dengue virus importation to generate fine-scale dynamic risk maps with direct application to dengue containment and epidemic preparedness. PMID:26351662

Resting state brain networks in the prairie vole.

PubMed

Ortiz, Juan J; Portillo, Wendy; Paredes, Raul G; Young, Larry J; Alcauter, Sarael

2018-01-19

Resting state functional magnetic resonance imaging (rsfMRI) has shown the hierarchical organization of the human brain into large-scale complex networks, referred as resting state networks. This technique has turned into a promising translational research tool after the finding of similar resting state networks in non-human primates, rodents and other animal models of great value for neuroscience. Here, we demonstrate and characterize the presence of resting states networks in Microtus ochrogaster, the prairie vole, an extraordinary animal model to study complex human-like social behavior, with potential implications for the research of normal social development, addiction and neuropsychiatric disorders. Independent component analysis of rsfMRI data from isoflurane-anestethized prairie voles resulted in cortical and subcortical networks, including primary motor and sensory networks, but also included putative salience and default mode networks. We further discuss how future research could help to close the gap between the properties of the large scale functional organization and the underlying neurobiology of several aspects of social cognition. These results contribute to the evidence of preserved resting state brain networks across species and provide the foundations to explore the use of rsfMRI in the prairie vole for basic and translational research.

Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics.

PubMed

Sridharan, Gautham Vivek; Bruinsma, Bote Gosse; Bale, Shyam Sundhar; Swaminathan, Anandh; Saeidi, Nima; Yarmush, Martin L; Uygun, Korkut

2017-11-13

Large-scale -omics data are now ubiquitously utilized to capture and interpret global responses to perturbations in biological systems, such as the impact of disease states on cells, tissues, and whole organs. Metabolomics data, in particular, are difficult to interpret for providing physiological insight because predefined biochemical pathways used for analysis are inherently biased and fail to capture more complex network interactions that span multiple canonical pathways. In this study, we introduce a nov-el approach coined Metabolomic Modularity Analysis (MMA) as a graph-based algorithm to systematically identify metabolic modules of reactions enriched with metabolites flagged to be statistically significant. A defining feature of the algorithm is its ability to determine modularity that highlights interactions between reactions mediated by the production and consumption of cofactors and other hub metabolites. As a case study, we evaluated the metabolic dynamics of discarded human livers using time-course metabolomics data and MMA to identify modules that explain the observed physiological changes leading to liver recovery during subnormothermic machine perfusion (SNMP). MMA was performed on a large scale liver-specific human metabolic network that was weighted based on metabolomics data and identified cofactor-mediated modules that would not have been discovered by traditional metabolic pathway analyses.

A Scalable Framework For Segmenting Magnetic Resonance Images

PubMed Central

Hore, Prodip; Goldgof, Dmitry B.; Gu, Yuhua; Maudsley, Andrew A.; Darkazanli, Ammar

2009-01-01

A fast, accurate and fully automatic method of segmenting magnetic resonance images of the human brain is introduced. The approach scales well allowing fast segmentations of fine resolution images. The approach is based on modifications of the soft clustering algorithm, fuzzy c-means, that enable it to scale to large data sets. Two types of modifications to create incremental versions of fuzzy c-means are discussed. They are much faster when compared to fuzzy c-means for medium to extremely large data sets because they work on successive subsets of the data. They are comparable in quality to application of fuzzy c-means to all of the data. The clustering algorithms coupled with inhomogeneity correction and smoothing are used to create a framework for automatically segmenting magnetic resonance images of the human brain. The framework is applied to a set of normal human brain volumes acquired from different magnetic resonance scanners using different head coils, acquisition parameters and field strengths. Results are compared to those from two widely used magnetic resonance image segmentation programs, Statistical Parametric Mapping and the FMRIB Software Library (FSL). The results are comparable to FSL while providing significant speed-up and better scalability to larger volumes of data. PMID:20046893

Materials for stem cell factories of the future

NASA Astrophysics Data System (ADS)

Celiz, Adam D.; Smith, James G. W.; Langer, Robert; Anderson, Daniel G.; Winkler, David A.; Barrett, David A.; Davies, Martyn C.; Young, Lorraine E.; Denning, Chris; Alexander, Morgan R.

2014-06-01

Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.

A Spatial Method to Calculate Small-Scale Fisheries Extent

NASA Astrophysics Data System (ADS)

Johnson, A. F.; Moreno-Báez, M.; Giron-Nava, A.; Corominas, J.; Erisman, B.; Ezcurra, E.; Aburto-Oropeza, O.

2016-02-01

Despite global catch per unit effort having redoubled since the 1950's, the global fishing fleet is estimated to be twice the size that the oceans can sustainably support. In order to gauge the collateral impacts of fishing intensity, we must be able to estimate the spatial extent and amount of fishing vessels in the oceans. Methods that do currently exist are built around electronic tracking and log book systems and generally focus on industrial fisheries. Spatial extent for small-scale fisheries therefore remains elusive for many small-scale fishing fleets; even though these fisheries land the same biomass for human consumption as industrial fisheries. Current methods are data-intensive and require extensive extrapolation when estimated across large spatial scales. We present an accessible, spatial method of calculating the extent of small-scale fisheries based on two simple measures that are available, or at least easily estimable, in even the most data poor fisheries: the number of boats and the local coastal human population. We demonstrate this method is fishery-type independent and can be used to quantitatively evaluate the efficacy of growth in small-scale fisheries. This method provides an important first step towards estimating the fishing extent of the small-scale fleet, globally.

The evolution of altruistic social preferences in human groups

PubMed Central

Silk, Joan B.; House, Bailey R.

2016-01-01

In this paper, we consider three hypotheses to account for the evolution of the extraordinary capacity for large-scale cooperation and altruistic social preferences within human societies. One hypothesis is that human cooperation is built on the same evolutionary foundations as cooperation in other animal societies, and that fundamental elements of the social preferences that shape our species' cooperative behaviour are also shared with other closely related primates. Another hypothesis is that selective pressures favouring cooperative breeding have shaped the capacity for cooperation and the development of social preferences, and produced a common set of behavioural dispositions and social preferences in cooperatively breeding primates and humans. The third hypothesis is that humans have evolved derived capacities for collaboration, group-level cooperation and altruistic social preferences that are linked to our capacity for culture. We draw on naturalistic data to assess differences in the form, scope and scale of cooperation between humans and other primates, experimental data to evaluate the nature of social preferences across primate species, and comparative analyses to evaluate the evolutionary origins of cooperative breeding and related forms of behaviour. PMID:26729936

A transparently scalable visualization architecture for exploring the universe.

PubMed

Fu, Chi-Wing; Hanson, Andrew J

2007-01-01

Modern astronomical instruments produce enormous amounts of three-dimensional data describing the physical Universe. The currently available data sets range from the solar system to nearby stars and portions of the Milky Way Galaxy, including the interstellar medium and some extrasolar planets, and extend out to include galaxies billions of light years away. Because of its gigantic scale and the fact that it is dominated by empty space, modeling and rendering the Universe is very different from modeling and rendering ordinary three-dimensional virtual worlds at human scales. Our purpose is to introduce a comprehensive approach to an architecture solving this visualization problem that encompasses the entire Universe while seeking to be as scale-neutral as possible. One key element is the representation of model-rendering procedures using power scaled coordinates (PSC), along with various PSC-based techniques that we have devised to generalize and optimize the conventional graphics framework to the scale domains of astronomical visualization. Employing this architecture, we have developed an assortment of scale-independent modeling and rendering methods for a large variety of astronomical models, and have demonstrated scale-insensitive interactive visualizations of the physical Universe covering scales ranging from human scale to the Earth, to the solar system, to the Milky Way Galaxy, and to the entire observable Universe.

Hunting as a management tool? Cougar-human conflict is positively related to trophy hunting.

PubMed

Teichman, Kristine J; Cristescu, Bogdan; Darimont, Chris T

2016-10-11

Overexploitation and persecution of large carnivores resulting from conflict with humans comprise major causes of declines worldwide. Although little is known about the interplay between these mortality types, hunting of predators remains a common management strategy aimed at reducing predator-human conflict. Emerging theory and data, however, caution that such policy can alter the age structure of populations, triggering increased conflict in which conflict-prone juveniles are involved. Using a 30-year dataset on human-caused cougar (Puma concolor) kills in British Columbia (BC), Canada, we examined relationships between hunter-caused and conflict-associated mortality. Individuals that were killed via conflict with humans were younger than hunted cougars. Accounting for human density and habitat productivity, human hunting pressure during or before the year of conflict comprised the most important variables. Both were associated with increased male cougar-human conflict. Moreover, in each of five regions assessed, conflict was higher with increased human hunting pressure for at least one cougar sex. Although only providing correlative evidence, such patterns over large geographic and temporal scales suggest that alternative approaches to conflict mitigation might yield more effective outcomes for humans as well as cougar populations and the individuals within populations.

Identification of the key ecological factors influencing vegetation degradation in semi-arid agro-pastoral ecotone considering spatial scales

NASA Astrophysics Data System (ADS)

Peng, Yu; Wang, Qinghui; Fan, Min

2017-11-01

When assessing re-vegetation project performance and optimizing land management, identification of the key ecological factors inducing vegetation degradation has crucial implications. Rainfall, temperature, elevation, slope, aspect, land use type, and human disturbance are ecological factors affecting the status of vegetation index. However, at different spatial scales, the key factors may vary. Using Helin County, Inner-Mongolia, China as the study site and combining remote sensing image interpretation, field surveying, and mathematical methods, this study assesses key ecological factors affecting vegetation degradation under different spatial scales in a semi-arid agro-pastoral ecotone. It indicates that the key factors are different at various spatial scales. Elevation, rainfall, and temperature are identified as crucial for all spatial extents. Elevation, rainfall and human disturbance are key factors for small-scale quadrats of 300 m × 300 m and 600 m × 600 m, temperature and land use type are key factors for a medium-scale quadrat of 1 km × 1 km, and rainfall, temperature, and land use are key factors for large-scale quadrats of 2 km × 2 km and 5 km × 5 km. For this region, human disturbance is not the key factor for vegetation degradation across spatial scales. It is necessary to consider spatial scale for the identification of key factors determining vegetation characteristics. The eco-restoration programs at various spatial scales should identify key influencing factors according their scales so as to take effective measurements. The new understanding obtained in this study may help to explore the forces which driving vegetation degradation in the degraded regions in the world.

MetaMap: An atlas of metatranscriptomic reads in human disease-related RNA-seq data.

PubMed

Simon, L M; Karg, S; Westermann, A J; Engel, M; Elbehery, A H A; Hense, B; Heinig, M; Deng, L; Theis, F J

2018-06-12

With the advent of the age of big data in bioinformatics, large volumes of data and high performance computing power enable researchers to perform re-analyses of publicly available datasets at an unprecedented scale. Ever more studies imply the microbiome in both normal human physiology and a wide range of diseases. RNA sequencing technology (RNA-seq) is commonly used to infer global eukaryotic gene expression patterns under defined conditions, including human disease-related contexts, but its generic nature also enables the detection of microbial and viral transcripts. We developed a bioinformatic pipeline to screen existing human RNA-seq datasets for the presence of microbial and viral reads by re-inspecting the non-human-mapping read fraction. We validated this approach by recapitulating outcomes from 6 independent controlled infection experiments of cell line models and comparison with an alternative metatranscriptomic mapping strategy. We then applied the pipeline to close to 150 terabytes of publicly available raw RNA-seq data from >17,000 samples from >400 studies relevant to human disease using state-of-the-art high performance computing systems. The resulting data of this large-scale re-analysis are made available in the presented MetaMap resource. Our results demonstrate that common human RNA-seq data, including those archived in public repositories, might contain valuable information to correlate microbial and viral detection patterns with diverse diseases. The presented MetaMap database thus provides a rich resource for hypothesis generation towards the role of the microbiome in human disease. Additionally, codes to process new datasets and perform statistical analyses are made available at https://github.com/theislab/MetaMap.

A large-scale measurement of dielectric properties of normal and malignant colorectal tissues obtained from cancer surgeries at Larmor frequencies.

PubMed

Li, Zhou; Deng, Guanhua; Li, Zhe; Xin, Sherman Xuegang; Duan, Song; Lan, Maoying; Zhang, Sa; Gao, Yixin; He, Jun; Zhang, Songtao; Tang, Hongming; Wang, Weiwei; Han, Shuai; Yang, Qing X; Zhuang, Ling; Hu, Jiani; Liu, Feng

2016-11-01

Knowledge of dielectric properties of malignant human tissues is necessary for the recently developed magnetic resonance (MR) technique called MR electrical property tomography. This technique may be used in early tumor detection based on the obvious differentiation of the dielectric properties between normal and malignant tissues. However, the dielectric properties of malignant human tissues in the scale of the Larmor frequencies are not completely available in the literature. In this study, the authors focused only on the dielectric properties of colorectal tumor tissue. The dielectric properties of 504 colorectal malignant samples excised from 85 patients in the scale of the Larmor frequencies were measured using the precision open-ended coaxial probe method. The obtained complex-permittivity data were fitted to the single-pole Cole-Cole model. The median permittivity and conductivity for the malignant tissue sample were 79.3 and 0.881 S/m at 128 MHz, which were 14.6% and 17.0% higher, respectively, than those of normal tissue samples. Significant differences between normal and malignant tissues were found for the dielectric properties (p < 0.05). Experimental results indicated that the dielectric properties were significantly different between normal and malignant tissues for colorectal tissue. This large-scale clinical measurement provides more subtle base data to validate the technique of MR electrical property tomography.

Behavioral responses of wolves to roads: scale-dependent ambivalence

PubMed Central

Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-01-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves (Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km2), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km2), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km2), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality. PMID:25419085

Behavioral responses of wolves to roads: scale-dependent ambivalence.

PubMed

Zimmermann, Barbara; Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-11-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves ( Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km 2 ), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km 2 ), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km 2 ), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality.

On humanity's role in space

NASA Technical Reports Server (NTRS)

Von Puttkamer, J.

1978-01-01

Manned spaceflight is considered within the framework of two broad categories: human exploitation of space for economic or scientific gain, and human habitation of space as a place where man may live, grow, and actualize himself. With the advent of the Space Shuttle, exploitation of space will take the form of new product development. This will continue during the 1990s as the new products are manufactured on a scale large enough to be profitable. The turn of the century should see major industries in space, and large space habitats. Thus, the question of mankind's existential needs arises. In addition to basic physical needs, the spiritual and cultural requirements of human beings must be considered. The impact of man's presence in space upon human culture in general is discussed with reference to international cooperation, public interest in space programs, scientific advancement, the basic urge to explore, and the density of mankind as a whole; which will become free of external constraints as we step into the cosmos.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization

PubMed Central

Mankiw, Catherine; Park, Min Tae M.; Reardon, P.K.; Fish, Ari M.; Clasen, Liv S.; Greenstein, Deanna; Blumenthal, Jonathan D.; Lerch, Jason P.; Chakravarty, M. Mallar

2017-01-01

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences—including their spatial distribution, potential biological determinants, and independence from brain volume variation—lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male–female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. PMID:28314818

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 and the human imprint override the geomorphic signal. The study demonstrates that human activities associated with creating and maintaining coastal infrastructure alter the natural behavior of the coast over hundreds of kilometers and time spans greater than a century. This suggests that future assessments of vulnerability, based largely on rates of change along developed coastlines, need to take the role of human alterations into account.

The relation between land use and subsidence in the Vietnamese Mekong delta

EPA Science Inventory

The Vietnamese Mekong delta is subsiding due to a combination of natural and human-induced causes. Over the past several decades, large-scale anthropogenic land-use changes have taken place as a result of increased agricultural production, population growth and urbanization in th...

Thinking big: linking rivers to landscapes

Treesearch

Joan O’Callaghan; Ashley E. Steel; Kelly M. Burnett

2012-01-01

Exploring relationships between landscape characteristics and rivers is an emerging field, enabled by the proliferation of satellite date, advances in statistical analysis, and increased emphasis on large-scale monitoring. Landscapes features such as road networks, underlying geology, and human developments, determine the characteristics of the rivers flowing through...

Dynamics of coupled human-landscape systems

NASA Astrophysics Data System (ADS)

Werner, B. T.; McNamara, D. E.

2007-11-01

A preliminary dynamical analysis of landscapes and humans as hierarchical complex systems suggests that strong coupling between the two that spreads to become regionally or globally pervasive should be focused at multi-year to decadal time scales. At these scales, landscape dynamics is dominated by water, sediment and biological routing mediated by fluvial, oceanic, atmospheric processes and human dynamics is dominated by simplifying, profit-maximizing market forces and political action based on projection of economic effect. Also at these scales, landscapes impact humans through patterns of natural disasters and trends such as sea level rise; humans impact landscapes by the effect of economic activity and changes meant to mitigate natural disasters and longer term trends. Based on this analysis, human-landscape coupled systems can be modeled using heterogeneous agents employing prediction models to determine actions to represent the nonlinear behavior of economic and political systems and rule-based routing algorithms to represent landscape processes. A cellular model for the development of New Orleans illustrates this approach, with routing algorithms for river and hurricane-storm surge determining flood extent, five markets (home, labor, hotel, tourism and port services) connecting seven types of economic agents (home buyers/laborers, home developers, hotel owners/ employers, hotel developers, tourists, port services developer and port services owners/employers), building of levees or a river spillway by political agents and damage to homes, hotels or port services within cells determined by the passage or depth of flood waters. The model reproduces historical aspects of New Orleans economic development and levee construction and the filtering of frequent small-scale floods at the expense of large disasters.

On inclusion of water resource management in Earth system models - Part 1: Problem definition and representation of water demand

NASA Astrophysics Data System (ADS)

Nazemi, A.; Wheater, H. S.

2015-01-01

Human activities have caused various changes to the Earth system, and hence the interconnections between human activities and the Earth system should be recognized and reflected in models that simulate Earth system processes. One key anthropogenic activity is water resource management, which determines the dynamics of human-water interactions in time and space and controls human livelihoods and economy, including energy and food production. There are immediate needs to include water resource management in Earth system models. First, the extent of human water requirements is increasing rapidly at the global scale and it is crucial to analyze the possible imbalance between water demands and supply under various scenarios of climate change and across various temporal and spatial scales. Second, recent observations show that human-water interactions, manifested through water resource management, can substantially alter the terrestrial water cycle, affect land-atmospheric feedbacks and may further interact with climate and contribute to sea-level change. Due to the importance of water resource management in determining the future of the global water and climate cycles, the World Climate Research Program's Global Energy and Water Exchanges project (WRCP-GEWEX) has recently identified gaps in describing human-water interactions as one of the grand challenges in Earth system modeling (GEWEX, 2012). Here, we divide water resource management into two interdependent elements, related firstly to water demand and secondly to water supply and allocation. In this paper, we survey the current literature on how various components of water demand have been included in large-scale models, in particular land surface and global hydrological models. Issues of water supply and allocation are addressed in a companion paper. The available algorithms to represent the dominant demands are classified based on the demand type, mode of simulation and underlying modeling assumptions. We discuss the pros and cons of available algorithms, address various sources of uncertainty and highlight limitations in current applications. We conclude that current capability of large-scale models to represent human water demands is rather limited, particularly with respect to future projections and coupled land-atmospheric simulations. To fill these gaps, the available models, algorithms and data for representing various water demands should be systematically tested, intercompared and improved. In particular, human water demands should be considered in conjunction with water supply and allocation, particularly in the face of water scarcity and unknown future climate.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts

PubMed Central

Chong, James J.H.; Yang, Xiulan; Don, Creighton W.; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M.; Van Biber, Benjamin; Cook, Savannah M.; Palpant, Nathan J; Gantz, Jay; Fugate, James A.; Muskheli, Veronica; Gough, G. Michael; Vogel, Keith W.; Astley, Cliff A.; Hotchkiss, Charlotte E.; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A.; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A.; Murry, Charles E.

