Ancestry Estimation in Forensic Anthropology: Geometric Morphometric versus Standard and Nonstandard Interlandmark Distances.

PubMed

Katherine Spradley, M; Jantz, Richard L

2016-07-01

Standard cranial measurements are commonly used for ancestry estimation; however, 3D digitizers have made cranial landmark data collection and geometric morphometric (GM) analyses more popular within forensic anthropology. Yet there has been little focus on which data type works best. The goal of the present research is to test the discrimination ability of standard and nonstandard craniometric measurements and data derived from GM analysis. A total of 31 cranial landmarks were used to generate 465 interlandmark distances, including a subset of 20 commonly used measurements, and to generate principal component scores from procrustes coordinates. All were subjected to discriminant function analysis to ascertain which type of data performed best for ancestry estimation of American Black and White and Hispanic males and females. The nonstandard interlandmark distances generated the highest classification rates for females (90.5%) and males (88.2%). Using nonstandard interlandmark distances over more commonly used measurements leads to better ancestry estimates for our current population structure. © 2016 American Academy of Forensic Sciences.

Image encryption algorithm based on multiple mixed hash functions and cyclic shift

NASA Astrophysics Data System (ADS)

Wang, Xingyuan; Zhu, Xiaoqiang; Wu, Xiangjun; Zhang, Yingqian

2018-08-01

This paper proposes a new one-time pad scheme for chaotic image encryption that is based on the multiple mixed hash functions and the cyclic-shift function. The initial value is generated using both information of the plaintext image and the chaotic sequences, which are calculated from the SHA1 and MD5 hash algorithms. The scrambling sequences are generated by the nonlinear equations and logistic map. This paper aims to improve the deficiencies of traditional Baptista algorithms and its improved algorithms. We employ the cyclic-shift function and piece-wise linear chaotic maps (PWLCM), which give each shift number the characteristics of chaos, to diffuse the image. Experimental results and security analysis show that the new scheme has better security and can resist common attacks.

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

Trahan, Alexis Chanel

The objectives of this presentation are to introduce the basic physics of neutron production, interactions and detection; identify the processes that generate neutrons; explain the most common neutron mechanism, spontaneous and induced fission and (a,n) reactions; describe the properties of neutron from different sources; recognize advantages of neutron measurements techniques; recognize common neutrons interactions; explain neutron cross section measurements; describe the fundamental of 3He detector function and designs; and differentiate between passive and active assay techniques.

Generalized compliant motion primitive

NASA Technical Reports Server (NTRS)

Backes, Paul G. (Inventor)

1994-01-01

This invention relates to a general primitive for controlling a telerobot with a set of input parameters. The primitive includes a trajectory generator; a teleoperation sensor; a joint limit generator; a force setpoint generator; a dither function generator, which produces telerobot motion inputs in a common coordinate frame for simultaneous combination in sensor summers. Virtual return spring motion input is provided by a restoration spring subsystem. The novel features of this invention include use of a single general motion primitive at a remote site to permit the shared and supervisory control of the robot manipulator to perform tasks via a remotely transferred input parameter set.

Relating the "mirrorness" of mirror neurons to their origins.

PubMed

Kilner, James M; Friston, Karl J

2014-04-01

Ever since their discovery, mirror neurons have generated much interest and debate. A commonly held view of mirror neuron function is that they transform "visual information into knowledge," thus enabling action understanding and non-verbal social communication between con-specifics (Rizzolatti & Craighero 2004). This functionality is thought to be so important that it has been argued that mirror neurons must be a result of selective pressure.

Schizotypal thinking and associative processing: a response commonality analysis of verbal fluency.

PubMed Central

Duchêne, A; Graves, R E; Brugger, P

1998-01-01

OBJECTIVE: To determine whether people with high scores for schizotypal thinking generate more uncommon words in a letter fluency task than people with low scores. DESIGN: Prospective study. SETTING: University psychology department. PATIENTS: Forty healthy, right-handed students. INTERVENTIONS: Students were administered the Magical Ideation (MI) Scale and a 2-minute letter fluency task in which they named as many nouns as possible beginning with "A" or "F," in any order. OUTCOME MEASURES: Total number of words produced and percentage of unique, rare and common words (as determined by the responses of the whole group); scores on MI scale. RESULTS: Participants with high scores (above the median) on the MI scale generated as many words as those who had low scores. People in both groups also generated a comparable number of unique words (named by only 1 person) and common words (named by 6 or more people). As hypothesized, people with high scores on the MI scale generated more rare words (named by fewer than 6 people) than those with low scores. CONCLUSIONS: These findings support the view of a disinhibition of semantic network functioning as the neuropsychological basis of creative thought, magical ideation and thought disorder. PMID:9505061

A Feasibility Assessment of a Single Contracting Office for Common-User Transportation Services

DTIC Science & Technology

1990-09-01

feasibility of consolidating the contracting functions that purchase common-user transportation services and occurs within the headquarters of the three...responsible for and the dollars spent in the procurement of those services. A complete breakdown of the services purchased is in chapter three. The...34 while contracting is the process a’contracting officer completes to satisfy a funded purchase request generated in response to a identified

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.

PubMed

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M; Brunet, Jean-Francois; Ericson, Johan

2003-03-15

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates.

A common-aperture X- and S-band four-function feedcone. [hornfeed design for antennas of Deep Space Network

NASA Technical Reports Server (NTRS)

Withington, J. R.; Williams, W. F.

1982-01-01

Williams and Withington (1979) have considered a prototype X-S-band feedhorn which enabled simultaneous X- and S-band reception from a Cassegrain antenna. This feedhorn has quite successfully demonstrated an alternate method to the standard Deep Space Network (DSN) system of multiple subreflectors and dichroic plate for dual-band reception. In connection with a Network Consolidation Program, involving centralized control of existing antennas and construction of new reflector antennas, a second-generation feedhorn/combiner was conceived to show that this common-aperture feedhorn system was capable of performing all necessary functions the DSN would be called upon to perform with existing and future X-S-band spacecraft. Attention is given to the feedhorn concept, the combiner concept, the first and the second generation of the horn, Sand X-band tuning, and planned capabilities. The feedhorn greatly extends the state of the art in DSN performance and will enhance DSN capabilities in the future.

Exploiting the functional and taxonomic structure of genomic data by probabilistic topic modeling.

PubMed

Chen, Xin; Hu, Xiaohua; Lim, Tze Y; Shen, Xiajiong; Park, E K; Rosen, Gail L

2012-01-01

In this paper, we present a method that enable both homology-based approach and composition-based approach to further study the functional core (i.e., microbial core and gene core, correspondingly). In the proposed method, the identification of major functionality groups is achieved by generative topic modeling, which is able to extract useful information from unlabeled data. We first show that generative topic model can be used to model the taxon abundance information obtained by homology-based approach and study the microbial core. The model considers each sample as a “document,” which has a mixture of functional groups, while each functional group (also known as a “latent topic”) is a weight mixture of species. Therefore, estimating the generative topic model for taxon abundance data will uncover the distribution over latent functions (latent topic) in each sample. Second, we show that, generative topic model can also be used to study the genome-level composition of “N-mer” features (DNA subreads obtained by composition-based approaches). The model consider each genome as a mixture of latten genetic patterns (latent topics), while each functional pattern is a weighted mixture of the “N-mer” features, thus the existence of core genomes can be indicated by a set of common N-mer features. After studying the mutual information between latent topics and gene regions, we provide an explanation of the functional roles of uncovered latten genetic patterns. The experimental results demonstrate the effectiveness of proposed method.

Concurrent generation of functional smooth muscle and endothelial cells via a vascular progenitor.

PubMed

Marchand, Melanie; Anderson, Erica K; Phadnis, Smruti M; Longaker, Michael T; Cooke, John P; Chen, Bertha; Reijo Pera, Renee A

2014-01-01

Smooth muscle cells (SMCs) and endothelial cells (ECs) are typically derived separately, with low efficiencies, from human pluripotent stem cells (hPSCs). The concurrent generation of these cell types might lead to potential applications in regenerative medicine to model, elucidate, and eventually treat vascular diseases. Here we report a robust two-step protocol that can be used to simultaneously generate large numbers of functional SMCs and ECs from a common proliferative vascular progenitor population via a two-dimensional culture system. We show here that coculturing hPSCs with OP9 cells in media supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and bone morphogenetic protein 4 yields a higher percentage of CD31(+)CD34(+) cells on day 8 of differentiation. Upon exposure to endothelial differentiation media and SM differentiation media, these vascular progenitors were able to differentiate and mature into functional endothelial cells and smooth muscle cells, respectively. Furthermore, we were able to expand the intermediate population more than a billion fold to generate sufficient numbers of ECs and SMCs in parallel for potential therapeutic transplantations.

Data Management Plan and Functional System Design for the Information Management System of the Clinch River Remedial Investigation and Waste Area Grouping 6

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

Ball, T.; Brandt, C.; Calfee, J.

1994-03-01

The Data Management Plan and Functional System Design supports the Clinch River Remedial Investigation (CRRI) and Waste Area Grouping (WAG) 6 Environmental Monitoring Program. The objective of the Data Management Plan and Functional System Design is to provide organization, integrity, security, traceability, and consistency of the data generated during the CRRI and WAG 6 projects. Proper organization will ensure that the data are consistent with the procedures and requirements of the projects. The Information Management Groups (IMGs) for these two programs face similar challenges and share many common objectives. By teaming together, the IMGs have expedited the development and implementationmore » of a common information management strategy that benefits each program.« less

htsint: a Python library for sequencing pipelines that combines data through gene set generation.

PubMed

Richards, Adam J; Herrel, Anthony; Bonneaud, Camille

2015-09-24

Sequencing technologies provide a wealth of details in terms of genes, expression, splice variants, polymorphisms, and other features. A standard for sequencing analysis pipelines is to put genomic or transcriptomic features into a context of known functional information, but the relationships between ontology terms are often ignored. For RNA-Seq, considering genes and their genetic variants at the group level enables a convenient way to both integrate annotation data and detect small coordinated changes between experimental conditions, a known caveat of gene level analyses. We introduce the high throughput data integration tool, htsint, as an extension to the commonly used gene set enrichment frameworks. The central aim of htsint is to compile annotation information from one or more taxa in order to calculate functional distances among all genes in a specified gene space. Spectral clustering is then used to partition the genes, thereby generating functional modules. The gene space can range from a targeted list of genes, like a specific pathway, all the way to an ensemble of genomes. Given a collection of gene sets and a count matrix of transcriptomic features (e.g. expression, polymorphisms), the gene sets produced by htsint can be tested for 'enrichment' or conditional differences using one of a number of commonly available packages. The database and bundled tools to generate functional modules were designed with sequencing pipelines in mind, but the toolkit nature of htsint allows it to also be used in other areas of genomics. The software is freely available as a Python library through GitHub at https://github.com/ajrichards/htsint.

Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line.

PubMed

Stephenson, Sarah E M; Aumann, Timothy D; Taylor, Juliet M; Riseley, Jessica R; Li, Ruili; Mann, Jeffrey R; Tomas, Doris; Lockhart, Paul J

2018-05-14

Mutations in PARK2 (parkin) can result in Parkinson's disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone. Successful modification of the targeted allele was confirmed at the genomic, transcriptional and steady state protein levels for both genes. At 18-20 months of age, there were no significant differences in the behaviour of parental and mutant lines when assessed by openfield, rotarod and balance beam. Subsequent neuropathological examination suggested there was no gross abnormality of the dopaminergic system in the substantia nigra and no significant difference in the number of dopaminergic neurons in either knockout model compared to wildtype mice.

Identification of dietary alanine toxicity and trafficking dysfunction in a Drosophila model of hereditary sensory and autonomic neuropathy type 1

PubMed Central

Oswald, Matthew C. W.; West, Ryan J. H.; Lloyd-Evans, Emyr; Sweeney, Sean T.

2015-01-01

Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is characterized by a loss of distal peripheral sensory and motorneuronal function, neuropathic pain and tissue necrosis. The most common cause of HSAN1 is due to dominant mutations in serine palmitoyl-transferase subunit 1 (SPT1). SPT catalyses the condensation of serine with palmitoyl-CoA, the initial step in sphingolipid biogenesis. Identified mutations in SPT1 are known to both reduce sphingolipid synthesis and generate catalytic promiscuity, incorporating alanine or glycine into the precursor sphingolipid to generate a deoxysphingoid base (DSB). Why either loss of function in SPT1, or generation of DSBs should generate deficits in distal sensory function remains unclear. To address these questions, we generated a Drosophila model of HSAN1. Expression of dSpt1 bearing a disease-related mutation induced morphological deficits in synapse growth at the larval neuromuscular junction consistent with a dominant-negative action. Expression of mutant dSpt1 globally was found to be mildly toxic, but was completely toxic when the diet was supplemented with alanine, when DSBs were observed in abundance. Expression of mutant dSpt1 in sensory neurons generated developmental deficits in dendritic arborization with concomitant sensory deficits. A membrane trafficking defect was observed in soma of sensory neurons expressing mutant dSpt1, consistent with endoplasmic reticulum (ER) to Golgi block. We found that we could rescue sensory function in neurons expressing mutant dSpt1 by co-expressing an effector of ER–Golgi function, Rab1 suggesting compromised ER function in HSAN1 affected dendritic neurons. Our Drosophila model identifies a novel strategy to explore the pathological mechanisms of HSAN1. PMID:26395456

HEPMath 1.4: A mathematica package for semi-automatic computations in high energy physics

NASA Astrophysics Data System (ADS)

Wiebusch, Martin

2015-10-01

This article introduces the Mathematica package HEPMath which provides a number of utilities and algorithms for High Energy Physics computations in Mathematica. Its functionality is similar to packages like FormCalc or FeynCalc, but it takes a more complete and extensible approach to implementing common High Energy Physics notations in the Mathematica language, in particular those related to tensors and index contractions. It also provides a more flexible method for the generation of numerical code which is based on new features for C code generation in Mathematica. In particular it can automatically generate Python extension modules which make the compiled functions callable from Python, thus eliminating the need to write any code in a low-level language like C or Fortran. It also contains seamless interfaces to LHAPDF, FeynArts, and LoopTools.

Divergent hydraulic strategies to cope with freezing in co-occurring temperate tree species with special reference to root and stem pressure generation.

PubMed

Yin, Xiao-Han; Sterck, Frank; Hao, Guang-You

2018-04-23

Some temperate tree species mitigate the negative impacts of frost-induced xylem cavitation by restoring impaired hydraulic function via positive pressures, and may therefore be more resistant to frost fatigue (the phenomenon that post-freezing xylem becomes more susceptible to hydraulic dysfunction) than nonpressure-generating species. We test this hypothesis and investigate underlying anatomical/physiological mechanisms. Using a common garden experiment, we studied key hydraulic traits and detailed xylem anatomical characteristics of 18 sympatric tree species. These species belong to three functional groups, that is, one generating both root and stem pressures (RSP), one generating only root pressure (RP), and one unable to generate such pressures (NP). The three functional groups diverged substantially in hydraulic efficiency, resistance to drought-induced cavitation, and frost fatigue resistance. Most notably, RSP and RP were more resistant to frost fatigue than NP, but this was at the cost of reduced hydraulic conductivity for RSP and reduced resistance to drought-induced cavitation for RP. Our results show that, in environments with strong frost stress: these groups diverge in hydraulic functioning following multiple trade-offs between hydraulic efficiency, resistance to drought and resistance to frost fatigue; and how differences in anatomical characteristics drive such divergence across species. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Generalized functional linear models for gene-based case-control association studies.

PubMed

Fan, Ruzong; Wang, Yifan; Mills, James L; Carter, Tonia C; Lobach, Iryna; Wilson, Alexander F; Bailey-Wilson, Joan E; Weeks, Daniel E; Xiong, Momiao

2014-11-01

By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT-O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT-O. In practice, it is not known whether rare variants or common variants in a gene region are disease related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT-O on real neural tube defects and Hirschsprung's disease datasets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT-O in the real data analysis. Our methods can be used in either gene-disease genome-wide/exome-wide association studies or candidate gene analyses. © 2014 WILEY PERIODICALS, INC.

Generalized Functional Linear Models for Gene-based Case-Control Association Studies

PubMed Central

Mills, James L.; Carter, Tonia C.; Lobach, Iryna; Wilson, Alexander F.; Bailey-Wilson, Joan E.; Weeks, Daniel E.; Xiong, Momiao

2014-01-01

By using functional data analysis techniques, we developed generalized functional linear models for testing association between a dichotomous trait and multiple genetic variants in a genetic region while adjusting for covariates. Both fixed and mixed effect models are developed and compared. Extensive simulations show that Rao's efficient score tests of the fixed effect models are very conservative since they generate lower type I errors than nominal levels, and global tests of the mixed effect models generate accurate type I errors. Furthermore, we found that the Rao's efficient score test statistics of the fixed effect models have higher power than the sequence kernel association test (SKAT) and its optimal unified version (SKAT-O) in most cases when the causal variants are both rare and common. When the causal variants are all rare (i.e., minor allele frequencies less than 0.03), the Rao's efficient score test statistics and the global tests have similar or slightly lower power than SKAT and SKAT-O. In practice, it is not known whether rare variants or common variants in a gene are disease-related. All we can assume is that a combination of rare and common variants influences disease susceptibility. Thus, the improved performance of our models when the causal variants are both rare and common shows that the proposed models can be very useful in dissecting complex traits. We compare the performance of our methods with SKAT and SKAT-O on real neural tube defects and Hirschsprung's disease data sets. The Rao's efficient score test statistics and the global tests are more sensitive than SKAT and SKAT-O in the real data analysis. Our methods can be used in either gene-disease genome-wide/exome-wide association studies or candidate gene analyses. PMID:25203683

A Versatile Room-Temperature Route to Di- and Trisubstituted Allenes Using Flow-Generated Diazo Compounds.

PubMed

Poh, Jian-Siang; Tran, Duc N; Battilocchio, Claudio; Hawkins, Joel M; Ley, Steven V

2015-06-26

A copper-catalyzed coupling reaction between flow-generated unstabilized diazo compounds and terminal alkynes provides di- and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Transcriptome analysis of two recombinant inbred lines of common bean contrasting for symbiotic nitrogen fixation

PubMed Central

Kamfwa, Kelvin; Zhao, Dongyan; Kelly, James D.

2017-01-01

Common bean (Phaseolus vulgaris L.) fixes atmospheric nitrogen (N2) through symbiotic nitrogen fixation (SNF) at levels lower than other grain legume crops. An understanding of the genes and molecular mechanisms underlying SNF will enable more effective strategies for the genetic improvement of SNF traits in common bean. In this study, transcriptome profiling was used to identify genes and molecular mechanisms underlying SNF differences between two common bean recombinant inbred lines that differed in their N-fixing abilities. Differential gene expression and functional enrichment analyses were performed on leaves, nodules and roots of the two lines when grown under N-fixing and non-fixing conditions. Receptor kinases, transmembrane transporters, and transcription factors were among the differentially expressed genes identified under N-fixing conditions, but not under non-fixing conditions. Genes up-regulated in the stronger nitrogen fixer, SA36, included those involved in molecular functions such as purine nucleoside binding, oxidoreductase and transmembrane receptor activities in nodules, and transport activity in roots. Transcription factors identified in this study are candidates for future work aimed at understanding the functional role of these genes in SNF. Information generated in this study will support the development of gene-based markers to accelerate genetic improvement of SNF in common bean. PMID:28192540

How Prediction Errors Shape Perception, Attention, and Motivation

PubMed Central

den Ouden, Hanneke E. M.; Kok, Peter; de Lange, Floris P.

2012-01-01

Prediction errors (PE) are a central notion in theoretical models of reinforcement learning, perceptual inference, decision-making and cognition, and prediction error signals have been reported across a wide range of brain regions and experimental paradigms. Here, we will make an attempt to see the forest for the trees and consider the commonalities and differences of reported PE signals in light of recent suggestions that the computation of PE forms a fundamental mode of brain function. We discuss where different types of PE are encoded, how they are generated, and the different functional roles they fulfill. We suggest that while encoding of PE is a common computation across brain regions, the content and function of these error signals can be very different and are determined by the afferent and efferent connections within the neural circuitry in which they arise. PMID:23248610

Structure-function covariation with nonfeeding ecological variables influences evolution of feeding specialization in Carnivora

PubMed Central

Tseng, Z. Jack; Flynn, John J.

2018-01-01

Skull shape convergence is pervasive among vertebrates. Although this is frequently inferred to indicate similar functional underpinnings, neither the specific structure-function linkages nor the selective environments in which the supposed functional adaptations arose are commonly identified and tested. We demonstrate that nonfeeding factors relating to sexual maturity and precipitation-related arboreality also can generate structure-function relationships in the skulls of carnivorans (dogs, cats, seals, and relatives) through covariation with masticatory performance. We estimated measures of masticatory performance related to ecological variables that covary with cranial shape in the mammalian order Carnivora, integrating geometric morphometrics and finite element analyses. Even after accounting for phylogenetic autocorrelation, cranial shapes are significantly correlated to both feeding and nonfeeding ecological variables, and covariation with both variable types generated significant masticatory performance gradients. This suggests that mechanisms of obligate shape covariation with nonfeeding variables can produce performance changes resembling those arising from feeding adaptations in Carnivora. PMID:29441363

Price dynamics and market power in an agent-based power exchange

NASA Astrophysics Data System (ADS)

Cincotti, Silvano; Guerci, Eric; Raberto, Marco

2005-05-01

This paper presents an agent-based model of a power exchange. Supply of electric power is provided by competing generating companies, whereas demand is assumed to be inelastic with respect to price and is constant over time. The transmission network topology is assumed to be a fully connected graph and no transmission constraints are taken into account. The price formation process follows a common scheme for real power exchanges: a clearing house mechanism with uniform price, i.e., with price set equal across all matched buyer-seller pairs. A single class of generating companies is considered, characterized by linear cost function for each technology. Generating companies compete for the sale of electricity through repeated rounds of the uniform auction and determine their supply functions according to production costs. However, an individual reinforcement learning algorithm characterizes generating companies behaviors in order to attain the expected maximum possible profit in each auction round. The paper investigates how the market competitive equilibrium is affected by market microstructure and production costs.

Creativity and the default network: A functional connectivity analysis of the creative brain at rest☆

PubMed Central

Beaty, Roger E.; Benedek, Mathias; Wilkins, Robin W.; Jauk, Emanuel; Fink, Andreas; Silvia, Paul J.; Hodges, Donald A.; Koschutnig, Karl; Neubauer, Aljoscha C.

2014-01-01

The present research used resting-state functional magnetic resonance imaging (fMRI) to examine whether the ability to generate creative ideas corresponds to differences in the intrinsic organization of functional networks in the brain. We examined the functional connectivity between regions commonly implicated in neuroimaging studies of divergent thinking, including the inferior prefrontal cortex and the core hubs of the default network. Participants were prescreened on a battery of divergent thinking tests and assigned to high- and low-creative groups based on task performance. Seed-based functional connectivity analysis revealed greater connectivity between the left inferior frontal gyrus (IFG) and the entire default mode network in the high-creative group. The right IFG also showed greater functional connectivity with bilateral inferior parietal cortex and the left dorsolateral prefrontal cortex in the high-creative group. The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes. PMID:25245940

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors

PubMed Central

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M.; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M.; Brunet, Jean-Francois; Ericson, Johan

2003-01-01

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates. PMID:12651891

ViennaNGS: A toolbox for building efficient next- generation sequencing analysis pipelines

PubMed Central

Wolfinger, Michael T.; Fallmann, Jörg; Eggenhofer, Florian; Amman, Fabian

2015-01-01

Recent achievements in next-generation sequencing (NGS) technologies lead to a high demand for reuseable software components to easily compile customized analysis workflows for big genomics data. We present ViennaNGS, an integrated collection of Perl modules focused on building efficient pipelines for NGS data processing. It comes with functionality for extracting and converting features from common NGS file formats, computation and evaluation of read mapping statistics, as well as normalization of RNA abundance. Moreover, ViennaNGS provides software components for identification and characterization of splice junctions from RNA-seq data, parsing and condensing sequence motif data, automated construction of Assembly and Track Hubs for the UCSC genome browser, as well as wrapper routines for a set of commonly used NGS command line tools. PMID:26236465

The mechanical role of the cervix in pregnancy

PubMed Central

Myers, Kristin M.; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J.; Hall, Timothy J.; House, Michael

2015-01-01

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineation of normal and abnormal cervical function in pregnancy. PMID:25841293

The mechanical role of the cervix in pregnancy.