2014-01-01

Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure 1 by providing human cardiomyocytes to support heart regeneration 2. Studies of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in small animal models have shown favorable effects of this treatment 3–7. It remains unknown, however, whether clinical scale hESC-CMs transplantation is feasible, safe or can provide large-scale myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (>1 billion cells/batch) and cryopreserved with good viability. Using a non-human primate (NHP) model of myocardial ischemia-reperfusion, we show that that cryopreservation and intra-myocardial delivery of 1 billion hESC-CMs generates significant remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a three-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small animal models 7, non-fatal ventricular arrhythmias were observed in hESC-CM engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome. PMID:24776797

Linking the influence and dependence of people on biodiversity across scales.

PubMed

Isbell, Forest; Gonzalez, Andrew; Loreau, Michel; Cowles, Jane; Díaz, Sandra; Hector, Andy; Mace, Georgina M; Wardle, David A; O'Connor, Mary I; Duffy, J Emmett; Turnbull, Lindsay A; Thompson, Patrick L; Larigauderie, Anne

2017-05-31

Biodiversity enhances many of nature's benefits to people, including the regulation of climate and the production of wood in forests, livestock forage in grasslands and fish in aquatic ecosystems. Yet people are now driving the sixth mass extinction event in Earth's history. Human dependence and influence on biodiversity have mainly been studied separately and at contrasting scales of space and time, but new multiscale knowledge is beginning to link these relationships. Biodiversity loss substantially diminishes several ecosystem services by altering ecosystem functioning and stability, especially at the large temporal and spatial scales that are most relevant for policy and conservation.

Detecting natural occlusion boundaries using local cues

PubMed Central

DiMattina, Christopher; Fox, Sean A.; Lewicki, Michael S.

2012-01-01

Occlusion boundaries and junctions provide important cues for inferring three-dimensional scene organization from two-dimensional images. Although several investigators in machine vision have developed algorithms for detecting occlusions and other edges in natural images, relatively few psychophysics or neurophysiology studies have investigated what features are used by the visual system to detect natural occlusions. In this study, we addressed this question using a psychophysical experiment where subjects discriminated image patches containing occlusions from patches containing surfaces. Image patches were drawn from a novel occlusion database containing labeled occlusion boundaries and textured surfaces in a variety of natural scenes. Consistent with related previous work, we found that relatively large image patches were needed to attain reliable performance, suggesting that human subjects integrate complex information over a large spatial region to detect natural occlusions. By defining machine observers using a set of previously studied features measured from natural occlusions and surfaces, we demonstrate that simple features defined at the spatial scale of the image patch are insufficient to account for human performance in the task. To define machine observers using a more biologically plausible multiscale feature set, we trained standard linear and neural network classifiers on the rectified outputs of a Gabor filter bank applied to the image patches. We found that simple linear classifiers could not match human performance, while a neural network classifier combining filter information across location and spatial scale compared well. These results demonstrate the importance of combining a variety of cues defined at multiple spatial scales for detecting natural occlusions. PMID:23255731

Small-scale societies exhibit fundamental variation in the role of intentions in moral judgment

PubMed Central

Barrett, H. Clark; Bolyanatz, Alexander; Crittenden, Alyssa N.; Fessler, Daniel M. T.; Fitzpatrick, Simon; Gurven, Michael; Henrich, Joseph; Kanovsky, Martin; Kushnick, Geoff; Pisor, Anne; Scelza, Brooke A.; Stich, Stephen; von Rueden, Chris; Zhao, Wanying; Laurence, Stephen

2016-01-01

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Although these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment. PMID:27035959

Small-scale societies exhibit fundamental variation in the role of intentions in moral judgment.

PubMed

Barrett, H Clark; Bolyanatz, Alexander; Crittenden, Alyssa N; Fessler, Daniel M T; Fitzpatrick, Simon; Gurven, Michael; Henrich, Joseph; Kanovsky, Martin; Kushnick, Geoff; Pisor, Anne; Scelza, Brooke A; Stich, Stephen; von Rueden, Chris; Zhao, Wanying; Laurence, Stephen

2016-04-26

Intent and mitigating circumstances play a central role in moral and legal assessments in large-scale industrialized societies. Although these features of moral assessment are widely assumed to be universal, to date, they have only been studied in a narrow range of societies. We show that there is substantial cross-cultural variation among eight traditional small-scale societies (ranging from hunter-gatherer to pastoralist to horticulturalist) and two Western societies (one urban, one rural) in the extent to which intent and mitigating circumstances influence moral judgments. Although participants in all societies took such factors into account to some degree, they did so to very different extents, varying in both the types of considerations taken into account and the types of violations to which such considerations were applied. The particular patterns of assessment characteristic of large-scale industrialized societies may thus reflect relatively recently culturally evolved norms rather than inherent features of human moral judgment.

What are the Outstanding Questions in Biosphere-Atmosphere Exchange?

NASA Astrophysics Data System (ADS)

Katul, G.; Finnigan, J.

2002-12-01

Our answer to this question has three parts. At the highest level human population is now so large (and will grow to 10-12 million by 2050 before stabilizing and reversing) and our capacity to influence the biosphere is so profound that we must now treat human, biophysical and geophysical processes as a single interacting system: the Anthroposphere. The Anthroposphere is a complex adaptive system (CAS) in the sense that action of humans individually or in groups (as large as nations) are a response to an environment that includes not just the geosphere and biosphere but the sum of human interactions as well. These actions, in turn, will change this system that provides critical ecosystem services that we are just now realizing are finite and threatened. At present we lack the tools and understanding even to frame key questions about the Anthroposphere although the emerging discipline of Complex System Science is hinting at ways this might be done. At the next level we address the problems posed by cross-scale interactions central to the state and function of the geosphere and biosphere, where processes at the cellular level, (e.g. photosynthesis and respiration), have consequences on the global level and vice-versa through a sequence of non-linear upscale and downscale interactions. Currently there are large gaps in our understanding of this scale cascade that inhibit our ability to parameterize, model and predict phenomena such as the rapid shifts in climate that recent studies of the paleo record have revealed. In short, we need to quantify the risk that our current actions may cause abrupt climate changes that may then feed upon the Anthrosphere. Unless we can reduce the uncertainty with which we describe quantitatively the non-human parts of the Anthroposphere, the injection of models of human interaction, initially tentative, may reduce our predictive ability to unusable levels. Finally we can detail a set of key processes that are themselves critical to geosphere-biosphere functioning but which are poorly understood as yet.

Multi-scale integration and predictability in resting state brain activity

PubMed Central

Kolchinsky, Artemy; van den Heuvel, Martijn P.; Griffa, Alessandra; Hagmann, Patric; Rocha, Luis M.; Sporns, Olaf; Goñi, Joaquín

2014-01-01

The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales. PMID:25104933

Universal scaling laws in metro area election results.

PubMed

Bokányi, Eszter; Szállási, Zoltán; Vattay, Gábor

2018-01-01

We explain the anomaly of election results between large cities and rural areas in terms of urban scaling in the 1948-2016 US elections and in the 2016 EU referendum of the UK. The scaling curves are all universal and depend on a single parameter only, and one of the parties always shows superlinear scaling and drives the process, while the sublinear exponent of the other party is merely the consequence of probability conservation. Based on the recently developed model of urban scaling, we give a microscopic model of voter behavior in which we replace diversity characterizing humans in creative aspects with social diversity and tolerance. The model can also predict new political developments such as the fragmentation of the left and the immigration paradox.

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.

Recent changes of sediment flux to the western Pacific Ocean from major rivers in East and Southeast Asia

NASA Astrophysics Data System (ADS)

Wang, Houjie; Saito, Yoshiki; Zhang, Yong; Bi, Naishuang; Sun, Xiaoxiao; Yang, Zuosheng

2011-09-01

The five largest rivers in East and Southeast Asia (Yellow, Yangtze, Pearl, Red and Mekong) are important contributors of terrigenous sediment to the western Pacific Ocean. Although they have annually delivered ~ 2000 × 10 9 kg of sediment to the ocean since 1000 yr BP, they presently contribute only ~ 600 × 10 9 kg/yr, which is reverting to a level typical of the relatively undisturbed watersheds before the rise in human activities in East and Southeast Asia at 2000 yr BP. During the most recent decades flow regulation by dams and sediment entrapment by reservoirs, as well as human-influenced soil erosion in the river basins, have sharply reduced the sediment delivered from the large river basins to the ocean. We constructed a time series of data on annual water discharges and sediment fluxes from these large rivers to the western Pacific Ocean covering the period 1950-2008. These data indicate that the short-term (interannual scale) variation of sediment flux is dominated by natural climatic oscillations such as the El Niño/La Niña cycle and that anthropogenic causes involving dams and land use control the long-term (decadal scale) decrease in sediment flux to the ocean. In contrast to the relatively slow historical increase in sediment flux during the period 2000-1000 yr BP, the recent sediment flux has been decreased at an accelerating rate over centennial scales. The alterations of these large river systems by both natural and anthropogenic forcing present severe environmental challenges in the coastal ocean, including the sinking of deltas and declines in coastal wetland areas due to the decreasing sediment supply. Our work thus provides a regional perspective on the large river-derived sediment flux to the ocean over millennial and decadal scales, which will be important for understanding and managing the present and future trends of delivery of terrigenous sediment to the ocean in the context of global change.

Microscale depletion of high abundance proteins in human biofluids using IgY14 immunoaffinity resin: analysis of human plasma and cerebrospinal fluid.

PubMed

Hyung, Seok-Won; Piehowski, Paul D; Moore, Ronald J; Orton, Daniel J; Schepmoes, Athena A; Clauss, Therese R; Chu, Rosalie K; Fillmore, Thomas L; Brewer, Heather; Liu, Tao; Zhao, Rui; Smith, Richard D

2014-11-01

Removal of highly abundant proteins in plasma is often carried out using immunoaffinity depletion to extend the dynamic range of measurements to lower abundance species. While commercial depletion columns are available for this purpose, they generally are not applicable to limited sample quantities (<20 μL) due to low yields stemming from losses caused by nonspecific binding to the column matrix and concentration of large eluent volumes. Additionally, the cost of the depletion media can be prohibitive for larger-scale studies. Modern LC-MS instrumentation provides the sensitivity necessary to scale-down depletion methods with minimal sacrifice to proteome coverage, which makes smaller volume depletion columns desirable for maximizing sample recovery when samples are limited, as well as for reducing the expense of large-scale studies. We characterized the performance of a 346 μL column volume microscale depletion system, using four different flow rates to determine the most effective depletion conditions for ∼6-μL injections of human plasma proteins and then evaluated depletion reproducibility at the optimum flow rate condition. Depletion of plasma using a commercial 10-mL depletion column served as the control. Results showed depletion efficiency of the microscale column increased as flow rate decreased, and that our microdepletion was reproducible. In an initial application, a 600-μL sample of human cerebrospinal fluid (CSF) pooled from multiple sclerosis patients was depleted and then analyzed using reversed phase liquid chromatography-mass spectrometry to demonstrate the utility of the system for this important biofluid where sample quantities are more commonly limited.

Lithic Landscapes: Early Human Impact from Stone Tool Production on the Central Saharan Environment

PubMed Central

Foley, Robert A.; Lahr, Marta Mirazón

2015-01-01

Humans have had a major impact on the environment. This has been particularly intense in the last millennium but has been noticeable since the development of food production and the associated higher population densities in the last 10,000 years. The use of fire and over-exploitation of large mammals has also been recognized as having an effect on the world’s ecology, going back perhaps 100,000 years or more. Here we report on an earlier anthropogenic environmental change. The use of stone tools, which dates back over 2.5 million years, and the subsequent evolution of a technologically-dependent lineage required the exploitation of very large quantities of rock. However, measures of the impact of hominin stone exploitation are rare and inherently difficult. The Messak Settafet, a sandstone massif in the Central Sahara (Libya), is littered with Pleistocene stone tools on an unprecedented scale and is, in effect, a man-made landscape. Surveys showed that parts of the Messak Settafet have as much as 75 lithics per square metre and that this fractured debris is a dominant element of the environment. The type of stone tools—Acheulean and Middle Stone Age—indicates that extensive stone tool manufacture occurred over the last half million years or more. The lithic-strewn pavement created by this ancient stone tool manufacture possibly represents the earliest human environmental impact at a landscape scale and is an example of anthropogenic change. The nature of the lithics and inferred age may suggest that hominins other than modern humans were capable of unintentionally modifying their environment. The scale of debris also indicates the significance of stone as a critical resource for hominins and so provides insights into a novel evolutionary ecology. PMID:25760999

Continental synchronicity of human influenza virus epidemics despite climatic variation.

PubMed

Geoghegan, Jemma L; Saavedra, Aldo F; Duchêne, Sebastián; Sullivan, Sheena; Barr, Ian; Holmes, Edward C

2018-01-01

The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain. Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation, the spatiotemporal dynamics of influenza in Australia, a country and continent of approximately similar size and climate complexity but with a far smaller population, are not known. Using a unique combination of large-scale laboratory-confirmed influenza surveillance comprising >450,000 entries and genomic sequence data we determined the local-level spatial diffusion of this important human pathogen nationwide in Australia. We used laboratory-confirmed influenza data to characterize the spread of influenza virus across Australia during 2007-2016. The onset of established epidemics varied across seasons, with highly synchronized epidemics coinciding with the emergence of antigenically distinct viruses, particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely synchronized between the most populous cities, even those separated by distances of >3000 km and those that experience vastly diverse climates. In addition, by analyzing global phylogeographic patterns we show that the synchronized dissemination of influenza across Australian cities involved multiple introductions from the global influenza population, coupled with strong domestic connectivity, rather than through the distinct radial patterns of geographic dispersal that are driven by work-flow transmission as observed in the United States. In addition, by comparing the spatial structure of influenza A and B, we found that these viruses tended to occupy different geographic regions, and peak in different seasons, perhaps indicative of moderate cross-protective immunity or viral interference effects. The highly synchronized outbreaks of influenza virus at a continental-scale revealed here highlight the importance of coordinated public health responses in the event of the emergence of a novel, human-to-human transmissible, virus.

Energy Constraints for Building Large-Scale Systems

DTIC Science & Technology

2016-03-17

power (and energy) constrained in their communication. The human cortex consumes about 20W of power, of which, only a fraction (< 25%) of this power...neurobiological systems use a similar approach in the fact that over 90% of neurons in cortex project locally to nearby neurons (i.e. nearest 1000 pyramidal...are constrained in their communication because of power constraints [1]. The human cortex consumes about 20W of power, of which, only a fraction (25

A Large-scale Benchmark Dataset for Event Recognition in Surveillance Video

DTIC Science & Technology

2011-06-01

orders of magnitude larger than existing datasets such CAVIAR [7]. TRECVID 2008 airport dataset [16] contains 100 hours of video, but, it provides only...entire human figure (e.g., above shoulder), amounting to 500% human to video 2Some statistics are approximate, obtained from the CAVIAR 1st scene and...and diversity in both col- lection sites and viewpoints. In comparison to surveillance datasets such as CAVIAR [7] and TRECVID [16] shown in Fig. 3

Vulnerability of ecosystems to climate change moderated by habitat intactness.

PubMed

Eigenbrod, Felix; Gonzalez, Patrick; Dash, Jadunandan; Steyl, Ilse

2015-01-01

The combined effects of climate change and habitat loss represent a major threat to species and ecosystems around the world. Here, we analyse the vulnerability of ecosystems to climate change based on current levels of habitat intactness and vulnerability to biome shifts, using multiple measures of habitat intactness at two spatial scales. We show that the global extent of refugia depends highly on the definition of habitat intactness and spatial scale of the analysis of intactness. Globally, 28% of terrestrial vegetated area can be considered refugia if all natural vegetated land cover is considered. This, however, drops to 17% if only areas that are at least 50% wilderness at a scale of 48×48 km are considered and to 10% if only areas that are at least 50% wilderness at a scale of 4.8×4.8 km are considered. Our results suggest that, in regions where relatively large, intact wilderness areas remain (e.g. Africa, Australia, boreal regions, South America), conservation of the remaining large-scale refugia is the priority. In human-dominated landscapes, (e.g. most of Europe, much of North America and Southeast Asia), focusing on finer scale refugia is a priority because large-scale wilderness refugia simply no longer exist. Action to conserve such refugia is particularly urgent since only 1 to 2% of global terrestrial vegetated area is classified as refugia and at least 50% covered by the global protected area network. © 2014 John Wiley & Sons Ltd.

Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis

PubMed Central

Sung, Jaeyun; Kim, Seunghyeon; Cabatbat, Josephine Jill T.; Jang, Sungho; Jin, Yong-Su; Jung, Gyoo Yeol; Chia, Nicholas; Kim, Pan-Jun

2017-01-01

A system-level framework of complex microbe–microbe and host–microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ∼570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut. PMID:28585563

Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis.

PubMed

Sung, Jaeyun; Kim, Seunghyeon; Cabatbat, Josephine Jill T; Jang, Sungho; Jin, Yong-Su; Jung, Gyoo Yeol; Chia, Nicholas; Kim, Pan-Jun

2017-06-06

A system-level framework of complex microbe-microbe and host-microbe chemical cross-talk would help elucidate the role of our gut microbiota in health and disease. Here we report a literature-curated interspecies network of the human gut microbiota, called NJS16. This is an extensive data resource composed of ∼570 microbial species and 3 human cell types metabolically interacting through >4,400 small-molecule transport and macromolecule degradation events. Based on the contents of our network, we develop a mathematical approach to elucidate representative microbial and metabolic features of the gut microbial community in a given population, such as a disease cohort. Applying this strategy to microbiome data from type 2 diabetes patients reveals a context-specific infrastructure of the gut microbial ecosystem, core microbial entities with large metabolic influence, and frequently produced metabolic compounds that might indicate relevant community metabolic processes. Our network presents a foundation towards integrative investigations of community-scale microbial activities within the human gut.