PubMed

Myers, Kristin M; Feltovich, Helen; Mazza, Edoardo; Vink, Joy; Bajka, Michael; Wapner, Ronald J; Hall, Timothy J; House, Michael

2015-06-25

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interactive Sonification Exploring Emergent Behavior Applying Models for Biological Information and Listening

PubMed Central

Choi, Insook

2018-01-01

Sonification is an open-ended design task to construct sound informing a listener of data. Understanding application context is critical for shaping design requirements for data translation into sound. Sonification requires methodology to maintain reproducibility when data sources exhibit non-linear properties of self-organization and emergent behavior. This research formalizes interactive sonification in an extensible model to support reproducibility when data exhibits emergent behavior. In the absence of sonification theory, extensibility demonstrates relevant methods across case studies. The interactive sonification framework foregrounds three factors: reproducible system implementation for generating sonification; interactive mechanisms enhancing a listener's multisensory observations; and reproducible data from models that characterize emergent behavior. Supramodal attention research suggests interactive exploration with auditory feedback can generate context for recognizing irregular patterns and transient dynamics. The sonification framework provides circular causality as a signal pathway for modeling a listener interacting with emergent behavior. The extensible sonification model adopts a data acquisition pathway to formalize functional symmetry across three subsystems: Experimental Data Source, Sound Generation, and Guided Exploration. To differentiate time criticality and dimensionality of emerging dynamics, tuning functions are applied between subsystems to maintain scale and symmetry of concurrent processes and temporal dynamics. Tuning functions accommodate sonification design strategies that yield order parameter values to render emerging patterns discoverable as well as rehearsable, to reproduce desired instances for clinical listeners. Case studies are implemented with two computational models, Chua's circuit and Swarm Chemistry social agent simulation, generating data in real-time that exhibits emergent behavior. Heuristic Listening is introduced as an informal model of a listener's clinical attention to data sonification through multisensory interaction in a context of structured inquiry. Three methods are introduced to assess the proposed sonification framework: Listening Scenario classification, data flow Attunement, and Sonification Design Patterns to classify sound control. Case study implementations are assessed against these methods comparing levels of abstraction between experimental data and sound generation. Outcomes demonstrate the framework performance as a reference model for representing experimental implementations, also for identifying common sonification structures having different experimental implementations, identifying common functions implemented in different subsystems, and comparing impact of affordances across multiple implementations of listening scenarios. PMID:29755311

Feasibility of generating quantitative composition images in dual energy mammography: a simulation study

NASA Astrophysics Data System (ADS)

Lee, Donghoon; Kim, Ye-seul; Choi, Sunghoon; Lee, Haenghwa; Choi, Seungyeon; Kim, Hee-Joung

2016-03-01

Breast cancer is one of the most common malignancies in women. For years, mammography has been used as the gold standard for localizing breast cancer, despite its limitation in determining cancer composition. Therefore, the purpose of this simulation study is to confirm the feasibility of obtaining tumor composition using dual energy digital mammography. To generate X-ray sources for dual energy mammography, 26 kVp and 39 kVp voltages were generated for low and high energy beams, respectively. Additionally, the energy subtraction and inverse mapping functions were applied to provide compositional images. The resultant images showed that the breast composition obtained by the inverse mapping function with cubic fitting achieved the highest accuracy and least noise. Furthermore, breast density analysis with cubic fitting showed less than 10% error compare to true values. In conclusion, this study demonstrated the feasibility of creating individual compositional images and capability of analyzing breast density effectively.

Quantum mechanical energy-based screening of combinatorially generated library of tautomers. TauTGen: a tautomer generator program.

PubMed

Harańczyk, Maciej; Gutowski, Maciej

2007-01-01

We describe a procedure of finding low-energy tautomers of a molecule. The procedure consists of (i) combinatorial generation of a library of tautomers, (ii) screening based on the results of geometry optimization of initial structures performed at the density functional level of theory, and (iii) final refinement of geometry for the top hits at the second-order Möller-Plesset level of theory followed by single-point energy calculations at the coupled cluster level of theory with single, double, and perturbative triple excitations. The library of initial structures of various tautomers is generated with TauTGen, a tautomer generator program. The procedure proved to be successful for these molecular systems for which common chemical knowledge had not been sufficient to predict the most stable structures.

Function and evolution of sex determination mechanisms, genes and pathways in insects

PubMed Central

Gempe, Tanja; Beye, Martin

2011-01-01

Animals have evolved a bewildering diversity of mechanisms to determine the two sexes. Studies of sex determination genes – their history and function – in non-model insects and Drosophila have allowed us to begin to understand the generation of sex determination diversity. One common theme from these studies is that evolved mechanisms produce activities in either males or females to control a shared gene switch that regulates sexual development. Only a few small-scale changes in existing and duplicated genes are sufficient to generate large differences in sex determination systems. This review summarises recent findings in insects, surveys evidence of how and why sex determination mechanisms can change rapidly and suggests fruitful areas of future research. PMID:21110346

Role of the terminator hairpin in the biogenesis of functional Hfq-binding sRNAs

PubMed Central

Morita, Teppei; Nishino, Ryo; Aiba, Hiroji

2017-01-01

Rho-independent transcription terminators of the genes encoding bacterial Hfq-binding sRNAs possess a set of seven or more T residues at the 3′ end, as noted in previous studies. Here, we have studied the role of the terminator hairpin in the biogenesis of sRNAs focusing on SgrS and RyhB in Escherichia coli. We constructed variant sRNA genes in which the GC-rich inverted repeat sequences are extended to stabilize the terminator hairpins. We demonstrate that the extension of the hairpin stem leads to generation of heterogeneous transcripts in which the poly(U) tail is shortened. The transcripts with shortened poly(U) tails no longer bind to Hfq and lose the ability to repress the target mRNAs. The shortened transcripts are generated in an in vitro transcription system with purified RNA polymerase, indicating that the generation of shortened transcripts is caused by premature transcription termination. We conclude that the terminator structure of sRNA genes is optimized to generate functional sRNAs. Thus, the Rho-independent terminators of sRNA genes possess two common features: a long T residue stretch that is a prerequisite for generation of functional sRNAs and a moderate strength of hairpin structure that ensures the termination at the seventh or longer position within the consecutive T stretch. The modulation of the termination position at the Rho-independent terminators is critical for biosynthesis of functional sRNAs. PMID:28606943

Beam Instrument Development System

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

DOOLITTLE, LAWRENCE; HUANG, GANG; DU, QIANG

Beam Instrumentation Development System (BIDS) is a collection of common support libraries and modules developed during a series of Low-Level Radio Frequency (LLRF) control and timing/synchronization projects. BIDS includes a collection of Hardware Description Language (HDL) libraries and software libraries. The BIDS can be used for the development of any FPGA-based system, such as LLRF controllers. HDL code in this library is generic and supports common Digital Signal Processing (DSP) functions, FPGA-specific drivers (high-speed serial link wrappers, clock generation, etc.), ADC/DAC drivers, Ethernet MAC implementation, etc.

Nonlinear model for an optical read-only-memory disk readout channel based on an edge-spread function.

PubMed

Kobayashi, Seiji

2002-05-10

A point-spread function (PSF) is commonly used as a model of an optical disk readout channel. However, the model given by the PSF does not contain the quadratic distortion generated by the photo-detection process. We introduce a model for calculating an approximation of the quadratic component of a signal. We show that this model can be further simplified when a read-only-memory (ROM) disk is assumed. We introduce an edge-spread function by which a simple nonlinear model of an optical ROM disk readout channel is created.

2D Mesh Manipulation

DTIC Science & Technology

2011-11-01

the Poisson form of the equations can also be generated by manipulating the computational space , so forcing functions become superfluous . The...ABSTRACT Unstructured methods for region discretization have become common in computational fluid dynamics (CFD) analysis because of certain benefits...application of Winslow elliptic smoothing equations to unstructured meshes. It has been shown that it is not necessary for the computational space of

Discovering Green, Aqueous Suzuki Coupling Reactions: Synthesis of Ethyl (4-Phenylphenyl)Acetate, a Biaryl with Anti-Arthritic Potential

ERIC Educational Resources Information Center

Costa, Nancy E.; Pelotte, Andrea L.; Simard, Joseph M.; Syvinski, Christopher A.; Deveau, Amy M.

2012-01-01

Suzuki couplings are powerful chemical reactions commonly employed in academic and industrial research settings to generate functionalized biaryls. We have developed and implemented a discovery-based, microscale experiment for the undergraduate organic chemistry laboratory that explores green Suzuki coupling using water as the primary solvent.…

Scaling properties of the aerodynamic noise generated by low-speed fans

NASA Astrophysics Data System (ADS)

Canepa, Edward; Cattanei, Andrea; Mazzocut Zecchin, Fabio

2017-11-01

The spectral decomposition algorithm presented in the paper may be applied to selected parts of the SPL spectrum, i.e. to specific noise generating mechanisms. It yields the propagation and the generation functions, and indeed the Mach number scaling exponent associated with each mechanism as a function of the Strouhal number. The input data are SPL spectra obtained from measurements taken during speed ramps. Firstly, the basic theory and the implemented algorithm are described. Then, the behaviour of the new method is analysed with reference to numerically generated spectral data and the results are compared with the ones of an existing method based on the assumption that the scaling exponent is constant. Guidelines for the employment of both methods are provided. Finally, the method is applied to measurements taken on a cooling fan mounted on a test plenum designed following the ISO 10302 standards. The most common noise generating mechanisms are present and attention is focused on the low-frequency part of the spectrum, where the mechanisms are superposed. Generally, both propagation and generation functions are determined with better accuracy than the scaling exponent, whose values are usually consistent with expectations based on coherence and compactness of the acoustic sources. For periodic noise, the computed exponent is less accurate, as the related SPL data set has usually a limited size. The scaling exponent is very sensitive to the details of the experimental data, e.g. to slight inconsistencies or random errors.

Creativity and the default network: A functional connectivity analysis of the creative brain at rest.

PubMed

Beaty, Roger E; Benedek, Mathias; Wilkins, Robin W; Jauk, Emanuel; Fink, Andreas; Silvia, Paul J; Hodges, Donald A; Koschutnig, Karl; Neubauer, Aljoscha C

2014-11-01

The present research used resting-state functional magnetic resonance imaging (fMRI) to examine whether the ability to generate creative ideas corresponds to differences in the intrinsic organization of functional networks in the brain. We examined the functional connectivity between regions commonly implicated in neuroimaging studies of divergent thinking, including the inferior prefrontal cortex and the core hubs of the default network. Participants were prescreened on a battery of divergent thinking tests and assigned to high- and low-creative groups based on task performance. Seed-based functional connectivity analysis revealed greater connectivity between the left inferior frontal gyrus (IFG) and the entire default mode network in the high-creative group. The right IFG also showed greater functional connectivity with bilateral inferior parietal cortex and the left dorsolateral prefrontal cortex in the high-creative group. The results suggest that the ability to generate creative ideas is characterized by increased functional connectivity between the inferior prefrontal cortex and the default network, pointing to a greater cooperation between brain regions associated with cognitive control and low-level imaginative processes. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

High speed reaction wheels for satellite attitude control and energy storage

NASA Technical Reports Server (NTRS)

Studer, P.; Rodriguez, E.

1985-01-01

The combination of spacecraft attitude control and energy storage (ACES) functions in common hardware, to synergistically maintain three-axis attitude control while supplying electrical power during earth orbital eclipses, allows the generation of control torques by high rotating speed wheels that react against the spacecraft structure via a high efficiency bidirectional energy conversion motor/generator. An ACES system encompasses a minimum of four wheels, controlling power and the three torque vectors. Attention is given to the realization of such a system with composite flywheel rotors that yield high energy density, magnetic suspension technology yielding low losses at high rotational speeds, and an ironless armature permanent magnet motor/generator yielding high energy conversion efficiency.

Arraying proteins by cell-free synthesis.

PubMed

He, Mingyue; Wang, Ming-Wei

2007-10-01

Recent advances in life science have led to great motivation for the development of protein arrays to study functions of genome-encoded proteins. While traditional cell-based methods have been commonly used for generating protein arrays, they are usually a time-consuming process with a number of technical challenges. Cell-free protein synthesis offers an attractive system for making protein arrays, not only does it rapidly converts the genetic information into functional proteins without the need for DNA cloning, but also presents a flexible environment amenable to production of folded proteins or proteins with defined modifications. Recent advancements have made it possible to rapidly generate protein arrays from PCR DNA templates through parallel on-chip protein synthesis. This article reviews current cell-free protein array technologies and their proteomic applications.

Metagenomics of Thermophiles with a Focus on Discovery of Novel Thermozymes

PubMed Central

DeCastro, María-Eugenia; Rodríguez-Belmonte, Esther; González-Siso, María-Isabel

2016-01-01

Microbial populations living in environments with temperatures above 50°C (thermophiles) have been widely studied, increasing our knowledge in the composition and function of these ecological communities. Since these populations express a broad number of heat-resistant enzymes (thermozymes), they also represent an important source for novel biocatalysts that can be potentially used in industrial processes. The integrated study of the whole-community DNA from an environment, known as metagenomics, coupled with the development of next generation sequencing (NGS) technologies, has allowed the generation of large amounts of data from thermophiles. In this review, we summarize the main approaches commonly utilized for assessing the taxonomic and functional diversity of thermophiles through metagenomics, including several bioinformatics tools and some metagenome-derived methods to isolate their thermozymes. PMID:27729905

Computational Prediction of the Global Functional Genomic Landscape: Applications, Methods and Challenges

PubMed Central

Zhou, Weiqiang; Sherwood, Ben; Ji, Hongkai

2017-01-01

Technological advances have led to an explosive growth of high-throughput functional genomic data. Exploiting the correlation among different data types, it is possible to predict one functional genomic data type from other data types. Prediction tools are valuable in understanding the relationship among different functional genomic signals. They also provide a cost-efficient solution to inferring the unknown functional genomic profiles when experimental data are unavailable due to resource or technological constraints. The predicted data may be used for generating hypotheses, prioritizing targets, interpreting disease variants, facilitating data integration, quality control, and many other purposes. This article reviews various applications of prediction methods in functional genomics, discusses analytical challenges, and highlights some common and effective strategies used to develop prediction methods for functional genomic data. PMID:28076869

Power system market implementation in a deregulated environment

NASA Astrophysics Data System (ADS)

Silva, Carlos

2000-10-01

The opening of the power system markets (also known as deregulation) gives rise to issues never seen before by this industry. One of the most important is the control of information about the cost of generation. Information that used to be common knowledge is now kept private by the new agents of the system (generator companies, distribution companies, etc.). Data such as the generator cost functions are now known only by the owning companies. The result is a new system consisting of a group of independent firms seeking the maximization of their own profit. There have been many proposals to organize the new market in an economically efficient manner. Nevertheless, the uniqueness of the electric power system has prevented the development of such a market. This thesis evaluates the most common proposals using simulations in an auction setting. In addition a new methodology is proposed based on mechanism design, a common technique in economics, that solves some of the practical problems of power system markets (such as the management of limited transmission capacity). In this methodology, when each company acts in its best interest, the outcome is efficient in spite of the information problem cited above. This new methodology, along with the existing methodologies, are tested using simulation and analyzed to create a clear comparison of benefits and disadvantages.

Role of the terminator hairpin in the biogenesis of functional Hfq-binding sRNAs.

PubMed

Morita, Teppei; Nishino, Ryo; Aiba, Hiroji

2017-09-01

Rho-independent transcription terminators of the genes encoding bacterial Hfq-binding sRNAs possess a set of seven or more T residues at the 3' end, as noted in previous studies. Here, we have studied the role of the terminator hairpin in the biogenesis of sRNAs focusing on SgrS and RyhB in Escherichia coli. We constructed variant sRNA genes in which the GC-rich inverted repeat sequences are extended to stabilize the terminator hairpins. We demonstrate that the extension of the hairpin stem leads to generation of heterogeneous transcripts in which the poly(U) tail is shortened. The transcripts with shortened poly(U) tails no longer bind to Hfq and lose the ability to repress the target mRNAs. The shortened transcripts are generated in an in vitro transcription system with purified RNA polymerase, indicating that the generation of shortened transcripts is caused by premature transcription termination. We conclude that the terminator structure of sRNA genes is optimized to generate functional sRNAs. Thus, the Rho-independent terminators of sRNA genes possess two common features: a long T residue stretch that is a prerequisite for generation of functional sRNAs and a moderate strength of hairpin structure that ensures the termination at the seventh or longer position within the consecutive T stretch. The modulation of the termination position at the Rho-independent terminators is critical for biosynthesis of functional sRNAs. © 2017 Morita et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Planar harmonic polynomials of type B

NASA Astrophysics Data System (ADS)

Dunkl, Charles F.

1999-11-01

The hyperoctahedral group acting on icons/Journals/Common/BbbR" ALT="BbbR" ALIGN="TOP"/>N is the Weyl group of type B and is associated with a two-parameter family of differential-difference operators {Ti:1icons/Journals/Common/leq" ALT="leq" ALIGN="TOP"/> iicons/Journals/Common/leq" ALT="leq" ALIGN="TOP"/> N}. These operators are analogous to partial derivative operators. This paper finds all the polynomials h on icons/Journals/Common/BbbR" ALT="BbbR" ALIGN="TOP"/>N which are harmonic, icons/Journals/Common/Delta" ALT="Delta" ALIGN="TOP"/>Bh = 0 and annihilated by Ti for i>2, where the Laplacian 0305-4470/32/46/308/img1" ALT="(sum). They are given explicitly in terms of a novel basis of polynomials, defined by generating functions. The harmonic polynomials can be used to find wavefunctions for the quantum many-body spin Calogero model.

Individual Pressure Vessel (PV) and Common Pressure Vessel (CPV) Nickel-Hydrogen Battery Performance Under LEO Cycling Conditions

NASA Technical Reports Server (NTRS)

Miller, Thomas B.; Lewis, Harlan L.

2004-01-01

LEO life cycle testing of Individual Pressure Vessel (PV) and Common Pressure Vessel (CPV) nickel-hydrogen cell packs have been sponsored by the NASA Aerospace Flight Battery Program. The cell packs have cycled under both 35% and 60% depth-of- discharge and temperature conditions of -5 C and +lO C. The packs have been on test since as early as 1992 and have generated a substantial database. This report will provide insight into performance trends as a function of the specific cell configuration and manufacturer for eight separate nickel-hydrogen battery cell packs.

Plant resource history effects on contemporary microbial processes

NASA Astrophysics Data System (ADS)

Bradford, Mark

2010-05-01

Background/Questions/Methods Soil microbial communities play a pivotal role in providing ecosystem services, given that they are key drivers of biogeochemical processes such as carbon and nitrogen cycling. As species-rich communities, made-up of populations with short generation times, it is commonly assumed that there is a high degree of functional redundancy within soil communities with respect to broad-physiological processes, such as organic carbon decomposition. This assumption underlies the majority of terrestrial ecosystem models, where relationships between processes and controlling factors are parameterized using statistical relationships generated from measurements across space. However, microbial communities display biogeographic patterns, even at fine scales and it is possible that these patterns extend to influence their function. I first present experiments that combine common garden and reciprocal transplant approaches to test whether microbial communities sourced from distinct habitats across the contiguous United States exhibit functional similarity (i.e. redundancy) or dissimilarity in common environments. The environments are experimental microcosms composed of leaf litters differing markedly in recalcitrance. Following inoculation with the microbial communities, decomposition rates are followed across 300 days. Next, using a similar experimental microcosm design, I present experiments that test whether a common resource history might cause communities, which are initially dissimilar, to converge functionally. Distinct microbial communities are introduced into a fresh litter environment every 100 days for 300 days total. Finally, I present an experiment to test whether functional convergence (either partial or complete) is associated with a reduction in function in alternate environments (essentially a functional ‘trade-off'). In this last experiment decomposition rates are measured for 100 days in alternate environments following 300 days of successive exposure to a single litter type. Results/Conclusions I show in the first experiment that rates of carbon dioxide production from litter decomposition are strongly dependent on the microbial inoculum, with differences in the microbial community alone accounting for substantial (up to 85%) variation in total carbon mineralized. Communities that share a common history with a given foliar litter exhibit higher decomposition rates when compared to communities foreign to that habitat, suggestive of local adaptation. In the second experiment, decomposition rates (measured as cumulative carbon dioxide values per 100-day run) converge partially in the second 100-day run, and cumulative values for all six inocula increase toward the highest values observed in the initial 100-day run. Convergence continues but at a reduced rate in the third 100-day run; yet increases in function appear to asymptote. The increasing similarity in cumulative values between inocula, observed in the successive 100-day runs, is consistent with partial functional convergence of communities exposed to a common environment. In the final experiment, microbial inocula crossed to an alternate environment (e.g. those communities maintained in a grass environment then inoculated into a hardwood litter environment) results in cumulative values in the alternate environments that are approximately half those observed for communities inoculated into the same environment. Collectively, our results suggest that the implicit assumption in ecosystem models (i.e. microbial communities in the same environment are functionally equivalent) is incorrect. The increasing similarity across time in function in common environments of inocula sourced from different resource habitats shows the potential for function to converge. Yet this convergence is only partial and is associated with "apparent' trade-offs in the ability to decompose substrates from the original environments from which the inocula were sourced. To predict accurately how biogeochemical processes will respond to global change may require consideration of the community composition and/or adaptation of microbial communities to past resource environments and the consequences of their (partial) adaptation to new ones.

Pleasure systems in the brain

PubMed Central

Berridge, Kent C.; Kringelbach, Morten L.

2015-01-01

Pleasure is mediated by well-developed mesocorticolimbic circuitry, and serves adaptive functions. In affective disorders anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for rewards is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hotspots within limbic circuitry. Those hotspots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders. PMID:25950633

The digital generation and nursing robotics: A netnographic study about nursing care robots posted on social media.

PubMed

Eriksson, Henrik; Salzmann-Erikson, Martin

2017-04-01

The aim of this study was to present the functionality and design of nursing care robots as depicted in pictures posted on social media. A netnographic study was conducted using social media postings over a period of 3 years. One hundred and Seventy-two images were analyzed using netnographic methodology. The findings show that nursing care robots exist in various designs and functionalities, all with a common denominator of supporting the care of one's own and others' health and/or well-being as a main function. The results also show that functionality and design are influenced by recent popular sci-fi/cartoon contexts as portrayed in blockbuster movies, for example. Robots'designs seem more influenced by popular sci-fi/cartoon culture than professional nursing culture. We therefore stress that it is relevant for nursing researchers to critically reflect upon the development of nursing care robots as a thoughtful discussion about embracing technology also might generate a range of epistemological possibilities when entering a postmodern era of science and practice. © 2016 John Wiley & Sons Ltd.

Boundary-fitted coordinate systems for numerical solution of partial differential equations - A review

NASA Technical Reports Server (NTRS)

Thompson, J. F.; Warsi, Z. U. A.; Mastin, C. W.

1982-01-01

A comprehensive review of methods of numerically generating curvilinear coordinate systems with coordinate lines coincident with all boundary segments is given. Some general mathematical framework and error analysis common to such coordinate systems is also included. The general categories of generating systems are those based on conformal mapping, orthogonal systems, nearly orthogonal systems, systems produced as the solution of elliptic and hyperbolic partial differential equations, and systems generated algebraically by interpolation among the boundaries. Also covered are the control of coordinate line spacing by functions embedded in the partial differential operators of the generating system and by subsequent stretching transformation. Dynamically adaptive coordinate systems, coupled with the physical solution, and time-dependent systems that follow moving boundaries are treated. References reporting experience using such coordinate systems are reviewed as well as those covering the system development.

Modulated Modularity Clustering as an Exploratory Tool for Functional Genomic Inference

PubMed Central

Stone, Eric A.; Ayroles, Julien F.

2009-01-01

In recent years, the advent of high-throughput assays, coupled with their diminishing cost, has facilitated a systems approach to biology. As a consequence, massive amounts of data are currently being generated, requiring efficient methodology aimed at the reduction of scale. Whole-genome transcriptional profiling is a standard component of systems-level analyses, and to reduce scale and improve inference clustering genes is common. Since clustering is often the first step toward generating hypotheses, cluster quality is critical. Conversely, because the validation of cluster-driven hypotheses is indirect, it is critical that quality clusters not be obtained by subjective means. In this paper, we present a new objective-based clustering method and demonstrate that it yields high-quality results. Our method, modulated modularity clustering (MMC), seeks community structure in graphical data. MMC modulates the connection strengths of edges in a weighted graph to maximize an objective function (called modularity) that quantifies community structure. The result of this maximization is a clustering through which tightly-connected groups of vertices emerge. Our application is to systems genetics, and we quantitatively compare MMC both to the hierarchical clustering method most commonly employed and to three popular spectral clustering approaches. We further validate MMC through analyses of human and Drosophila melanogaster expression data, demonstrating that the clusters we obtain are biologically meaningful. We show MMC to be effective and suitable to applications of large scale. In light of these features, we advocate MMC as a standard tool for exploration and hypothesis generation. PMID:19424432

The Berlin Airlift And The Use Of Air Mobility As A Function Of US Policy

DTIC Science & Technology

2016-02-13

for future generations to efficiently and effectively conduct humanitarian relief operations. The Crisis...as a Triparte council; and 2) The nations of France, the United Kingdom, Holland, Belgium, and Luxembourg agreed to provide for a common defense ... for the inhabitants were subject to permit and inspection. Guidance from the Pentagon limited Clay’s actions.40 Clay requested authorization

Receiver functions from west Antarctica; crust and mantle properties from POLENET

NASA Astrophysics Data System (ADS)

Aster, R. C.; Chaput, J. A.; Hansen, S. E.; Nyblade, A.; Wiens, D. A.; Huerta, A. D.; Wilson, T. J.; Anandakrishnan, S.

2011-12-01

We use receiver functions to extract crustal thickness and mantle transition zone depths across a wide extent of West Antarctica and the Transantarctic mountains using POLENET data, including recently recovered data from a 14-station West Antarctic Rift Zone transect. An adaptive approach for generating and analyzing P-receiver functions over ice sheets and sedimentary basins (similar to Winberry and Anandakrishnan, 2004) is applied using an extended time multitaper deconvolution algorithm and forward modeling synthetic seismogram fitting. We model P-S receiver functions via a layer stripping methodology (beginning with the ice sheet, if present), and fit increasingly longer sections of synthetic receiver functions to model the multiples observed in the data derived receiver functions. We additionally calculate S-P receiver functions, which provide complementary structural constraints, to generate consistent common conversion point stacks to image crustal and upper mantle discontinuities under West Antarctica. Crust throughout West Antarctica is generally thin (23-29 km; comparable to the U.S. Basin and Range) with relative thickening under the Marie Byrd Land volcanic province (to 32 km) and the Transantarctic Mountains. All constrained west Antarctic crust is substantially thicker than that in the vicinity of Ross Island, where crust as thin as 17 km is inferred in the Terror Rift region.

Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

PubMed

Hitomi, Yuki; Tokunaga, Katsushi

2017-01-01

Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

Entanglement and Wigner Function Negativity of Multimode Non-Gaussian States

NASA Astrophysics Data System (ADS)

Walschaers, Mattia; Fabre, Claude; Parigi, Valentina; Treps, Nicolas

2017-11-01

Non-Gaussian operations are essential to exploit the quantum advantages in optical continuous variable quantum information protocols. We focus on mode-selective photon addition and subtraction as experimentally promising processes to create multimode non-Gaussian states. Our approach is based on correlation functions, as is common in quantum statistical mechanics and condensed matter physics, mixed with quantum optics tools. We formulate an analytical expression of the Wigner function after the subtraction or addition of a single photon, for arbitrarily many modes. It is used to demonstrate entanglement properties specific to non-Gaussian states and also leads to a practical and elegant condition for Wigner function negativity. Finally, we analyze the potential of photon addition and subtraction for an experimentally generated multimode Gaussian state.