Genetic Structures of Copy Number Variants Revealed by Genotyping Single Sperm

PubMed Central

Luo, Minjie; Cui, Xiangfeng; Fredman, David; Brookes, Anthony J.; Azaro, Marco A.; Greenawalt, Danielle M.; Hu, Guohong; Wang, Hui-Yun; Tereshchenko, Irina V.; Lin, Yong; Shentu, Yue; Gao, Richeng; Shen, Li; Li, Honghua

2009-01-01

Background Copy number variants (CNVs) occupy a significant portion of the human genome and may have important roles in meiotic recombination, human genome evolution and gene expression. Many genetic diseases may be underlain by CNVs. However, because of the presence of their multiple copies, variability in copy numbers and the diploidy of the human genome, detailed genetic structure of CNVs cannot be readily studied by available techniques. Methodology/Principal Findings Single sperm samples were used as the primary subjects for the study so that CNV haplotypes in the sperm donors could be studied individually. Forty-eight CNVs characterized in a previous study were analyzed using a microarray-based high-throughput genotyping method after multiplex amplification. Seventeen single nucleotide polymorphisms (SNPs) were also included as controls. Two single-base variants, either allelic or paralogous, could be discriminated for all markers. Microarray data were used to resolve SNP alleles and CNV haplotypes, to quantitatively assess the numbers and compositions of the paralogous segments in each CNV haplotype. Conclusions/Significance This is the first study of the genetic structure of CNVs on a large scale. Resulting information may help understand evolution of the human genome, gain insight into many genetic processes, and discriminate between CNVs and SNPs. The highly sensitive high-throughput experimental system with haploid sperm samples as subjects may be used to facilitate detailed large-scale CNV analysis. PMID:19384415

Mobile element biology – new possibilities with high-throughput sequencing

PubMed Central

Xing, Jinchuan; Witherspoon, David J.; Jorde, Lynn B.

2014-01-01

Mobile elements compose more than half of the human genome, but until recently their large-scale detection was time-consuming and challenging. With the development of new high-throughput sequencing technologies, the complete spectrum of mobile element variation in humans can now be identified and analyzed. Thousands of new mobile element insertions have been discovered, yielding new insights into mobile element biology, evolution, and genomic variation. We review several high-throughput methods, with an emphasis on techniques that specifically target mobile element insertions in humans, and we highlight recent applications of these methods in evolutionary studies and in the analysis of somatic alterations in human cancers. PMID:23312846

Explaining human uniqueness: genome interactions with environment, behaviour and culture.

PubMed

Varki, Ajit; Geschwind, Daniel H; Eichler, Evan E

2008-10-01

What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, 'anthropogeny' (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any 'genes versus environment' dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture - perhaps relaxing allowable thresholds for large-scale genomic diversity.

Explaining human uniqueness: genome interactions with environment, behaviour and culture

PubMed Central

Varki, Ajit; Geschwind, Daniel H.; Eichler, Evan E.

2009-01-01

What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, ‘anthropogeny’ (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any ‘genes versus environment’ dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture — perhaps relaxing allowable thresholds for large-scale genomic diversity. PMID:18802414

Understanding and Managing the Assessment Process

Treesearch

Gene Lessard; Scott Archer; John R. Probst; Sandra Clark

1999-01-01

Taking an ecological approach to management, or ecosystem management, is a developing approach for managing natural resources within the context of large geogaphic scales and over multiple time frames. Recently, the Council on Environmental Quality (CEQ) (IEMTF 1995) defined an ecosystem as "...an interconnected community of living things, including humans, and...

Robust Detection of Examinees with Aberrant Answer Changes

ERIC Educational Resources Information Center

Belov, Dmitry I.

2015-01-01

The statistical analysis of answer changes (ACs) has uncovered multiple testing irregularities on large-scale assessments and is now routinely performed at testing organizations. However, AC data has an uncertainty caused by technological or human factors. Therefore, existing statistics (e.g., number of wrong-to-right ACs) used to detect examinees…

Effects of Landscape Conditions and Management Practices on Lakes in Northeastern USA.

EPA Science Inventory

Lakes continue to face escalating pressures associated with land cover change and growing human populations. The U.S. EPA National Lakes Assessment, which sampled 1,028 lakes during the summer of 2007 using a probabilistic survey, was the first large scale effort to determine the...

Patterns and processes of Mycobacterium bovis evolution revealed by phylogenomic analyses

USDA-ARS?s Scientific Manuscript database

Mycobacterium bovis is an important animal pathogen worldwide that parasitizes wild and domesticated vertebrate livestock as well as humans. A comparison of the five M. bovis complete genomes from UK, South Korea, Brazil and USA revealed four novel large-scale structural variations of at least 2,000...

Large-scale removal of invasive honeysuckle decreases mosquito and avian host abundance

USDA-ARS?s Scientific Manuscript database

Invasive species rank second only to habitat destruction as a threat to native biodiversity. One consequence of biological invasions is altered risk of exposure to infectious diseases in human and animal populations. The distribution and prevalence of mosquito-borne diseases depend on the complex in...

Monitoring Ecological Impacts of Environmental Surface Waters using Cell-based Metabolomics

EPA Science Inventory

Optimized cell-based metabolomics has been used to study the impacts of contaminants in surface waters on human and fish metabolomes. This method has proven to be resource- and time-effective, as well as sustainable for long term and large scale studies. In the current study, cel...

Cellular Factors Shape 3D Genome Landscape

Cancer.gov

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

THE SAN PEDRO RIVER, AN EXAMPLE OF AN INTEGRATED SYSTEM FOR TRANSBORDER ENVIRONMENTAL MANAGEMENT USING GEOSPATIAL DATA AND PROCESS MODELS

EPA Science Inventory

These technologies provide the basis for developing landscape compostion and pattern indicators as sensitive measures of large-scale environmental change and thus may provide an effective and economical method for evaluating watershed conition related to disturbance from human an...

The genetic architecture of coronary artery disease: current knowledge and future opportunities

USDA-ARS?s Scientific Manuscript database

Recent Findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part mod...

Developing a Drosophila Model of Schwannomatosis

DTIC Science & Technology

2012-08-01

the entire Drosophila melanogaster genome and compared...et al., 2009; Hanahan and Weinberg, 2011). Over the last decade, the fruit fly Drosophila melanogaster has become an important model system for cancer...studies. Reduced redundancy in the Drosophila genome compared with that of humans, coupled with the ability to conduct large-scale genetic screens

Astronomy Demonstrations and Models.

ERIC Educational Resources Information Center

Eckroth, Charles A.

Demonstrations in astronomy classes seem to be more necessary than in physics classes for three reasons. First, many of the events are very large scale and impossibly remote from human senses. Secondly, while physics courses use discussions of one- and two-dimensional motion, three-dimensional motion is the normal situation in astronomy; thus,…

AN EVALUATION OF HYDROLOGIC RESPONSE TO 25 YEARS OF LANDSCAPE CHANGE IN A SEMI-ARID WATERSHED

EPA Science Inventory

The assessment of land use and land cover is an extremely important activity for contemporary land management. A large body of current literature suggests that human land-use practices are the most important factor influencing natural resource management at multiple scales. D...

32 CFR 767.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... means any object or assemblage of objects, regardless of age, whether in situ or not, that may carry... structure made up of interdependent and interrelated parts in a definite pattern or organization. Constructed by humans, it is often an engineering project large in scale. An aircraft wreck or shipwreck is a...

Defining biotypes for depression and anxiety based on large-scale circuit dysfunction: A theoretical review of the evidence and future directions for clinical translation

PubMed Central

Williams, Leanne M

2016-01-01

Complex emotional, cognitive and self-reflective functions rely on the activation and connectivity of large-scale neural circuits. These circuits offer a relevant scale of focus for conceptualizing a taxonomy for depression and anxiety based on specific profiles (or biotypes) of neural circuit dysfunction. Here, the theoretical review first outlined the current consensus as to what constitutes the organization of large-scale circuits in the human brain identified using parcellation and meta-analysis. The focus is on neural circuits implicated in resting reflection (“default mode”), detection of “salience”, affective processing (“threat” and “reward”), “attention” and “cognitive control”. Next, the current evidence regarding which type of dysfunctions in these circuits characterize depression and anxiety disorders was reviewed, with an emphasis on published meta-analyses and reviews of circuit dysfunctions that have been identified in at least two well-powered case:control studies. Grounded in the review of these topics, a conceptual framework is proposed for considering neural circuit-defined “biotypes”. In this framework, biotypes are defined by profiles of extent of dysfunction on each large-scale circuit. The clinical implications of a biotype approach for guiding classification and treatment of depression and anxiety is considered. Future research directions will develop the validity and clinical utility of a neural circuit biotype model that spans diagnostic categories and helps to translate neuroscience into clinical practice in the real world. PMID:27653321

The SCALE-UP Project

NASA Astrophysics Data System (ADS)

Beichner, Robert

2015-03-01

The Student Centered Active Learning Environment with Upside-down Pedagogies (SCALE-UP) project was developed nearly 20 years ago as an economical way to provide collaborative, interactive instruction even for large enrollment classes. Nearly all research-based pedagogies have been designed with fairly high faculty-student ratios. The economics of introductory courses at large universities often precludes that situation, so SCALE-UP was created as a way to facilitate highly collaborative active learning with large numbers of students served by only a few faculty and assistants. It enables those students to learn and succeed not only in acquiring content, but also to practice important 21st century skills like problem solving, communication, and teamsmanship. The approach was initially targeted at undergraduate science and engineering students taking introductory physics courses in large enrollment sections. It has since expanded to multiple content areas, including chemistry, math, engineering, biology, business, nursing, and even the humanities. Class sizes range from 24 to over 600. Data collected from multiple sites around the world indicates highly successful implementation at more than 250 institutions. NSF support was critical for initial development and dissemination efforts. Generously supported by NSF (9752313, 9981107) and FIPSE (P116B971905, P116B000659).

Diversity of herbaceous plants and bacterial communities regulates soil resistome across forest biomes.

PubMed

Hu, Hang-Wei; Wang, Jun-Tao; Singh, Brajesh K; Liu, Yu-Rong; Chen, Yong-Liang; Zhang, Yu-Jing; He, Ji-Zheng

2018-04-24

Antibiotic resistance is ancient and prevalent in natural ecosystems and evolved long before the utilization of synthetic antibiotics started, but factors influencing the large-scale distribution patterns of natural antibiotic resistance genes (ARGs) remain largely unknown. Here, a large-scale investigation over 4000 km was performed to profile soil ARGs, plant communities and bacterial communities from 300 quadrats across five forest biomes with minimal human impact. We detected diverse and abundant ARGs in forests, including over 160 genes conferring resistance to eight major categories of antibiotics. The diversity of ARGs was strongly and positively correlated with the diversity of bacteria, herbaceous plants and mobile genetic elements (MGEs). The ARG composition was strongly correlated with the taxonomic structure of bacteria and herbs. Consistent with this strong correlation, structural equation modelling demonstrated that the positive effects of bacterial and herb communities on ARG patterns were maintained even when simultaneously accounting for multiple drivers (climate, spatial predictors and edaphic factors). These findings suggest a paradigm that the interactions between aboveground and belowground communities shape the large-scale distribution of soil resistomes, providing new knowledge for tackling the emerging environmental antibiotic resistance. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Scale-dependent climatic drivers of human epidemics in ancient China.

PubMed

Tian, Huidong; Yan, Chuan; Xu, Lei; Büntgen, Ulf; Stenseth, Nils C; Zhang, Zhibin

2017-12-05

A wide range of climate change-induced effects have been implicated in the prevalence of infectious diseases. Disentangling causes and consequences, however, remains particularly challenging at historical time scales, for which the quality and quantity of most of the available natural proxy archives and written documentary sources often decline. Here, we reconstruct the spatiotemporal occurrence patterns of human epidemics for large parts of China and most of the last two millennia. Cold and dry climate conditions indirectly increased the prevalence of epidemics through the influences of locusts and famines. Our results further reveal that low-frequency, long-term temperature trends mainly contributed to negative associations with epidemics, while positive associations of epidemics with droughts, floods, locusts, and famines mainly coincided with both higher and lower frequency temperature variations. Nevertheless, unstable relationships between human epidemics and temperature changes were observed on relatively smaller time scales. Our study suggests that an intertwined, direct, and indirect array of biological, ecological, and societal responses to different aspects of past climatic changes strongly depended on the frequency domain and study period chosen.

Serial grouping of 2D-image regions with object-based attention in humans

PubMed Central

Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R

2016-01-01

After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas. DOI: http://dx.doi.org/10.7554/eLife.14320.001 PMID:27291188

BioPlex Display: An Interactive Suite for Large-Scale AP-MS Protein-Protein Interaction Data.

PubMed

Schweppe, Devin K; Huttlin, Edward L; Harper, J Wade; Gygi, Steven P

2018-01-05

The development of large-scale data sets requires a new means to display and disseminate research studies to large audiences. Knowledge of protein-protein interaction (PPI) networks has become a principle interest of many groups within the field of proteomics. At the confluence of technologies, such as cross-linking mass spectrometry, yeast two-hybrid, protein cofractionation, and affinity purification mass spectrometry (AP-MS), detection of PPIs can uncover novel biological inferences at a high-throughput. Thus new platforms to provide community access to large data sets are necessary. To this end, we have developed a web application that enables exploration and dissemination of the growing BioPlex interaction network. BioPlex is a large-scale interactome data set based on AP-MS of baits from the human ORFeome. The latest BioPlex data set release (BioPlex 2.0) contains 56 553 interactions from 5891 AP-MS experiments. To improve community access to this vast compendium of interactions, we developed BioPlex Display, which integrates individual protein querying, access to empirical data, and on-the-fly annotation of networks within an easy-to-use and mobile web application. BioPlex Display enables rapid acquisition of data from BioPlex and development of hypotheses based on protein interactions.

A comparison of single- and multi-site calibration and validation: a case study of SWAT in the Miyun Reservoir watershed, China

NASA Astrophysics Data System (ADS)

Bai, Jianwen; Shen, Zhenyao; Yan, Tiezhu

2017-09-01

An essential task in evaluating global water resource and pollution problems is to obtain the optimum set of parameters in hydrological models through calibration and validation. For a large-scale watershed, single-site calibration and validation may ignore spatial heterogeneity and may not meet the needs of the entire watershed. The goal of this study is to apply a multi-site calibration and validation of the Soil andWater Assessment Tool (SWAT), using the observed flow data at three monitoring sites within the Baihe watershed of the Miyun Reservoir watershed, China. Our results indicate that the multi-site calibration parameter values are more reasonable than those obtained from single-site calibrations. These results are mainly due to significant differences in the topographic factors over the large-scale area, human activities and climate variability. The multi-site method involves the division of the large watershed into smaller watersheds, and applying the calibrated parameters of the multi-site calibration to the entire watershed. It was anticipated that this case study could provide experience of multi-site calibration in a large-scale basin, and provide a good foundation for the simulation of other pollutants in followup work in the Miyun Reservoir watershed and other similar large areas.

Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

NASA Astrophysics Data System (ADS)

Bershteyn, Marina; Hayashi, Yohei; Desachy, Guillaume; Hsiao, Edward C.; Sami, Salma; Tsang, Kathryn M.; Weiss, Lauren A.; Kriegstein, Arnold R.; Yamanaka, Shinya; Wynshaw-Boris, Anthony

2014-03-01

Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of `chromosome therapy' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.

Users matter : multi-agent systems model of high performance computing cluster users.

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

North, M. J.; Hood, C. S.; Decision and Information Sciences

2005-01-01

High performance computing clusters have been a critical resource for computational science for over a decade and have more recently become integral to large-scale industrial analysis. Despite their well-specified components, the aggregate behavior of clusters is poorly understood. The difficulties arise from complicated interactions between cluster components during operation. These interactions have been studied by many researchers, some of whom have identified the need for holistic multi-scale modeling that simultaneously includes network level, operating system level, process level, and user level behaviors. Each of these levels presents its own modeling challenges, but the user level is the most complex duemore » to the adaptability of human beings. In this vein, there are several major user modeling goals, namely descriptive modeling, predictive modeling and automated weakness discovery. This study shows how multi-agent techniques were used to simulate a large-scale computing cluster at each of these levels.« less

Entangled communities and spatial synchronization lead to criticality in urban traffic

PubMed Central

Petri, Giovanni; Expert, Paul; Jensen, Henrik J.; Polak, John W.

2013-01-01

Understanding the relation between patterns of human mobility and the scaling of dynamical features of urban environments is a great importance for today's society. Although recent advancements have shed light on the characteristics of individual mobility, the role and importance of emerging human collective phenomena across time and space are still unclear. In this Article, we show by using two independent data-analysis techniques that the traffic in London is a combination of intertwined clusters, spanning the whole city and effectively behaving as a single correlated unit. This is due to algebraically decaying spatio-temporal correlations, that are akin to those shown by systems near a critical point. We describe these correlations in terms of Taylor's law for fluctuations and interpret them as the emerging result of an underlying spatial synchronisation. Finally, our results provide the first evidence for a large-scale spatial human system reaching a self-organized critical state. PMID:23660823

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation.

PubMed

Keates, Tracy; Cooper, Christopher D O; Savitsky, Pavel; Allerston, Charles K; Phillips, Claire; Hammarström, Martin; Daga, Neha; Berridge, Georgina; Mahajan, Pravin; Burgess-Brown, Nicola A; Müller, Susanne; Gräslund, Susanne; Gileadi, Opher

2012-06-15

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome. Copyright © 2011 Elsevier B.V. All rights reserved.

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

PubMed Central

Keates, Tracy; Cooper, Christopher D.O.; Savitsky, Pavel; Allerston, Charles K.; Phillips, Claire; Hammarström, Martin; Daga, Neha; Berridge, Georgina; Mahajan, Pravin; Burgess-Brown, Nicola A.; Müller, Susanne; Gräslund, Susanne; Gileadi, Opher

2012-01-01

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome. PMID:22027370

Enhanced Stem Cell Differentiation and Immunopurification of Genome Engineered Human Retinal Ganglion Cells.

PubMed

Sluch, Valentin M; Chamling, Xitiz; Liu, Melissa M; Berlinicke, Cynthia A; Cheng, Jie; Mitchell, Katherine L; Welsbie, Derek S; Zack, Donald J

2017-11-01

Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1.2, are expressed under the control of the retinal ganglion cell (RGC)-enriched gene BRN3B. Using these reporter cell lines, we greatly improved adherent stem cell differentiation to the RGC lineage by optimizing a novel combination of small molecules and established an anti-THY1.2-based protocol that allows for large-scale RGC immunopurification. RNA-sequencing confirmed the similarity of the stem cell-derived RGCs to their endogenous human counterparts. Additionally, we developed an in vitro axonal injury model suitable for studying signaling pathways and mechanisms of human RGC cell death and for high-throughput screening for neuroprotective compounds. Using this system in combination with RNAi-based knockdown, we show that knockdown of dual leucine kinase (DLK) promotes survival of human RGCs, expanding to the human system prior reports that DLK inhibition is neuroprotective for murine RGCs. These improvements will facilitate the development and use of large-scale experimental paradigms that require numbers of pure RGCs that were not previously obtainable. Stem Cells Translational Medicine 2017;6:1972-1986. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Escape behaviour of birds in urban parks and cemeteries across Europe: Evidence of behavioural adaptation to human activity.