Entanglement and Wigner Function Negativity of Multimode Non-Gaussian States.

PubMed

Walschaers, Mattia; Fabre, Claude; Parigi, Valentina; Treps, Nicolas

2017-11-03

Non-Gaussian operations are essential to exploit the quantum advantages in optical continuous variable quantum information protocols. We focus on mode-selective photon addition and subtraction as experimentally promising processes to create multimode non-Gaussian states. Our approach is based on correlation functions, as is common in quantum statistical mechanics and condensed matter physics, mixed with quantum optics tools. We formulate an analytical expression of the Wigner function after the subtraction or addition of a single photon, for arbitrarily many modes. It is used to demonstrate entanglement properties specific to non-Gaussian states and also leads to a practical and elegant condition for Wigner function negativity. Finally, we analyze the potential of photon addition and subtraction for an experimentally generated multimode Gaussian state.

A dataset of multiresolution functional brain parcellations in an elderly population with no or mild cognitive impairment.

PubMed

Tam, Angela; Dansereau, Christian; Badhwar, AmanPreet; Orban, Pierre; Belleville, Sylvie; Chertkow, Howard; Dagher, Alain; Hanganu, Alexandru; Monchi, Oury; Rosa-Neto, Pedro; Shmuel, Amir; Breitner, John; Bellec, Pierre

2016-12-01

We present group eight resolutions of brain parcellations for clusters generated from resting-state functional magnetic resonance images for 99 cognitively normal elderly persons and 129 patients with mild cognitive impairment, pooled from four independent datasets. This dataset was generated as part of the following study: Common Effects of Amnestic Mild Cognitive Impairment on Resting-State Connectivity Across Four Independent Studies (Tam et al., 2015) [1]. The brain parcellations have been registered to both symmetric and asymmetric MNI brain templates and generated using a method called bootstrap analysis of stable clusters (BASC) (Bellec et al., 2010) [2]. We present two variants of these parcellations. One variant contains bihemisphereic parcels (4, 6, 12, 22, 33, 65, 111, and 208 total parcels across eight resolutions). The second variant contains spatially connected regions of interest (ROIs) that span only one hemisphere (10, 17, 30, 51, 77, 199, and 322 total ROIs across eight resolutions). We also present maps illustrating functional connectivity differences between patients and controls for four regions of interest (striatum, dorsal prefrontal cortex, middle temporal lobe, and medial frontal cortex). The brain parcels and associated statistical maps have been publicly released as 3D volumes, available in .mnc and .nii file formats on figshare and on Neurovault. Finally, the code used to generate this dataset is available on Github.

A second generation human haplotype map of over 3.1 million SNPs.

PubMed

Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

2007-10-18

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r2 of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r2 of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.

A comparison of small-field tissue phantom ratio data generation methods for an Elekta Agility 6 MV photon beam

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

Richmond, Neil, E-mail: neil.richmond@stees.nhs.uk; Brackenridge, Robert

2014-04-01

Tissue-phantom ratios (TPRs) are a common dosimetric quantity used to describe the change in dose with depth in tissue. These can be challenging and time consuming to measure. The conversion of percentage depth dose (PDD) data using standard formulae is widely employed as an alternative method in generating TPR. However, the applicability of these formulae for small fields has been questioned in the literature. Functional representation has also been proposed for small-field TPR production. This article compares measured TPR data for small 6 MV photon fields against that generated by conversion of PDD using standard formulae to assess the efficacymore » of the conversion data. By functionally fitting the measured TPR data for square fields greater than 4 cm in length, the TPR curves for smaller fields are generated and compared with measurements. TPRs and PDDs were measured in a water tank for a range of square field sizes. The PDDs were converted to TPRs using standard formulae. TPRs for fields of 4 × 4 cm{sup 2} and larger were used to create functional fits. The parameterization coefficients were used to construct extrapolated TPR curves for 1 × 1 cm{sup 2}, 2 × 2-cm{sup 2}, and 3 × 3-cm{sup 2} fields. The TPR data generated using standard formulae were in excellent agreement with direct TPR measurements. The TPR data for 1 × 1-cm{sup 2}, 2 × 2-cm{sup 2}, and 3 × 3-cm{sup 2} fields created by extrapolation of the larger field functional fits gave inaccurate initial results. The corresponding mean differences for the 3 fields were 4.0%, 2.0%, and 0.9%. Generation of TPR data using a standard PDD-conversion methodology has been shown to give good agreement with our directly measured data for small fields. However, extrapolation of TPR data using the functional fit to fields of 4 × 4 cm{sup 2} or larger resulted in generation of TPR curves that did not compare well with the measured data.« less

Paternal alcoholism and offspring conduct disorder: evidence for the 'common genes' hypothesis.

PubMed

Haber, Jon R; Jacob, Theodore; Heath, Andrew C

2005-04-01

Not only are alcoholism and externalizing disorders frequently comorbid, they often co-occur in families across generations; for example, paternal alcoholism predicts offspring conduct disorder just as it does offspring alcoholism. To clarify this relationship, the current study examined the 'common genes' hypothesis utilizing a children-of-twins research design. Participants were male monozygotic (MZ) and dizygotic (DZ) twins from the Vietnam Era Twin Registry who were concordant or discordant for alcohol dependence together with their offspring and the mothers of those offspring. All participants were conducted through a structured psychiatric interview. Offspring risk of conduct disorder was examined as a function of alcoholism genetic risk (due to paternal and co-twin alcohol dependence) and alcoholism environmental risk (due to being reared by a father with an alcohol dependence diagnosis). After controlling for potentially confounding variables, the offspring of alcohol-dependent fathers were significantly more likely to exhibit conduct disorder diagnoses than were offspring of nonalcohol-dependent fathers, thus indicating diagnostic crossover in generational family transmission. Comparing offspring at high genetic and high environmental risk with offspring at high genetic and low environmental risk indicated that genetic factors were most likely responsible for the alcoholism-conduct disorder association. The observed diagnostic crossover (from paternal alcoholism to offspring conduct disorder) across generations in the context of both high and low environmental risk (while genetic risk remained high) supported the common genes hypothesis.

The forkhead domain gene unc-130 generates chemosensory neuron diversity in C. elegans

PubMed Central

Sarafi-Reinach, Trina R.; Sengupta, Piali

2000-01-01

Caenorhabditis elegans responds to its complex chemical environment using a small number of chemosensory neurons. Each of these neurons exhibits a unique sensory response repertoire. The developmental mechanisms that generate this diversity of function are largely unknown. Many C. elegans chemosensory neurons, including the AWA and ASG neurons, arise as lineal sisters of an asymmetric division. Here we describe the gene unc-130, which plays a role in the generation of the AWA and ASG neurons. In unc-130 mutants, the ASG neurons adopt the fate of the AWA neurons. unc-130 encodes a member of the forkhead domain family of transcription factors, and is expressed in the precursors to AWA and ASG neurons. Misexpression of unc-130 in the AWA neurons is partly sufficient to repress the AWA fate, but not to promote ASG fate. unc-130 also plays a role in the development of additional chemosensory neurons. Our experiments show that the ASG neurons share a developmental default state in common with three types of olfactory neurons. We propose that distinct cell fates and hence diversity of function in the chemosensory neurons of C. elegans are generated in a hierarchical manner, utilizing both lineage-dependent and independent mechanisms. PMID:11018015

Reference values for developing responsive functional outcome measures across the lifespan.

PubMed

McKay, Marnee J; Baldwin, Jennifer N; Ferreira, Paulo; Simic, Milena; Vanicek, Natalie; Burns, Joshua

2017-04-18

To generate a reference dataset of commonly performed functional outcome measures in 1,000 children and adults and investigate the influence of demographic, anthropometric, strength, and flexibility characteristics. Twelve functional outcome measures were collected from 1,000 healthy individuals aged 3-101 years: 6-minute walk test, 30-second chair stand test, timed stairs test, long jump, vertical jump, choice stepping reaction time, balance (Star Excursion Balance Test, tandem stance eyes open and closed, single-leg stance eyes closed), and dexterity (9-hole peg test, Functional Dexterity Test). Correlation and multiple regression analyses were performed to identify factors independently associated with each measure. Age- and sex-stratified reference values for functional outcome measures were generated. Functional performance increased through childhood and adolescence, plateaued during adulthood, and declined in older adulthood. While balance did not differ between the sexes, male participants generally performed better at gross motor tasks while female participants performed better at dexterous tasks. Height was the most consistent correlate of functional performance in children, while lower limb muscle strength was a major determinant in adolescents and adults. In older adults, age, lower limb strength, and joint flexibility explained up to 63% of the variance in functional measures. These normative reference values provide a framework to accurately track functional decline associated with neuromuscular disorders and assist development and validation of responsive outcome measures for therapeutic trials. © 2017 American Academy of Neurology.

LipidPedia: a comprehensive lipid knowledgebase.

PubMed

Kuo, Tien-Chueh; Tseng, Yufeng Jane

2018-04-10

Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

Competitive technologies of third generation infrared photon detectors

NASA Astrophysics Data System (ADS)

Rogalski, A.

2006-03-01

Hitherto, two families of multielement infrared (IR) detectors are used for principal military and civilian infrared applications; one is used for scanning systems (first generation) and the other is used for staring systems (second generation). Third generation systems are being developed nowadays. In the common understanding, third generation IR systems provide enhanced capabilities like larger number of pixels, higher frame rates, better thermal resolution as well as multicolour functionality and other on-chip functions. In the paper, issues associated with the development and exploitation of materials used in fabrication of third generation infrared photon detectors are discussed. In this class of detectors two main competitors, HgCdTe photodiodes and quantum well IR photoconductors (QWIPs) are considered. The performance figures of merit of state-of-the-art HgCdTe and QWIP focal plane arrays (FPAs) are similar because the main limitations come from the readout circuits. However, the metallurgical issues of the epitaxial layers such as uniformity and number of defected elements are the serious problems in the case of long wavelength infrared (LWIR) and very LWIR (VLWIR) HgCdTe FPAs. It is predicted that superlattice based InAs/GaInSb system grown on GaSb substrate seems to be an attractive to HgCdTe with good spatial uniformity and an ability to span cutoff wavelength from 3 to 25 μm.

Competitive technologies for third generation infrared photon detectors

NASA Astrophysics Data System (ADS)

Rogalski, A.

2006-05-01

Hitherto, two families of multielement infrared (IR) detectors are used for principal military and civilian infrared applications; one is used for scanning systems (first generation) and the other is used for staring systems (second generation). Third generation systems are being developed nowadays. In the common understanding, third generation IR systems provide enhanced capabilities like larger number of pixels, higher frame rates, better thermal resolution as well as multicolor functionality and other on-chip functions. In the paper, issues associated with the development and exploitation of materials used in fabrication of third generation infrared photon detectors are discussed. In this class of detectors two main competitors, HgCdTe photodiodes and quantum well photoconductors are considered. The performance figures of merit of state-of-the-art HgCdTe and QWIP focal plane arrays (FPAs) are similar because the main limitations come from the readout circuits. The metallurgical issues of the epitaxial layers such as uniformity and number of defected elements are the serious problems in the case of long wavelength infrared (LWIR) and very LWIR (VLWIR) HgCdTe FPAs. It is predicted that superlattice based InAs/GaInSb system grown on GaSb substrate seems to be an attractive to HgCdTe with good spatial uniformity and an ability to span cutoff wavelength from 3 to 25 μm. In this context the material properties of type II superlattices are considered more in detail.

Colloquium paper: bioenergetics, the origins of complexity, and the ascent of man.

PubMed

Wallace, Douglas C

2010-05-11

Complex structures are generated and maintained through energy flux. Structures embody information, and biological information is stored in nucleic acids. The progressive increase in biological complexity over geologic time is thus the consequence of the information-generating power of energy flow plus the information-accumulating capacity of DNA, winnowed by natural selection. Consequently, the most important component of the biological environment is energy flow: the availability of calories and their use for growth, survival, and reproduction. Animals can exploit and adapt to available energy resources at three levels. They can evolve different anatomical forms through nuclear DNA (nDNA) mutations permitting exploitation of alternative energy reservoirs, resulting in new species. They can evolve modified bioenergetic physiologies within a species, primarily through the high mutation rate of mitochondrial DNA (mtDNA)-encoded bioenergetic genes, permitting adjustment to regional energetic environments. They can alter the epigenomic regulation of the thousands of dispersed bioenergetic genes via mitochondrially generated high-energy intermediates permitting individual accommodation to short-term environmental energetic fluctuations. Because medicine pertains to a single species, Homo sapiens, functional human variation often involves sequence changes in bioenergetic genes, most commonly mtDNA mutations, plus changes in the expression of bioenergetic genes mediated by the epigenome. Consequently, common nDNA polymorphisms in anatomical genes may represent only a fraction of the genetic variation associated with the common "complex" diseases, and the ascent of man has been the product of 3.5 billion years of information generation by energy flow, accumulated and preserved in DNA and edited by natural selection.

Understanding the Cellular Function of TRPV2 Channel through Generation of Specific Monoclonal Antibodies

PubMed Central

Cohen, Matthew R.; Huynh, Kevin W.; Cawley, Daniel; Moiseenkova-Bell, Vera Y.

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function. PMID:24392006

Understanding the cellular function of TRPV2 channel through generation of specific monoclonal antibodies.

PubMed

Cohen, Matthew R; Huynh, Kevin W; Cawley, Daniel; Moiseenkova-Bell, Vera Y

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca(2+)-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function.

Conditioning of FRF measurements for use with frequency based substructuring

NASA Astrophysics Data System (ADS)

Nicgorski, Dana; Avitabile, Peter

2010-02-01

Frequency based substructuring approaches have been used for the generation of system models from component data. While numerical models show successful results, there have been many difficulties with actual measurements in many instances. Previous work has identified some of these typical problems using simulated data to incorporate specific measurement difficulties commonly observed along with approaches to overcome some of these difficulties. This paper presents the results using actual measured data for a laboratory structure subjected to both analytical and experimental studies. Various commonly used approaches are shown to illustrate some of the difficulties with measured data. A new approach to better condition the measured functions and purge commonly found data measurement contaminants is utilized to provide dramatically improved results. Several cases are explored to show the difficulties commonly observed as well as the improved conditioning of the measured data to obtain acceptable results.

astroplan: An Open Source Observation Planning Package in Python

NASA Astrophysics Data System (ADS)

Morris, Brett M.; Tollerud, Erik; Sipőcz, Brigitta; Deil, Christoph; Douglas, Stephanie T.; Berlanga Medina, Jazmin; Vyhmeister, Karl; Smith, Toby R.; Littlefair, Stuart; Price-Whelan, Adrian M.; Gee, Wilfred T.; Jeschke, Eric

2018-03-01

We present astroplan—an open source, open development, Astropy affiliated package for ground-based observation planning and scheduling in Python. astroplan is designed to provide efficient access to common observational quantities such as celestial rise, set, and meridian transit times and simple transformations from sky coordinates to altitude-azimuth coordinates without requiring a detailed understanding of astropy’s implementation of coordinate systems. astroplan provides convenience functions to generate common observational plots such as airmass and parallactic angle as a function of time, along with basic sky (finder) charts. Users can determine whether or not a target is observable given a variety of observing constraints, such as airmass limits, time ranges, Moon illumination/separation ranges, and more. A selection of observation schedulers are included that divide observing time among a list of targets, given observing constraints on those targets. Contributions to the source code from the community are welcome.

General Linker Diversification Approach to Bivalent Ligand Assembly: Generation of an Array of Ligands for the Cation-Independent Mannose 6-Phosphate Receptor.

PubMed

Fei, Xiang; Zavorka, Megan E; Malik, Guillaume; Connelly, Christopher M; MacDonald, Richard G; Berkowitz, David B

2017-08-18

A generalized strategy is presented for the rapid assembly of a set of bivalent ligands with a variety of linking functionalities from a common monomer. Herein, an array of phosphatase-inert mannose-6-phosphonate-presenting ligands for the cation-independent-mannose 6-phosphate receptor (CI-MPR) is constructed. Receptor binding affinity varies with linking functionality-the simple amide and 1,5-triazole(tetrazole) being preferred over the 1,4-triazole. This approach is expected to find application across chemical biology, particularly in glycoscience, wherein multivalency often governs molecular recognition.

Scaffold Diversity Synthesis Delivers Complex, Structurally, and Functionally Distinct Tetracyclic Benzopyrones

PubMed Central

Sankar, Muthukumar G.; Roy, Sayantani; Tran, Tuyen Thi Ngoc; Wittstein, Kathrin; Bauer, Jonathan O.; Strohmann, Carsten; Ziegler, Slava

2018-01-01

Abstract Complexity‐generating chemical transformations that afford novel molecular scaffolds enriched in sp 3 character are highly desired. Here, we present a highly stereoselective scaffold diversity synthesis approach that utilizes cascade double‐annulation reactions of diverse pairs of zwitterionic and non‐zwitterionic partners with 3‐formylchromones to generate highly complex tetracyclic benzopyrones. Each pair of annulation partners adds to the common chroman‐4‐one scaffold to build two new rings, supporting up to four contiguous chiral centers that include an all‐carbon quaternary center. Differently ring‐fused benzopyrones display different biological activities, thus demonstrating their immense potential in medicinal chemistry and chemical biology research. PMID:29721402

Identification of novel drought-tolerant-associated SNPs in common bean (Phaseolus vulgaris)

PubMed Central

Villordo-Pineda, Emiliano; González-Chavira, Mario M.; Giraldo-Carbajo, Patricia; Acosta-Gallegos, Jorge A.; Caballero-Pérez, Juan

2015-01-01

Common bean (Phaseolus vulgaris L.) is a leguminous in high demand for human nutrition and a very important agricultural product. Production of common bean is constrained by environmental stresses such as drought. Although conventional plant selection has been used to increase production yield and stress tolerance, drought tolerance selection based on phenotype is complicated by associated physiological, anatomical, cellular, biochemical, and molecular changes. These changes are modulated by differential gene expression. A common method to identify genes associated with phenotypes of interest is the characterization of Single Nucleotide Polymorphims (SNPs) to link them to specific functions. In this work, we selected two drought-tolerant parental lines from Mesoamerica, Pinto Villa, and Pinto Saltillo. The parental lines were used to generate a population of 282 families (F3:5) and characterized by 169 SNPs. We associated the segregation of the molecular markers in our population with phenotypes including flowering time, physiological maturity, reproductive period, plant, seed and total biomass, reuse index, seed yield, weight of 100 seeds, and harvest index in three cultivation cycles. We observed 83 SNPs with significant association (p < 0.0003 after Bonferroni correction) with our quantified phenotypes. Phenotypes most associated were days to flowering and seed biomass with 58 and 44 associated SNPs, respectively. Thirty-seven out of the 83 SNPs were annotated to a gene with a potential function related to drought tolerance or relevant molecular/biochemical functions. Some SNPs such as SNP28 and SNP128 are related to starch biosynthesis, a common osmotic protector; and SNP18 is related to proline biosynthesis, another well-known osmotic protector. PMID:26257755

Identification of novel drought-tolerant-associated SNPs in common bean (Phaseolus vulgaris).

PubMed

Villordo-Pineda, Emiliano; González-Chavira, Mario M; Giraldo-Carbajo, Patricia; Acosta-Gallegos, Jorge A; Caballero-Pérez, Juan

2015-01-01

Common bean (Phaseolus vulgaris L.) is a leguminous in high demand for human nutrition and a very important agricultural product. Production of common bean is constrained by environmental stresses such as drought. Although conventional plant selection has been used to increase production yield and stress tolerance, drought tolerance selection based on phenotype is complicated by associated physiological, anatomical, cellular, biochemical, and molecular changes. These changes are modulated by differential gene expression. A common method to identify genes associated with phenotypes of interest is the characterization of Single Nucleotide Polymorphims (SNPs) to link them to specific functions. In this work, we selected two drought-tolerant parental lines from Mesoamerica, Pinto Villa, and Pinto Saltillo. The parental lines were used to generate a population of 282 families (F3:5) and characterized by 169 SNPs. We associated the segregation of the molecular markers in our population with phenotypes including flowering time, physiological maturity, reproductive period, plant, seed and total biomass, reuse index, seed yield, weight of 100 seeds, and harvest index in three cultivation cycles. We observed 83 SNPs with significant association (p < 0.0003 after Bonferroni correction) with our quantified phenotypes. Phenotypes most associated were days to flowering and seed biomass with 58 and 44 associated SNPs, respectively. Thirty-seven out of the 83 SNPs were annotated to a gene with a potential function related to drought tolerance or relevant molecular/biochemical functions. Some SNPs such as SNP28 and SNP128 are related to starch biosynthesis, a common osmotic protector; and SNP18 is related to proline biosynthesis, another well-known osmotic protector.

Long-range correlations in time series generated by time-fractional diffusion: A numerical study

NASA Astrophysics Data System (ADS)

Barbieri, Davide; Vivoli, Alessandro

2005-09-01

Time series models showing power law tails in autocorrelation functions are common in econometrics. A special non-Markovian model for such kind of time series is provided by the random walk introduced by Gorenflo et al. as a discretization of time fractional diffusion. The time series so obtained are analyzed here from a numerical point of view in terms of autocorrelations and covariance matrices.

Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease.

PubMed

Buvelot, Helene; Posfay-Barbe, Klara M; Linder, Patrick; Schrenzel, Jacques; Krause, Karl-Heinz

2017-03-01

Dysfunction of phagocytes is a relevant risk factor for staphylococcal infection. The most common hereditary phagocyte dysfunction is chronic granulomatous disease (CGD), characterized by impaired generation of reactive oxygen species (ROS) due to loss of function mutations within the phagocyte NADPH oxidase NOX2. Phagocytes ROS generation is fundamental to eliminate pathogens and to regulate the inflammatory response to infection. CGD is characterized by recurrent and severe bacterial and fungal infections, with Staphylococcus aureus as the most frequent pathogen, and skin and lung abscesses as the most common clinical entities. Staphylococcus aureus infection may occur in virtually any human host, presumably because of the many virulence factors of the bacterium. However, in the presence of functional NOX2, staphylococcal infections remain rare and are mainly linked to breaches of the skin barrier. In contrast, in patients with CGD, S. aureus readily survives and frequently causes clinically apparent disease. Astonishingly, little is known why S. aureus, which possesses a wide range of antioxidant enzymes (e.g. catalase, SOD), is particularly sensitive to control through NOX2. In this review, we will evaluate the discovery of CGD and our present knowledge of the role of NOX2 in S. aureus infection. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Functional Characterization of a Novel Marine Microbial GDSL Lipase and Its Utilization in the Resolution of (±)-1-Phenylethanol.

PubMed

Deng, Dun; Zhang, Yun; Sun, Aijun; Liang, Jiayuan; Hu, Yunfeng

2016-04-01

A novel GDSL lipase (MT6) was cloned from the genome of Marinactinospora thermotolerans SCSIO 00652 identified from the South China Sea. MT6 showed its maximum identity of 59 % with a putative lipase from Nocardiopsis dassonville. MT6 was heterologously expressed in E. coli BL21(DE3) and further functionally characterized. MT6 could efficiently resolve racemic 1-phenylethanol and generate (R)-1-phenylethanol with high enantiomeric excess (99 %) and conversion rate (54 %) through transesterification reactions after process optimization. Our report was the first one report about the utilization of one GDSL lipase in the preparation of chiral chemicals by transesterification reactions, and the optical selectivity of MT6 was interestingly opposite to those of other common lipases. GDSL lipases represented by MT6 possess great potential for the generation of valuable chiral chemicals in industry.

Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 4: IPAD system design

NASA Technical Reports Server (NTRS)

Goldfarb, W.; Carpenter, L. C.; Redhed, D. D.; Hansen, S. D.; Anderson, L. O.; Kawaguchi, A. S.

1973-01-01

The computing system design of IPAD is described and the requirements which form the basis for the system design are discussed. The system is presented in terms of a functional design description and technical design specifications. The functional design specifications give the detailed description of the system design using top-down structured programming methodology. Human behavioral characteristics, which specify the system design at the user interface, security considerations, and standards for system design, implementation, and maintenance are also part of the technical design specifications. Detailed specifications of the two most common computing system types in use by the major aerospace companies which could support the IPAD system design are presented. The report of a study to investigate migration of IPAD software between the two candidate 3rd generation host computing systems and from these systems to a 4th generation system is included.

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

PubMed Central

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; DeLay, Michael; Driks, Adam; Sahin, Ozgur

2015-01-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment. PMID:26079632

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

NASA Astrophysics Data System (ADS)

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; Delay, Michael; Driks, Adam; Sahin, Ozgur

2015-06-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air-water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A non-JKL density matrix functional for intergeminal correlation between closed-shell geminals from analysis of natural orbital configuration interaction expansions

NASA Astrophysics Data System (ADS)

van Meer, R.; Gritsenko, O. V.; Baerends, E. J.

2018-03-01

Almost all functionals that are currently used in density matrix functional theory have been created by some a priori ansatz that generates approximations to the second-order reduced density matrix (2RDM). In this paper, a more consistent approach is used: we analyze the 2RDMs (in the natural orbital basis) of rather accurate multi-reference configuration interaction expansions for several small molecules (CH4, NH3, H2O, FH, and N2) and use the knowledge gained to generate new functionals. The analysis shows that a geminal-like structure is present in the 2RDMs, even though no geminal theory has been applied from the onset. It is also shown that the leading non-geminal dynamical correlation contributions are generated by a specific set of double excitations. The corresponding determinants give rise to non-JKL (non Coulomb/Exchange like) multipole-multipole dispersive attractive terms between geminals. Due to the proximity of the geminals, these dispersion terms are large and cannot be omitted, proving pure JKL functionals to be essentially deficient. A second correction emerges from the observation that the "normal" geminal-like exchange between geminals breaks down when one breaks multiple bonds. This problem can be fixed by doubling the exchange between bond broken geminals, effectively restoring the often physically correct high-spin configurations on the bond broken fragments. Both of these corrections have been added to the commonly used antisymmetrized product of strongly orthogonal geminals functional. The resulting non-JKL functional Extended Löwdin-Shull Dynamical-Multibond is capable of reproducing complete active space self-consistent field curves, in which one active orbital is used for each valence electron.