PubMed

Morelli, Federico; Mikula, Peter; Benedetti, Yanina; Bussière, Raphaël; Jerzak, Leszek; Tryjanowski, Piotr

2018-08-01

Urban environments are very heterogeneous, and birds living in the proximity of humans have to adapt to local conditions, e.g. by changing their behavioural response to potential predators. In this study, we tested whether the escape distance of birds (measured as flight initiation distance; FID) differed between parks and cemeteries, areas characterized by different microhabitat conditions and human conduct, that are determinants of animal behaviour at large spatial scales. While escape behaviour of park populations of birds was often examined, cemetery populations have not been studied to the same extent and a large-scale comparison is still missing. Overall, we collected 2139 FID estimates for 44 bird species recorded in 79 parks and 90 cemeteries in four European countries: Czech Republic, France, Italy and Poland. Mixed model procedure was applied to study escape behaviour in relation to type of area (park or cemetery), environmental characteristics (area size, coverage by trees, shrubs, grass, chapels, tombstones, flowerbeds, number of street lamps) and human activity (human density, pedestrians speed and ratio of men/women). Birds allowed people closer in cemeteries than in parks in all countries. This pattern was persistent even when focusing on intraspecific differences in FID between populations of the most common bird species. Escape distance of birds was negatively correlated with the size of parks/cemeteries, while positively associated with tombstone coverage and human density in both types of habitat. Our findings highlight the ability of birds to adapt their behaviour to different types of urban areas, based on local environmental conditions, including the character of human-bird interactions. Our results also suggest that this behavioural pattern may be widespread across urban landscapes. Copyright © 2018 Elsevier B.V. All rights reserved.

10th Anniversary Review: a changing climate for coral reefs.

PubMed

Lough, Janice M

2008-01-01

Tropical coral reefs are charismatic ecosystems that house a significant proportion of the world's marine biodiversity. Their valuable goods and services are fundamental to the livelihood of large coastal populations in the tropics. The health of many of the world's coral reefs, and the goods and services they provide, have already been severely compromised, largely due to over-exploitation by a range of human activities. These local-scale impacts, with the appropriate government instruments, support and management actions, can potentially be controlled and even ameliorated. Unfortunately, other human actions (largely in countries outside of the tropics), by changing global climate, have added additional global-scale threats to the continued survival of present-day coral reefs. Moderate warming of the tropical oceans has already resulted in an increase in mass coral bleaching events, affecting nearly all of the world's coral reef regions. The frequency of these events will only increase as global temperatures continue to rise. Weakening of coral reef structures will be a more insidious effect of changing ocean chemistry, as the oceans absorb part of the excess atmospheric carbon dioxide. More intense tropical cyclones, changed atmospheric and ocean circulation patterns will all affect coral reef ecosystems and the many associated plants and animals. Coral reefs will not disappear but their appearance, structure and community make-up will radically change. Drastic greenhouse gas mitigation strategies are necessary to prevent the full consequences of human activities causing such alterations to coral reef ecosystems.

Liquidation sales: Land speculation and landscape change

NASA Astrophysics Data System (ADS)

Lazarus, E.

2012-12-01

Large-scale land-use transitions can occur with astonishing speed, and landscape stability can change with equal suddenness: for example, the catastrophic dustbowl that paralyzed the Midwestern US in the early 1930s came barely 40 years after the derby for homestead land in Oklahoma in 1889. Some human-landscape systems, like the large prehistoric settlements in the Brazilian Amazon, persisted for centuries without environmental collapse. Others quickly exhausted all of the environmental resources available, as occurred with phosphate mining on the Pacific Island of Nauru. Although abrupt shifts from resource plenty to resource scarcity are theoretically interesting for their complexity, the very real consequences of modern social and environmental boom-bust dynamics can catalyze humanitarian crises. Drawing on historical examples and investigative reporting of current events, I explore the hypothesis that land speculation drives rapid transitions in physical landscapes at large spatial scales. "Land grabs" is one of four core environmental justice and equality issues Oxfam International is targeting in its GROW campaign, citing evidence that foreign investors are buying up vast tracts of land in developing countries, and as a consequence exacerbating food scarcity and marginalization of poor families. Al Jazeera has reported extensively on land-rights disputes in Honduras and investment deals involving foreign ownership of large areas of agricultural land in New Zealand, India, Africa, and South America. Overlapping coverage has also appeared in the New York Times, the Washington Post, the BBC News, the Guardian, and other outlets. Although land itself is only one kind of natural resource, land rights typically determine access to other natural resources (e.g. water, timber, minerals, fossil fuels). Consideration of land speculation therefore includes speculative bubbles in natural-resource markets more broadly. There are categorical commonalities in agricultural change and deforestation around the world. Although the details differ at local scales, even disparate cases of land use and landscape changes may express similar patterns and structures. Records of sediment flux in salt marshes and fluvial deposits indicate rates of past landscape responses to human activities; the 1930s dustbowl event left a sedimentary signature in western North American lakes. Petrochemicals and fertilizers from agricultural runnoff are causing hypoxic dead zones in coastal waters to expand. In the Brazilian Amazon, regional-scale changes in weather and climate have been linked to deforestation, and deforestation has been linked to patterns of boom-bust development. But even when rampant land acquisition for agriculture or housing has been identified as problematic, the attendant environmental consequences are not necessarily obvious. The nonlinear attenuation of cause and effect is a function of the hierarchy of scales that typify these complex, human-landscape systems: the emergence of long-term, large-scale environmental dynamics lag behind the short-term, localized dynamics of a resource bubble. Insight into how these coupled systems behave may reveal the scales at which government, institutional, or self-organized social intervention may be most effective, and presents an opportunity to integrate evolving spheres of research from the behavioural sciences and Earth-surface processes.

Effects of land use pattern on soil water in revegetation watersheds in semi-arid Chinese Loess Plateau

NASA Astrophysics Data System (ADS)

Yang, Lei; Chen, Liding; Wei, Wei

2017-04-01

Soil water stored below rainfall infiltration depth is a reliable water resource for plant growth in arid and semi-arid regions. For decreasing serious soil erosion, large-scale human-introduced vegetation restoration was initiated in Chinese Loess Plateau in late 1990s. However, these activities may result in excessive water consumption and soil water deficit if no appropriate scientific guidance were offered. This in turn impacts the regional ecological restoration and sustainable management of water resources. In this study, soil water content data in depth of 0-5 m was obtained by long-term field observation and geostatistical method in 6 small watersheds covered with different land use pattern. Profile characteristics and spatial-temporal patterns of soil water were compared between different land use types, hillslopes, and watersheds. The results showed that: (1) Introduced vegetation consumed excessive amount of water when compared with native grassland and farmland, and induced temporally stable soil desiccation in depth of 0-5 m. The introduced vegetation decreased soil water content to levels lower than the reference value representing no human impact in all soil layers. (2) The analysis of differences in soil water at hillslope and watershed scales indicated that land use determined the spatial and temporal variability of soil water. Soil water at watershed scale increased with the increasing area of farmland, and decreased with increasing percentage of introduced vegetation. Land use structure determined the soil water condition and land use pattern determined the spatial-temporal variability of soil water at watershed scale. (3) Large-scale revegetation with introduced vegetation diminished the spatial heterogeneity of soil water at different scales. Land use pattern adjustment could be used to improve the water resources management and maintain the sustainability of vegetation restoration.

Bioremediation at a global scale: from the test tube to planet Earth.

PubMed

de Lorenzo, Víctor; Marlière, Philippe; Solé, Ricard

2016-09-01

Planet Earth's biosphere has evolved over billions of years as a balanced bio-geological system ultimately sustained by sunpower and the large-scale cycling of elements largely run by the global environmental microbiome. Humans have been part of this picture for much of their existence. But the industrial revolution started in the XIX century and the subsequent advances in medicine, chemistry, agriculture and communications have impacted such balances to an unprecedented degree - and the problem has nothing but exacerbated in the last 20 years. Human overpopulation, industrial growth along with unsustainable use of natural resources have driven many sites and perhaps the planetary ecosystem as a whole, beyond recovery by spontaneous natural means, even if the immediate causes could be stopped. The most conspicuous indications of such a state of affairs include the massive change in land use, the accelerated increase in the levels of greenhouse gases, the frequent natural disasters associated to climate change and the growing non-recyclable waste (e.g. plastics and recalcitrant chemicals) that we release to the Environment. While the whole planet is afflicted at a global scale by chemical pollution and anthropogenic emissions, the ongoing development of systems and synthetic biology, metagenomics, modern chemistry and some key concepts from ecological theory allow us to tackle this phenomenal challenge and propose large-scale interventions aimed at reversing and even improving the situation. This involves (i) identification of key reactions or processes that need to be re-established (or altogether created) for ecosystem reinstallation, (ii) implementation of such reactions in natural or designer hosts able to self-replicate and deliver the corresponding activities when/where needed in a fashion guided by sound ecological modelling, (iii) dispersal of niche-creating agents at a global scale and (iv) containment, monitoring and risk assessment of the whole process. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Punctuated Evolution of Influenza Virus Neuraminidase (A/H1N1) under Opposing Migration and Vaccination Pressures

PubMed Central

Phillips, J. C.

2014-01-01

Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945–2011) Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC). Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains. PMID:25143953

Linking rapid erosion of the Mekong River delta to human activities.

PubMed

Anthony, Edward J; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

2015-10-08

As international concern for the survival of deltas grows, the Mekong River delta, the world's third largest delta, densely populated, considered as Southeast Asia's most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river's discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams.

Linking rapid erosion of the Mekong River delta to human activities

PubMed Central

Anthony, Edward J.; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

2015-01-01

As international concern for the survival of deltas grows, the Mekong River delta, the world’s third largest delta, densely populated, considered as Southeast Asia’s most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river’s discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams. PMID:26446752

Living laboratory: whole-genome sequencing as a learning healthcare enterprise.

PubMed

Angrist, M; Jamal, L

2015-04-01

With the proliferation of affordable large-scale human genomic data come profound and vexing questions about management of such data and their clinical uncertainty. These issues challenge the view that genomic research on human beings can (or should) be fully segregated from clinical genomics, either conceptually or practically. Here, we argue that the sharp distinction between clinical care and research is especially problematic in the context of large-scale genomic sequencing of people with suspected genetic conditions. Core goals of both enterprises (e.g. understanding genotype-phenotype relationships; generating an evidence base for genomic medicine) are more likely to be realized at a population scale if both those ordering and those undergoing sequencing for diagnostic reasons are routinely and longitudinally studied. Rather than relying on expensive and lengthy randomized clinical trials and meta-analyses, we propose leveraging nascent clinical-research hybrid frameworks into a broader, more permanent instantiation of exploratory medical sequencing. Such an investment could enlighten stakeholders about the real-life challenges posed by whole-genome sequencing, such as establishing the clinical actionability of genetic variants, returning 'off-target' results to families, developing effective service delivery models and monitoring long-term outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Towards Development of Clustering Applications for Large-Scale Comparative Genotyping and Kinship Analysis Using Y-Short Tandem Repeats.

PubMed

Seman, Ali; Sapawi, Azizian Mohd; Salleh, Mohd Zaki

2015-06-01

Y-chromosome short tandem repeats (Y-STRs) are genetic markers with practical applications in human identification. However, where mass identification is required (e.g., in the aftermath of disasters with significant fatalities), the efficiency of the process could be improved with new statistical approaches. Clustering applications are relatively new tools for large-scale comparative genotyping, and the k-Approximate Modal Haplotype (k-AMH), an efficient algorithm for clustering large-scale Y-STR data, represents a promising method for developing these tools. In this study we improved the k-AMH and produced three new algorithms: the Nk-AMH I (including a new initial cluster center selection), the Nk-AMH II (including a new dominant weighting value), and the Nk-AMH III (combining I and II). The Nk-AMH III was the superior algorithm, with mean clustering accuracy that increased in four out of six datasets and remained at 100% in the other two. Additionally, the Nk-AMH III achieved a 2% higher overall mean clustering accuracy score than the k-AMH, as well as optimal accuracy for all datasets (0.84-1.00). With inclusion of the two new methods, the Nk-AMH III produced an optimal solution for clustering Y-STR data; thus, the algorithm has potential for further development towards fully automatic clustering of any large-scale genotypic data.

Geomorphic change in Dingzi Bay, East China since the 1950s: impacts of human activity and fluvial input

NASA Astrophysics Data System (ADS)

Tian, Qing; Wang, Qing; Liu, Yalong

2017-06-01

This study examines the geomorphic evolution of Dingzi Bay, East China in response to human activity and variations in fluvial input since the 1950s. The analysis is based on data from multiple mathematical methods, along with information obtained from Remote Sensing, Geographic Information System and Global Position System technology. The results show that the annual runoff and sediment load discharged into Dingzi Bay display significant decreasing trends overall, and marked downward steps were observed in 1966 and 1980. Around 60%-80% of the decline is attributed to decreasing precipitation in the Wulong River Basin. The landform types in Dingzi Bay have changed significantly since the 1950s, especially over the period between 1981 and 1995. Large areas of tidal flats, swamp, salt fields, and paddy fields have been reclaimed, and aquaculture ponds have been constructed. Consequently, the patterns of erosion and deposition in the bay have changed substantially. Despite a reduction in sediment input of 65.68% after 1966, low rates of sediment deposition continued in the bay. However, deposition rates changed significantly after 1981 owing to large-scale development in the bay, with a net depositional area approximately 10 times larger than that during 1961-1981. This geomorphic evolution stabilized following the termination of large-scale human activity in the bay after 1995. Overall, Dingzi Bay has shown a tendency towards silting-up during 1952-2010, with the bay head migrating seaward, the number of channels in the tidal creek system decreasing, and the tidal inlet becoming narrower and shorter. In conclusion, largescale development and human activity in Dingzi Bay have controlled the geomorphic evolution of the bay since the 1950s.

Mammal responses to the human footprint vary across species and stressors.

PubMed

Toews, Mary; Juanes, Francis; Burton, A Cole

2018-07-01

A rapidly expanding human footprint - comprised of anthropogenic land-use change and infrastructure - is profoundly affecting wildlife distributions worldwide. Cumulative effects management (CEM) is a regional approach that seeks to manage combined effects of the human footprint on biodiversity across large spatial scales. Challenges to implementing this approach include a lack of ecological data at large spatial scales, the high cost of monitoring multiple indicators, and the need to manage multiple footprints across industries. To inform development of effective CEM, we used large mammals as indicators to address the following questions: a) do species respond more strongly to individual footprint features or to cumulative effects (combined area of all footprint types, measured as total footprint), b) which features elicit the strongest responses across species, and c) are the direction of responses to footprint consistent? We used data from 12 years of snowtrack surveys (2001-2013) in the boreal forest of Alberta, coupled with regional footprint and landcover data, to develop generalized linear mixed-effects models relating the relative abundance of five boreal mammals [gray wolf (Canis lupus), Canada lynx (Lynx canadensis), coyote (Canis latrans), white-tailed deer (Odocoileus virginianus) and moose (Alces alces)] to individual and cumulative effects of the human footprint. We found that across species the strongest responses were to agriculture, roads, and young cutblocks (<10 years), suggesting these as potential priority stressors to address within CEM. Most species also responded to total footprint, indicating that in the absence of detailed information on individual features, this coarse measure can serve as an index of cumulative effects. There was high variability in direction and magnitude of responses across species, indicating that community-level responses are likely and should be considered within CEM planning. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extreme-Scale De Novo Genome Assembly

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

Georganas, Evangelos; Hofmeyr, Steven; Egan, Rob

De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and themore » large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.« less

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.

Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease.

PubMed

Winfree, Seth; Dagher, Pierre C; Dunn, Kenneth W; Eadon, Michael T; Ferkowicz, Michael; Barwinska, Daria; Kelly, Katherine J; Sutton, Timothy A; El-Achkar, Tarek M

2018-06-05

Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease. © 2018 S. Karger AG, Basel.

Sign: large-scale gene network estimation environment for high performance computing.

PubMed

Tamada, Yoshinori; Shimamura, Teppei; Yamaguchi, Rui; Imoto, Seiya; Nagasaki, Masao; Miyano, Satoru

2011-01-01

Our research group is currently developing software for estimating large-scale gene networks from gene expression data. The software, called SiGN, is specifically designed for the Japanese flagship supercomputer "K computer" which is planned to achieve 10 petaflops in 2012, and other high performance computing environments including Human Genome Center (HGC) supercomputer system. SiGN is a collection of gene network estimation software with three different sub-programs: SiGN-BN, SiGN-SSM and SiGN-L1. In these three programs, five different models are available: static and dynamic nonparametric Bayesian networks, state space models, graphical Gaussian models, and vector autoregressive models. All these models require a huge amount of computational resources for estimating large-scale gene networks and therefore are designed to be able to exploit the speed of 10 petaflops. The software will be available freely for "K computer" and HGC supercomputer system users. The estimated networks can be viewed and analyzed by Cell Illustrator Online and SBiP (Systems Biology integrative Pipeline). The software project web site is available at http://sign.hgc.jp/ .

Natural disasters and population mobility in Bangladesh.

PubMed

Gray, Clark L; Mueller, Valerie

2012-04-17

The consequences of environmental change for human migration have gained increasing attention in the context of climate change and recent large-scale natural disasters, but as yet relatively few large-scale and quantitative studies have addressed this issue. We investigate the consequences of climate-related natural disasters for long-term population mobility in rural Bangladesh, a region particularly vulnerable to environmental change, using longitudinal survey data from 1,700 households spanning a 15-y period. Multivariate event history models are used to estimate the effects of flooding and crop failures on local population mobility and long-distance migration while controlling for a large set of potential confounders at various scales. The results indicate that flooding has modest effects on mobility that are most visible at moderate intensities and for women and the poor. However, crop failures unrelated to flooding have strong effects on mobility in which households that are not directly affected but live in severely affected areas are the most likely to move. These results point toward an alternate paradigm of disaster-induced mobility that recognizes the significant barriers to migration for vulnerable households as well their substantial local adaptive capacity.

Was monogamy a key step on the hominin road? Reevaluating the monogamy hypothesis in the evolution of cooperative breeding.

PubMed

Kramer, Karen L; Russell, Andrew F

2015-01-01

Because human mothers routinely rely on others to help raise their young, humans have been characterized as cooperative breeders.(1-9) Several large-scale phylogenetic analyses have presented compelling evidence that monogamy preceded the evolution of cooperative breeding in a wide variety of nonhuman animals.(10-14) These studies have suggested that monogamy provides a general rule (the monogamy hypothesis) for explaining evolutionary transitions to cooperative breeding.(15) Given the prevalence of cooperative breeding in contemporary human societies, we evaluate whether this suggests a monogamous hominin past. © 2015 Wiley Periodicals, Inc.

Managing conflict between large carnivores and livestock.

PubMed

van Eeden, Lily M; Crowther, Mathew S; Dickman, Chris R; Macdonald, David W; Ripple, William J; Ritchie, Euan G; Newsome, Thomas M

2018-02-01

Large carnivores are persecuted globally because they threaten human industries and livelihoods. How this conflict is managed has consequences for the conservation of large carnivores and biodiversity more broadly. Mitigating human-predator conflict should be evidence-based and accommodate people's values while protecting carnivores. Despite much research into human and large-carnivore coexistence strategies, there have been few attempts to document the success of conflict-mitigation strategies on a global scale. We conducted a meta-analysis of global research on conflict mitigation related to large carnivores and humans. We focused on conflicts that arise from the threat large carnivores pose to livestock. We first used structured and unstructured searching to identify replicated studies that used before-after or control-impact design to measure change in livestock loss as a result of implementing a management intervention. We then extracted relevant data from these studies to calculate an overall effect size for each intervention type. Research effort and focus varied among continents and aligned with the histories and cultures that shaped livestock production and attitudes toward carnivores. Livestock guardian animals most effectively reduced livestock losses. Lethal control was the second most effective control, although its success varied the most, and guardian animals and lethal control did not differ significantly. Financial incentives have promoted tolerance of large carnivores in some settings and reduced retaliatory killings. We suggest coexistence strategies be location-specific, incorporate cultural values and environmental conditions, and be designed such that return on financial investment can be evaluated. Improved monitoring of mitigation measures is urgently required to promote effective evidence-based policy. © 2017 Society for Conservation Biology.

Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.

PubMed

Guadalupe, Tulio; Zwiers, Marcel P; Teumer, Alexander; Wittfeld, Katharina; Vasquez, Alejandro Arias; Hoogman, Martine; Hagoort, Peter; Fernandez, Guillen; Buitelaar, Jan; Hegenscheid, Katrin; Völzke, Henry; Franke, Barbara; Fisher, Simon E; Grabe, Hans J; Francks, Clyde

2014-07-01

Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries. Copyright © 2013 Wiley Periodicals, Inc.

An Allometric Analysis of Sex and Sex Chromosome Dosage Effects on Subcortical Anatomy in Humans

PubMed Central

Clasen, Liv; Giedd, Jay N.; Blumenthal, Jonathan; Lerch, Jason P.; Chakravarty, M. Mallar; Raznahan, Armin

2016-01-01

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings. SIGNIFICANCE STATEMENT Sex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover, regional brain allometry (nonlinear scaling) poses largely unaddressed methodological and theoretical challenges for such research. We build the first set of allometric norms for global and regional subcortical anatomy, and use these to dissect out the complex, distributed and topologically organized patterns of areal contraction and expansion, which characterize sex and SCD effects on subcortical anatomy. Our data inform basic research into the patterning of neuroanatomical variation, and the clinical neuroscience of sex-chromosome aneuploidy. PMID:26911691

Small Traditional Human Communities Sustain Genomic Diversity over Microgeographic Scales despite Linguistic Isolation

PubMed Central

Cox, Murray P.; Hudjashov, Georgi; Sim, Andre; Savina, Olga; Karafet, Tatiana M.; Sudoyo, Herawati; Lansing, J. Stephen

2016-01-01

At least since the Neolithic, humans have largely lived in networks of small, traditional communities. Often socially isolated, these groups evolved distinct languages and cultures over microgeographic scales of just tens of kilometers. Population genetic theory tells us that genetic drift should act quickly in such isolated groups, thus raising the question: do networks of small human communities maintain levels of genetic diversity over microgeographic scales? This question can no longer be asked in most parts of the world, which have been heavily impacted by historical events that make traditional society structures the exception. However, such studies remain possible in parts of Island Southeast Asia and Oceania, where traditional ways of life are still practiced. We captured genome-wide genetic data, together with linguistic records, for a case–study system—eight villages distributed across Sumba, a small, remote island in eastern Indonesia. More than 4,000 years after these communities were established during the Neolithic period, most speak different languages and can be distinguished genetically. Yet their nuclear diversity is not reduced, instead being comparable to other, even much larger, regional groups. Modeling reveals a separation of time scales: while languages and culture can evolve quickly, creating social barriers, sporadic migration averaged over many generations is sufficient to keep villages linked genetically. This loosely-connected network structure, once the global norm and still extant on Sumba today, provides a living proxy to explore fine-scale genome dynamics in the sort of small traditional communities within which the most recent episodes of human evolution occurred. PMID:27274003

The genomic organization of a human creatine transporter (CRTR) gene located in Xq28

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

Sandoval, N.; Bauer, D.; Brenner, V.

1996-07-15

During the course of a large-scale sequencing project in Xq28, a human creatine transporter (CRTR) gene was discovered. The gene is located approximately 36 kb centromeric to ALD. The gene contains 13 exons and spans about 8.5 kb of genomic DNA. Since the creatine transporter has a prominent function in muscular physiology, it is a candidate gene for Barth syndrome and infantile cardiomyopathy mapped to Xq28. 19 refs., 1 fig., 1 tab.

Recent advances in research on climate and human conflict

NASA Astrophysics Data System (ADS)

Hsiang, S. M.

2014-12-01

A rapidly growing body of empirical, quantitative research examines whether rates of human conflict can be systematically altered by climatic changes. We discuss recent advances in this field, including Bayesian meta-analyses of the effect of temperature and rainfall on current and future large-scale conflicts, the impact of climate variables on gang violence and suicides in Mexico, and probabilistic projections of personal violence and property crime in the United States under RCP scenarios. Criticisms of this research field will also be explained and addressed.

Making Sense in the Edge of Chaos: A Framework for Effective Initial Response Efforts to Large-Scale Incidents

DTIC Science & Technology

2010-09-01

working with equally experienced partners who can, cumulatively, help each other make sense of chaotic situations. “Human brains collect, organize...but a process reinforced by years of Fire Department training. No matter what we do, even an optimally functioning human brain will prepare for...trick or reorganize the brain of those who will be first responding incident commanders to an edge-of-chaos event into creatively making sense of

Emerging factors associated with the decline of a gray fox population and multi-scale land cover associations of mesopredators in the Chicago metropolitan area.

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

Willingham, Alison N.; /Ohio State U.

Statewide surveys of furbearers in Illinois indicate gray (Urocyon cinereoargenteus) and red (Vulpes vulpes) foxes have experienced substantial declines in relative abundance, whereas other species such as raccoons (Procyon lotor) and coyotes (Canis latrans) have exhibited dramatic increases during the same time period. The cause of the declines of gray and red foxes has not been identified, and the current status of gray foxes remains uncertain. Therefore, I conducted a large-scale predator survey and tracked radiocollared gray foxes from 2004 to 2007 in order to determine the distribution, survival, cause-specific mortality sources and land cover associations of gray foxes inmore » an urbanized region of northeastern Illinois, and examined the relationships between the occurrence of gray fox and the presence other species of mesopredators, specifically coyotes and raccoons. Although generalist mesopredators are common and can reach high densities in many urban areas their urban ecology is poorly understood due to their secretive nature and wariness of humans. Understanding how mesopredators utilize urbanized landscapes can be useful in the management and control of disease outbreaks, mitigation of nuisance wildlife issues, and gaining insight into how mesopredators shape wildlife communities in highly fragmented areas. I examined habitat associations of raccoons, opossums (Didelphis virginiana), domestic cats (Felis catus), coyotes, foxes (gray and red), and striped skunks (Mephitis mephitis) at multiple spatial scales in an urban environment. Gray fox occurrence was rare and widely dispersed, and survival estimates were similar to other studies. Gray fox occurrence was negatively associated with natural and semi-natural land cover types. Fox home range size increased with increasing urban development suggesting that foxes may be negatively influenced by urbanization. Gray fox occurrence was not associated with coyote or raccoon presence. However, spatial avoidance and mortality due to coyote predation was documented and disease was a major mortality source for foxes. The declining relative abundance of gray fox in Illinois is likely a result of a combination of factors. Assessment of habitat associations indicated that urban mesopredators, particularly coyotes and foxes, perceived the landscape as relatively homogeneous and that urban mesopredators interacted with the environment at scales larger than that accommodated by remnant habitat patches. Coyote and fox presence was found to be associated with a high degree of urban development at large and intermediate spatial scales. However, at a small spatial scale fox presence was associated with high density urban land cover whereas coyote presence was associated with urban development with increased forest cover. Urban habitats can offer a diversity of prey items and anthropogenic resources and natural land cover could offer coyotes daytime resting opportunities in urban areas where they may not be as tolerated as smaller foxes. Raccoons and opossums were found to utilize moderately developed landscapes with interspersed natural and semi-natural land covers at a large spatial scale, which may facilitate dispersal movements. At intermediate and small spatial scales, both species were found to utilize areas that were moderately developed and included forested land cover. These results indicated that raccoons and opossums used natural areas in proximity to anthropogenic resources. At a large spatial scale, skunk presence was associated with highly developed landscapes with interspersed natural and semi-natural land covers. This may indicate that skunks perceived the urban matrix as more homogeneous than raccoons or opossums. At an intermediate spatial scale skunks were associated with moderate levels of development and increased forest cover, which indicated that they might utilize natural land cover in proximity to human-dominated land cover. At the smallest spatial scale skunk presence was associated with forested land cover surrounded by a suburban matrix. Compared to raccoons and opossums, skunks may not be tolerated in close proximity to human development in urban areas. Domestic cat presence was positively associated with increasingly urbanized and less diverse landscapes with decreased amounts of forest and urban open space at the largest spatial scale. At an intermediate spatial scale, cat presence was associated with a moderate degree of urban development characterized by increased forest cover, and at a small spatial scale cat presence was associated with a high degree of urbanization. Free-ranging domestic cats are often associated with human-dominated landscapes and likely utilize remnant natural habitat patches for hunting purposes, which may have implications for native predator and prey species existing in fragmented habitat patches in proximity to human development.« less

Pediatric material properties: a review of human child and animal surrogates.

PubMed

Franklyn, Melanie; Peiris, Sujanie; Huber, Christina; Yang, King H

2007-01-01

Because pediatric tissue is difficult for researchers to obtain, the biomechanical responses of adult humans have been studied much more extensively than those of children. Piglets, chimpanzees, and other animals have been used as child surrogates, but the tissue properties and responses to impact forces obtained from these animals may not directly correlate with the human child, and this correlation is not well understood. Consequently, only a handful of human pediatric tissue properties are known. Child anthropomorphic test devices employed in automotive safety have been developed largely by scaling data obtained from adult human cadaveric tests, where various scaling methods have been used to account for differences in geometry, material properties, or a combination of these two parameters. Similar scaling techniques have also been implemented to develop injury assessment reference values for child anthropomorphic test devices. Nevertheless, these scaling techniques have not yet proven to be accurate, in part because of the lack of pediatric data. In this review, the properties of pediatric human and animal surrogate tissue that have been mechanically tested are evaluated. It was found that most of the pediatric tissue that has previously been tested pertains to the head, neck, cervical spine, and extremities. It is evident that some body regions, such as the head and neck, have been tested to some extent since injuries to these regions are critical from an injury perspective. On the other hand, there is limited pediatric data available for the thorax, abdomen, thoracic and lumbar spines and fetal-related tissue. This review presents the pediatric data available in the literature and highlights the body regions where further testing is needed.

Proteome-wide search for functional motifs altered in tumors: Prediction of nuclear export signals inactivated by cancer-related mutations

PubMed Central

Prieto, Gorka; Fullaondo, Asier; Rodríguez, Jose A.

2016-01-01

Large-scale sequencing projects are uncovering a growing number of missense mutations in human tumors. Understanding the phenotypic consequences of these alterations represents a formidable challenge. In silico prediction of functionally relevant amino acid motifs disrupted by cancer mutations could provide insight into the potential impact of a mutation, and guide functional tests. We have previously described Wregex, a tool for the identification of potential functional motifs, such as nuclear export signals (NESs), in proteins. Here, we present an improved version that allows motif prediction to be combined with data from large repositories, such as the Catalogue of Somatic Mutations in Cancer (COSMIC), and to be applied to a whole proteome scale. As an example, we have searched the human proteome for candidate NES motifs that could be altered by cancer-related mutations included in the COSMIC database. A subset of the candidate NESs identified was experimentally tested using an in vivo nuclear export assay. A significant proportion of the selected motifs exhibited nuclear export activity, which was abrogated by the COSMIC mutations. In addition, our search identified a cancer mutation that inactivates the NES of the human deubiquitinase USP21, and leads to the aberrant accumulation of this protein in the nucleus. PMID:27174732

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

PubMed Central

Samoylenko, Anatoly; Hossain, Jubayer Al; Mennerich, Daniela; Kellokumpu, Sakari; Hiltunen, Jukka Kalervo

2013-01-01

Abstract Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent large-scale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials. Antioxid. Redox Signal. 19, 2157–2196. PMID:23458328

Monitoring carnivore populations at the landscape scale: occupancy modelling of tigers from sign surveys

USGS Publications Warehouse

Karanth, Kota Ullas; Gopalaswamy, Arjun M.; Kumar, Narayanarao Samba; Vaidyanathan, Srinivas; Nichols, James D.; MacKenzie, Darryl I.

2011-01-01

1. Assessing spatial distributions of threatened large carnivores at landscape scales poses formidable challenges because of their rarity and elusiveness. As a consequence of logistical constraints, investigators typically rely on sign surveys. Most survey methods, however, do not explicitly address the central problem of imperfect detections of animal signs in the field, leading to underestimates of true habitat occupancy and distribution. 2. We assessed habitat occupancy for a tiger Panthera tigris metapopulation across a c. 38 000-km2 landscape in India, employing a spatially replicated survey to explicitly address imperfect detections. Ecological predictions about tiger presence were confronted with sign detection data generated from occupancy sampling of 205 sites, each of 188 km2. 3. A recent occupancy model that considers Markovian dependency among sign detections on spatial replicates performed better than the standard occupancy model (ΔAIC = 184·9). A formulation of this model that fitted the data best showed that density of ungulate prey and levels of human disturbance were key determinants of local tiger presence. Model averaging resulted in a replicate-level detection probability [inline image] = 0·17 (0·17) for signs and a tiger habitat occupancy estimate of [inline image] = 0·665 (0·0857) or 14 076 (1814) km2 of potential habitat of 21 167 km2. In contrast, a traditional presence-versus-absence approach underestimated occupancy by 47%. Maps of probabilities of local site occupancy clearly identified tiger source populations at higher densities and matched observed tiger density variations, suggesting their potential utility for population assessments at landscape scales. 4. Synthesis and applications. Landscape-scale sign surveys can efficiently assess large carnivore spatial distributions and elucidate the factors governing their local presence, provided ecological and observation processes are both explicitly modelled. Occupancy sampling using spatial replicates can be used to reliably and efficiently identify tiger population sources and help monitor metapopulations. Our results reinforce earlier findings that prey depletion and human disturbance are key drivers of local tiger extinctions and tigers can persist even in human-dominated landscapes through effective protection of source populations. Our approach facilitates efficient targeting of tiger conservation interventions and, more generally, provides a basis for the reliable integration of large carnivore monitoring data between local and landscape scales.

Human activities change marine ecosystems by altering predation risk.

PubMed

Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

2016-01-01

In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. © 2015 John Wiley & Sons Ltd.

Universal scaling laws in metro area election results

PubMed Central

Szállási, Zoltán; Vattay, Gábor

2018-01-01

We explain the anomaly of election results between large cities and rural areas in terms of urban scaling in the 1948–2016 US elections and in the 2016 EU referendum of the UK. The scaling curves are all universal and depend on a single parameter only, and one of the parties always shows superlinear scaling and drives the process, while the sublinear exponent of the other party is merely the consequence of probability conservation. Based on the recently developed model of urban scaling, we give a microscopic model of voter behavior in which we replace diversity characterizing humans in creative aspects with social diversity and tolerance. The model can also predict new political developments such as the fragmentation of the left and the immigration paradox. PMID:29470518

The Human Genome Project: big science transforms biology and medicine.

PubMed

Hood, Leroy; Rowen, Lee

2013-01-01

The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called 'big science' - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project.

Cell fiber-based three-dimensional culture system for highly efficient expansion of human induced pluripotent stem cells.

PubMed

Ikeda, Kazuhiro; Nagata, Shogo; Okitsu, Teru; Takeuchi, Shoji

2017-06-06

Human pluripotent stem cells are a potentially powerful cellular resource for application in regenerative medicine. Because such applications require large numbers of human pluripotent stem cell-derived cells, a scalable culture system of human pluripotent stem cell needs to be developed. Several suspension culture systems for human pluripotent stem cell expansion exist; however, it is difficult to control the thickness of cell aggregations in these systems, leading to increased cell death likely caused by limited diffusion of gases and nutrients into the aggregations. Here, we describe a scalable culture system using the cell fiber technology for the expansion of human induced pluripotent stem (iPS) cells. The cells were encapsulated and cultured within the core region of core-shell hydrogel microfibers, resulting in the formation of rod-shaped or fiber-shaped cell aggregations with sustained thickness and high viability. By encapsulating the cells with type I collagen, we demonstrated a long-term culture of the cells by serial passaging at a high expansion rate (14-fold in four days) while retaining its pluripotency. Therefore, our culture system could be used for large-scale expansion of human pluripotent stem cells for use in regenerative medicine.

The Human Genome Project: big science transforms biology and medicine

PubMed Central

2013-01-01

The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called ‘big science’ - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project. PMID:24040834

Linking the influence and dependence of people on biodiversity across scales

PubMed Central

Isbell, Forest; Gonzalez, Andrew; Loreau, Michel; Cowles, Jane; Díaz, Sandra; Hector, Andy; Mace, Georgina M.; Wardle, David A.; O’Connor, Mary I.; Duffy, J. Emmett; Turnbull, Lindsay A.; Thompson, Patrick L.; Larigauderie, Anne

2017-01-01

Biodiversity enhances many of nature’s benefits to people, including the regulation of climate and the production of wood in forests, livestock forage in grasslands and fish in aquatic ecosystems. Yet people are now driving the sixth mass extinction event in Earth’s history. Human dependence and influence on biodiversity have mainly been studied separately and at contrasting scales of space and time, but new multiscale knowledge is beginning to link these relationships. Biodiversity loss substantially diminishes several ecosystem services by altering ecosystem functioning and stability, especially at the large temporal and spatial scales that are most relevant for policy and conservation. PMID:28569811

Drought in the Horn of Africa: attribution of a damaging and repeating extreme event

NASA Astrophysics Data System (ADS)

Marthews, Toby; Otto, Friederike; Mitchell, Daniel; Dadson, Simon; Jones, Richard

2015-04-01

We have applied detection and attribution techniques to the severe drought that hit the Horn of Africa in 2014. The short rains failed in late 2013 in Kenya, South Sudan, Somalia and southern Ethiopia, leading to a very dry growing season January to March 2014, and subsequently to the current drought in many agricultural areas of the sub-region. We have made use of the weather@home project, which uses publicly-volunteered distributed computing to provide a large ensemble of simulations sufficient to sample regional climate uncertainty. Based on this, we have estimated the occurrence rates of the kinds of the rare and extreme events implicated in this large-scale drought. From land surface model runs based on these ensemble simulations, we have estimated the impacts of climate anomalies during this period and therefore we can reliably identify some factors of the ongoing drought as attributable to human-induced climate change. The UNFCCC's Adaptation Fund is attempting to support projects that bring about an adaptation to "the adverse effects of climate change", but in order to formulate such projects we need a much clearer way to assess how much climate change is human-induced and how much is a consequence of climate anomalies and large-scale teleconnections, which can only be provided by robust attribution techniques.

Engineered human skin substitutes undergo large-scale genomic reprogramming and normal skin-like maturation after transplantation to athymic mice.