In Silico Comparative Transcriptome Analysis of Two Color Morphs of the Common Coral Trout (Plectropomus Leopardus)

PubMed Central

Wang, Le; Yu, Cuiping; Guo, Liang; Lin, Haoran; Meng, Zining

2015-01-01

The common coral trout is one species of major importance in commercial fisheries and aquaculture. Recently, two different color morphs of Plectropomus leopardus were discovered and the biological importance of the color difference is unknown. Since coral trout species are poorly characterized at the molecular level, we undertook the transcriptomic characterization of the two color morphs, one black and one red coral trout, using Illumina next generation sequencing technologies. The study produced 55162966 and 54588952 paired-end reads, for black and red trout, respectively. De novo transcriptome assembly generated 95367 and 99424 unique sequences in black and red trout, respectively, with 88813 sequences shared between them. Approximately 50% of both trancriptomes were functionally annotated by BLAST searches against protein databases. The two trancriptomes were enriched into 25 functional categories and showed similar profiles of Gene Ontology category compositions. 34110 unigenes were grouped into 259 KEGG pathways. Moreover, we identified 14649 simple sequence repeats (SSRs) and designed primers for potential application. We also discovered 130524 putative single nucleotide polymorphisms (SNPs) in the two transcriptomes, supplying potential genomic resources for the coral trout species. In addition, we identified 936 fast-evolving genes and 165 candidate genes under positive selection between the two color morphs. Finally, 38 candidate genes underlying the mechanism of color and pigmentation were also isolated. This study presents the first transcriptome resources for the common coral trout and provides basic information for the development of genomic tools for the identification, conservation, and understanding of the speciation and local adaptation of coral reef fish species. PMID:26713756

Analysis and modeling of localized heat generation by tumor-targeted nanoparticles (Monte Carlo methods)

NASA Astrophysics Data System (ADS)

Sanattalab, Ehsan; SalmanOgli, Ahmad; Piskin, Erhan

2016-04-01

We investigated the tumor-targeted nanoparticles that influence heat generation. We suppose that all nanoparticles are fully functionalized and can find the target using active targeting methods. Unlike the commonly used methods, such as chemotherapy and radiotherapy, the treatment procedure proposed in this study is purely noninvasive, which is considered to be a significant merit. It is found that the localized heat generation due to targeted nanoparticles is significantly higher than other areas. By engineering the optical properties of nanoparticles, including scattering, absorption coefficients, and asymmetry factor (cosine scattering angle), the heat generated in the tumor's area reaches to such critical state that can burn the targeted tumor. The amount of heat generated by inserting smart agents, due to the surface Plasmon resonance, will be remarkably high. The light-matter interactions and trajectory of incident photon upon targeted tissues are simulated by MIE theory and Monte Carlo method, respectively. Monte Carlo method is a statistical one by which we can accurately probe the photon trajectories into a simulation area.

Enzymatic Oxidation of Cholesterol: Properties and Functional Effects of Cholestenone in Cell Membranes

PubMed Central

Neuvonen, Maarit; Manna, Moutusi; Mokkila, Sini; Javanainen, Matti; Rog, Tomasz; Liu, Zheng; Bittman, Robert; Vattulainen, Ilpo; Ikonen, Elina

2014-01-01

Bacterial cholesterol oxidase is commonly used as an experimental tool to reduce cellular cholesterol content. That the treatment also generates the poorly degradable metabolite 4-cholesten-3-one (cholestenone) has received less attention. Here, we investigated the membrane partitioning of cholestenone using simulations and cell biological experiments and assessed the functional effects of cholestenone in human cells. Atomistic simulations predicted that cholestenone reduces membrane order, undergoes faster flip-flop and desorbs more readily from membranes than cholesterol. In primary human fibroblasts, cholestenone was released from membranes to physiological extracellular acceptors more avidly than cholesterol, but without acceptors it remained in cells over a day. To address the functional effects of cholestenone, we studied fibroblast migration during wound healing. When cells were either cholesterol oxidase treated or part of cellular cholesterol was exchanged for cholestenone with cyclodextrin, cell migration during 22 h was markedly inhibited. Instead, when a similar fraction of cholesterol was removed using cyclodextrin, cells replenished their cholesterol content in 3 h and migrated similarly to control cells. Thus, cholesterol oxidation produces long-term functional effects in cells and these are in part due to the generated membrane active cholestenone. PMID:25157633

Gradient descent for robust kernel-based regression

NASA Astrophysics Data System (ADS)

Guo, Zheng-Chu; Hu, Ting; Shi, Lei

2018-06-01

In this paper, we study the gradient descent algorithm generated by a robust loss function over a reproducing kernel Hilbert space (RKHS). The loss function is defined by a windowing function G and a scale parameter σ, which can include a wide range of commonly used robust losses for regression. There is still a gap between theoretical analysis and optimization process of empirical risk minimization based on loss: the estimator needs to be global optimal in the theoretical analysis while the optimization method can not ensure the global optimality of its solutions. In this paper, we aim to fill this gap by developing a novel theoretical analysis on the performance of estimators generated by the gradient descent algorithm. We demonstrate that with an appropriately chosen scale parameter σ, the gradient update with early stopping rules can approximate the regression function. Our elegant error analysis can lead to convergence in the standard L 2 norm and the strong RKHS norm, both of which are optimal in the mini-max sense. We show that the scale parameter σ plays an important role in providing robustness as well as fast convergence. The numerical experiments implemented on synthetic examples and real data set also support our theoretical results.

Alterations in emotion generation and regulation neurocircuitry in depression and eating disorders: A comparative review of structural and functional neuroimaging studies.

PubMed

Donofry, Shannon D; Roecklein, Kathryn A; Wildes, Jennifer E; Miller, Megan A; Erickson, Kirk I

2016-09-01

Major depression and eating disorders (EDs) are highly co-morbid and may share liability. Impaired emotion regulation may represent a common etiological or maintaining mechanism. Research has demonstrated that depressed individuals and individuals with EDs exhibit impaired emotion regulation, with these impairments being associated with changes in brain structure and function. The goal of this review was to evaluate findings from neuroimaging studies of depression and EDs to determine whether there are overlapping alterations in the brain regions known to be involved in emotion regulation, evidence of which would aid in the diagnosis and treatment of these conditions. Our review of the literature suggests that depression and EDs exhibit common structural and functional alterations in brain regions involved in emotion regulation, including the amygdala, ventral striatum and nucleus accumbens, anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. We present preliminary support for a shared etiological mechanism. Future studies should consider manipulating emotion regulation in a sample of individuals with depression and EDs to better characterize abnormalities in these brain circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rotor noise due to blade-turbulence interaction

NASA Astrophysics Data System (ADS)

Ishimaru, K.

1983-01-01

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)-(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function.

The DNA Data Bank of Japan launches a new resource, the DDBJ Omics Archive of functional genomics experiments.

PubMed

Kodama, Yuichi; Mashima, Jun; Kaminuma, Eli; Gojobori, Takashi; Ogasawara, Osamu; Takagi, Toshihisa; Okubo, Kousaku; Nakamura, Yasukazu

2012-01-01

The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists of public, open-access nucleotide sequence databases including raw sequence reads, assembly information and functional annotation. Database content is exchanged with EBI and NCBI within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). In 2011, DDBJ launched two new resources: the 'DDBJ Omics Archive' (DOR; http://trace.ddbj.nig.ac.jp/dor) and BioProject (http://trace.ddbj.nig.ac.jp/bioproject). DOR is an archival database of functional genomics data generated by microarray and highly parallel new generation sequencers. Data are exchanged between the ArrayExpress at EBI and DOR in the common MAGE-TAB format. BioProject provides an organizational framework to access metadata about research projects and the data from the projects that are deposited into different databases. In this article, we describe major changes and improvements introduced to the DDBJ services, and the launch of two new resources: DOR and BioProject.

Flexibility decline contributes to similarity of past and future thinking in Alzheimer's disease.

PubMed

El Haj, Mohamad; Antoine, Pascal; Kapogiannis, Dimitrios

2015-11-01

A striking similarity has been suggested between past and future thinking in Alzheimer's Disease (AD), a similarity attributable to abnormalities in common modular cognitive functions and neuroanatomical substrates. This study extends this literature by identifying specific executive function deficits underlying past and future thinking in AD. Twenty-four participants with a clinical diagnosis of probable (mild) AD and 26 older controls generated past and future events and underwent tests of binding and the executive functions of flexibility, inhibition, and updating. AD patients showed similar autobiographical performances in past and future event generation, and so did control participants. In each group, the similarity of past and future thinking was predicted by flexibility. Furthermore, AD patients with low flexibility showed higher similarity of past and future thinking than those with high flexibility. These findings are interpreted in terms of involvement of the hippocampus and frontal lobes in future thinking. Deficits in these brain regions in AD are likely to compromise the ability to recombine episodic information into novel and flexible configurations as scenarios for the future. © 2015 Wiley Periodicals, Inc.

Flexibility Decline Contributes to Similarity of Past and Future Thinking in Alzheimer’s Disease

PubMed Central

El Haj, Mohamad; Antoine, Pascal; Kapogiannis, Dimitrios

2017-01-01

A striking similarity has been suggested between past and future thinking in Alzheimer’s Disease (AD), a similarity attributable to abnormalities in common modular cognitive functions and neuroanatomical substrates. This study extends this literature by identifying specific executive function deficits underlying past and future thinking in AD. Twenty-four participants with a clinical diagnosis of probable (mild) AD and 26 older controls generated past and future events and underwent tests of binding and the executive functions of flexibility, inhibition, and updating. AD patients showed similar autobiographical performances in past and future event generation, and so did control participants. In each group, the similarity of past and future thinking was predicted by flexibility. Furthermore, AD patients with low flexibility showed higher similarity of past and future thinking than those with high flexibility. These findings are interpreted in terms of involvement of the hippocampus and frontal lobes in future thinking. Deficits in these brain regions in AD are likely to compromise the ability to recombine episodic information into novel and flexible configurations as scenarios for the future. PMID:25850800

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells

PubMed Central

Camp, J. Gray; Weiser, Matthew; Cocchiaro, Jordan L.; Kingsley, David M.; Furey, Terrence S.; Sheikh, Shehzad Z.; Rawls, John F.

2017-01-01

The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology. PMID:28850571

Age effect in generating mental images of buildings but not common objects.

PubMed

Piccardi, L; Nori, R; Palermo, L; Guariglia, C; Giusberti, F

2015-08-18

Imagining a familiar environment is different from imagining an environmental map and clinical evidence demonstrated the existence of double dissociations in brain-damaged patients due to the contents of mental images. Here, we assessed a large sample of young and old participants by considering their ability to generate different kinds of mental images, namely, buildings or common objects. As buildings are environmental stimuli that have an important role in human navigation, we expected that elderly participants would have greater difficulty in generating images of buildings than common objects. We found that young and older participants differed in generating both buildings and common objects. For young participants there were no differences between buildings and common objects, but older participants found easier to generate common objects than buildings. Buildings are a special type of visual stimuli because in urban environments they are commonly used as landmarks for navigational purposes. Considering that topographical orientation is one of the abilities mostly affected in normal and pathological aging, the present data throw some light on the impaired processes underlying human navigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

MDplot: Visualise Molecular Dynamics.

PubMed

Margreitter, Christian; Oostenbrink, Chris

2017-05-10

The MDplot package provides plotting functions to allow for automated visualisation of molecular dynamics simulation output. It is especially useful in cases where the plot generation is rather tedious due to complex file formats or when a large number of plots are generated. The graphs that are supported range from those which are standard, such as RMsD/RMsF (root-mean-square deviation and root-mean-square fluctuation, respectively) to less standard, such as thermodynamic integration analysis and hydrogen bond monitoring over time. All told, they address many commonly used analyses. In this article, we set out the MDplot package's functions, give examples of the function calls, and show the associated plots. Plotting and data parsing is separated in all cases, i.e. the respective functions can be used independently. Thus, data manipulation and the integration of additional file formats is fairly easy. Currently, the loading functions support GROMOS, GROMACS, and AMBER file formats. Moreover, we also provide a Bash interface that allows simple embedding of MDplot into Bash scripts as the final analysis step. The package can be obtained in the latest major version from CRAN (https://cran.r-project.org/package=MDplot) or in the most recent version from the project's GitHub page at https://github.com/MDplot/MDplot, where feedback is also most welcome. MDplot is published under the GPL-3 license.

Evolutionary evidence of the effect of rare variants on disease etiology.

PubMed

Gorlov, I P; Gorlova, O Y; Frazier, M L; Spitz, M R; Amos, C I

2011-03-01

The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single-nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk-associated rare SNPs. © 2010 John Wiley & Sons A/S.

Augmented Currents of an HCN2 Variant in Patients with Febrile Seizure Syndromes

PubMed Central

Dibbens, Leanne M.; Reid, Christopher A.; Hodgson, Bree; Thomas, Evan A.; Phillips, Alison M.; Gazina, Elena; Cromer, Brett A.; Clarke, Alison L.; Baram, Tallie Z.; Scheffer, Ingrid E.; Berkovic, Samuel F.; Petrou, Steven

2012-01-01

The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were ~35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy. PMID:20437590

Social psychology as a natural kind

PubMed Central

Mitchell, Jason P.

2010-01-01

Summary Although typically defined as the study of how people and groups interact, the field of social psychology comprises a number of disparate domains that make only indirect contributions to understanding interpersonal interaction, such as emotion, attitudes, and the self. Although these various phenomena may appear to have little in common, recent evidence suggests that the topics at the core of social psychology form a natural group of domains with a common functional neuroanatomy, centered on the medial prefrontal cortex. That self-referential, attitudinal, affective, and other social phenomena converge on this region may reflect their shared reliance on inexact and internally-generated estimates that differ from the more precise representations underlying other psychological phenomena. PMID:19427258

Functional linear models for association analysis of quantitative traits.

PubMed

Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

2013-11-01

Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY PERIODICALS, INC.

HangOut: generating clean PSI-BLAST profiles for domains with long insertions.

PubMed

Kim, Bong-Hyun; Cong, Qian; Grishin, Nick V

2010-06-15

Profile-based similarity search is an essential step in structure-function studies of proteins. However, inclusion of non-homologous sequence segments into a profile causes its corruption and results in false positives. Profile corruption is common in multidomain proteins, and single domains with long insertions are a significant source of errors. We developed a procedure (HangOut) that, for a single domain with specified insertion position, cleans erroneously extended PSI-BLAST alignments to generate better profiles. HangOut is implemented in Python 2.3 and runs on all Unix-compatible platforms. The source code is available under the GNU GPL license at http://prodata.swmed.edu/HangOut/. Supplementary data are available at Bioinformatics online.

Functional DNA quantification guides accurate next-generation sequencing mutation detection in formalin-fixed, paraffin-embedded tumor biopsies

PubMed Central

2013-01-01

The formalin-fixed, paraffin-embedded (FFPE) biopsy is a challenging sample for molecular assays such as targeted next-generation sequencing (NGS). We compared three methods for FFPE DNA quantification, including a novel PCR assay (‘QFI-PCR’) that measures the absolute copy number of amplifiable DNA, across 165 residual clinical specimens. The results reveal the limitations of commonly used approaches, and demonstrate the value of an integrated workflow using QFI-PCR to improve the accuracy of NGS mutation detection and guide changes in input that can rescue low quality FFPE DNA. These findings address a growing need for improved quality measures in NGS-based patient testing. PMID:24001039

Culture and Moral Distress: What's the Connection and Why Does It Matter?

PubMed

Berlinger, Nancy; Berlinger, Annalise

2017-06-01

Culture is learned behavior shared among members of a group and from generation to generation within that group. In health care work, references to "culture" may also function as code for ethical uncertainty or moral distress concerning patients, families, or populations. This paper analyzes how culture can be a factor in patient-care situations that produce moral distress. It discusses three common, problematic situations in which assumptions about culture may mask more complex problems concerning family dynamics, structural barriers to health care access, or implicit bias. We offer sets of practical recommendations to encourage learning, critical thinking, and professional reflection among students, clinicians, and clinical educators. © 2017 American Medical Association. All Rights Reserved.

Microdistribution of oxygen in silicon and its effects on electronic properties

NASA Technical Reports Server (NTRS)

Gatos, H. C.; Mao, B. Y.; Nauka, K.; Lagowski, J.

1982-01-01

The effects of interstitial oxygen on the electrical characteristics of Czochralski-grown silicon crystals were investigated for the first time on a microscale. It was found that the generation of thermal donors is not a direct function of the oxygen concentration. It was further found that the minority carrier life-time decreases with increasing oxygen concentration, on a microscale in as-grown crystals. It was thus shown, again for the first time, that oxygen in as grown crystals is not electronically inert as generally believed. Preannealing at 1200 C commonly employed in device fabrication, was found to suppress the donor generation at 450 C and to decrease the deep level concentrations.

Decoupling function and anatomy in atlases of functional connectivity patterns: language mapping in tumor patients.

PubMed

Langs, Georg; Sweet, Andrew; Lashkari, Danial; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J; Golland, Polina

2014-12-01

In this paper we construct an atlas that summarizes functional connectivity characteristics of a cognitive process from a population of individuals. The atlas encodes functional connectivity structure in a low-dimensional embedding space that is derived from a diffusion process on a graph that represents correlations of fMRI time courses. The functional atlas is decoupled from the anatomical space, and thus can represent functional networks with variable spatial distribution in a population. In practice the atlas is represented by a common prior distribution for the embedded fMRI signals of all subjects. We derive an algorithm for fitting this generative model to the observed data in a population. Our results in a language fMRI study demonstrate that the method identifies coherent and functionally equivalent regions across subjects. The method also successfully maps functional networks from a healthy population used as a training set to individuals whose language networks are affected by tumors. Copyright © 2014. Published by Elsevier Inc.

Luciferase reporter assay in Drosophila and mammalian tissue culture cells

PubMed Central

Yun, Chi

2014-01-01

Luciferase reporter gene assays are one of the most common methods for monitoring gene activity. Because of their sensitivity, dynamic range, and lack of endogenous activity, luciferase assays have been particularly useful for functional genomics in cell-based assays, such as RNAi screening. This unit describes delivery of two luciferase reporters with other nucleic acids (siRNA /dsRNA), measurement of the dual luciferase activities, and analysis of data generated. The systematic query of gene function (RNAi) combined with the advances in luminescent technology have made it possible to design powerful whole genome screens to address diverse and significant biological questions. PMID:24652620

Strategies for the generation of parametric images of [11C]PIB with plasma input functions considering discriminations and reproducibility.

PubMed

Edison, Paul; Brooks, David J; Turkheimer, Federico E; Archer, Hilary A; Hinz, Rainer

2009-11-01

Pittsburgh compound B or [11C]PIB is an amyloid imaging agent which shows a clear differentiation between subjects with Alzheimer's disease (AD) and controls. However the observed signal difference in other forms of dementia such as dementia with Lewy bodies (DLB) is smaller, and mild cognitively impaired (MCI) subjects and some healthy elderly normals may show intermediate levels of [11C]PIB binding. The cerebellum, a commonly used reference region for non-specific tracer uptake in [11C]PIB studies in AD may not be valid in Prion disorders or monogenic forms of AD. The aim of this work was to: 1-compare methods for generating parametric maps of [11C]PIB retention in tissue using a plasma input function in respect of their ability to discriminate between AD subjects and controls and 2-estimate the test-retest reproducibility in AD subjects. 12 AD subjects (5 of which underwent a repeat scan within 6 weeks) and 10 control subjects had 90 minute [11C]PIB dynamic PET scans, and arterial plasma input functions were measured. Parametric maps were generated with graphical analysis of reversible binding (Logan plot), irreversible binding (Patlak plot), and spectral analysis. Between group differentiation was calculated using Student's t-test and comparisons between different methods were made using p values. Reproducibility was assessed by intraclass correlation coefficients (ICC). We found that the 75 min value of the impulse response function showed the best group differentiation and had a higher ICC than volume of distribution maps generated from Logan and spectral analysis. Patlak analysis of [11C]PIB binding was the least reproducible.

Semi-autonomous remote sensing time series generation tool

NASA Astrophysics Data System (ADS)

Babu, Dinesh Kumar; Kaufmann, Christof; Schmidt, Marco; Dhams, Thorsten; Conrad, Christopher

2017-10-01

High spatial and temporal resolution data is vital for crop monitoring and phenology change detection. Due to the lack of satellite architecture and frequent cloud cover issues, availability of daily high spatial data is still far from reality. Remote sensing time series generation of high spatial and temporal data by data fusion seems to be a practical alternative. However, it is not an easy process, since it involves multiple steps and also requires multiple tools. In this paper, a framework of Geo Information System (GIS) based tool is presented for semi-autonomous time series generation. This tool will eliminate the difficulties by automating all the steps and enable the users to generate synthetic time series data with ease. Firstly, all the steps required for the time series generation process are identified and grouped into blocks based on their functionalities. Later two main frameworks are created, one to perform all the pre-processing steps on various satellite data and the other one to perform data fusion to generate time series. The two frameworks can be used individually to perform specific tasks or they could be combined to perform both the processes in one go. This tool can handle most of the known geo data formats currently available which makes it a generic tool for time series generation of various remote sensing satellite data. This tool is developed as a common platform with good interface which provides lot of functionalities to enable further development of more remote sensing applications. A detailed description on the capabilities and the advantages of the frameworks are given in this paper.

Comparative functional analyses of ultrabithorax reveal multiple steps and paths to diversification of legs in the adaptive radiation of semi-aquatic insects.

PubMed

Khila, Abderrahman; Abouheif, Ehab; Rowe, Locke

2014-08-01

Invasion of new ecological habitats is often associated with lineage diversification, yet the genetic changes underlying invasions and radiations are poorly understood. Over 200 million years ago, the semi-aquatic insects invaded water surface from a common terrestrial ancestor and diversified to exploit a wide array of niches. Here, we uncover the changes in regulation and function of the gene Ultrabithorax associated with both the invasion of water surface and the subsequent diversification of the group. In the common ancestor of the semi-aquatic insects, a novel deployment of Ubx protein in the mid-legs increased their length, thereby enhancing their role in water surface walking. In derived lineages that specialize in rowing on the open water, additional changes in the timing of Ubx expression further elongated the mid-legs thereby facilitating their function as oars. In addition, Ubx protein function was selectively reversed to shorten specific rear-leg segments, thereby enabling their function as rudders. These changes in Ubx have generated distinct niche-specialized morphologies that account for the remarkable diversification of the semi-aquatic insects. Therefore, changes in the regulation and function of a key developmental gene may facilitate both the morphological change necessary to transition to novel habitats and fuel subsequent morphological diversification. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction.

PubMed

Ma, Hong; Wang, Li; Liu, Jiandong; Qian, Li

2017-01-01

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

EDGE3: A web-based solution for management and analysis of Agilent two color microarray experiments

PubMed Central

Vollrath, Aaron L; Smith, Adam A; Craven, Mark; Bradfield, Christopher A

2009-01-01

Background The ability to generate transcriptional data on the scale of entire genomes has been a boon both in the improvement of biological understanding and in the amount of data generated. The latter, the amount of data generated, has implications when it comes to effective storage, analysis and sharing of these data. A number of software tools have been developed to store, analyze, and share microarray data. However, a majority of these tools do not offer all of these features nor do they specifically target the commonly used two color Agilent DNA microarray platform. Thus, the motivating factor for the development of EDGE3 was to incorporate the storage, analysis and sharing of microarray data in a manner that would provide a means for research groups to collaborate on Agilent-based microarray experiments without a large investment in software-related expenditures or extensive training of end-users. Results EDGE3 has been developed with two major functions in mind. The first function is to provide a workflow process for the generation of microarray data by a research laboratory or a microarray facility. The second is to store, analyze, and share microarray data in a manner that doesn't require complicated software. To satisfy the first function, EDGE3 has been developed as a means to establish a well defined experimental workflow and information system for microarray generation. To satisfy the second function, the software application utilized as the user interface of EDGE3 is a web browser. Within the web browser, a user is able to access the entire functionality, including, but not limited to, the ability to perform a number of bioinformatics based analyses, collaborate between research groups through a user-based security model, and access to the raw data files and quality control files generated by the software used to extract the signals from an array image. Conclusion Here, we present EDGE3, an open-source, web-based application that allows for the storage, analysis, and controlled sharing of transcription-based microarray data generated on the Agilent DNA platform. In addition, EDGE3 provides a means for managing RNA samples and arrays during the hybridization process. EDGE3 is freely available for download at . PMID:19732451

EDGE(3): a web-based solution for management and analysis of Agilent two color microarray experiments.

PubMed

Vollrath, Aaron L; Smith, Adam A; Craven, Mark; Bradfield, Christopher A

2009-09-04

The ability to generate transcriptional data on the scale of entire genomes has been a boon both in the improvement of biological understanding and in the amount of data generated. The latter, the amount of data generated, has implications when it comes to effective storage, analysis and sharing of these data. A number of software tools have been developed to store, analyze, and share microarray data. However, a majority of these tools do not offer all of these features nor do they specifically target the commonly used two color Agilent DNA microarray platform. Thus, the motivating factor for the development of EDGE(3) was to incorporate the storage, analysis and sharing of microarray data in a manner that would provide a means for research groups to collaborate on Agilent-based microarray experiments without a large investment in software-related expenditures or extensive training of end-users. EDGE(3) has been developed with two major functions in mind. The first function is to provide a workflow process for the generation of microarray data by a research laboratory or a microarray facility. The second is to store, analyze, and share microarray data in a manner that doesn't require complicated software. To satisfy the first function, EDGE3 has been developed as a means to establish a well defined experimental workflow and information system for microarray generation. To satisfy the second function, the software application utilized as the user interface of EDGE(3) is a web browser. Within the web browser, a user is able to access the entire functionality, including, but not limited to, the ability to perform a number of bioinformatics based analyses, collaborate between research groups through a user-based security model, and access to the raw data files and quality control files generated by the software used to extract the signals from an array image. Here, we present EDGE(3), an open-source, web-based application that allows for the storage, analysis, and controlled sharing of transcription-based microarray data generated on the Agilent DNA platform. In addition, EDGE(3) provides a means for managing RNA samples and arrays during the hybridization process. EDGE(3) is freely available for download at http://edge.oncology.wisc.edu/.

Mapping membrane activity in undiscovered peptide sequence space using machine learning

PubMed Central

Fulan, Benjamin M.; Wong, Gerard C. L.

2016-01-01

There are some ∼1,100 known antimicrobial peptides (AMPs), which permeabilize microbial membranes but have diverse sequences. Here, we develop a support vector machine (SVM)-based classifier to investigate ⍺-helical AMPs and the interrelated nature of their functional commonality and sequence homology. SVM is used to search the undiscovered peptide sequence space and identify Pareto-optimal candidates that simultaneously maximize the distance σ from the SVM hyperplane (thus maximize its “antimicrobialness”) and its ⍺-helicity, but minimize mutational distance to known AMPs. By calibrating SVM machine learning results with killing assays and small-angle X-ray scattering (SAXS), we find that the SVM metric σ correlates not with a peptide’s minimum inhibitory concentration (MIC), but rather its ability to generate negative Gaussian membrane curvature. This surprising result provides a topological basis for membrane activity common to AMPs. Moreover, we highlight an important distinction between the maximal recognizability of a sequence to a trained AMP classifier (its ability to generate membrane curvature) and its maximal antimicrobial efficacy. As mutational distances are increased from known AMPs, we find AMP-like sequences that are increasingly difficult for nature to discover via simple mutation. Using the sequence map as a discovery tool, we find a unexpectedly diverse taxonomy of sequences that are just as membrane-active as known AMPs, but with a broad range of primary functions distinct from AMP functions, including endogenous neuropeptides, viral fusion proteins, topogenic peptides, and amyloids. The SVM classifier is useful as a general detector of membrane activity in peptide sequences. PMID:27849600

Predicting protein functions from redundancies in large-scale protein interaction networks

NASA Technical Reports Server (NTRS)

Samanta, Manoj Pratim; Liang, Shoudan

2003-01-01

Interpreting data from large-scale protein interaction experiments has been a challenging task because of the widespread presence of random false positives. Here, we present a network-based statistical algorithm that overcomes this difficulty and allows us to derive functions of unannotated proteins from large-scale interaction data. Our algorithm uses the insight that if two proteins share significantly larger number of common interaction partners than random, they have close functional associations. Analysis of publicly available data from Saccharomyces cerevisiae reveals >2,800 reliable functional associations, 29% of which involve at least one unannotated protein. By further analyzing these associations, we derive tentative functions for 81 unannotated proteins with high certainty. Our method is not overly sensitive to the false positives present in the data. Even after adding 50% randomly generated interactions to the measured data set, we are able to recover almost all (approximately 89%) of the original associations.

An Approach to Function Annotation for Proteins of Unknown Function (PUFs) in the Transcriptome of Indian Mulberry.

PubMed

Dhanyalakshmi, K H; Naika, Mahantesha B N; Sajeevan, R S; Mathew, Oommen K; Shafi, K Mohamed; Sowdhamini, Ramanathan; N Nataraja, Karaba

2016-01-01

The modern sequencing technologies are generating large volumes of information at the transcriptome and genome level. Translation of this information into a biological meaning is far behind the race due to which a significant portion of proteins discovered remain as proteins of unknown function (PUFs). Attempts to uncover the functional significance of PUFs are limited due to lack of easy and high throughput functional annotation tools. Here, we report an approach to assign putative functions to PUFs, identified in the transcriptome of mulberry, a perennial tree commonly cultivated as host of silkworm. We utilized the mulberry PUFs generated from leaf tissues exposed to drought stress at whole plant level. A sequence and structure based computational analysis predicted the probable function of the PUFs. For rapid and easy annotation of PUFs, we developed an automated pipeline by integrating diverse bioinformatics tools, designated as PUFs Annotation Server (PUFAS), which also provides a web service API (Application Programming Interface) for a large-scale analysis up to a genome. The expression analysis of three selected PUFs annotated by the pipeline revealed abiotic stress responsiveness of the genes, and hence their potential role in stress acclimation pathways. The automated pipeline developed here could be extended to assign functions to PUFs from any organism in general. PUFAS web server is available at http://caps.ncbs.res.in/pufas/ and the web service is accessible at http://capservices.ncbs.res.in/help/pufas.

Common Risk Criteria Standards for National Test Ranges

DTIC Science & Technology

2017-09-01

critical assets. Equipment and facilities that comprise part of an on- or off-base renewable energy system, such as wind turbine generation facilities...to be protected. As an example, for a wind turbine farm, the unit component would be a single wind turbine . A unit component can be considered...functionality of the larger system to which the unit component belongs. For example, a single wind turbine is a unit component of a wind turbine farm. A

Color synesthesia. Insight into perception, emotion, and consciousness

PubMed Central

Safran, Avinoam B.; Sanda, Nicolae

2015-01-01

Purpose of review Synesthesia is an extraordinary perceptual phenomenon, in which individuals experience unusual percepts elicited by the activation of an unrelated sensory modality or by a cognitive process. Emotional reactions are commonly associated. The condition prompted philosophical debates on the nature of perception and impacted the course of art history. It recently generated a considerable interest among neuroscientists, but its clinical significance apparently remains underevaluated. This review focuses on the recent studies regarding variants of color synesthesia, the commonest form of the condition. Recent findings Synesthesia is commonly classified as developmental and acquired. Developmental forms predispose to changes in primary sensory processing and cognitive functions, usually with better performances in certain aspects and worse in others, and to heightened creativity. Acquired forms of synesthesia commonly arise from drug ingestion or neurological disorders, including thalamic lesions and sensory deprivation (e.g., blindness). Cerebral exploration using structural and functional imaging has demonstrated distinct patterns in cortical activation and brain connectivity for controls and synesthetes. Artworks of affected painters are most illustrative of the nature of synesthetic experiences. Summary Results of the recent investigations on synesthesia offered a remarkable insight into the mechanisms of perception, emotion and consciousness, and deserve attention both from neuroscientists and from clinicians. PMID:25545055

Color synesthesia. Insight into perception, emotion, and consciousness.

PubMed

Safran, Avinoam B; Sanda, Nicolae

2015-02-01

Synesthesia is an extraordinary perceptual phenomenon, in which individuals experience unusual percepts elicited by the activation of an unrelated sensory modality or by a cognitive process. Emotional reactions are commonly associated. The condition prompted philosophical debates on the nature of perception and impacted the course of art history. It recently generated a considerable interest among neuroscientists, but its clinical significance apparently remains underevaluated. This review focuses on the recent studies regarding variants of color synesthesia, the commonest form of the condition. Synesthesia is commonly classified as developmental and acquired. Developmental forms predispose to changes in primary sensory processing and cognitive functions, usually with better performances in certain aspects and worse in others, and to heightened creativity. Acquired forms of synesthesia commonly arise from drug ingestion or neurological disorders, including thalamic lesions and sensory deprivation (e.g., blindness). Cerebral exploration using structural and functional imaging has demonstrated distinct patterns in cortical activation and brain connectivity for controls and synesthetes. Artworks of affected painters are most illustrative of the nature of synesthetic experiences. Results of the recent investigations on synesthesia offered a remarkable insight into the mechanisms of perception, emotion and consciousness, and deserve attention both from neuroscientists and from clinicians.

Dypas: A dynamic payload scheduler for shuttle missions

NASA Technical Reports Server (NTRS)

Davis, Stephen

1988-01-01

Decision and analysis systems have had broad and very practical application areas in the human decision making process. These software systems range from the help sections in simple accounting packages, to the more complex computer configuration programs. Dypas is a decision and analysis system that aids prelaunch shutlle scheduling, and has added functionality to aid the rescheduling done in flight. Dypas is written in Common Lisp on a Symbolics Lisp machine. Dypas differs from other scheduling programs in that it can draw its knowledge from different rule bases and apply them to different rule interpretation schemes. The system has been coded with Flavors, an object oriented extension to Common Lisp on the Symbolics hardware. This allows implementation of objects (experiments) to better match the problem definition, and allows a more coherent solution space to be developed. Dypas was originally developed to test a programmer's aptitude toward Common Lisp and the Symbolics software environment. Since then the system has grown into a large software effort with several programmers and researchers thrown into the effort. Dypas is currently using two expert systems and three inferencing procedures to generate a many object schedule. The paper will review the abilities of Dypas and comment on its functionality.

A ligand-directed divergent catalytic approach to establish structural and functional scaffold diversity

NASA Astrophysics Data System (ADS)

Lee, Yen-Chun; Patil, Sumersing; Golz, Christopher; Strohmann, Carsten; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2017-02-01

The selective transformation of different starting materials by different metal catalysts under individually optimized reaction conditions to structurally different intermediates and products is a powerful approach to generate diverse molecular scaffolds. In a more unified albeit synthetically challenging strategy, common starting materials would be exposed to a common metal catalysis, leading to a common intermediate and giving rise to different scaffolds by tuning the reactivity of the metal catalyst through different ligands. Herein we present a ligand-directed synthesis approach for the gold(I)-catalysed cycloisomerization of oxindole-derived 1,6-enynes that affords distinct molecular scaffolds following different catalytic reaction pathways. Varying electronic properties and the steric demand of the gold(I) ligands steers the fate of a common intermediary gold carbene to selectively form spirooxindoles, quinolones or df-oxindoles. Investigation of a synthesized compound collection in cell-based assays delivers structurally novel, selective modulators of the Hedgehog and Wnt signalling pathways, autophagy and of cellular proliferation.

How are 'Barack Obama' and 'President Elect' differentially stored in the brain? An ERP investigation on the processing of proper and common noun pairs.

PubMed

Proverbio, Alice Mado; Mariani, Serena; Zani, Alberto; Adorni, Roberta

2009-09-23

One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. 780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related ("Woody Allen" or "social security"), while the others were not ("Sigmund Parodi" or "judicial cream"). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes.

How Are ‘Barack Obama’ and ‘President Elect’ Differentially Stored in the Brain? An ERP Investigation on the Processing of Proper and Common Noun Pairs

PubMed Central

Proverbio, Alice Mado; Mariani, Serena; Zani, Alberto; Adorni, Roberta

2009-01-01

Background One of the most debated issues in the cognitive neuroscience of language is whether distinct semantic domains are differentially represented in the brain. Clinical studies described several anomic dissociations with no clear neuroanatomical correlate. Neuroimaging studies have shown that memory retrieval is more demanding for proper than common nouns in that the former are purely arbitrary referential expressions. In this study a semantic relatedness paradigm was devised to investigate neural processing of proper and common nouns. Methodology/Principal Findings 780 words (arranged in pairs of Italian nouns/adjectives and the first/last names of well known persons) were presented. Half pairs were semantically related (“Woody Allen” or “social security”), while the others were not (“Sigmund Parodi” or “judicial cream”). All items were balanced for length, frequency, familiarity and semantic relatedness. Participants were to decide about the semantic relatedness of the two items in a pair. RTs and N400 data suggest that the task was more demanding for common nouns. The LORETA neural generators for the related-unrelated contrast (for proper names) included the left fusiform gyrus, right medial temporal gyrus, limbic and parahippocampal regions, inferior parietal and inferior frontal areas, which are thought to be involved in the conjoined processing a familiar face with the relevant episodic information. Person name was more emotional and sensory vivid than common noun semantic access. Conclusions/Significance When memory retrieval is not required, proper name access (conspecifics knowledge) is not more demanding. The neural generators of N400 to unrelated items (unknown persons and things) did not differ as a function of lexical class, thus suggesting that proper and common nouns are not treated differently as belonging to different grammatical classes. PMID:19774070

Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

PubMed

Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

2015-06-01

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. Copyright © 2015 the American Physiological Society.

Novel pre-mRNA splicing of intronically integrated HBV generates oncogenic chimera in hepatocellular carcinoma.

PubMed

Chiu, Yung-Tuen; Wong, John K L; Choi, Shing-Wan; Sze, Karen M F; Ho, Daniel W H; Chan, Lo-Kong; Lee, Joyce M F; Man, Kwan; Cherny, Stacey; Yang, Wan-Ling; Wong, Chun-Ming; Sham, Pak-Chung; Ng, Irene O L

2016-06-01

Hepatitis B virus (HBV) integration is common in HBV-associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs. Transcriptome sequencing was performed on paired HBV-associated HCCs and corresponding non-tumorous liver tissues to identify viral-human chimeric sites. Validation was further performed in an expanded cohort of human HCCs. Here we report the discovery of a novel pre-mRNA splicing mechanism in generating HBV-human chimeric protein. This mechanism was exemplified by the formation of a recurrent HBV-cyclin A2 (CCNA2) chimeric transcript (A2S), as detected in 12.5% (6 of 48) of HCC patients, but in none of the 22 non-HCC HBV-associated cirrhotic liver samples examined. Upon the integration of HBV into the intron of the CCNA2 gene, the mammalian splicing machinery utilized the foreign splice sites at 282nt. and 458nt. of the HBV genome to generate a pseudo-exon, forming an in-frame chimeric fusion with CCNA2. The A2S chimeric protein gained a non-degradable property and promoted cell cycle progression, demonstrating its potential oncogenic functions. A pre-mRNA splicing mechanism is involved in the formation of HBV-human chimeric proteins. This represents a novel and possibly common mechanism underlying the formation of HBV-human chimeric transcripts from intronically integrated HBV genome with functional impact. HBV is involved in the mammalian pre-mRNA splicing machinery in the generation of potential tumorigenic HBV-human chimeras. This study also provided insight on the impact of intronic HBV integration with the gain of splice sites in the development of HBV-associated HCC. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos

PubMed Central

Schrank, Bertold; Götz, Rudolf; Gunnersen, Jennifer M.; Ure, Janice M.; Toyka, Klaus V.; Smith, Austin G.; Sendtner, Michael

1997-01-01

Proximal spinal muscular atrophy is an autosomal recessive human disease of spinal motor neurons leading to muscular weakness with onset predominantly in infancy and childhood. With an estimated heterozygote frequency of 1/40 it is the most common monogenic disorder lethal to infants; milder forms represent the second most common pediatric neuromuscular disorder. Two candidate genes—survival motor neuron (SMN) and neuronal apoptosis inhibitory protein have been identified on chromosome 5q13 by positional cloning. However, the functional impact of these genes and the mechanism leading to a degeneration of motor neurons remain to be defined. To analyze the role of the SMN gene product in vivo we generated SMN-deficient mice. In contrast to the human genome, which contains two copies, the mouse genome contains only one SMN gene. Mice with homozygous SMN disruption display massive cell death during early embryonic development, indicating that the SMN gene product is necessary for cellular survival and function. PMID:9275227

Bayesian Computation Emerges in Generic Cortical Microcircuits through Spike-Timing-Dependent Plasticity

PubMed Central

Nessler, Bernhard; Pfeiffer, Michael; Buesing, Lars; Maass, Wolfgang

2013-01-01

The principles by which networks of neurons compute, and how spike-timing dependent plasticity (STDP) of synaptic weights generates and maintains their computational function, are unknown. Preceding work has shown that soft winner-take-all (WTA) circuits, where pyramidal neurons inhibit each other via interneurons, are a common motif of cortical microcircuits. We show through theoretical analysis and computer simulations that Bayesian computation is induced in these network motifs through STDP in combination with activity-dependent changes in the excitability of neurons. The fundamental components of this emergent Bayesian computation are priors that result from adaptation of neuronal excitability and implicit generative models for hidden causes that are created in the synaptic weights through STDP. In fact, a surprising result is that STDP is able to approximate a powerful principle for fitting such implicit generative models to high-dimensional spike inputs: Expectation Maximization. Our results suggest that the experimentally observed spontaneous activity and trial-to-trial variability of cortical neurons are essential features of their information processing capability, since their functional role is to represent probability distributions rather than static neural codes. Furthermore it suggests networks of Bayesian computation modules as a new model for distributed information processing in the cortex. PMID:23633941

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations.

PubMed

Sakaguchi, Aisa; Sarkies, Peter; Simon, Matt; Doebley, Anna-Lisa; Goldstein, Leonard D; Hedges, Ashley; Ikegami, Kohta; Alvares, Stacy M; Yang, Liwei; LaRocque, Jeannine R; Hall, Julie; Miska, Eric A; Ahmed, Shawn

2014-10-14

Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing.

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

PubMed Central

Sakaguchi, Aisa; Sarkies, Peter; Simon, Matt; Doebley, Anna-Lisa; Goldstein, Leonard D.; Hedges, Ashley; Ikegami, Kohta; Alvares, Stacy M.; Yang, Liwei; LaRocque, Jeannine R.; Hall, Julie; Miska, Eric A.; Ahmed, Shawn

2014-01-01

Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing. PMID:25258416

Predicting gene regulatory networks of soybean nodulation from RNA-Seq transcriptome data.

PubMed

Zhu, Mingzhu; Dahmen, Jeremy L; Stacey, Gary; Cheng, Jianlin

2013-09-22

High-throughput RNA sequencing (RNA-Seq) is a revolutionary technique to study the transcriptome of a cell under various conditions at a systems level. Despite the wide application of RNA-Seq techniques to generate experimental data in the last few years, few computational methods are available to analyze this huge amount of transcription data. The computational methods for constructing gene regulatory networks from RNA-Seq expression data of hundreds or even thousands of genes are particularly lacking and urgently needed. We developed an automated bioinformatics method to predict gene regulatory networks from the quantitative expression values of differentially expressed genes based on RNA-Seq transcriptome data of a cell in different stages and conditions, integrating transcriptional, genomic and gene function data. We applied the method to the RNA-Seq transcriptome data generated for soybean root hair cells in three different development stages of nodulation after rhizobium infection. The method predicted a soybean nodulation-related gene regulatory network consisting of 10 regulatory modules common for all three stages, and 24, 49 and 70 modules separately for the first, second and third stage, each containing both a group of co-expressed genes and several transcription factors collaboratively controlling their expression under different conditions. 8 of 10 common regulatory modules were validated by at least two kinds of validations, such as independent DNA binding motif analysis, gene function enrichment test, and previous experimental data in the literature. We developed a computational method to reliably reconstruct gene regulatory networks from RNA-Seq transcriptome data. The method can generate valuable hypotheses for interpreting biological data and designing biological experiments such as ChIP-Seq, RNA interference, and yeast two hybrid experiments.

Design of Mobile Health Tools to Promote Goal Achievement in Self-Management Tasks

PubMed Central

Henderson, Geoffrey; Parmanto, Bambang

2017-01-01

Background Goal-setting within rehabilitation is a common practice ultimately geared toward helping patients make functional progress. Objective The purposes of this study were to (1) qualitatively analyze data from a wellness program for patients with spina bifida (SB) and spinal cord injury (SCI) in order to generate software requirements for a goal-setting module to support their complex goal-setting routines, (2) design a prototype of a goal-setting module within an existing mobile health (mHealth) system, and (3) identify what educational content might be necessary to integrate into the system. Methods A total of 750 goals were analyzed from patients with SB and SCI enrolled in a wellness program. These goals were qualitatively analyzed in order to operationalize a set of software requirements for an mHealth goal-setting module and identify important educational content. Results Those of male sex (P=.02) and with SCI diagnosis (P<.001) were more likely to achieve goals than females or those with SB. Temporality (P<.001) and type (P<.001) of goal were associated with likelihood that the goal would be achieved. Nearly all (210/213; 98.6%) of the fact-finding goals were achieved. There was no significant difference in achievement based on goal theme. Checklists, data tracking, and fact-finding tools were identified as three functionalities that could support goal-setting and achievement in an mHealth system. Based on the qualitative analysis, a list of software requirements for a goal-setting module was generated, and a prototype was developed. Targets for educational content were also generated. Conclusions Innovative mHealth tools can be developed to support commonly set goals by individuals with disabilities. PMID:28739558

Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles.

PubMed

Woo, Sang Su; James, Declan J; Martin, Thomas F J

2017-03-15

Munc13-4 is a Ca 2+ -dependent SNARE (soluble N -ethylmaleimide-sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca 2+ -evoked secretion in various secretory cells. Studies in mast cell-like RBL-2H3 cells provide direct evidence that Munc13-4 with its two Ca 2+ -binding C2 domains functions as a Ca 2+ sensor for SG exocytosis. Unexpectedly, Ca 2+ stimulation also generated large (>2.4 μm in diameter) Munc13-4 + /Rab7 + /Rab11 + endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4 + /Rab7 + SGs, followed by a merge with Rab11 + endosomes, and depended on Ca 2+ binding to Munc13-4. Munc13-4 promoted the Ca 2+ -stimulated fusion of VAMP8-containing liposomes with liposomes containing exocytic or endosomal Q-SNAREs and directly interacted with late endosomal SNARE complexes. Thus Munc13-4 is a tethering/priming factor and Ca 2+ sensor for both heterotypic SG-plasma membrane and homotypic SG-SG fusion. Total internal reflection fluorescence microscopy imaging revealed that vacuoles were exocytic and mediated secretion of β-hexosaminidase and cytokines accompanied by Munc13-4 diffusion onto the plasma membrane. The results provide new molecular insights into the mechanism of multigranular compound exocytosis commonly observed in various secretory cells. © 2017 Woo et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Examining the influence of link function misspecification in conventional regression models for developing crash modification factors.

PubMed

Wu, Lingtao; Lord, Dominique

2017-05-01

This study further examined the use of regression models for developing crash modification factors (CMFs), specifically focusing on the misspecification in the link function. The primary objectives were to validate the accuracy of CMFs derived from the commonly used regression models (i.e., generalized linear models or GLMs with additive linear link functions) when some of the variables have nonlinear relationships and quantify the amount of bias as a function of the nonlinearity. Using the concept of artificial realistic data, various linear and nonlinear crash modification functions (CM-Functions) were assumed for three variables. Crash counts were randomly generated based on these CM-Functions. CMFs were then derived from regression models for three different scenarios. The results were compared with the assumed true values. The main findings are summarized as follows: (1) when some variables have nonlinear relationships with crash risk, the CMFs for these variables derived from the commonly used GLMs are all biased, especially around areas away from the baseline conditions (e.g., boundary areas); (2) with the increase in nonlinearity (i.e., nonlinear relationship becomes stronger), the bias becomes more significant; (3) the quality of CMFs for other variables having linear relationships can be influenced when mixed with those having nonlinear relationships, but the accuracy may still be acceptable; and (4) the misuse of the link function for one or more variables can also lead to biased estimates for other parameters. This study raised the importance of the link function when using regression models for developing CMFs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phase stable RF transport system

DOEpatents

Curtin, Michael T.; Natter, Eckard F.; Denney, Peter M.

1992-01-01

An RF transport system delivers a phase-stable RF signal to a load, such as an RF cavity of a charged particle accelerator. A circuit generates a calibration signal at an odd multiple frequency of the RF signal where the calibration signal is superimposed with the RF signal on a common cable that connects the RF signal with the load. Signal isolating diplexers are located at both the RF signal source end and load end of the common cable to enable the calibration to be inserted and extracted from the cable signals without any affect on the RF signal. Any phase shift in the calibration signal during traverse of the common cable is then functionally related to the phase shift in the RF signal. The calibration phase shift is used to control a phase shifter for the RF signal to maintain a stable RF signal at the load.

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

DOE PAGES

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; ...

2015-06-16

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth’s climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. In this work, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on watermore » while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.« less

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

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

Chen, Xi; Goodnight, Davis; Gao, Zhenghan

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth’s climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. In this work, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on watermore » while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.« less

An Extended IEEE 118-Bus Test System With High Renewable Penetration

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

Pena, Ivonne; Martinez-Anido, Carlo Brancucci; Hodge, Bri-Mathias

This article describes a new publicly available version of the IEEE 118-bus test system, named NREL-118. The database is based on the transmission representation (buses and lines) of the IEEE 118-bus test system, with a reconfigured generation representation using three regions of the US Western Interconnection from the latest Western Electricity Coordination Council (WECC) 2024 Common Case [1]. Time-synchronous hourly load, wind, and solar time series are provided for over one year (8784 hours). The public database presented and described in this manuscript will allow researchers to model a test power system using detailed transmission, generation, load, wind, and solarmore » data. This database includes key additional features that add to the current IEEE 118-bus test model, such as: the inclusion of 10 generation technologies with different heat rate functions, minimum stable levels and ramping rates, GHG emissions rates, regulation and contingency reserves, and hourly time series data for one full year for load, wind and solar generation.« less

Recycled PET Nanofibers for Water Filtration Applications

PubMed Central

Zander, Nicole E.; Gillan, Margaret; Sweetser, Daniel

2016-01-01

Water shortage is an immediate and serious threat to our world population. Inexpensive and scalable methods to clean freshwater and wastewater are in high demand. Nanofiber filtration membranes represent a next generation nonwoven filter media due to their unique properties. Polyethlyene terephthalate (PET) is often used in the packaging of water and other commonly used materials, leading to a large amount of plastic waste often with limited incentive for recycling (few value-added uses). Here, we present work in the generation of nanofiber liquid filtration membranes from PET plastic bottles and demonstrate their use in microfiltration. PET nanofiber membranes were formed via solution electrospinning with fiber diameters as low as ca. 100 nm. Filtration efficiency was tested with latex beads with sizes ranging from 30 to 2000 nm. Greater than 99% of the beads as small as 500 nm were removed using gravity filtration. To reduce biofouling, the mats were functionalized with quaternary ammonium and biguanide biocides. The biguanide functionalized mats achieved 6 log reduction for both gram negative and gram positive bacteria. PMID:28773380

Behavioral and neural Darwinism: selectionist function and mechanism in adaptive behavior dynamics.