PubMed

Klingenberg, Jennifer M; McFarland, Kevin L; Friedman, Aaron J; Boyce, Steven T; Aronow, Bruce J; Supp, Dorothy M

2010-02-01

Bioengineered skin substitutes can facilitate wound closure in severely burned patients, but deficiencies limit their outcomes compared with native skin autografts. To identify gene programs associated with their in vivo capabilities and limitations, we extended previous gene expression profile analyses to now compare engineered skin after in vivo grafting with both in vitro maturation and normal human skin. Cultured skin substitutes were grafted on full-thickness wounds in athymic mice, and biopsy samples for microarray analyses were collected at multiple in vitro and in vivo time points. Over 10,000 transcripts exhibited large-scale expression pattern differences during in vitro and in vivo maturation. Using hierarchical clustering, 11 different expression profile clusters were partitioned on the basis of differential sample type and temporal stage-specific activation or repression. Analyses show that the wound environment exerts a massive influence on gene expression in skin substitutes. For example, in vivo-healed skin substitutes gained the expression of many native skin-expressed genes, including those associated with epidermal barrier and multiple categories of cell-cell and cell-basement membrane adhesion. In contrast, immunological, trichogenic, and endothelial gene programs were largely lacking. These analyses suggest important areas for guiding further improvement of engineered skin for both increased homology with native skin and enhanced wound healing.

Design for a Study of American Youth.

ERIC Educational Resources Information Center

Flanagan, John C.; And Others

Project TALENT is a large-scale, long-range educational research effort aimed at developing methods for the identification, development, and utilization of human talents, which has involved some 440,000 students in 1,353 public, private, and parochial secondary schools in all parts of the country. Data collected through teacher-administered tests,…

The Water Turbine: An Integrative STEM Education Context

ERIC Educational Resources Information Center

Grubbs, Michael E.; Deck, Anita

2015-01-01

Water turbines have long been used to make work easier for humans while minimizing energy consumption. They are not only used in small- and large-scale operations, but also provide a great context for Integrative STEM education. Students can begin to understand the technological processes available by designing, building, and testing different…

Large-scale analysis of pedigree and sperm-typing data reveals PRDM9 allele-specific recombination maps in cattle

USDA-ARS?s Scientific Manuscript database

Meiotic recombination is a major driving force in promoting genetic and phenotypic variations in sexually reproducing organisms. Although PRDM9 is known to modulate the binding-specificity and location of recombination hotspots in humans and mice, its role, especially in domesticated animals like ca...

Perceptions of Crowding: Predicting at the Residence, Neighborhood, and City Levels.

ERIC Educational Resources Information Center

Schmidt, Donald E.; And Others

1979-01-01

Details the results of a large-scale field study aimed at testing two theories on human crowding. Found that psychological factors are increasingly important for the prediction of crowding as one moved from the immediate residence to the less immediate city level. Implications, limitations and further results are discussed. (Author/MA)

Lake Diatoms as Indicators of Land Use Effects, Changing Environmental Conditions, and the Effectiveness of Management Practices

EPA Science Inventory

Lakes continue to face escalating pressures associated with land cover change and growing human populations. The U.S. EPA National Lakes Assessment, which sampled more than 1000 lakes in a probabilistic survey, was the first large scale effort to characterize the condition of lak...

Large-Scale Economic Change and Youth Development: The Case of Urban China

ERIC Educational Resources Information Center

Yoshikawa, Hirokazu; Way, Niobe; Chen, Xinyin

2012-01-01

Social ecological and dynamic systems theories propose that human development is shaped by the cumulative impact of social interactions in proximal and distal settings, which are themselves influenced by social and economic forces. The understanding of the links between microsystem-level factors (such as parenting styles and parent-child…

Effects of Child Maltreatment and Inherited Liability on Antisocial Development: An Official Records Study

ERIC Educational Resources Information Center

Jonson-Reid, Melissa; Presnall, Ned; Drake, Brett; Fox, Louis; Bierut, Laura; Reich, Wendy; Kane, Phyllis; Todd, Richard D.; Constantino, John N.

2010-01-01

Objective: Evidence is steadily accumulating that a preventable environmental hazard, child maltreatment, exerts causal influences on the development of long-standing patterns of antisocial behavior in humans. The relationship between child maltreatment and antisocial outcome, however, has never previously been tested in a large-scale study in…

Analyzing animal movement patterns using potential functions

Treesearch

H. K. Preisler; A. A. Ager; M. J. Wisdom

2013-01-01

The advent of GPS technology has made it possible to study human-wildlife interactions on large landscapes and quantify behavioral responses to recreation and other anthropogenic disturbances at increasingly fine scales. Of particular interest are the potential impacts on habitat use patterns, energetics, and cascading impacts on fecundity and other life history traits...

One Spatial Map or Many? Spatial Coding of Connected Environments

ERIC Educational Resources Information Center

Han, Xue; Becker, Suzanna

2014-01-01

We investigated how humans encode large-scale spatial environments using a virtual taxi game. We hypothesized that if 2 connected neighborhoods are explored jointly, people will form a single integrated spatial representation of the town. However, if the neighborhoods are first learned separately and later observed to be connected, people will…

Coalescence computations for large samples drawn from populations of time-varying sizes

PubMed Central

Polanski, Andrzej; Szczesna, Agnieszka; Garbulowski, Mateusz; Kimmel, Marek

2017-01-01

We present new results concerning probability distributions of times in the coalescence tree and expected allele frequencies for coalescent with large sample size. The obtained results are based on computational methodologies, which involve combining coalescence time scale changes with techniques of integral transformations and using analytical formulae for infinite products. We show applications of the proposed methodologies for computing probability distributions of times in the coalescence tree and their limits, for evaluation of accuracy of approximate expressions for times in the coalescence tree and expected allele frequencies, and for analysis of large human mitochondrial DNA dataset. PMID:28170404

Quality Assessments of Long-Term Quantitative Proteomic Analysis of Breast Cancer Xenograft Tissues

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

Zhou, Jian-Ying; Chen, Lijun; Zhang, Bai

The identification of protein biomarkers requires large-scale analysis of human specimens to achieve statistical significance. In this study, we evaluated the long-term reproducibility of an iTRAQ (isobaric tags for relative and absolute quantification) based quantitative proteomics strategy using one channel for universal normalization across all samples. A total of 307 liquid chromatography tandem mass spectrometric (LC-MS/MS) analyses were completed, generating 107 one-dimensional (1D) LC-MS/MS datasets and 8 offline two-dimensional (2D) LC-MS/MS datasets (25 fractions for each set) for human-in-mouse breast cancer xenograft tissues representative of basal and luminal subtypes. Such large-scale studies require the implementation of robust metrics to assessmore » the contributions of technical and biological variability in the qualitative and quantitative data. Accordingly, we developed a quantification confidence score based on the quality of each peptide-spectrum match (PSM) to remove quantification outliers from each analysis. After combining confidence score filtering and statistical analysis, reproducible protein identification and quantitative results were achieved from LC-MS/MS datasets collected over a 16 month period.« less

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells.

PubMed

Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y; Tanaka, Minoru; Miyajima, Atsushi

2015-10-13

To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM(+) cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM(+) cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM(+) cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

PubMed Central

Kido, Taketomo; Koui, Yuta; Suzuki, Kaori; Kobayashi, Ayaka; Miura, Yasushi; Chern, Edward Y.; Tanaka, Minoru; Miyajima, Atsushi

2015-01-01

Summary To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM+ cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM+ cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM+ cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes. PMID:26365514

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

Computational biomedicine: a challenge for the twenty-first century.

PubMed

Coveney, Peter V; Shublaq, Nour W

2012-01-01

With the relentless increase of computer power and the widespread availability of digital patient-specific medical data, we are now entering an era when it is becoming possible to develop predictive models of human disease and pathology, which can be used to support and enhance clinical decision-making. The approach amounts to a grand challenge to computational science insofar as we need to be able to provide seamless yet secure access to large scale heterogeneous personal healthcare data in a facile way, typically integrated into complex workflows-some parts of which may need to be run on high performance computers-in a facile way that is integrated into clinical decision support software. In this paper, we review the state of the art in terms of case studies drawn from neurovascular pathologies and HIV/AIDS. These studies are representative of a large number of projects currently being performed within the Virtual Physiological Human initiative. They make demands of information technology at many scales, from the desktop to national and international infrastructures for data storage and processing, linked by high performance networks.

The Army’s National Training Center: A Case Study in Management of a Large Defense Project

DTIC Science & Technology

1983-04-26

34Desining . . .," op cit, p. 130. IT. M3l Ior-ritc’h and C. K. Prahalad , "Managing Multi-Organization Enterprises: The Emerging Strategic Frontier...Rational Altor TModel "assumes that what must be explained is an action, i.e., behavior that reflects purpose or intention .Ŗ It assumes "that what human...a fourth element is essential to the success of large-scale commerciali- zation programs: a favorable corporate strategic environment. This element

Performance/price estimates for cortex-scale hardware: a design space exploration.

PubMed

Zaveri, Mazad S; Hammerstrom, Dan

2011-04-01

In this paper, we revisit the concept of virtualization. Virtualization is useful for understanding and investigating the performance/price and other trade-offs related to the hardware design space. Moreover, it is perhaps the most important aspect of a hardware design space exploration. Such a design space exploration is a necessary part of the study of hardware architectures for large-scale computational models for intelligent computing, including AI, Bayesian, bio-inspired and neural models. A methodical exploration is needed to identify potentially interesting regions in the design space, and to assess the relative performance/price points of these implementations. As an example, in this paper we investigate the performance/price of (digital and mixed-signal) CMOS and hypothetical CMOL (nanogrid) technology based hardware implementations of human cortex-scale spiking neural systems. Through this analysis, and the resulting performance/price points, we demonstrate, in general, the importance of virtualization, and of doing these kinds of design space explorations. The specific results suggest that hybrid nanotechnology such as CMOL is a promising candidate to implement very large-scale spiking neural systems, providing a more efficient utilization of the density and storage benefits of emerging nano-scale technologies. In general, we believe that the study of such hypothetical designs/architectures will guide the neuromorphic hardware community towards building large-scale systems, and help guide research trends in intelligent computing, and computer engineering. Copyright © 2010 Elsevier Ltd. All rights reserved.

A small-scale, rolled-membrane microfluidic artificial lung designed towards future large area manufacturing.

PubMed

Thompson, A J; Marks, L H; Goudie, M J; Rojas-Pena, A; Handa, H; Potkay, J A

2017-03-01

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the μ l/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10  μ m tall artificial capillaries, and a 66  μ m thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O 2 , atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO 2 removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

Novel Miscanthus Germplasm-Based Value Chains: A Life Cycle Assessment

PubMed Central

Wagner, Moritz; Kiesel, Andreas; Hastings, Astley; Iqbal, Yasir; Lewandowski, Iris

2017-01-01

In recent years, considerable progress has been made in miscanthus research: improvement of management practices, breeding of new genotypes, especially for marginal conditions, and development of novel utilization options. The purpose of the current study was a holistic analysis of the environmental performance of such novel miscanthus-based value chains. In addition, the relevance of the analyzed environmental impact categories was assessed. A Life Cycle Assessment was conducted to analyse the environmental performance of the miscanthus-based value chains in 18 impact categories. In order to include the substitution of a reference product, a system expansion approach was used. In addition, a normalization step was applied. This allowed the relevance of these impact categories to be evaluated for each utilization pathway. The miscanthus was cultivated on six sites in Europe (Aberystwyth, Adana, Moscow, Potash, Stuttgart and Wageningen) and the biomass was utilized in the following six pathways: (1) small-scale combustion (heat)—chips; (2) small-scale combustion (heat)—pellets; (3) large-scale combustion (CHP)—biomass baled for transport and storage; (4) large-scale combustion (CHP)—pellets; (5) medium-scale biogas plant—ensiled miscanthus biomass; and (6) large-scale production of insulation material. Thus, in total, the environmental performance of 36 site × pathway combinations was assessed. The comparatively high normalized results of human toxicity, marine, and freshwater ecotoxicity, and freshwater eutrophication indicate the relevance of these impact categories in the assessment of miscanthus-based value chains. Differences between the six sites can almost entirely be attributed to variations in biomass yield. However, the environmental performance of the utilization pathways analyzed varied widely. The largest differences were shown for freshwater and marine ecotoxicity, and freshwater eutrophication. The production of insulation material had the lowest impact on the environment, with net benefits in all impact categories expect three (marine eutrophication, human toxicity, agricultural land occupation). This performance can be explained by the multiple use of the biomass, first as material and subsequently as an energy carrier, and by the substitution of an emission-intensive reference product. The results of this study emphasize the importance of assessing all environmental impacts when selecting appropriate utilization pathways. PMID:28642784

Large-scale water projects in the developing world: Revisiting the past and looking to the future

NASA Astrophysics Data System (ADS)

Sivakumar, Bellie; Chen, Ji

2014-05-01

During the past half a century or so, the developing world has been witnessing a significant increase in freshwater demands due to a combination of factors, including population growth, increased food demand, improved living standards, and water quality degradation. Since there exists significant variability in rainfall and river flow in both space and time, large-scale storage and distribution of water has become a key means to meet these increasing demands. In this regard, large dams and water transfer schemes (including river-linking schemes and virtual water trades) have been playing a key role. While the benefits of such large-scale projects in supplying water for domestic, irrigation, industrial, hydropower, recreational, and other uses both in the countries of their development and in other countries are undeniable, concerns on their negative impacts, such as high initial costs and damages to our ecosystems (e.g. river environment and species) and socio-economic fabric (e.g. relocation and socio-economic changes of affected people) have also been increasing in recent years. These have led to serious debates on the role of large-scale water projects in the developing world and on their future, but the often one-sided nature of such debates have inevitably failed to yield fruitful outcomes thus far. The present study aims to offer a far more balanced perspective on this issue. First, it recognizes and emphasizes the need for still additional large-scale water structures in the developing world in the future, due to the continuing increase in water demands, inefficiency in water use (especially in the agricultural sector), and absence of equivalent and reliable alternatives. Next, it reviews a few important success and failure stories of large-scale water projects in the developing world (and in the developed world), in an effort to arrive at a balanced view on the future role of such projects. Then, it discusses some major challenges in future water planning and management, with proper consideration to potential technological developments and new options. Finally, it highlights the urgent need for a broader framework that integrates the physical science-related aspects ("hard sciences") and the human science-related aspects ("soft sciences").

Segmental Duplications and Copy-Number Variation in the Human Genome

PubMed Central

Sharp, Andrew J. ; Locke, Devin P. ; McGrath, Sean D. ; Cheng, Ze ; Bailey, Jeffrey A. ; Vallente, Rhea U. ; Pertz, Lisa M. ; Clark, Royden A. ; Schwartz, Stuart ; Segraves, Rick ; Oseroff, Vanessa V. ; Albertson, Donna G. ; Pinkel, Daniel ; Eichler, Evan E. 

2005-01-01

The human genome contains numerous blocks of highly homologous duplicated sequence. This higher-order architecture provides a substrate for recombination and recurrent chromosomal rearrangement associated with genomic disease. However, an assessment of the role of segmental duplications in normal variation has not yet been made. On the basis of the duplication architecture of the human genome, we defined a set of 130 potential rearrangement hotspots and constructed a targeted bacterial artificial chromosome (BAC) microarray (with 2,194 BACs) to assess copy-number variation in these regions by array comparative genomic hybridization. Using our segmental duplication BAC microarray, we screened a panel of 47 normal individuals, who represented populations from four continents, and we identified 119 regions of copy-number polymorphism (CNP), 73 of which were previously unreported. We observed an equal frequency of duplications and deletions, as well as a 4-fold enrichment of CNPs within hotspot regions, compared with control BACs (P < .000001), which suggests that segmental duplications are a major catalyst of large-scale variation in the human genome. Importantly, segmental duplications themselves were also significantly enriched >4-fold within regions of CNP. Almost without exception, CNPs were not confined to a single population, suggesting that these either are recurrent events, having occurred independently in multiple founders, or were present in early human populations. Our study demonstrates that segmental duplications define hotspots of chromosomal rearrangement, likely acting as mediators of normal variation as well as genomic disease, and it suggests that the consideration of genomic architecture can significantly improve the ascertainment of large-scale rearrangements. Our specialized segmental duplication BAC microarray and associated database of structural polymorphisms will provide an important resource for the future characterization of human genomic disorders. PMID:15918152

Computational methods to extract meaning from text and advance theories of human cognition.

PubMed

McNamara, Danielle S

2011-01-01

Over the past two decades, researchers have made great advances in the area of computational methods for extracting meaning from text. This research has to a large extent been spurred by the development of latent semantic analysis (LSA), a method for extracting and representing the meaning of words using statistical computations applied to large corpora of text. Since the advent of LSA, researchers have developed and tested alternative statistical methods designed to detect and analyze meaning in text corpora. This research exemplifies how statistical models of semantics play an important role in our understanding of cognition and contribute to the field of cognitive science. Importantly, these models afford large-scale representations of human knowledge and allow researchers to explore various questions regarding knowledge, discourse processing, text comprehension, and language. This topic includes the latest progress by the leading researchers in the endeavor to go beyond LSA. Copyright © 2010 Cognitive Science Society, Inc.

Evaluating 20th Century precipitation characteristics between multi-scale atmospheric models with different land-atmosphere coupling

NASA Astrophysics Data System (ADS)

Phillips, M.; Denning, A. S.; Randall, D. A.; Branson, M.

2016-12-01

Multi-scale models of the atmosphere provide an opportunity to investigate processes that are unresolved by traditional Global Climate Models while at the same time remaining viable in terms of computational resources for climate-length time scales. The MMF represents a shift away from large horizontal grid spacing in traditional GCMs that leads to overabundant light precipitation and lack of heavy events, toward a model where precipitation intensity is allowed to vary over a much wider range of values. Resolving atmospheric motions on the scale of 4 km makes it possible to recover features of precipitation, such as intense downpours, that were previously only obtained by computationally expensive regional simulations. These heavy precipitation events may have little impact on large-scale moisture and energy budgets, but are outstanding in terms of interaction with the land surface and potential impact on human life. Three versions of the Community Earth System Model were used in this study; the standard CESM, the multi-scale `Super-Parameterized' CESM where large-scale parameterizations have been replaced with a 2D cloud-permitting model, and a multi-instance land version of the SP-CESM where each column of the 2D CRM is allowed to interact with an individual land unit. These simulations were carried out using prescribed Sea Surface Temperatures for the period from 1979-2006 with daily precipitation saved for all 28 years. Comparisons of the statistical properties of precipitation between model architectures and against observations from rain gauges were made, with specific focus on detection and evaluation of extreme precipitation events.

[Mycology in the 21st century: crisis and revitalization].

PubMed

Silar, Philippe

2013-01-01

Although they are key players in the biosphere and have important roles in human industry, agriculture and health, fungi are largely understudied and, more disturbingly, often underrepresented in biology classes at all levels. Nevertheless, it is most likely that mycology will soon undergo a renewal of interest. Firstly, because fungi are becoming more prominent in human concerns, as their impact on human, animal and ecosystem health are increasing, animal and plant biologists become more aware of their importance. Moreover, mycologists have organized to make their discipline more visible and to enable large scale scientific projects, such as the global analyses of fungal phylogeny and of their genome structure, function and evolution. This, combined with the next generation of sequencing technologies, now permits an in depth and global understanding on how fungi are organized and how they function. It also enables the development of strategies that will help to fight fungi when they negatively interfere with human concerns, as in human mycosis, or to use them in industries such as in renewable energy usage. © Société de Biologie, 2014.

NASA's Advanced Life Support Systems Human-Rated Test Facility

NASA Technical Reports Server (NTRS)

Henninger, D. L.; Tri, T. O.; Packham, N. J.

1996-01-01

Future NASA missions to explore the solar system will be long-duration missions, requiring human life support systems which must operate with very high reliability over long periods of time. Such systems must be highly regenerative, requiring minimum resupply, to enable the crews to be largely self-sufficient. These regenerative life support systems will use a combination of higher plants, microorganisms, and physicochemical processes to recycle air and water, produce food, and process wastes. A key step in the development of these systems is establishment of a human-rated test facility specifically tailored to evaluation of closed, regenerative life supports systems--one in which long-duration, large-scale testing involving human test crews can be performed. Construction of such a facility, the Advanced Life Support Program's (ALS) Human-Rated Test Facility (HRTF), has begun at NASA's Johnson Space Center, and definition of systems and development of initial outfitting concepts for the facility are underway. This paper will provide an overview of the HRTF project plan, an explanation of baseline configurations, and descriptive illustrations of facility outfitting concepts.

Anaerobic Probiotics: The Key Microbes for Human Health.

PubMed

El Enshasy, Hesham; Malik, Khairuddin; Malek, Roslinda Abd; Othman, Nor Zalina; Elsayed, Elsayed Ahmed; Wadaan, Mohammad

Human gastrointestinal microbiota (HGIM) incorporate a large number of microbes from different species. Anaerobic bacteria are the dominant organisms in this microbial consortium and play a crucial role in human health. In addition to their functional role as the main source of many essential metabolites for human health, they are considered as biotherapeutic agents in the regulation of different human metabolites. They are also important in the prevention and in the treatment of different physical and mental diseases. Bifidobacteria are the dominant anaerobic bacteria in HGIM and are widely used in the development of probiotic products for infants, children and adults. To develop bifidobacteria-based bioproducts, therefore, it is necessary to develop a large-scale biomass production platform based on a good understanding of the ideal medium and bioprocessing parameters for their growth and viability. In addition, high cell viability should be maintained during downstream processing and storage of probiotic cell powder or the final formulated product. In this work we review the latest information about the biology, therapeutic activities, cultivation and industrial production of bifidobacteria.

Understanding the heavy-tailed dynamics in human behavior

NASA Astrophysics Data System (ADS)

Ross, Gordon J.; Jones, Tim

2015-06-01

The recent availability of electronic data sets containing large volumes of communication data has made it possible to study human behavior on a larger scale than ever before. From this, it has been discovered that across a diverse range of data sets, the interevent times between consecutive communication events obey heavy-tailed power law dynamics. Explaining this has proved controversial, and two distinct hypotheses have emerged. The first holds that these power laws are fundamental, and arise from the mechanisms such as priority queuing that humans use to schedule tasks. The second holds that they are statistical artifacts which only occur in aggregated data when features such as circadian rhythms and burstiness are ignored. We use a large social media data set to test these hypotheses, and find that although models that incorporate circadian rhythms and burstiness do explain part of the observed heavy tails, there is residual unexplained heavy-tail behavior which suggests a more fundamental cause. Based on this, we develop a quantitative model of human behavior which improves on existing approaches and gives insight into the mechanisms underlying human interactions.

Report on the Human Genome Initiative for the Office of Health and Environmental Research

DOE R&D Accomplishments Database

Tinoco, I.; Cahill, G.; Cantor, C.; Caskey, T.; Dulbecco, R.; Engelhardt, D. L.; Hood, L.; Lerman, L. S.; Mendelsohn, M. L.; Sinsheimer, R. L.; Smith, T.; Soll, D.; Stormo, G.; White, R. L.

1987-04-01

The report urges DOE and the Nation to commit to a large, multi-year, multidisciplinary, technological undertaking to order and sequence the human genome. This effort will first require significant innovation in general capability to manipulate DNA, major new analytical methods for ordering and sequencing, theoretical developments in computer science and mathematical biology, and great expansions in our ability to store and manipulate the information and to interface it with other large and diverse genetic databases. The actual ordering and sequencing involves the coordinated processing of some 3 billion bases from a reference human genome. Science is poised on the rudimentary edge of being able to read and understand human genes. A concerted, broadly based, scientific effort to provide new methods of sufficient power and scale should transform this activity from an inefficient one-gene-at-a-time, single laboratory effort into a coordinated, worldwide, comprehensive reading of "the book of man". The effort will be extraordinary in scope and magnitude, but so will be the benefit to biological understanding, new technology and the diagnosis and treatment of human disease.

Rank Dynamics of Word Usage at Multiple Scales

NASA Astrophysics Data System (ADS)

Morales, José A.; Colman, Ewan; Sánchez, Sergio; Sánchez-Puig, Fernanda; Pineda, Carlos; Iñiguez, Gerardo; Cocho, Germinal; Flores, Jorge; Gershenson, Carlos

2018-05-01

The recent dramatic increase in online data availability has allowed researchers to explore human culture with unprecedented detail, such as the growth and diversification of language. In particular, it provides statistical tools to explore whether word use is similar across languages, and if so, whether these generic features appear at different scales of language structure. Here we use the Google Books N-grams dataset to analyze the temporal evolution of word usage in several languages. We apply measures proposed recently to study rank dynamics, such as the diversity of N-grams in a given rank, the probability that an N-gram changes rank between successive time intervals, the rank entropy, and the rank complexity. Using different methods, results show that there are generic properties for different languages at different scales, such as a core of words necessary to minimally understand a language. We also propose a null model to explore the relevance of linguistic structure across multiple scales, concluding that N-gram statistics cannot be reduced to word statistics. We expect our results to be useful in improving text prediction algorithms, as well as in shedding light on the large-scale features of language use, beyond linguistic and cultural differences across human populations.

Assessing Human Modifications to Floodplains using Large-Scale Hydrogeomorphic Floodplain Modeling

NASA Astrophysics Data System (ADS)

Morrison, R. R.; Scheel, K.; Nardi, F.; Annis, A.

2017-12-01

Human modifications to floodplains for water resource and flood management purposes have significantly transformed river-floodplain connectivity dynamics in many watersheds. Bridges, levees, reservoirs, shifts in land use, and other hydraulic engineering works have altered flow patterns and caused changes in the timing and extent of floodplain inundation processes. These hydrogeomorphic changes have likely resulted in negative impacts to aquatic habitat and ecological processes. The availability of large-scale topographic datasets at high resolution provide an opportunity for detecting anthropogenic impacts by means of geomorphic mapping. We have developed and are implementing a methodology for comparing a hydrogeomorphic floodplain mapping technique to hydraulically-modeled floodplain boundaries to estimate floodplain loss due to human activities. Our hydrogeomorphic mapping methodology assumes that river valley morphology intrinsically includes information on flood-driven erosion and depositional phenomena. We use a digital elevation model-based algorithm to identify the floodplain as the area of the fluvial corridor laying below water reference levels, which are estimated using a simplified hydrologic model. Results from our hydrogeomorphic method are compared to hydraulically-derived flood zone maps and spatial datasets of levee protected-areas to explore where water management features, such as levees, have changed floodplain dynamics and landscape features. Parameters associated with commonly used F-index functions are quantified and analyzed to better understand how floodplain areas have been reduced within a basin. Preliminary results indicate that the hydrogeomorphic floodplain model is useful for quickly delineating floodplains at large watershed scales, but further analyses are needed to understand the caveats for using the model in determining floodplain loss due to levees. We plan to continue this work by exploring the spatial dependencies of the F-index function. Results from this work have implications for loss of aquatic habitat and ecological functions, and can inform management and restoration activities by highlighting regions with significant floodplain loss.

Taking the first step towards entrenching mental health in the workplace: insights from a pilot study among HR personnel in Nigeria.

PubMed

Atilola, O; Akinyemi, O; Atilola, B

2014-01-01

The continued relevance of optimal employee mental health to sustainable human capital development in the workplace underscores the need to start harnessing all resources that can be mobilized to promote the entrenchment of workplace mental health. The strategic place of workplace Human Resource (HR) units in formulating and implementing workplace welfare schemes makes them potential partners. To actualize this, it is important to initially assess the preparedness of HR personnel for, and the possible barriers to entrenching mental health in the workplace. To suggest the initial course of action and to serve as a template for a robust large-scale study, we conduct a pilot assessment of the experience with, attitudes towards, and level of prioritization of mental health in the workplace among a cohort of HR personnel in Nigeria. Participants were recruited in the course of a seminar/workshop and questionnaires were developed by authors to assess variables of interest. Attitudes were examined using an adapted form of the Link's Discrimination-Devaluation (LD-D) scale. A total of 90 human-resource personnel completed the questionnaires. Only 16% of the participants reported having handled the case of an employee with a suspected mental health problem in the preceding 2 years. Attitudes toward employees and prospective employees with mental illness were largely poor. For instance, more than 70% were likely to consider for employment someone with a pre-existing physical disability than for someone with a history of mental illness. In terms of workplace health promotion priorities, physical health seminars took wide precedence over mental health seminars. The preliminary findings of this pilot study justify a need to conduct a large scale study. Significant challenges encountered in the course of this pilot study were highlighted while insights were drawn for the conduct of the main study/project.

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

Large-scale production of lipoplexes with long shelf-life.

PubMed

Clement, Jule; Kiefer, Karin; Kimpfler, Andrea; Garidel, Patrick; Peschka-Süss, Regine

2005-01-01

The instability of lipoplex formulations is a major obstacle to overcome before their commercial application in gene therapy. In this study, a continuous mixing technique for the large-scale preparation of lipoplexes followed by lyophilisation for increased stability and shelf-life has been developed. Lipoplexes were analysed for transfection efficiency and cytotoxicity in human aorta smooth muscle cells (HASMC) and a rat smooth muscle cell line (A-10 SMC). Homogeneity of lipid/DNA-products was investigated by photon correlation spectroscopy (PCS) and cryotransmission electron microscopy (cryo-TEM). Studies have been undertaken with DAC-30, a composition of 3beta-[N-(N,N'-dimethylaminoethane)-carbamoyl]-cholesterol (DAC-Chol) and dioleylphosphatidylethanolamine (DOPE) and a green fluorescent protein (GFP) expressing marker plasmid. A continuous mixing technique was compared to the small-scale preparation of lipoplexes by pipetting. Individual steps of the continuous mixing process were evaluated in order to optimise the manufacturing technique: lipid/plasmid ratio, composition of transfection medium, pre-treatment of the lipid, size of the mixing device, mixing procedure and the influence of the lyophilisation process. It could be shown that the method developed for production of lipoplexes on a large scale under sterile conditions led to lipoplexes with good transfection efficiencies combined with low cytotoxicity, improved characteristics and long shelf-life.

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

PubMed

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

2016-11-01

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.

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

Large-scale metabolite analysis of standards and human serum by laser desorption ionization mass spectrometry from silicon nanopost arrays

DOE PAGES

Korte, Andrew R.; Stopka, Sylwia A.; Morris, Nicholas; ...

2016-07-11

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 analysismore » 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. Finally, the broad coverage demonstrated by this large-scale screening experiment opens the door for use of NAPA-LDI-MS in numerous metabolite analysis applications« less

Large-scale metabolite analysis of standards and human serum by laser desorption ionization mass spectrometry from silicon nanopost arrays

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

Korte, Andrew R.; Stopka, Sylwia A.; Morris, Nicholas

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 analysismore » 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. Finally, the broad coverage demonstrated by this large-scale screening experiment opens the door for use of NAPA-LDI-MS in numerous metabolite analysis applications« less

A multi-scale study of Orthoptera species richness and human population size controlling for sampling effort

NASA Astrophysics Data System (ADS)

Cantarello, Elena; Steck, Claude E.; Fontana, Paolo; Fontaneto, Diego; Marini, Lorenzo; Pautasso, Marco

2010-03-01

Recent large-scale studies have shown that biodiversity-rich regions also tend to be densely populated areas. The most obvious explanation is that biodiversity and human beings tend to match the distribution of energy availability, environmental stability and/or habitat heterogeneity. However, the species-people correlation can also be an artefact, as more populated regions could show more species because of a more thorough sampling. Few studies have tested this sampling bias hypothesis. Using a newly collated dataset, we studied whether Orthoptera species richness is related to human population size in Italy’s regions (average area 15,000 km2) and provinces (2,900 km2). As expected, the observed number of species increases significantly with increasing human population size for both grain sizes, although the proportion of variance explained is minimal at the provincial level. However, variations in observed Orthoptera species richness are primarily associated with the available number of records, which is in turn well correlated with human population size (at least at the regional level). Estimated Orthoptera species richness (Chao2 and Jackknife) also increases with human population size both for regions and provinces. Both for regions and provinces, this increase is not significant when controlling for variation in area and number of records. Our study confirms the hypothesis that broad-scale human population-biodiversity correlations can in some cases be artefactual. More systematic sampling of less studied taxa such as invertebrates is necessary to ascertain whether biogeographical patterns persist when sampling effort is kept constant or included in models.

Soil organic carbon across scales.

PubMed

O'Rourke, Sharon M; Angers, Denis A; Holden, Nicholas M; McBratney, Alex B

2015-10-01

Mechanistic understanding of scale effects is important for interpreting the processes that control the global carbon cycle. Greater attention should be given to scale in soil organic carbon (SOC) science so that we can devise better policy to protect/enhance existing SOC stocks and ensure sustainable use of soils. Global issues such as climate change require consideration of SOC stock changes at the global and biosphere scale, but human interaction occurs at the landscape scale, with consequences at the pedon, aggregate and particle scales. This review evaluates our understanding of SOC across all these scales in the context of the processes involved in SOC cycling at each scale and with emphasis on stabilizing SOC. Current synergy between science and policy is explored at each scale to determine how well each is represented in the management of SOC. An outline of how SOC might be integrated into a framework of soil security is examined. We conclude that SOC processes at the biosphere to biome scales are not well understood. Instead, SOC has come to be viewed as a large-scale pool subjects to carbon flux. Better understanding exists for SOC processes operating at the scales of the pedon, aggregate and particle. At the landscape scale, the influence of large- and small-scale processes has the greatest interaction and is exposed to the greatest modification through agricultural management. Policy implemented at regional or national scale tends to focus at the landscape scale without due consideration of the larger scale factors controlling SOC or the impacts of policy for SOC at the smaller SOC scales. What is required is a framework that can be integrated across a continuum of scales to optimize SOC management. © 2015 John Wiley & Sons Ltd.

Large-scale production of embryonic red blood cells from human embryonic stem cells.

PubMed

Olivier, Emmanuel N; Qiu, Caihong; Velho, Michelle; Hirsch, Rhoda Elison; Bouhassira, Eric E

2006-12-01

To develop a method to produce in culture large number of erythroid cells from human embryonic stem cells. Human H1 embryonic stem cells were differentiated into hematopoietic cells by coculture with a human fetal liver cell line, and the resulting CD34-positive cells were expanded in vitro in liquid culture using a three-step method. The erythroid cells produced were then analyzed by light microscopy and flow cytometry. Globin expression was characterized by quantitative reverse-transcriptase polymerase chain reaction and by high-performance liquid chromatography. CD34-positive cells produced from human embryonic stem cells could be efficiently differentiated into erythroid cells in liquid culture leading to a more than 5000-fold increase in cell number. The erythroid cells produced are similar to primitive erythroid cells present in the yolk sac of early human embryos and did not enucleate. They are fully hemoglobinized and express a mixture of embryonic and fetal globins but no beta-globin. We have developed an experimental protocol to produce large numbers of primitive erythroid cells starting from undifferentiated human embryonic stem cells. As the earliest human erythroid cells, the nucleated primitive erythroblasts, are not very well characterized because experimental material at this stage of development is very difficult to obtain, this system should prove useful to answer a number of experimental questions regarding the biology of these cells. In addition, production of mature red blood cells from human embryonic stem cells is of great potential practical importance because it could eventually become an alternate source of cell for transfusion.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

PubMed

Mankiw, Catherine; Park, Min Tae M; Reardon, P K; Fish, Ari M; Clasen, Liv S; Greenstein, Deanna; Giedd, Jay N; Blumenthal, Jonathan D; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

2017-05-24

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. Copyright © 2017 the authors 0270-6474/17/375222-11$15.00/0.

Predicting Species Distributions Using Record Centre Data: Multi-Scale Modelling of Habitat Suitability for Bat Roosts.

PubMed

Bellamy, Chloe; Altringham, John

2015-01-01

Conservation increasingly operates at the landscape scale. For this to be effective, we need landscape scale information on species distributions and the environmental factors that underpin them. Species records are becoming increasingly available via data centres and online portals, but they are often patchy and biased. We demonstrate how such data can yield useful habitat suitability models, using bat roost records as an example. We analysed the effects of environmental variables at eight spatial scales (500 m - 6 km) on roost selection by eight bat species (Pipistrellus pipistrellus, P. pygmaeus, Nyctalus noctula, Myotis mystacinus, M. brandtii, M. nattereri, M. daubentonii, and Plecotus auritus) using the presence-only modelling software MaxEnt. Modelling was carried out on a selection of 418 data centre roost records from the Lake District National Park, UK. Target group pseudoabsences were selected to reduce the impact of sampling bias. Multi-scale models, combining variables measured at their best performing spatial scales, were used to predict roosting habitat suitability, yielding models with useful predictive abilities. Small areas of deciduous woodland consistently increased roosting habitat suitability, but other habitat associations varied between species and scales. Pipistrellus were positively related to built environments at small scales, and depended on large-scale woodland availability. The other, more specialist, species were highly sensitive to human-altered landscapes, avoiding even small rural towns. The strength of many relationships at large scales suggests that bats are sensitive to habitat modifications far from the roost itself. The fine resolution, large extent maps will aid targeted decision-making by conservationists and planners. We have made available an ArcGIS toolbox that automates the production of multi-scale variables, to facilitate the application of our methods to other taxa and locations. Habitat suitability modelling has the potential to become a standard tool for supporting landscape-scale decision-making as relevant data and open source, user-friendly, and peer-reviewed software become widely available.

Radiocarbon Dating the Anthropocene

NASA Astrophysics Data System (ADS)

Chaput, M. A.; Gajewski, K. J.

2015-12-01

The Anthropocene has no agreed start date since current suggestions for its beginning range from Pre-Industrial times to the Industrial Revolution, and from the mid-twentieth century to the future. To set the boundary of the Anthropocene in geological time, we must first understand when, how and to what extent humans began altering the Earth system. One aspect of this involves reconstructing the effects of prehistoric human activity on the physical landscape. However, for global reconstructions of land use and land cover change to be more accurately interpreted in the context of human interaction with the landscape, large-scale spatio-temporal demographic changes in prehistoric populations must be known. Estimates of the relative number of prehistoric humans in different regions of the world and at different moments in time are needed. To this end, we analyze a dataset of radiocarbon dates from the Canadian Archaeological Radiocarbon Database (CARD), the Palaeolithic Database of Europe and the AustArch Database of Australia, as well as published dates from South America. This is the first time such a large quantity of dates (approximately 60,000) has been mapped and studied at a global scale. Initial results from the analysis of temporal frequency distributions of calibrated radiocarbon dates, assumed to be proportional to population density, will be discussed. The utility of radiocarbon dates in studies of the Anthropocene will be evaluated and potential links between population density and changes in atmospheric greenhouse gas concentrations, climate, migration patterning and fire frequency coincidence will be considered.