PubMed

McDowell, J J

2010-05-01

An evolutionary theory of behavior dynamics and a theory of neuronal group selection share a common selectionist framework. The theory of behavior dynamics instantiates abstractly the idea that behavior is selected by its consequences. It implements Darwinian principles of selection, reproduction, and mutation to generate adaptive behavior in virtual organisms. The behavior generated by the theory has been shown to be quantitatively indistinguishable from that of live organisms. The theory of neuronal group selection suggests a mechanism whereby the abstract principles of the evolutionary theory may be implemented in the nervous systems of biological organisms. According to this theory, groups of neurons subserving behavior may be selected by synaptic modifications that occur when the consequences of behavior activate value systems in the brain. Together, these theories constitute a framework for a comprehensive account of adaptive behavior that extends from brain function to the behavior of whole organisms in quantitative detail. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

PubMed

Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

2017-08-01

Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium.

PubMed

Turco, Margherita Y; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G E; Brosens, Jan J; Critchley, Hilary O; Simons, Benjamin D; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J

2017-05-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation.

Long-term, hormone-responsive organoid cultures of human endometrium in a chemically-defined medium

PubMed Central

Turco, Margherita Y.; Gardner, Lucy; Hughes, Jasmine; Cindrova-Davies, Tereza; Gomez, Maria J.; Farrell, Lydia; Hollinshead, Michael; Marsh, Steven G.E.; Brosens, Jan J.; Critchley, Hilary O.; Simons, Benjamin D.; Hemberger, Myriam; Koo, Bon-Kyoung; Moffett, Ashley; Burton, Graham J.

2017-01-01

In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem cell-derived organoid cultures to generate 3D cultures of normal and decidualised human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones. Single cells from both endometrium and decidua can generate a fully functional organoid. Transcript analysis confirmed great similarity between organoids and the primary tissue of origin. On exposure to pregnancy signals, endometrial organoids develop characteristics of early pregnancy. We also derived organoids from malignant endometrium, and so provide a foundation to study common diseases, such as endometriosis and endometrial cancer, as well as the physiology of early gestation. PMID:28394884

Eccentric Contraction-Induced Muscle Injury: Reproducible, Quantitative, Physiological Models to Impair Skeletal Muscle’s Capacity to Generate Force

PubMed Central

Call, Jarrod A.; Lowe, Dawn A.

2018-01-01

In order to investigate the molecular and cellular mechanisms of muscle regeneration an experimental injury model is required. Advantages of eccentric contraction-induced injury are that it is a controllable, reproducible, and physiologically relevant model to cause muscle injury, with injury being defined as a loss of force generating capacity. While eccentric contractions can be incorporated into conscious animal study designs such as downhill treadmill running, electrophysiological approaches to elicit eccentric contractions and examine muscle contractility, for example before and after the injurious eccentric contractions, allows researchers to circumvent common issues in determining muscle function in a conscious animal (e.g., unwillingness to participate). Herein, we describe in vitro and in vivo methods that are reliable, repeatable, and truly maximal because the muscle contractions are evoked in a controlled, quantifiable manner independent of subject motivation. Both methods can be used to initiate eccentric contraction-induced injury and are suitable for monitoring functional muscle regeneration hours to days to weeks post-injury. PMID:27492161

A Proton-Cyclotron Wave Storm Generated by Unstable Proton Distribution Functions in the Solar Wind

NASA Technical Reports Server (NTRS)

Wicks, R. T.; Alexander, R. L.; Stevens, M.; Wilson, L. B., III; Moya, P. S.; Vinas, A.; Jian, L. K.; Roberts, D. A.; O’Modhrain, S.; Gilbert, J. A.;

Occupational therapy during the first 10 years of rheumatoid arthritis.

PubMed

Malcus-Johnson, Pia; Carlqvist, Carin; Sturesson, Anna-Lena; Eberhardt, Kerstin

2005-01-01

To describe disease development and occupational therapy during the first 10 years of rheumatoid arthritis (RA), and to assess patients' experiences of occupational therapy and comprehensive care. A total of 168 early RA patients with variable disease severity were followed up with regular team visits. The occupational therapist evaluated hand function and activity and performed the necessary interventions. These were recorded and the number of visits generating interventions was calculated. Semi-structured interview of 11 patients regarding their views of occupational therapy and team contact was performed. Impairments of hand function were in general mild to moderate and remained fairly unchanged over time. Activity limitations increased slowly. Half of the follow-up visits generated interventions. Most common were prescriptions of assistive devices and orthoses, hand-training instructions and patient education. The patients interviewed were positive regarding occupational therapy and felt safe with comprehensive care. RA patients in all stages of the disease benefit from regular contact with an occupational therapist and team care.

Functional Fixedness in Creative Thinking Tasks Depends on Stimulus Modality.

PubMed

Chrysikou, Evangelia G; Motyka, Katharine; Nigro, Cristina; Yang, Song-I; Thompson-Schill, Sharon L

2016-11-01

Pictorial examples during creative thinking tasks can lead participants to fixate on these examples and reproduce their elements even when yielding suboptimal creative products. Semantic memory research may illuminate the cognitive processes underlying this effect. Here, we examined whether pictures and words differentially influence access to semantic knowledge for object concepts depending on whether the task is close- or open-ended. Participants viewed either names or pictures of everyday objects, or a combination of the two, and generated common, secondary, or ad hoc uses for them. Stimulus modality effects were assessed quantitatively through reaction times and qualitatively through a novel coding system, which classifies creative output on a continuum from top-down-driven to bottom-up-driven responses. Both analyses revealed differences across tasks. Importantly, for ad hoc uses, participants exposed to pictures generated more top-down-driven responses than those exposed to object names. These findings have implications for accounts of functional fixedness in creative thinking, as well as theories of semantic memory for object concepts.

Functional Fixedness in Creative Thinking Tasks Depends on Stimulus Modality

PubMed Central

Chrysikou, Evangelia G.; Motyka, Katharine; Nigro, Cristina; Yang, Song-I; Thompson-Schill, Sharon L.

2015-01-01

Pictorial examples during creative thinking tasks can lead participants to fixate on these examples and reproduce their elements even when yielding suboptimal creative products. Semantic memory research may illuminate the cognitive processes underlying this effect. Here, we examined whether pictures and words differentially influence access to semantic knowledge for object concepts depending on whether the task is close- or open-ended. Participants viewed either names or pictures of everyday objects, or a combination of the two, and generated common, secondary, or ad hoc uses for them. Stimulus modality effects were assessed quantitatively through reaction times and qualitatively through a novel coding system, which classifies creative output on a continuum from top-down-driven to bottom-up-driven responses. Both analyses revealed differences across tasks. Importantly, for ad hoc uses, participants exposed to pictures generated more top-down-driven responses than those exposed to object names. These findings have implications for accounts of functional fixedness in creative thinking, as well as theories of semantic memory for object concepts. PMID:28344724

Generation of Individual Whole-Brain Atlases With Resting-State fMRI Data Using Simultaneous Graph Computation and Parcellation.

PubMed

Wang, J; Hao, Z; Wang, H

2018-01-01

The human brain can be characterized as functional networks. Therefore, it is important to subdivide the brain appropriately in order to construct reliable networks. Resting-state functional connectivity-based parcellation is a commonly used technique to fulfill this goal. Here we propose a novel individual subject-level parcellation approach based on whole-brain resting-state functional magnetic resonance imaging (fMRI) data. We first used a supervoxel method known as simple linear iterative clustering directly on resting-state fMRI time series to generate supervoxels, and then combined similar supervoxels to generate clusters using a clustering method known as graph-without-cut (GWC). The GWC approach incorporates spatial information and multiple features of the supervoxels by energy minimization, simultaneously yielding an optimal graph and brain parcellation. Meanwhile, it theoretically guarantees that the actual cluster number is exactly equal to the initialized cluster number. By comparing the results of the GWC approach and those of the random GWC approach, we demonstrated that GWC does not rely heavily on spatial structures, thus avoiding the challenges encountered in some previous whole-brain parcellation approaches. In addition, by comparing the GWC approach to two competing approaches, we showed that GWC achieved better parcellation performances in terms of different evaluation metrics. The proposed approach can be used to generate individualized brain atlases for applications related to cognition, development, aging, disease, personalized medicine, etc. The major source codes of this study have been made publicly available at https://github.com/yuzhounh/GWC.

Likelihood analysis of the pMSSM11 in light of LHC 13-TeV data

NASA Astrophysics Data System (ADS)

Bagnaschi, E.; Sakurai, K.; Borsato, M.; Buchmueller, O.; Citron, M.; Costa, J. C.; De Roeck, A.; Dolan, M. J.; Ellis, J. R.; Flächer, H.; Heinemeyer, S.; Lucio, M.; Martínez Santos, D.; Olive, K. A.; Richards, A.; Spanos, V. C.; Suárez Fernández, I.; Weiglein, G.

2018-03-01

We use MasterCode to perform a frequentist analysis of the constraints on a phenomenological MSSM model with 11 parameters, the pMSSM11, including constraints from ˜ 36/fb of LHC data at 13 TeV and PICO, XENON1T and PandaX-II searches for dark matter scattering, as well as previous accelerator and astrophysical measurements, presenting fits both with and without the (g-2)_μ constraint. The pMSSM11 is specified by the following parameters: 3 gaugino masses M_{1,2,3}, a common mass for the first-and second-generation squarks m_{\\tilde{q}} and a distinct third-generation squark mass m_{\\tilde{q}_3}, a common mass for the first-and second-generation sleptons m_{\\tilde{ℓ }} and a distinct third-generation slepton mass m_{\\tilde{τ }}, a common trilinear mixing parameter A, the Higgs mixing parameter μ , the pseudoscalar Higgs mass M_A and tan β . In the fit including (g-2)_μ , a Bino-like \\tilde{χ }^01 is preferred, whereas a Higgsino-like \\tilde{χ }^01 is mildly favoured when the (g-2)_μ constraint is dropped. We identify the mechanisms that operate in different regions of the pMSSM11 parameter space to bring the relic density of the lightest neutralino, \\tilde{χ }^01, into the range indicated by cosmological data. In the fit including (g-2)_μ , coannihilations with \\tilde{χ }^02 and the Wino-like \\tilde{χ }^± 1 or with nearly-degenerate first- and second-generation sleptons are active, whereas coannihilations with the \\tilde{χ }^02 and the Higgsino-like \\tilde{χ }^± 1 or with first- and second-generation squarks may be important when the (g-2)_μ constraint is dropped. In the two cases, we present χ ^2 functions in two-dimensional mass planes as well as their one-dimensional profile projections and best-fit spectra. Prospects remain for discovering strongly-interacting sparticles at the LHC, in both the scenarios with and without the (g-2)_μ constraint, as well as for discovering electroweakly-interacting sparticles at a future linear e^+ e^- collider such as the ILC or CLIC.

System analysis identifies distinct and common functional networks governed by transcription factor ASCL1, in glioma and small cell lung cancer.

PubMed

Donakonda, Sainitin; Sinha, Swati; Dighe, Shrinivas Nivrutti; Rao, Manchanahalli R Satyanarayana

2017-07-25

ASCL1 is a basic Helix-Loop-Helix transcription factor (TF), which is involved in various cellular processes like neuronal development and signaling pathways. Transcriptome profiling has shown that ASCL1 overexpression plays an important role in the development of glioma and Small Cell Lung Carcinoma (SCLC), but distinct and common molecular mechanisms regulated by ASCL1 in these cancers are unknown. In order to understand how it drives the cellular functional network in these two tumors, we generated a gene expression profile in a glioma cell line (U87MG) to identify ASCL1 gene targets by an si RNA silencing approach and then compared this with a publicly available dataset of similarly silenced SCLC (NCI-H1618 cells). We constructed TF-TF and gene-gene interactions, as well as protein interaction networks of ASCL1 regulated genes in glioma and SCLC cells. Detailed network analysis uncovered various biological processes governed by ASCL1 target genes in these two tumor cell lines. We find that novel ASCL1 functions related to mitosis and signaling pathways influencing development and tumor growth are affected in both glioma and SCLC cells. In addition, we also observed ASCL1 governed functional networks that are distinct to glioma and SCLC.

Constructing general partial differential equations using polynomial and neural networks.

PubMed

Zjavka, Ladislav; Pedrycz, Witold

2016-01-01

Sum fraction terms can approximate multi-variable functions on the basis of discrete observations, replacing a partial differential equation definition with polynomial elementary data relation descriptions. Artificial neural networks commonly transform the weighted sum of inputs to describe overall similarity relationships of trained and new testing input patterns. Differential polynomial neural networks form a new class of neural networks, which construct and solve an unknown general partial differential equation of a function of interest with selected substitution relative terms using non-linear multi-variable composite polynomials. The layers of the network generate simple and composite relative substitution terms whose convergent series combinations can describe partial dependent derivative changes of the input variables. This regression is based on trained generalized partial derivative data relations, decomposed into a multi-layer polynomial network structure. The sigmoidal function, commonly used as a nonlinear activation of artificial neurons, may transform some polynomial items together with the parameters with the aim to improve the polynomial derivative term series ability to approximate complicated periodic functions, as simple low order polynomials are not able to fully make up for the complete cycles. The similarity analysis facilitates substitutions for differential equations or can form dimensional units from data samples to describe real-world problems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products.

PubMed

Jamison, Christopher R; Badillo, Joseph J; Lipshultz, Jeffrey M; Comito, Robert J; MacMillan, David W C

2017-12-01

In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

Generating a Double-Scroll Attractor by Connecting a Pair of Mutual Mirror-Image Attractors via Planar Switching Control

NASA Astrophysics Data System (ADS)

Sun, Changchun; Chen, Zhongtang; Xu, Qicheng

2017-12-01

An original three-dimensional (3D) smooth continuous chaotic system and its mirror-image system with eight common parameters are constructed and a pair of symmetric chaotic attractors can be generated simultaneously. Basic dynamical behaviors of two 3D chaotic systems are investigated respectively. A double-scroll chaotic attractor by connecting the pair of mutual mirror-image attractors is generated via a novel planar switching control approach. Chaos can also be controlled to a fixed point, a periodic orbit and a divergent orbit respectively by switching between two chaotic systems. Finally, an equivalent 3D chaotic system by combining two 3D chaotic systems with a switching law is designed by utilizing a sign function. Two circuit diagrams for realizing the double-scroll attractor are depicted by employing an improved module-based design approach.

Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products

NASA Astrophysics Data System (ADS)

Jamison, Christopher R.; Badillo, Joseph J.; Lipshultz, Jeffrey M.; Comito, Robert J.; MacMillan, David W. C.

2017-12-01

In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

High-Frequency Network Oscillations in Cerebellar Cortex

PubMed Central

Middleton, Steven J.; Racca, Claudia; Cunningham, Mark O.; Traub, Roger D.; Monyer, Hannah; Knöpfel, Thomas; Schofield, Ian S.; Jenkins, Alistair; Whittington, Miles A.

2016-01-01

SUMMARY Both cerebellum and neocortex receive input from the somatosensory system. Interaction between these regions has been proposed to underpin the correct selection and execution of motor commands, but it is not clear how such interactions occur. In neocortex, inputs give rise to population rhythms, providing a spatiotemporal coding strategy for inputs and consequent outputs. Here, we show that similar patterns of rhythm generation occur in cerebellum during nicotinic receptor subtype activation. Both gamma oscillations (30–80 Hz) and very fast oscillations (VFOs, 80–160 Hz) were generated by intrinsic cerebellar cortical circuitry in the absence of functional glutamatergic connections. As in neocortex, gamma rhythms were dependent on GABAA receptor-mediated inhibition, whereas VFOs required only nonsynaptically connected intercellular networks. The ability of cerebellar cortex to generate population rhythms within the same frequency bands as neocortex suggests that they act as a common spatiotemporal code within which corticocerebellar dialog may occur. PMID:18549787

Specification of hepatopancreas progenitors in zebrafish by hnf1ba and wnt2bb

PubMed Central

Lancman, Joseph J.; Zvenigorodsky, Natasha; Gates, Keith P.; Zhang, Danhua; Solomon, Keely; Humphrey, Rohan K.; Kuo, Taiyi; Setiawan, Linda; Verkade, Heather; Chi, Young-In; Jhala, Ulupi S.; Wright, Christopher V. E.; Stainier, Didier Y. R.; Dong, P. Duc Si

2013-01-01

Although the liver and ventral pancreas are thought to arise from a common multipotent progenitor pool, it is unclear whether these progenitors of the hepatopancreas system are specified by a common genetic mechanism. Efforts to determine the role of Hnf1b and Wnt signaling in this crucial process have been confounded by a combination of factors, including a narrow time frame for hepatopancreas specification, functional redundancy among Wnt ligands, and pleiotropic defects caused by either severe loss of Wnt signaling or Hnf1b function. Using a novel hypomorphic hnf1ba zebrafish mutant that exhibits pancreas hypoplasia, as observed in HNF1B monogenic diabetes, we show that hnf1ba plays essential roles in regulating β-cell number and pancreas specification, distinct from its function in regulating pancreas size and liver specification, respectively. By combining Hnf1ba partial loss of function with conditional loss of Wnt signaling, we uncover a crucial developmental window when these pathways synergize to specify the entire ventrally derived hepatopancreas progenitor population. Furthermore, our in vivo genetic studies demonstrate that hnf1ba generates a permissive domain for Wnt signaling activity in the foregut endoderm. Collectively, our findings provide a new model for HNF1B function, yield insight into pancreas and β-cell development, and suggest a new mechanism for hepatopancreatic specification. PMID:23720049

IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice.

PubMed

Denton, P W; Nochi, T; Lim, A; Krisko, J F; Martinez-Torres, F; Choudhary, S K; Wahl, A; Olesen, R; Zou, W; Di Santo, J P; Margolis, D M; Garcia, J V

2012-09-01

Intestinal immune cells are important in host defense, yet the determinants for human lymphoid homeostasis in the intestines are poorly understood. In contrast, lymphoid homeostasis has been studied extensively in mice, where the requirement for a functional common γ-chain molecule has been established. We hypothesized that humanized mice could offer insights into human intestinal lymphoid homeostasis if generated in a strain with an intact mouse common γ-chain molecule. To address this hypothesis, we used three mouse strains (non-obese diabetic (NOD)/severe-combined immunodeficient (SCID) (N/S); NOD/SCID γ-chain(-/-) (NSG); and Rag2(-/-) γ-chain(-/-) (DKO)) and two humanization techniques (bone marrow liver thymus (BLT) and human CD34(+) cell bone marrow transplant of newborn mice (hu)) to generate four common types of humanized mice: N/S-BLT, NSG-BLT, NSG-hu, and DKO-hu mice. The highest levels of intestinal human T cells throughout the small and large intestines were observed in N/S-BLT mice, which have an intact common γ-chain molecule. Furthermore, the small intestine lamina propria T-cell populations of N/S-BLT mice exhibit a human intestine-specific surface phenotype. Thus, the extensive intestinal immune reconstitution of N/S-BLT mice was both quantitatively and qualitatively better when compared with the other models tested such that N/S-BLT mice are well suited for the analysis of human intestinal lymphocyte trafficking and human-specific diseases affecting the intestines.

Real-Time Fall Risk Assessment Using Functional Reach Test.

PubMed

Williams, Brian; Allen, Brandon; Hu, Zhen; True, Hanna; Cho, Jin; Harris, Austin; Fell, Nancy; Sartipi, Mina

2017-01-01

Falls are common and dangerous for survivors of stroke at all stages of recovery. The widespread need to assess fall risk in real time for individuals after stroke has generated emerging requests for a reliable, inexpensive, quantifiable, and remote clinical measure/tool. In order to meet these requests, we explore the Functional Reach Test (FRT) for real-time fall risk assessment and implement the FRT function in mStroke , a real-time and automatic mobile health system for poststroke recovery and rehabilitation. mStroke is designed, developed, and delivered as an Application (App) running on a hardware platform consisting of an iPad and one or two wireless body motion sensors based on different mobile health functions. The FRT function in mStroke is extensively tested on healthy human subjects to verify its concept and feasibility. Preliminary performance will be presented to justify the further exploration of the FRT function in mStroke through clinical trials on individuals after stroke, which may guide its ubiquitous exploitation in the near future.

Influence of the exchange and correlation functional on the structure of amorphous InSb and In3SbTe2 compounds

NASA Astrophysics Data System (ADS)

Gabardi, Silvia; Caravati, Sebastiano; Los, Jan H.; Kühne, Thomas D.; Bernasconi, Marco

2016-05-01

We have investigated the structural, vibrational, and electronic properties of the amorphous phase of InSb and In3SbTe2 compounds of interest for applications in phase change non-volatile memories. Models of the amorphous phase have been generated by quenching from the melt by molecular dynamics simulations based on density functional theory. In particular, we have studied the dependence of the structural properties on the choice of the exchange-correlation functional. It turns out that the use of the Becke-Lee-Yang-Parr functional provides models with a much larger fraction of In atoms in a tetrahedral bonding geometry with respect to previous results obtained with the most commonly used Perdew-Becke-Ernzerhof functional. This outcome is at odd with the properties of Ge2Sb2Te5 phase change compound for which the two exchange-correlation functionals yield very similar results on the structure of the amorphous phase.

Influence of the exchange and correlation functional on the structure of amorphous InSb and In3SbTe2 compounds.

PubMed

Gabardi, Silvia; Caravati, Sebastiano; Los, Jan H; Kühne, Thomas D; Bernasconi, Marco

2016-05-28

We have investigated the structural, vibrational, and electronic properties of the amorphous phase of InSb and In3SbTe2 compounds of interest for applications in phase change non-volatile memories. Models of the amorphous phase have been generated by quenching from the melt by molecular dynamics simulations based on density functional theory. In particular, we have studied the dependence of the structural properties on the choice of the exchange-correlation functional. It turns out that the use of the Becke-Lee-Yang-Parr functional provides models with a much larger fraction of In atoms in a tetrahedral bonding geometry with respect to previous results obtained with the most commonly used Perdew-Becke-Ernzerhof functional. This outcome is at odd with the properties of Ge2Sb2Te5 phase change compound for which the two exchange-correlation functionals yield very similar results on the structure of the amorphous phase.

Functional modules, mutational load and human genetic disease.

PubMed

Zaghloul, Norann A; Katsanis, Nicholas

2010-04-01

The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

Functional modules, mutational load and human genetic disease

PubMed Central

Zaghloul, Norann A.; Katsanis, Nicholas

2013-01-01

The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically-relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. PMID:20226561

MetAMOS: a modular and open source metagenomic assembly and analysis pipeline

PubMed Central

2013-01-01

We describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS. PMID:23320958

Drug addiction, love, and the higher power.

PubMed

Sussman, Steve; Reynaud, Michel; Aubin, Henri-Jean; Leventhal, Adam M

2011-09-01

This discussion piece suggests that reliance on a Higher Power in drug abuse recovery programs is entertained among some addicts for its psychobiological effects. Prayer, meditation, early romantic love, and drug abuse may have in common activation of mesolimbic dopaminergic pathways of the brain and the generation of intense emotional states. In this sense, reliance on a Higher Power may operate as a substitute addiction, which replaces the psychobiological functions formerly served by drug use. Implications of this perspective are discussed.

Electrode geometry for electrostatic generators and motors

DOEpatents

Post, Richard F.

2016-02-23

An electrostatic (ES) device is described with electrodes that improve its performance metrics. Devices include ES generators and ES motors, which are comprised of one or more stators (stationary members) and one or more rotors (rotatable members). The stator and rotors are configured as a pair of concentric cylindrical structures and aligned about a common axis. The stator and rotor are comprised of an ensemble of discrete, longitudinal electrodes, which are axially oriented in an annular arrangement. The shape of the electrodes described herein enables the ES device to function at voltages significantly greater than that of the existing art, resulting in devices with greater power-handling capability and overall efficiency. Electrode shapes include, but are not limited to, rods, corrugated sheets and emulations thereof.

Automating FEA programming

NASA Technical Reports Server (NTRS)

Sharma, Naveen

1992-01-01

In this paper we briefly describe a combined symbolic and numeric approach for solving mathematical models on parallel computers. An experimental software system, PIER, is being developed in Common Lisp to synthesize computationally intensive and domain formulation dependent phases of finite element analysis (FEA) solution methods. Quantities for domain formulation like shape functions, element stiffness matrices, etc., are automatically derived using symbolic mathematical computations. The problem specific information and derived formulae are then used to generate (parallel) numerical code for FEA solution steps. A constructive approach to specify a numerical program design is taken. The code generator compiles application oriented input specifications into (parallel) FORTRAN77 routines with the help of built-in knowledge of the particular problem, numerical solution methods and the target computer.

Relative Critical Points

NASA Astrophysics Data System (ADS)

Lewis, Debra

2013-05-01

Relative equilibria of Lagrangian and Hamiltonian systems with symmetry are critical points of appropriate scalar functions parametrized by the Lie algebra (or its dual) of the symmetry group. Setting aside the structures - symplectic, Poisson, or variational - generating dynamical systems from such functions highlights the common features of their construction and analysis, and supports the construction of analogous functions in non-Hamiltonian settings. If the symmetry group is nonabelian, the functions are invariant only with respect to the isotropy subgroup of the given parameter value. Replacing the parametrized family of functions with a single function on the product manifold and extending the action using the (co)adjoint action on the algebra or its dual yields a fully invariant function. An invariant map can be used to reverse the usual perspective: rather than selecting a parametrized family of functions and finding their critical points, conditions under which functions will be critical on specific orbits, typically distinguished by isotropy class, can be derived. This strategy is illustrated using several well-known mechanical systems - the Lagrange top, the double spherical pendulum, the free rigid body, and the Riemann ellipsoids - and generalizations of these systems.

Post-transcriptional labeling by using Suzuki-Miyaura cross-coupling generates functional RNA probes.