Dynamic social networks promote cooperation in experiments with humans

PubMed Central

Rand, David G.; Arbesman, Samuel; Christakis, Nicholas A.

2011-01-01

Human populations are both highly cooperative and highly organized. Human interactions are not random but rather are structured in social networks. Importantly, ties in these networks often are dynamic, changing in response to the behavior of one's social partners. This dynamic structure permits an important form of conditional action that has been explored theoretically but has received little empirical attention: People can respond to the cooperation and defection of those around them by making or breaking network links. Here, we present experimental evidence of the power of using strategic link formation and dissolution, and the network modification it entails, to stabilize cooperation in sizable groups. Our experiments explore large-scale cooperation, where subjects’ cooperative actions are equally beneficial to all those with whom they interact. Consistent with previous research, we find that cooperation decays over time when social networks are shuffled randomly every round or are fixed across all rounds. We also find that, when networks are dynamic but are updated only infrequently, cooperation again fails. However, when subjects can update their network connections frequently, we see a qualitatively different outcome: Cooperation is maintained at a high level through network rewiring. Subjects preferentially break links with defectors and form new links with cooperators, creating an incentive to cooperate and leading to substantial changes in network structure. Our experiments confirm the predictions of a set of evolutionary game theoretic models and demonstrate the important role that dynamic social networks can play in supporting large-scale human cooperation. PMID:22084103

Climate change as a driver for future human migration

NASA Astrophysics Data System (ADS)

Chen, M.; Ricke, K.; Caldeira, K.

2016-12-01

Human migration is driven by a multitude of factors, both socioeconomic and environmental. However, as impacts of anthropogenic climate change emerge and grow, it is widely conjectured that climate change will induce migration of human populations from areas that are adversely affected by climate change to areas that are less adversely or positively affected by climate change. Both low- and high-frequency climate changes have been empirically linked to migration in areas across the globe, but there has been little global-scale quantitative analysis projecting the scale and geography of climate-motivated migration. Considering temperature and precipitation in isolation from all other factors, here we project climate-driven impacts on the areal-density of human population. From this, we infer potential destinations and origins for the climate-motivated migration. Our results indicate that tropical and sub-tropical countries are the largest likely sources of migrants, with India being the country with the greatest number of potential climate emigrants. Global warming has the potential to motivate hundreds of millions of people to migrate in the coming decades, largely from warm tropical and subtropical countries to cooler temperate countries. Migration decisions will depend on many factors beyond climate; nevertheless our work establishes a foundation for quantifying future climate-motivated migration that can act as a starting point of more comprehensive assessments. The large number of potential climate migrants indicated by our analyses provides additional incentive to reduce greenhouse gas emissions, take adaptive measures, and carefully consider migration policy.

Comprehensive identification and analysis of human accelerated regulatory DNA

PubMed Central

Gittelman, Rachel M.; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S.; Hawkins, R. David; Akey, Joshua M.

2015-01-01

It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

Application of computer vision to automatic prescription verification in pharmaceutical mail order

NASA Astrophysics Data System (ADS)

Alouani, Ali T.

2005-05-01

In large volume pharmaceutical mail order, before shipping out prescriptions, licensed pharmacists ensure that the drug in the bottle matches the information provided in the patient prescription. Typically, the pharmacist has about 2 sec to complete the prescription verification process of one prescription. Performing about 1800 prescription verification per hour is tedious and can generate human errors as a result of visual and brain fatigue. Available automatic drug verification systems are limited to a single pill at a time. This is not suitable for large volume pharmaceutical mail order, where a prescription can have as many as 60 pills and where thousands of prescriptions are filled every day. In an attempt to reduce human fatigue, cost, and limit human error, the automatic prescription verification system (APVS) was invented to meet the need of large scale pharmaceutical mail order. This paper deals with the design and implementation of the first prototype online automatic prescription verification machine to perform the same task currently done by a pharmacist. The emphasis here is on the visual aspects of the machine. The system has been successfully tested on 43,000 prescriptions.

Human Y chromosome copy number variation in the next generation sequencing era and beyond.

PubMed

Massaia, Andrea; Xue, Yali

2017-05-01

The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

Conserving tigers in working landscapes.

PubMed

Chanchani, Pranav; Noon, Barry R; Bailey, Larissa L; Warrier, Rekha A

2016-06-01

Tiger (Panthera tigris) conservation efforts in Asia are focused on protected areas embedded in human-dominated landscapes. A system of protected areas is an effective conservation strategy for many endangered species if the network is large enough to support stable metapopulations. The long-term conservation of tigers requires that the species be able to meet some of its life-history needs beyond the boundaries of small protected areas and within the working landscape, including multiple-use forests with logging and high human use. However, understanding of factors that promote or limit the occurrence of tigers in working landscapes is incomplete. We assessed the relative influence of protection status, prey occurrence, extent of grasslands, intensity of human use, and patch connectivity on tiger occurrence in the 5400 km(2) Central Terai Landscape of India, adjacent to Nepal. Two observer teams independently surveyed 1009 km of forest trails and water courses distributed across 60 166-km(2) cells. In each cell, the teams recorded detection of tiger signs along evenly spaced trail segments. We used occupancy models that permitted multiscale analysis of spatially correlated data to estimate cell-scale occupancy and segment-scale habitat use by tigers as a function of management and environmental covariates. Prey availability and habitat quality, rather than protected-area designation, influenced tiger occupancy. Tiger occupancy was low in some protected areas in India that were connected to extensive areas of tiger habitat in Nepal, which brings into question the efficacy of current protection and management strategies in both India and Nepal. At a finer spatial scale, tiger habitat use was high in trail segments associated with abundant prey and large grasslands, but it declined as human and livestock use increased. We speculate that riparian grasslands may provide tigers with critical refugia from human activity in the daytime and thereby promote tiger occurrence in some multiple-use forests. Restrictions on human-use in high-quality tiger habitat in multiple-use forests may complement existing protected areas and collectively promote the persistence of tiger populations in working landscapes. © 2015 Society for Conservation Biology.

Toward a social-ecological theory of forest macrosystems for improved ecosystem management

USGS Publications Warehouse

Kleindl, William J.; Stoy, Paul C.; Binford, Michael W.; Desai, Ankur R.; Dietze, Michael C.; Schultz, Courtney A.; Starr, Gregory; Staudhammer, Christina; Wood, David J. A.

2018-01-01

The implications of cumulative land-use decisions and shifting climate on forests, require us to integrate our understanding of ecosystems, markets, policy, and resource management into a social-ecological system. Humans play a central role in macrosystem dynamics, which complicates ecological theories that do not explicitly include human interactions. These dynamics also impact ecological services and related markets, which challenges economic theory. Here, we use two forest macroscale management initiatives to develop a theoretical understanding of how management interacts with ecological functions and services at these scales and how the multiple large-scale management goals work either in consort or conflict with other forest functions and services. We suggest that calling upon theories developed for organismal ecology, ecosystem ecology, and ecological economics adds to our understanding of social-ecological macrosystems. To initiate progress, we propose future research questions to add rigor to macrosystem-scale studies: (1) What are the ecosystem functions that operate at macroscales, their necessary structural components, and how do we observe them? (2) How do systems at one scale respond if altered at another scale? (3) How do we both effectively measure these components and interactions, and communicate that information in a meaningful manner for policy and management across different scales?

Distributed intelligent urban environment monitoring system

NASA Astrophysics Data System (ADS)

Du, Jinsong; Wang, Wei; Gao, Jie; Cong, Rigang

2018-02-01

The current environmental pollution and destruction have developed into a world-wide major social problem that threatens human survival and development. Environmental monitoring is the prerequisite and basis of environmental governance, but overall, the current environmental monitoring system is facing a series of problems. Based on the electrochemical sensor, this paper designs a small, low-cost, easy to layout urban environmental quality monitoring terminal, and multi-terminal constitutes a distributed network. The system has been small-scale demonstration applications and has confirmed that the system is suitable for large-scale promotion

Exploration–exploitation trade-off features a saltatory search behaviour

PubMed Central

Volchenkov, Dimitri; Helbach, Jonathan; Tscherepanow, Marko; Kühnel, Sina

2013-01-01

Searching experiments conducted in different virtual environments over a gender-balanced group of people revealed a gender irrelevant scale-free spread of searching activity on large spatio-temporal scales. We have suggested and solved analytically a simple statistical model of the coherent-noise type describing the exploration–exploitation trade-off in humans (‘should I stay’ or ‘should I go’). The model exhibits a variety of saltatory behaviours, ranging from Lévy flights occurring under uncertainty to Brownian walks performed by a treasure hunter confident of the eventual success. PMID:23782535

Self and world: large scale installations at science museums.

PubMed

Shimojo, Shinsuke

2008-01-01

This paper describes three examples of illusion installation in a science museum environment from the author's collaboration with the artist and architect. The installations amplify the illusory effects, such as vection (visually-induced sensation of self motion) and motion-induced blindness, to emphasize that perception is not just to obtain structure and features of objects, but rather to grasp the dynamic relationship between the self and the world. Scaling up the size and utilizing the live human body turned out to be keys for installations with higher emotional impact.

Analyzing large scale genomic data on the cloud with Sparkhit

PubMed Central

Huang, Liren; Krüger, Jan

2018-01-01

Abstract Motivation The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform. Results Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92–157 times faster than MetaSpark on metagenomic fragment recruitment and 18–32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21 h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2 h, presenting an approach to easily associate large amounts of public datasets with reference data. Availability and implementation Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/. Contact asczyrba@cebitec.uni-bielefeld.de Supplementary information Supplementary data are available at Bioinformatics online. PMID:29253074

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

PubMed

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; Nimgaonkar, 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.

Organizing Principles of Human Cortical Development--Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy.

PubMed

Amlien, Inge K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Krogsrud, Stine K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

2016-01-01

The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whether the relationship only applies to surface area (SA), or also holds for cortical thickness (CT). In 331 participants aged 4 to 30, we calculated age functions of SA and CT, and examined the correspondence of human cortical development with macaque to human expansion, and with expansion across nonhuman primates. CT followed a linear negative age function from 4 to 30 years, while SA showed positive age functions until 12 years with little further development. Differential cortical expansion across primates was related to regional maturation of SA and CT, with age trajectories differing between high- and low-expanding cortical regions. This relationship adhered to allometric scaling laws rather than representing uniquely macaque-human differences: regional correspondence with human development was as large for expansion across nonhuman primates as between humans and macaque. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

a Model Study of Small-Scale World Map Generalization

NASA Astrophysics Data System (ADS)

Cheng, Y.; Yin, Y.; Li, C. M.; Wu, W.; Guo, P. P.; Ma, X. L.; Hu, F. M.

2018-04-01

With the globalization and rapid development every filed is taking an increasing interest in physical geography and human economics. There is a surging demand for small scale world map in large formats all over the world. Further study of automated mapping technology, especially the realization of small scale production on a large scale global map, is the key of the cartographic field need to solve. In light of this, this paper adopts the improved model (with the map and data separated) in the field of the mapmaking generalization, which can separate geographic data from mapping data from maps, mainly including cross-platform symbols and automatic map-making knowledge engine. With respect to the cross-platform symbol library, the symbol and the physical symbol in the geographic information are configured at all scale levels. With respect to automatic map-making knowledge engine consists 97 types, 1086 subtypes, 21845 basic algorithm and over 2500 relevant functional modules.In order to evaluate the accuracy and visual effect of our model towards topographic maps and thematic maps, we take the world map generalization in small scale as an example. After mapping generalization process, combining and simplifying the scattered islands make the map more explicit at 1 : 2.1 billion scale, and the map features more complete and accurate. Not only it enhance the map generalization of various scales significantly, but achieve the integration among map-makings of various scales, suggesting that this model provide a reference in cartographic generalization for various scales.

Food irradiation development in Pakistan

NASA Astrophysics Data System (ADS)

Khan, I.

The large scale trials were held to extend the storage life of potatoes, onions and dry fruits by gamma radiation. It was concluded that radiation preservation of potatoes and onions was much cheaper as compared to conventional methods. A dose of 1 kGy can control the insects in dry fruits and nuts. The consumers' acceptability and market testing performed during the last four years are also conducive to the commercialization of the technology in this country. The Government of Pakistan has accorded clearance for the irradiation of some food items like potatoes, onions, garlic and spices for human consumption. The Pakistan Radiation Services (PARAS), the commercial irradiator (200 Kci) at Lahore, has already started functioning in April, 1987. It is planned to start large scale sterilization of spices by gamma radiation in PARAS shortly.

Supersampling and Network Reconstruction of Urban Mobility.

PubMed

Sagarra, Oleguer; Szell, Michael; Santi, Paolo; Díaz-Guilera, Albert; Ratti, Carlo

2015-01-01

Understanding human mobility is of vital importance for urban planning, epidemiology, and many other fields that draw policies from the activities of humans in space. Despite the recent availability of large-scale data sets of GPS traces or mobile phone records capturing human mobility, typically only a subsample of the population of interest is represented, giving a possibly incomplete picture of the entire system under study. Methods to reliably extract mobility information from such reduced data and to assess their sampling biases are lacking. To that end, we analyzed a data set of millions of taxi movements in New York City. We first show that, once they are appropriately transformed, mobility patterns are highly stable over long time scales. Based on this observation, we develop a supersampling methodology to reliably extrapolate mobility records from a reduced sample based on an entropy maximization procedure, and we propose a number of network-based metrics to assess the accuracy of the predicted vehicle flows. Our approach provides a well founded way to exploit temporal patterns to save effort in recording mobility data, and opens the possibility to scale up data from limited records when information on the full system is required.

Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry.

PubMed

Harada, Sei; Hirayama, Akiyoshi; Chan, Queenie; Kurihara, Ayako; Fukai, Kota; Iida, Miho; Kato, Suzuka; Sugiyama, Daisuke; Kuwabara, Kazuyo; Takeuchi, Ayano; Akiyama, Miki; Okamura, Tomonori; Ebbels, Timothy M D; Elliott, Paul; Tomita, Masaru; Sato, Asako; Suzuki, Chizuru; Sugimoto, Masahiro; Soga, Tomoyoshi; Takebayashi, Toru

2018-01-01

Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

In Silico Evidence for Gluconeogenesis from Fatty Acids in Humans

PubMed Central

Kaleta, Christoph; de Figueiredo, Luís F.; Werner, Sarah; Guthke, Reinhard; Ristow, Michael; Schuster, Stefan

2011-01-01

The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is “No”. Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO2. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet. PMID:21814506

Visual texture perception via graph-based semi-supervised learning

NASA Astrophysics Data System (ADS)

Zhang, Qin; Dong, Junyu; Zhong, Guoqiang

2018-04-01

Perceptual features, for example direction, contrast and repetitiveness, are important visual factors for human to perceive a texture. However, it needs to perform psychophysical experiment to quantify these perceptual features' scale, which requires a large amount of human labor and time. This paper focuses on the task of obtaining perceptual features' scale of textures by small number of textures with perceptual scales through a rating psychophysical experiment (what we call labeled textures) and a mass of unlabeled textures. This is the scenario that the semi-supervised learning is naturally suitable for. This is meaningful for texture perception research, and really helpful for the perceptual texture database expansion. A graph-based semi-supervised learning method called random multi-graphs, RMG for short, is proposed to deal with this task. We evaluate different kinds of features including LBP, Gabor, and a kind of unsupervised deep features extracted by a PCA-based deep network. The experimental results show that our method can achieve satisfactory effects no matter what kind of texture features are used.

The animal-human interface and infectious disease in industrial food animal production: rethinking biosecurity and biocontainment.

PubMed

Graham, Jay P; Leibler, Jessica H; Price, Lance B; Otte, Joachim M; Pfeiffer, Dirk U; Tiensin, T; Silbergeld, Ellen K

2008-01-01

Understanding interactions between animals and humans is critical in preventing outbreaks of zoonotic disease. This is particularly important for avian influenza. Food animal production has been transformed since the 1918 influenza pandemic. Poultry and swine production have changed from small-scale methods to industrial-scale operations. There is substantial evidence of pathogen movement between and among these industrial facilities, release to the external environment, and exposure to farm workers, which challenges the assumption that modern poultry production is more biosecure and biocontained as compared with backyard or small holder operations in preventing introduction and release of pathogens. An analysis of data from the Thai government investigation in 2004 indicates that the odds of H5N1 outbreaks and infections were significantly higher in large-scale commercial poultry operations as compared with backyard flocks. These data suggest that successful strategies to prevent or mitigate the emergence of pandemic avian influenza must consider risk factors specific to modern industrialized food animal production.

Cancer Prevention by Tocopherols and Tea Polyphenols

PubMed Central

Yang, Chung S.; Li, Guangxun; Yang, Zhihong; Guan, Fei; Chen, Amber; Ju, Jihyeung

2013-01-01

Tocopherols (vitamin E) and tea polyphenols have been reported to have cancer preventive activities. Large-scale human trials with high doses of alpha-tocopherol, however, have produced disappointing results. This review presents data showing that γ- and δ-tocopherols inhibit colon, lung, mammary and prostate carcinogenesis in animal models, whereas α-tocopherol is ineffective in animal and human studies. Possible mechanisms of action are discussed. A broad cancer preventive activity of green tea polyphenols has been demonstrated in animal models, and many mechanisms have been proposed. The cancer preventive activity of green tea in humans, however, has not been conclusively demonstrated and remains to be further investigated. PMID:23403075

Large-scale protein-protein interaction analysis in Arabidopsis mesophyll protoplasts by split firefly luciferase complementation.

PubMed

Li, Jian-Feng; Bush, Jenifer; Xiong, Yan; Li, Lei; McCormack, Matthew

2011-01-01

Protein-protein interactions (PPIs) constitute the regulatory network that coordinates diverse cellular functions. There are growing needs in plant research for creating protein interaction maps behind complex cellular processes and at a systems biology level. However, only a few approaches have been successfully used for large-scale surveys of PPIs in plants, each having advantages and disadvantages. Here we present split firefly luciferase complementation (SFLC) as a highly sensitive and noninvasive technique for in planta PPI investigation. In this assay, the separate halves of a firefly luciferase can come into close proximity and transiently restore its catalytic activity only when their fusion partners, namely the two proteins of interest, interact with each other. This assay was conferred with quantitativeness and high throughput potential when the Arabidopsis mesophyll protoplast system and a microplate luminometer were employed for protein expression and luciferase measurement, respectively. Using the SFLC assay, we could monitor the dynamics of rapamycin-induced and ascomycin-disrupted interaction between Arabidopsis FRB and human FKBP proteins in a near real-time manner. As a proof of concept for large-scale PPI survey, we further applied the SFLC assay to testing 132 binary PPIs among 8 auxin response factors (ARFs) and 12 Aux/IAA proteins from Arabidopsis. Our results demonstrated that the SFLC assay is ideal for in vivo quantitative PPI analysis in plant cells and is particularly powerful for large-scale binary PPI screens.

Mercury concentrations in lentic fish populations related to ecosystem and watershed characteristics

Treesearch

Andrew L. Rypel

2010-01-01

Predicting mercury (Hg) concentrations of fishes at large spatial scales is a fundamental environmental challenge with the potential to improve human health. In this study, mercury concentrations were examined for five species across 161 lakes and ecosystem, and watershed parameters were investigated as explanatory variables in statistical models. For all species, Hg...