PubMed

Walunj, Manisha B; Tanpure, Arun A; Srivatsan, Seergazhi G

2018-06-20

Pd-catalyzed C-C bond formation, an important vertebra in the spine of synthetic chemistry, is emerging as a valuable chemoselective transformation for post-synthetic functionalization of biomacromolecules. While methods are available for labeling protein and DNA, development of an analogous procedure to label RNA by cross-coupling reactions remains a major challenge. Herein, we describe a new Pd-mediated RNA oligonucleotide (ON) labeling method that involves post-transcriptional functionalization of iodouridine-labeled RNA transcripts by using Suzuki-Miyaura cross-coupling reaction. 5-Iodouridine triphosphate (IUTP) is efficiently incorporated into RNA ONs at one or more sites by T7 RNA polymerase. Further, using a catalytic system made of Pd(OAc)2 and 2-aminopyrimidine-4,6-diol (ADHP) or dimethylamino-substituted ADHP (DMADHP), we established a modular method to functionalize iodouridine-labeled RNA ONs in the presence of various boronic acid and ester substrates under very mild conditions (37°C and pH 8.5). This method is highly chemoselective, and offers direct access to RNA ONs labeled with commonly used fluorescent and affinity tags and new fluorogenic environment-sensitive nucleoside probes in a ligand-controlled stereoselective fashion. Taken together, this simple approach of generating functional RNA ON probes by Suzuki-Miyaura coupling will be a very important addition to the resources and tools available for analyzing RNA motifs.

MDplot: Visualise Molecular Dynamics

PubMed Central

Margreitter, Christian; Oostenbrink, Chris

2017-01-01

The MDplot package provides plotting functions to allow for automated visualisation of molecular dynamics simulation output. It is especially useful in cases where the plot generation is rather tedious due to complex file formats or when a large number of plots are generated. The graphs that are supported range from those which are standard, such as RMsD/RMsF (root-mean-square deviation and root-mean-square fluctuation, respectively) to less standard, such as thermodynamic integration analysis and hydrogen bond monitoring over time. All told, they address many commonly used analyses. In this article, we set out the MDplot package′s functions, give examples of the function calls, and show the associated plots. Plotting and data parsing is separated in all cases, i.e. the respective functions can be used independently. Thus, data manipulation and the integration of additional file formats is fairly easy. Currently, the loading functions support GROMOS, GROMACS, and AMBER file formats. Moreover, we also provide a Bash interface that allows simple embedding of MDplot into Bash scripts as the final analysis step. Availability The package can be obtained in the latest major version from CRAN (https://cran.r-project.org/package=MDplot) or in the most recent version from the project′s GitHub page at https://github.com/MDplot/MDplot, where feedback is also most welcome. MDplot is published under the GPL-3 license. PMID:28845302

Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles.

PubMed

Johnson, Will L; Jindrich, Devin L; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2011-12-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb, which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model, we investigated the suitability of a lumped-parameter model for the prediction of muscle activation during dynamic tasks. Using the validated model, we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury.

Application of a Rat Hindlimb Model: A Prediction of Force Spaces Reachable Through Stimulation of Nerve Fascicles

PubMed Central

Johnson, Will L.; Jindrich, Devin L.; Zhong, Hui; Roy, Roland R.

2011-01-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model we investigated the suitability of a lumped-parameter model for prediction of muscle activation during dynamic tasks. Using the validated model we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury. PMID:21244999

A framework to enhance security of physically unclonable functions using chaotic circuits

NASA Astrophysics Data System (ADS)

Chen, Lanxiang

2018-05-01

As a new technique for authentication and key generation, physically unclonable function (PUF) has attracted considerable attentions, with extensive research results achieved already. To resist the popular machine learning modeling attacks, a framework to enhance the security of PUFs is proposed. The basic idea is to combine PUFs with a chaotic system of which the response is highly sensitive to initial conditions. For this framework, a specific construction which combines the common arbiter PUF circuit, a converter, and the Chua's circuit is given to implement a more secure PUF. Simulation experiments are presented to further validate the framework. Finally, some practical suggestions for the framework and specific construction are also discussed.

Altruistic functions for selfish DNA.

PubMed

Faulkner, Geoffrey J; Carninci, Piero

2009-09-15

Mammalian genomes are comprised of 30-50% transposed elements (TEs). The vast majority of these TEs are truncated and mutated fragments of retrotransposons that are no longer capable of transposition. Although initially regarded as important factors in the evolution of gene regulatory networks, TEs are now commonly perceived as neutrally evolving and non-functional genomic elements. In a major development, recent works have strongly contradicted this "selfish DNA" or "junk DNA" dogma by demonstrating that TEs use a host of novel promoters to generate RNA on a massive scale across most eukaryotic cells. This transcription frequently functions to control the expression of protein-coding genes via alternative promoters, cis regulatory non protein-coding RNAs and the formation of double stranded short RNAs. If considered in sum, these findings challenge the designation of TEs as selfish and neutrally evolving genomic elements. Here, we will expand upon these themes and discuss challenges in establishing novel TE functions in vivo.

Discriminating Among Probability Weighting Functions Using Adaptive Design Optimization

PubMed Central

Cavagnaro, Daniel R.; Pitt, Mark A.; Gonzalez, Richard; Myung, Jay I.

2014-01-01

Probability weighting functions relate objective probabilities and their subjective weights, and play a central role in modeling choices under risk within cumulative prospect theory. While several different parametric forms have been proposed, their qualitative similarities make it challenging to discriminate among them empirically. In this paper, we use both simulation and choice experiments to investigate the extent to which different parametric forms of the probability weighting function can be discriminated using adaptive design optimization, a computer-based methodology that identifies and exploits model differences for the purpose of model discrimination. The simulation experiments show that the correct (data-generating) form can be conclusively discriminated from its competitors. The results of an empirical experiment reveal heterogeneity between participants in terms of the functional form, with two models (Prelec-2, Linear in Log Odds) emerging as the most common best-fitting models. The findings shed light on assumptions underlying these models. PMID:24453406

Point Set Denoising Using Bootstrap-Based Radial Basis Function.

PubMed

Liew, Khang Jie; Ramli, Ahmad; Abd Majid, Ahmad

2016-01-01

This paper examines the application of a bootstrap test error estimation of radial basis functions, specifically thin-plate spline fitting, in surface smoothing. The presence of noisy data is a common issue of the point set model that is generated from 3D scanning devices, and hence, point set denoising is one of the main concerns in point set modelling. Bootstrap test error estimation, which is applied when searching for the smoothing parameters of radial basis functions, is revisited. The main contribution of this paper is a smoothing algorithm that relies on a bootstrap-based radial basis function. The proposed method incorporates a k-nearest neighbour search and then projects the point set to the approximated thin-plate spline surface. Therefore, the denoising process is achieved, and the features are well preserved. A comparison of the proposed method with other smoothing methods is also carried out in this study.

Partial correlation-based functional connectivity analysis for functional near-infrared spectroscopy signals

NASA Astrophysics Data System (ADS)

Akın, Ata

2017-12-01

A theoretical framework, a partial correlation-based functional connectivity (PC-FC) analysis to functional near-infrared spectroscopy (fNIRS) data, is proposed. This is based on generating a common background signal from a high passed version of fNIRS data averaged over all channels as the regressor in computing the PC between pairs of channels. This approach has been employed to real data collected during a Stroop task. The results show a strong significance in the global efficiency (GE) metric computed by the PC-FC analysis for neutral, congruent, and incongruent stimuli (NS, CS, IcS; GEN=0.10±0.009, GEC=0.11±0.01, GEIC=0.13±0.015, p=0.0073). A positive correlation (r=0.729 and p=0.0259) is observed between the interference of reaction times (incongruent-neutral) and interference of GE values (GEIC-GEN) computed from [HbO] signals.

Environmental costs resulting from the use of hard coal to electricity generation in Poland

NASA Astrophysics Data System (ADS)

Stala-Szlugaj, Katarzyna; Grudziński, Zbigniew

2017-10-01

In the world's fuel mix used for generating electricity, the most common fossil fuel is coal. In the EU, coal combustion and electricity generation entail the need to purchase emission allowances (EUA) whose purchase costs affect the costs of electricity generation significantly. The research described in the article shows how current market conditions shape the profitability of generating electricity from coal and how Clean Dark Spread (CDS) changes as a function of changes in energy and coal prices at the assumed levels of emission and prices of EUA allowances. The article compares the results of CDS calculations in two variants. Areas have been highlighted where prices of both coal and EUA allowances cause CDS to assume values at which the prices of generated electricity do not cover the costs of fuel (i) and CO2 emission allowances, cover all costs (ii), or constitute positive prices (iii), but still do not cover all fixed costs. With higher power plant efficiency, CO2 emissions are lower (0.722 t/MWh). The costs of purchasing fuel required to generate 1 MWh of electricity are also lower. In such case—even with relatively high prices of coal—a power plant can achieve profitability of electricity generation.

Beyond Picture Naming: Norms and Patient Data for a Verb Generation Task**

PubMed Central

Kurland, Jacquie; Reber, Alisson; Stokes, Polly

2014-01-01

Purpose The current study aimed to: 1) acquire a set of verb generation to picture norms; and 2) probe its utility as an outcomes measure in aphasia treatment. Method Fifty healthy volunteers participated in Phase I, the verb generation normative sample. They generated verbs for 218 pictures of common objects (ISI=5s). In Phase II, four persons with aphasia (PWA) generated verbs for 60 objects (ISI=10s). Their stimuli consisted of objects which were: 1) recently trained (for object naming; n=20); 2) untrained (a control set; n=20); or 3) from a set of pictures named correctly at baseline (n=20). Verb generation was acquired twice: two months into, and following, a six-month home practice program. Results No objects elicited perfect verb agreement in the normed sample. Stimuli with the highest percent agreement were mostly artifacts and dominant verbs primary functional associates. Although not targeted in treatment or home practice, PWA mostly improved performance in verb generation post-practice. Conclusions A set of clinically and experimentally useful verb generation norms was acquired for a subset of the Snodgrass and Vanderwart (1980) picture set. More cognitively demanding than confrontation naming, this task may help to fill the sizeable gap between object picture naming and propositional speech. PMID:24686752

47 CFR 64.1514 - Generation of signalling tones.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Generation of signalling tones. 64.1514 Section 64.1514 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Services § 64.1514 Generation of signalling tones. No common carrier shall assign a telephone number for...

47 CFR 64.1514 - Generation of signalling tones.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Generation of signalling tones. 64.1514 Section 64.1514 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Services § 64.1514 Generation of signalling tones. No common carrier shall assign a telephone number for...

47 CFR 64.1514 - Generation of signalling tones.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Generation of signalling tones. 64.1514 Section 64.1514 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Services § 64.1514 Generation of signalling tones. No common carrier shall assign a telephone number for...

47 CFR 64.1514 - Generation of signalling tones.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Generation of signalling tones. 64.1514 Section 64.1514 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... Services § 64.1514 Generation of signalling tones. No common carrier shall assign a telephone number for...

Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice.

PubMed

Xiong, Xiwen; Zhang, Cuicui; Zhang, Yang; Fan, Rui; Qian, Xinlai; Dong, X Charlie

2017-06-01

SIRT6 is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis and anti-inflammation. However, its function in the adipose tissue is not well understood. To examine the metabolic function of SIRT6 in the adipose tissue, we generated two mouse models that are deficient in Sirt6 using the Cre-lox approach. Two commonly used Cre lines that are driven by either the mouse Fabp4 or Adipoq gene promoter were chosen for this study. The Sirt6- knockout mice generated by the Fabp4-Cre line ( Sirt6 f/f : Fabp4-Cre) had a significant increase in both body weight and fat mass and exhibited glucose intolerance and insulin resistance as compared with the control wild-type mice. At the molecular levels, the Sirt6 f/f :Fabp4-Cre-knockout mice had increased expression of inflammatory genes including F4/80, TNFα, IL-6 and MCP-1 in both white and brown adipose tissues. Moreover, the knockout mice showed decreased expression of the adiponectin gene in the white adipose tissue and UCP1 in the brown adipose tissue, respectively. In contrast, the Sirt6 knockout mice generated by the Adipoq-Cre line ( Sirt6 f/f :Adipoq-Cre) only had modest insulin resistance. In conclusion, our data suggest that the function of SIRT6 in the Fabp4-Cre-expressing cells in addition to mature adipocytes plays a critical role in body weight maintenance and metabolic homeostasis. © 2017 Society for Endocrinology.

Solidarity in the Grandparent-Adult Grandchild Relationship and Trajectories of Depressive Symptoms.

PubMed

Moorman, Sara M; Stokes, Jeffrey E

2016-06-01

Grandparent-adult grandchild relationships are becoming longer and more common, and therefore potentially more influential in the lives of individuals. This study examined the influence of solidarity (i.e., affinity, contact, and functional exchange) in the grandparent-adult grandchild relationship upon the depressive symptoms of both members of the dyad. The study used data from the Longitudinal Study of Generations, a survey of 3- and 4-generation U.S. families that included 7 waves of data collection between 1985 and 2004. The sample was comprised of 374 grandparents and 356 adult grandchildren. We analyzed the data using multilevel growth curve models. For both grandparents and adult grandchildren, greater affinity reduced depressive symptoms and more frequent contact increased symptoms. For grandparents only, receiving functional support without also providing it increased depressive symptoms. The average grandparent-adult grandchild relationship is a source of both support and strain to both generations. These relationships exhibit great diversity, however, with large amounts of variation between dyads and within a single dyad over time. We suggest how policy makers and practitioners can identify the relational contexts that best promote the well-being of members of both generations. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

MetaStorm: A Public Resource for Customizable Metagenomics Annotation

PubMed Central

Arango-Argoty, Gustavo; Singh, Gargi; Heath, Lenwood S.; Pruden, Amy; Xiao, Weidong; Zhang, Liqing

2016-01-01

Metagenomics is a trending research area, calling for the need to analyze large quantities of data generated from next generation DNA sequencing technologies. The need to store, retrieve, analyze, share, and visualize such data challenges current online computational systems. Interpretation and annotation of specific information is especially a challenge for metagenomic data sets derived from environmental samples, because current annotation systems only offer broad classification of microbial diversity and function. Moreover, existing resources are not configured to readily address common questions relevant to environmental systems. Here we developed a new online user-friendly metagenomic analysis server called MetaStorm (http://bench.cs.vt.edu/MetaStorm/), which facilitates customization of computational analysis for metagenomic data sets. Users can upload their own reference databases to tailor the metagenomics annotation to focus on various taxonomic and functional gene markers of interest. MetaStorm offers two major analysis pipelines: an assembly-based annotation pipeline and the standard read annotation pipeline used by existing web servers. These pipelines can be selected individually or together. Overall, MetaStorm provides enhanced interactive visualization to allow researchers to explore and manipulate taxonomy and functional annotation at various levels of resolution. PMID:27632579

MetaStorm: A Public Resource for Customizable Metagenomics Annotation.

PubMed

Arango-Argoty, Gustavo; Singh, Gargi; Heath, Lenwood S; Pruden, Amy; Xiao, Weidong; Zhang, Liqing

2016-01-01

Metagenomics is a trending research area, calling for the need to analyze large quantities of data generated from next generation DNA sequencing technologies. The need to store, retrieve, analyze, share, and visualize such data challenges current online computational systems. Interpretation and annotation of specific information is especially a challenge for metagenomic data sets derived from environmental samples, because current annotation systems only offer broad classification of microbial diversity and function. Moreover, existing resources are not configured to readily address common questions relevant to environmental systems. Here we developed a new online user-friendly metagenomic analysis server called MetaStorm (http://bench.cs.vt.edu/MetaStorm/), which facilitates customization of computational analysis for metagenomic data sets. Users can upload their own reference databases to tailor the metagenomics annotation to focus on various taxonomic and functional gene markers of interest. MetaStorm offers two major analysis pipelines: an assembly-based annotation pipeline and the standard read annotation pipeline used by existing web servers. These pipelines can be selected individually or together. Overall, MetaStorm provides enhanced interactive visualization to allow researchers to explore and manipulate taxonomy and functional annotation at various levels of resolution.

Securing Digital Audio using Complex Quadratic Map

NASA Astrophysics Data System (ADS)

Suryadi, MT; Satria Gunawan, Tjandra; Satria, Yudi

2018-03-01

In This digital era, exchanging data are common and easy to do, therefore it is vulnerable to be attacked and manipulated from unauthorized parties. One data type that is vulnerable to attack is digital audio. So, we need data securing method that is not vulnerable and fast. One of the methods that match all of those criteria is securing the data using chaos function. Chaos function that is used in this research is complex quadratic map (CQM). There are some parameter value that causing the key stream that is generated by CQM function to pass all 15 NIST test, this means that the key stream that is generated using this CQM is proven to be random. In addition, samples of encrypted digital sound when tested using goodness of fit test are proven to be uniform, so securing digital audio using this method is not vulnerable to frequency analysis attack. The key space is very huge about 8.1×l031 possible keys and the key sensitivity is very small about 10-10, therefore this method is also not vulnerable against brute-force attack. And finally, the processing speed for both encryption and decryption process on average about 450 times faster that its digital audio duration.

Development of a Novel Guided Wave Generation System Using a Giant Magnetostrictive Actuator for Nondestructive Evaluation

PubMed Central

Luo, Mingzhang; Li, Weijie; Wang, Junming; Chen, Xuemin; Song, Gangbing

2018-01-01

As a common approach to nondestructive testing and evaluation, guided wave-based methods have attracted much attention because of their wide detection range and high detection efficiency. It is highly desirable to develop a portable guided wave testing system with high actuating energy and variable frequency. In this paper, a novel giant magnetostrictive actuator with high actuation power is designed and implemented, based on the giant magnetostrictive (GMS) effect. The novel GMS actuator design involves a conical energy-focusing head that can focus the amplified mechanical energy generated by the GMS actuator. This design enables the generation of stress waves with high energy, and the focusing of the generated stress waves on the test object. The guided wave generation system enables two kinds of output modes: the coded pulse signal and the sweep signal. The functionality and the advantages of the developed system are validated through laboratory testing in the quality assessment of rock bolt-reinforced structures. In addition, the developed GMS actuator and the supporting system are successfully implemented and applied in field tests. The device can also be used in other nondestructive testing and evaluation applications that require high-power stress wave generation. PMID:29510540

Development of a Novel Guided Wave Generation System Using a Giant Magnetostrictive Actuator for Nondestructive Evaluation.

PubMed

Luo, Mingzhang; Li, Weijie; Wang, Junming; Wang, Ning; Chen, Xuemin; Song, Gangbing

2018-03-04

As a common approach to nondestructive testing and evaluation, guided wave-based methods have attracted much attention because of their wide detection range and high detection efficiency. It is highly desirable to develop a portable guided wave testing system with high actuating energy and variable frequency. In this paper, a novel giant magnetostrictive actuator with high actuation power is designed and implemented, based on the giant magnetostrictive (GMS) effect. The novel GMS actuator design involves a conical energy-focusing head that can focus the amplified mechanical energy generated by the GMS actuator. This design enables the generation of stress waves with high energy, and the focusing of the generated stress waves on the test object. The guided wave generation system enables two kinds of output modes: the coded pulse signal and the sweep signal. The functionality and the advantages of the developed system are validated through laboratory testing in the quality assessment of rock bolt-reinforced structures. In addition, the developed GMS actuator and the supporting system are successfully implemented and applied in field tests. The device can also be used in other nondestructive testing and evaluation applications that require high-power stress wave generation.

Mutation that blocks ATP binding creates a pseudokinase stabilizing the scaffolding function of kinase suppressor of Ras, CRAF and BRAF.

PubMed

Hu, Jiancheng; Yu, Haiyang; Kornev, Alexandr P; Zhao, Jianping; Filbert, Erin L; Taylor, Susan S; Shaw, Andrey S

2011-04-12

Because mutations in RAS and BRAF represent the most common mutations found in human tumors, identification of inhibitors has been a major goal. Surprisingly, new oncogenic BRAF specific inhibitors inhibit cells transformed with mutated BRAF but paradoxically stimulate the growth of cells transformed with RAS. Here, we show that the mechanism for activation is via drug-induced dimer formation between CRAF and kinase suppressor of Ras (KSR)1. To understand the function of KSR1, we generated a KSR1 mutant that cannot bind ATP but stabilizes the closed, active conformation of KSR1. Molecular modeling suggested that the mutant stabilizes the two hydrophobic spines critical for the closed active conformation. We, therefore, could use the mutant to discriminate between the scaffold versus kinase functions of KSR1. The KSR1 mutant bound constitutively to RAF and mitogen-activated protein kinase kinase (MEK) but could not reconstitute activity suggesting that the catalytic activity of KSR1 is required for its function. Analogous mutations in BRAF and CRAF allowed us to test the generality of the model. The mutation induced changes consistent with the active, closed conformation of both kinases and confirmed that BRAF functions distinctly from CRAF in the MAP kinase pathway. Not only does this work suggest that KSR1 may function as a kinase, we anticipate that the mutation that we generated may be broadly applicable to stabilize the closed conformation of other kinases many of which may also form dimers.

Orthonormal vector polynomials in a unit circle, Part I: Basis set derived from gradients of Zernike polynomials.

PubMed

Zhao, Chunyu; Burge, James H

2007-12-24

Zernike polynomials provide a well known, orthogonal set of scalar functions over a circular domain, and are commonly used to represent wavefront phase or surface irregularity. A related set of orthogonal functions is given here which represent vector quantities, such as mapping distortion or wavefront gradient. These functions are generated from gradients of Zernike polynomials, made orthonormal using the Gram- Schmidt technique. This set provides a complete basis for representing vector fields that can be defined as a gradient of some scalar function. It is then efficient to transform from the coefficients of the vector functions to the scalar Zernike polynomials that represent the function whose gradient was fit. These new vector functions have immediate application for fitting data from a Shack-Hartmann wavefront sensor or for fitting mapping distortion for optical testing. A subsequent paper gives an additional set of vector functions consisting only of rotational terms with zero divergence. The two sets together provide a complete basis that can represent all vector distributions in a circular domain.

Estimation and Application of Ecological Memory Functions in Time and Space

NASA Astrophysics Data System (ADS)

Itter, M.; Finley, A. O.; Dawson, A.

2017-12-01

A common goal in quantitative ecology is the estimation or prediction of ecological processes as a function of explanatory variables (or covariates). Frequently, the ecological process of interest and associated covariates vary in time, space, or both. Theory indicates many ecological processes exhibit memory to local, past conditions. Despite such theoretical understanding, few methods exist to integrate observations from the recent past or within a local neighborhood as drivers of these processes. We build upon recent methodological advances in ecology and spatial statistics to develop a Bayesian hierarchical framework to estimate so-called ecological memory functions; that is, weight-generating functions that specify the relative importance of local, past covariate observations to ecological processes. Memory functions are estimated using a set of basis functions in time and/or space, allowing for flexible ecological memory based on a reduced set of parameters. Ecological memory functions are entirely data driven under the Bayesian hierarchical framework—no a priori assumptions are made regarding functional forms. Memory function uncertainty follows directly from posterior distributions for model parameters allowing for tractable propagation of error to predictions of ecological processes. We apply the model framework to simulated spatio-temporal datasets generated using memory functions of varying complexity. The framework is also applied to estimate the ecological memory of annual boreal forest growth to local, past water availability. Consistent with ecological understanding of boreal forest growth dynamics, memory to past water availability peaks in the year previous to growth and slowly decays to zero in five to eight years. The Bayesian hierarchical framework has applicability to a broad range of ecosystems and processes allowing for increased understanding of ecosystem responses to local and past conditions and improved prediction of ecological processes.

Role of dorsolateral periaqueductal grey in the coordinated regulation of cardiovascular and respiratory function.

PubMed

Dampney, Roger A L; Furlong, Teri M; Horiuchi, Jouji; Iigaya, Kamon

2013-04-01

The midbrain periaqueductal grey (PAG) contains four longitudinal columns, referred to as the dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) subdivisions, which collectively have a pivotal role in integrating behavioural and physiological responses to external stressors as well as other functions. This review is focussed on the dlPAG, which is believed to be an important component of the central mechanisms that generate the defensive response to acute psychological stressors, such as the presence of a predator or other immediate threat. The anatomical connections of the dlPAG are highly specific and distinctly different from those of the other PAG subregions. The chemical properties of the dlPAG are also distinctly different from the other PAG subregions (e.g. there is a very high density of neurons that synthesize nitric oxide in the dlPAG but very few such neurons in the other PAG subregions). Recent functional studies have demonstrated that neurons in the dlPAG exert a powerful control over both sympathetic and respiratory activity, and that the pattern of the evoked respiratory changes is also distinctly different from those evoked from other PAG subregions. These studies also showed that the sympathetic and respiratory changes evoked from the dlPAG are highly correlated, suggesting the possibility that a common population of "command neurons" within this region may generate the sympathetic and respiratory changes that accompany defensive behavioural responses to acute psychological stressors. Finally, although the anatomical connections and functional properties of the dlPAG are distinctly different from the other PAG subregions, they have many similarities with adjacent parts of the superior colliculus, suggesting that the dlPAG and deep layers of the superior colliculus may be part of a common defence system in the midbrain. Copyright © 2013 Elsevier B.V. All rights reserved.

Annotation of the Transcriptome from Taenia pisiformis and Its Comparative Analysis with Three Taeniidae Species

PubMed Central

Yang, Deying; Fu, Yan; Wu, Xuhang; Xie, Yue; Nie, Huaming; Chen, Lin; Nong, Xiang; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yan, Ning; Zhang, Runhui; Zheng, Wanpeng; Yang, Guangyou

2012-01-01

Background Taenia pisiformis is one of the most common intestinal tapeworms and can cause infections in canines. Adult T. pisiformis (canines as definitive hosts) and Cysticercus pisiformis (rabbits as intermediate hosts) cause significant health problems to the host and considerable socio-economic losses as a consequence. No complete genomic data regarding T. pisiformis are currently available in public databases. RNA-seq provides an effective approach to analyze the eukaryotic transcriptome to generate large functional gene datasets that can be used for further studies. Methodology/Principal Findings In this study, 2.67 million sequencing clean reads and 72,957 unigenes were generated using the RNA-seq technique. Based on a sequence similarity search with known proteins, a total of 26,012 unigenes (no redundancy) were identified after quality control procedures via the alignment of four databases. Overall, 15,920 unigenes were mapped to 203 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Through analyzing the glycolysis/gluconeogenesis and axonal guidance pathways, we achieved an in-depth understanding of the biochemistry of T. pisiformis. Here, we selected four unigenes at random and obtained their full-length cDNA clones using RACE PCR. Functional distribution characteristics were gained through comparing four cestode species (72,957 unigenes of T. pisiformis, 30,700 ESTs of T. solium, 1,058 ESTs of Eg+Em [conserved ESTs between Echinococcus granulosus and Echinococcus multilocularis]), with the cluster of orthologous groups (COG) and gene ontology (GO) functional classification systems. Furthermore, the conserved common genes in these four cestode species were obtained and aligned by the KEGG database. Conclusion This study provides an extensive transcriptome dataset obtained from the deep sequencing of T. pisiformis in a non-model whole genome. The identification of conserved genes may provide novel approaches for potential drug targets and vaccinations against cestode infections. Research can now accelerate into the functional genomics, immunity and gene expression profiles of cestode species. PMID:22514598

Scaling of Topologically Similar Functional Modules Defines Mouse Primary Auditory and Somatosensory Microcircuitry

PubMed Central

Sadovsky, Alexander J.

2013-01-01

Mapping the flow of activity through neocortical microcircuits provides key insights into the underlying circuit architecture. Using a comparative analysis we determined the extent to which the dynamics of microcircuits in mouse primary somatosensory barrel field (S1BF) and auditory (A1) neocortex generalize. We imaged the simultaneous dynamics of up to 1126 neurons spanning multiple columns and layers using high-speed multiphoton imaging. The temporal progression and reliability of reactivation of circuit events in both regions suggested common underlying cortical design features. We used circuit activity flow to generate functional connectivity maps, or graphs, to test the microcircuit hypothesis within a functional framework. S1BF and A1 present a useful test of the postulate as both regions map sensory input anatomically, but each area appears organized according to different design principles. We projected the functional topologies into anatomical space and found benchmarks of organization that had been previously described using physiology and anatomical methods, consistent with a close mapping between anatomy and functional dynamics. By comparing graphs representing activity flow we found that each region is similarly organized as highlighted by hallmarks of small world, scale free, and hierarchical modular topologies. Models of prototypical functional circuits from each area of cortex were sufficient to recapitulate experimentally observed circuit activity. Convergence to common behavior by these models was accomplished using preferential attachment to scale from an auditory up to a somatosensory circuit. These functional data imply that the microcircuit hypothesis be framed as scalable principles of neocortical circuit design. PMID:23986241

Phylogeny and phylogeography of functional genes shared among seven terrestrial subsurface metagenomes reveal N-cycling and microbial evolutionary relationships

PubMed Central

Lau, Maggie C. Y.; Cameron, Connor; Magnabosco, Cara; Brown, C. Titus; Schilkey, Faye; Grim, Sharon; Hendrickson, Sarah; Pullin, Michael; Sherwood Lollar, Barbara; van Heerden, Esta; Kieft, Thomas L.; Onstott, Tullis C.

2014-01-01

Comparative studies on community phylogenetics and phylogeography of microorganisms living in extreme environments are rare. Terrestrial subsurface habitats are valuable for studying microbial biogeographical patterns due to their isolation and the restricted dispersal mechanisms. Since the taxonomic identity of a microorganism does not always correspond well with its functional role in a particular community, the use of taxonomic assignments or patterns may give limited inference on how microbial functions are affected by historical, geographical and environmental factors. With seven metagenomic libraries generated from fracture water samples collected from five South African mines, this study was carried out to (1) screen for ubiquitous functions or pathways of biogeochemical cycling of CH4, S, and N; (2) to characterize the biodiversity represented by the common functional genes; (3) to investigate the subsurface biogeography as revealed by this subset of genes; and (4) to explore the possibility of using metagenomic data for evolutionary study. The ubiquitous functional genes are NarV, NPD, PAPS reductase, NifH, NifD, NifK, NifE, and NifN genes. Although these eight common functional genes were taxonomically and phylogenetically diverse and distinct from each other, the dissimilarity between samples did not correlate strongly with geographical or environmental parameters or residence time of the water. Por genes homologous to those of Thermodesulfovibrio yellowstonii detected in all metagenomes were deep lineages of Nitrospirae, suggesting that subsurface habitats have preserved ancestral genetic signatures that inform the study of the origin and evolution of prokaryotes. PMID:25400621

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

PubMed

Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

2017-09-01

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker. Copyright © 2017 Elsevier Ltd. All rights reserved.

Campbell's monkeys use affixation to alter call meaning.

PubMed

Ouattara, Karim; Lemasson, Alban; Zuberbühler, Klaus

2009-11-12

Human language has evolved on a biological substrate with phylogenetic roots deep in the primate lineage. Here, we describe a functional analogy to a common morphological process in human speech, affixation, in the alarm calls of free-ranging adult Campbell's monkeys (Cercopithecus campbelli campbelli). We found that male alarm calls are composed of an acoustically variable stem, which can be followed by an acoustically invariable suffix. Using long-term observations and predator simulation experiments, we show that suffixation in this species functions to broaden the calls' meaning by transforming a highly specific eagle alarm to a general arboreal disturbance call or by transforming a highly specific leopard alarm call to a general alert call. We concluded that, when referring to specific external events, non-human primates can generate meaningful acoustic variation during call production that is functionally equivalent to suffixation in human language.

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

PubMed

Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

2015-10-29

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.

Bird functional diversity decreases with time since disturbance: Does patchy prescribed fire enhance ecosystem function?.

PubMed

Sitters, Holly; Di Stefano, Julian; Christie, Fiona; Swan, Matthew; York, Alan

2016-01-01

Animal species diversity is often associated with time since disturbance, but the effects of disturbances such as fire on functional diversity are unknown. Functional diversity measures the range, abundance, and distribution of trait values in a community, and links changes in species composition with the consequences for ecosystem function. Improved understanding of the relationship between time since fire (TSF) and functional diversity is critical given that the frequency of both prescribed fire and wildfire is expected to increase. To address this knowledge gap, we examined responses of avian functional diversity to TSF and two direct measures of environmental heterogeneity, plant diversity, and structural heterogeneity. We surveyed birds across a 70-year chronosequence spanning four vegetation types in southeast Australia. Six bird functional traits were used to derive four functional diversity indices (richness, evenness, divergence, and dispersion) and the effects of TSF, plant diversity and structural heterogeneity on species richness and the functional diversity indices were examined using mixed models. We used a regression tree method to identify traits associated with species more common in young vegetation. Functional richness and dispersion were negatively associated with TSF in all vegetation types, suggesting that recent prescribed fire generates heterogeneous vegetation and provides greater opportunities for resource partitioning. Species richness was not significantly associated with TSF, and is probably an unreliable surrogate for functional diversity in fire-prone systems. A positive, relationship between functional evenness and structural heterogeneity was comnon to all vegetation types, suggesting that fine-scale (tens of meters) structural variation can enhance ecosystem function. Species more common in young vegetation were primarily linked by their specialist diets, indicating that ecosystem services such as seed dispersal and insect control are enhanced in more recently burnt vegetation. We suggest that patchy prescribed fire sustains functional diversity, and that controlled use of patchy fire to break up large expanses of mature vegetation will enhance ecosystem function.

Differentially Expressed Genes in Resistant and Susceptible Common Bean (Phaseolus vulgaris L.) Genotypes in Response to Fusarium oxysporum f. sp. phaseoli

PubMed Central

Xue, Renfeng; Wu, Jing; Zhu, Zhendong; Wang, Lanfen; Wang, Xiaoming; Wang, Shumin; Blair, Matthew W.

2015-01-01

Fusarium wilt of common bean (Phaseolus vulgaris L.), caused by Fusarium oxysporum Schlechtend.:Fr. f.sp. phaseoli (Fop), is one of the most important diseases of common beans worldwide. Few natural sources of resistance to Fop exist and provide only moderate or partial levels of protection. Despite the economic importance of the disease across multiple crops, only a few of Fop induced genes have been analyzed in legumes. Therefore, our goal was to identify transcriptionally regulated genes during an incompatible interaction between common bean and the Fop pathogen using the cDNA amplified fragment length polymorphism (cDNA-AFLP) technique. We generated a total of 8,730 transcript-derived fragments (TDFs) with 768 primer pairs based on the comparison of a moderately resistant and a susceptible genotype. In total, 423 TDFs (4.9%) displayed altered expression patterns after inoculation with Fop inoculum. We obtained full amplicon sequences for 122 selected TDFs, of which 98 were identified as annotated known genes in different functional categories based on their putative functions, 10 were predicted but non-annotated genes and 14 were not homologous to any known genes. The 98 TDFs encoding genes of known putative function were classified as related to metabolism (22), signal transduction (21), protein synthesis and processing (20), development and cytoskeletal organization (12), transport of proteins (7), gene expression and RNA metabolism (4), redox reactions (4), defense and stress responses (3), energy metabolism (3), and hormone responses (2). Based on the analyses of homology, 19 TDFs from different functional categories were chosen for expression analysis using quantitative RT-PCR. The genes found to be important here were implicated at various steps of pathogen infection and will allow a better understanding of the mechanisms of defense and resistance to Fop and similar pathogens. The differential response genes discovered here could also be used as molecular markers in association mapping or QTL analysis. PMID:26030070

On the assessment of coordination between upper extremities: towards a common language between rehabilitation engineers, clinicians and neuroscientists.

PubMed

Shirota, Camila; Jansa, Jelka; Diaz, Javier; Balasubramanian, Sivakumar; Mazzoleni, Stefano; Borghese, N Alberto; Melendez-Calderon, Alejandro

2016-09-08

Well-developed coordination of the upper extremities is critical for function in everyday life. Interlimb coordination is an intuitive, yet subjective concept that refers to spatio-temporal relationships between kinematic, kinetic and physiological variables of two or more limbs executing a motor task with a common goal. While both the clinical and neuroscience communities agree on the relevance of assessing and quantifying interlimb coordination, rehabilitation engineers struggle to translate the knowledge and needs of clinicians and neuroscientists into technological devices for the impaired. The use of ambiguous definitions in the scientific literature, and lack of common agreement on what should be measured, present large barriers to advancements in this area. Here, we present the different definitions and approaches to assess and quantify interlimb coordination in the clinic, in motor control studies, and by state-of-the-art robotic devices. We then propose a taxonomy of interlimb activities and give recommendations for future neuroscience-based robotic- and sensor-based assessments of upper limb function that are applicable to the everyday clinical practice. We believe this is the first step towards our long-term goal of unifying different fields and help the generation of more consistent and effective tools for neurorehabilitation.

Penguins reduced olfactory receptor genes common to other waterbirds

PubMed Central

Lu, Qin; Wang, Kai; Lei, Fumin; Yu, Dan; Zhao, Huabin

2016-01-01

The sense of smell, or olfaction, is fundamental in the life of animals. However, penguins (Aves: Sphenisciformes) possess relatively small olfactory bulbs compared with most other waterbirds such as Procellariiformes and Gaviiformes. To test whether penguins have a reduced reliance on olfaction, we analyzed the draft genome sequences of the two penguins, which diverged at the origin of the order Sphenisciformes; we also examined six closely related species with available genomes, and identified 29 one-to-one orthologous olfactory receptor genes (i.e. ORs) that are putatively functionally conserved and important across the eight birds. To survey the 29 one-to-one orthologous ORs in penguins and their relatives, we newly generated 34 sequences that are missing from the draft genomes. Through the analysis of totaling 378 OR sequences, we found that, of these functionally important ORs common to other waterbirds, penguins have a significantly greater percentage of OR pseudogenes than other waterbirds, suggesting a reduction of olfactory capability. The penguin-specific reduction of olfactory capability arose in the common ancestor of penguins between 23 and 60 Ma, which may have resulted from the aquatic specializations for underwater vision. Our study provides genetic evidence for a possible reduction of reliance on olfaction in penguins. PMID:27527385

Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing.

PubMed

Liu, Yu; Koyutürk, Mehmet; Maxwell, Sean; Xiang, Min; Veigl, Martina; Cooper, Richard S; Tayo, Bamidele O; Li, Li; LaFramboise, Thomas; Wang, Zhenghe; Zhu, Xiaofeng; Chance, Mark R

2014-08-16

Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human diversity. 76% of micSeqs were confirmed by a comparative genomics approach. Fourteen micSeqs are expressed in human brain or contain TF binding regions. Some micSeqs are primate-specific, conserved and may play a role in the evolution of primates.

Dissecting protein function: an efficient protocol for identifying separation-of-function mutations that encode structurally stable proteins.

PubMed

Lubin, Johnathan W; Rao, Timsi; Mandell, Edward K; Wuttke, Deborah S; Lundblad, Victoria

2013-03-01

Mutations that confer the loss of a single biochemical property (separation-of-function mutations) can often uncover a previously unknown role for a protein in a particular biological process. However, most mutations are identified based on loss-of-function phenotypes, which cannot differentiate between separation-of-function alleles vs. mutations that encode unstable/unfolded proteins. An alternative approach is to use overexpression dominant-negative (ODN) phenotypes to identify mutant proteins that disrupt function in an otherwise wild-type strain when overexpressed. This is based on the assumption that such mutant proteins retain an overall structure that is comparable to that of the wild-type protein and are able to compete with the endogenous protein (Herskowitz 1987). To test this, the in vivo phenotypes of mutations in the Est3 telomerase subunit from Saccharomyces cerevisiae were compared with the in vitro secondary structure of these mutant proteins as analyzed by circular-dichroism spectroscopy, which demonstrates that ODN is a more sensitive assessment of protein stability than the commonly used method of monitoring protein levels from extracts. Reverse mutagenesis of EST3, which targeted different categories of amino acids, also showed that mutating highly conserved charged residues to the oppositely charged amino acid had an increased likelihood of generating a severely defective est3(-) mutation, which nevertheless encoded a structurally stable protein. These results suggest that charge-swap mutagenesis directed at a limited subset of highly conserved charged residues, combined with ODN screening to eliminate partially unfolded proteins, may provide a widely applicable and efficient strategy for generating separation-of-function mutations.

An SQL query generator for CLIPS

NASA Technical Reports Server (NTRS)

Snyder, James; Chirica, Laurian

1990-01-01

As expert systems become more widely used, their access to large amounts of external information becomes increasingly important. This information exists in several forms such as statistical, tabular data, knowledge gained by experts and large databases of information maintained by companies. Because many expert systems, including CLIPS, do not provide access to this external information, much of the usefulness of expert systems is left untapped. The scope of this paper is to describe a database extension for the CLIPS expert system shell. The current industry standard database language is SQL. Due to SQL standardization, large amounts of information stored on various computers, potentially at different locations, will be more easily accessible. Expert systems should be able to directly access these existing databases rather than requiring information to be re-entered into the expert system environment. The ORACLE relational database management system (RDBMS) was used to provide a database connection within the CLIPS environment. To facilitate relational database access a query generation system was developed as a CLIPS user function. The queries are entered in a CLlPS-like syntax and are passed to the query generator, which constructs and submits for execution, an SQL query to the ORACLE RDBMS. The query results are asserted as CLIPS facts. The query generator was developed primarily for use within the ICADS project (Intelligent Computer Aided Design System) currently being developed by the CAD Research Unit in the California Polytechnic State University (Cal Poly). In ICADS, there are several parallel or distributed expert systems accessing a common knowledge base of facts. Expert system has a narrow domain of interest and therefore needs only certain portions of the information. The query generator provides a common method of accessing this information and allows the expert system to specify what data is needed without specifying how to retrieve it.

Confronting Common Folklore: Catching a Cold

ERIC Educational Resources Information Center

Keeley, Page

2012-01-01

Almost every child has experienced the sniffly, stuffy, and achy congestion of the common cold. In addition, many have encountered the "old wives tales" that forge a link between personal actions and coming down with this common respiratory infection. Much of this health folklore has been passed down from generation to generation (e.g., getting a…

JAGGED Controls Arabidopsis Petal Growth and Shape by Interacting with a Divergent Polarity Field

PubMed Central

Sauret-Güeto, Susanna; Schiessl, Katharina; Bangham, Andrew; Sablowski, Robert; Coen, Enrico

2013-01-01

A flowering plant generates many different organs such as leaves, petals, and stamens, each with a particular function and shape. These types of organ are thought to represent variations on a common underlying developmental program. However, it is unclear how this program is modulated under different selective constraints to generate the diversity of forms observed. Here we address this problem by analysing the development of Arabidopsis petals and comparing the results to models of leaf development. We show that petal development involves a divergent polarity field with growth rates perpendicular to local polarity increasing towards the distal end of the petal. The hypothesis is supported by the observed pattern of clones induced at various stages of development and by analysis of polarity markers, which show a divergent pattern. We also show that JAGGED (JAG) has a key role in promoting distal enhancement of growth rates and influences the extent of the divergent polarity field. Furthermore, we reveal links between the polarity field and auxin function: auxin-responsive markers such as DR5 have a broader distribution along the distal petal margin, consistent with the broad distal organiser of polarity, and PETAL LOSS (PTL), which has been implicated in the control of auxin dynamics during petal initiation, is directly repressed by JAG. By comparing these results with those from studies on leaf development, we show how simple modifications of an underlying developmental system may generate distinct forms, providing flexibility for the evolution of different organ functions. PMID:23653565

Longitudinal timed function tests in Duchenne muscular dystrophy: ImagingDMD cohort natural history.

PubMed

Arora, Harneet; Willcocks, Rebecca J; Lott, Donovan J; Harrington, Ann T; Senesac, Claudia R; Zilke, Kirsten L; Daniels, Michael J; Xu, Dandan; Tennekoon, Gihan I; Finanger, Erika L; Russman, Barry S; Finkel, Richard S; Triplett, William T; Byrne, Barry J; Walter, Glenn A; Sweeney, H Lee; Vandenborne, Krista

2018-05-09

Tests of ambulatory function are common clinical trial endpoints in Duchenne muscular dystrophy (DMD). The ImagingDMD study has generated a large data set using these tests, which can describe the contemporary natural history of DMD in 5-12.9 year olds. 92 corticosteroid treated boys with DMD and 45 controls participated in this longitudinal study. Subjects performed the 6 minute walk test (6MWT) and timed function tests (TFTs: 10m walk/run, 4 stairs, supine to stand). Boys with DMD had impaired functional performance even at 5-6.9 years. Boys older than 7 had significant declines in function over 1 year for 10m walk/run and 6MWT. 80% of subjects could perform all functional tests at 9 years old. TFTs appear to be slightly more responsive and predictive of disease progression than 6MWT in 7-12.9 year olds. This study provides insight into the contemporary natural history of key functional endpoints in DMD. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

InAs/GaInSb superlattices as a promising material system for third generation infrared detectors

NASA Astrophysics Data System (ADS)

Rogalski, A.; Martyniuk, P.

2006-04-01

Hitherto, two families of multielement detectors have been used for infrared applications: scanning systems (first generation) and staring systems (second generation). Third generation systems are being developed nowadays. In the common understanding, third generation IR systems provide enhanced capabilities like larger number of pixels, higher frame rates, better thermal resolution as well as multicolour functionality and other on-chip functions. In the class of third generation infrared photon detectors, two main competitors, HgCdTe photodiodes and AlGaAs/GaAs quantum well infrared photoconductors (QWIPs) are considered. However, in the long wavelength infrared (LWIR) region, the HgCdTe material fail to give the requirements of large format two-dimensional (2-D) arrays due to metallurgical problems of the epitaxial layers such as uniformity and number of defective elements. A superlattice based InAs/GaInSb system grown on GaSb substrate seems to be an attractive alternative to HgCdTe with good spatial uniformity and an ability to span cut-off wavelength from 3 to 25 μm. The recently published results have indicated that high performance middle wavelength infrared (MWIR) InAs/GaInSb superlattice focal plane arrays can be fabricated. Also LWIR photodiodes with the R0A values exceeding 100 Ωcm 2 even with a cut-off wavelength of 14 μm can be achieved. Based on these very promising results it is obvious now that the antimonide superlattice technology is competing with HgCdTe dual colour technology with the potential advantage of standard III-V technology to be more competitive in costs and as a consequence series production pricing.

Transgenerational programming of nephron deficits and hypertension.

PubMed

Briffa, Jessica F; Wlodek, Mary E; Moritz, Karen M

2018-06-07

Exposure to a sub-optimal environment in the womb can result in poor fetal growth and impair the normal development of organs. The kidney, specifically the process of nephrogenesis, has been shown to be impacted by many common pregnancy exposures including an inadequate diet, poor placental function, maternal stress as well as maternal smoking and alcohol consumption. This can result in offspring being born with a reduced nephron endowment, which places these individuals at increased risk of hypertension and chronic kidney disease (CKD). Of recent interest is whether this disease risk can be passed on to subsequent generations and, if so, what are the mechanisms and pathways involved. In this review, we highlight the growing body of evidence that a low birth weight and hypertension, which are both major risk factors for cardiovascular and CKD, can be transmitted across generations. However, as yet there is little data as to whether a low nephron endowment contributes to this disease transmission. The emerging data suggests transmission can occur both through both the maternal and paternal lines, which likely involves epigenetic mechanisms such chromatin remodelling (DNA methylation and histone modification) and non-coding RNA modifications. In addition, females who were born small and/or have a low nephron endowment are at an increased risk for pregnancy complications, which can influence the growth and development of the next generation. Future animal studies in this area should include examining nephron endowment across multiple generations and determining adult renal function. Clinically, long term follow-up studies of large birth cohorts need to be undertaken to more clearly determine the impact a sub-optimal environment in one generation has on the health outcomes in the second, and subsequent, generation. Copyright © 2018. Published by Elsevier Ltd.

Evidence for basal distortion-product otoacoustic emission components.

PubMed

Martin, Glen K; Stagner, Barden B; Lonsbury-Martin, Brenda L

2010-05-01

Distortion-product otoacoustic emissions (DPOAEs) were measured with traditional DP-grams and level/phase (L/P) maps in rabbits with either normal cochlear function or unique sound-induced cochlear losses that were characterized as either low-frequency or notched configurations. To demonstrate that emission generators distributed basal to the f(2) primary-tone contribute, in general, to DPOAE levels and phases, a high-frequency interference tone (IT) was presented at 1/3 of an octave (oct) above the f(2) primary-tone, and DPOAEs were re-measured as "augmented" DP-grams (ADP-grams) and L/P maps. The vector difference between the control and augmented functions was then computed to derive residual DP-grams (RDP-grams) and L/P maps. The resulting RDP-grams and L/P maps, which described the DPOAEs removed by the IT, supported the notion that basal DPOAE components routinely contribute to the generation of standard measures of DPOAEs. Separate experiments demonstrated that these components could not be attributed to the effects of the 1/3-oct IT on f(2), or DPOAEs generated by the addition of a third interfering tone. These basal components can "fill in" the lesion estimated by the commonly employed DP-gram. Thus, ADP-grams more accurately reveal the pattern of cochlear damage and may eventually lead to an improved DP-gram procedure.

Electronic nose for detecting multiple targets

NASA Astrophysics Data System (ADS)

Chakraborty, Anirban; Parthasarathi, Ganga; Poddar, Rakesh; Zhao, Weiqiang; Luo, Cheng

2006-05-01

The discovery of high conductivity in doped polyacetylene in 1977 (garnering the 2000 Nobel Prize in Chemistry for the three discovering scientists) has attracted considerable interest in the application of polymers as the semiconducting and conducting materials due to their promising potential to replace silicon and metals in building devices. Previous and current efforts in developing conducting polymer microsystems mainly focus on generating a device of a single function. When multiple micropatterns made of different conducting polymers are produced on the same substrate, many microsystems of multiple functions can be envisioned. For example, analogous to the mammalian olfactory system which includes over 1,000 receptor genes in detecting various odors (e.g., beer, soda etc.), a sensor consisting of multiple distinct conducting polymer sensing elements will be capable of detecting a number of analytes simultaneously. However, existing techniques present significant technical challenges of degradation, low throughput, low resolution, depth of field, and/or residual layer in producing conducting polymer microstructures. To circumvent these challenges, an intermediate-layer lithography method developed in our group is used to generate multiple micropatterns made of different, commonly used conducting polymers, Polypyrrole (PPy), Poly(3,4-ethylenedioxy)thiophene (PEDOT) and Polyaniline (PANI). The generated multiple micropatterns are further used in an "electronic nose" to detect water vapor, glucose, toluene and acetone.

A method of isolating treadmill shock and vibration on spacecraft

NASA Technical Reports Server (NTRS)

Thornton, William E.

1989-01-01

A major problem is currently felt to exist in the implementation of materials processing on a spacecraft. Crystal growers place requirements of one micro-g or less on the vehicle. Simple math produces startling figures for such a restriction e.g., for each ton of vehicle mass with 10(-6) g acceleration limit; Perturbing Force limit, F = .002 lb. For each 10(5) lbs F = 0.1 lb. For each 10(6) lbs F = 1.0 lb. Forces generated by normal human movement on spacecraft of 5x10(5) pounds weight are on an order-of-magnitude greater than allowed by this specification and forces generated by locomotion on a treadmill are more than two orders-of-magnitude greater. Other exercises and normal onboard functions generate forces in between. To accommodate many essential functions it is obvious that even on a vehicle as large as Space Station, a reduction of more than two orders of magnitude in force is required. Commonly used passive shock and vibration isolation devices are complex, heavy, and also would have difficulty meeting the requirements. However, by a new arrangement, adequate isolation can be obtained. Isolation of the treadmill will be treated since it is considered the most significant disturbance at this time.

Toxic effects of inhaled manganese on the olfactory bulb: an ultrastructural approach in mice.

PubMed

Colin-Barenque, L; Souza-Gallardo, L M; Fortoul, T I

2011-01-01

Olfactory dysfunction is a common symptom reported by patients with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Despite the knowledge gathered about the pathology of these diseases, little information has been generated regarding the ultrastructure modifications of the granule cells that regulate the information for odor identification. Swollen organelles and nuclear invaginations identified the exposed mice. Necrosis was evidenced at 4th week of exposure, whereas apoptosis arose at 8th week of exposure. A ruffled electron-dense membrane changes were also found. The changes observed could be explained by the reactive oxygen species generated by manganese and its effects on the membrane's structure and on the cytoskeleton's function. This study contributes to correlate metal air pollution and neurodegenerative changes with olfactory affection.

Approaches in highly parameterized inversion: TSPROC, a general time-series processor to assist in model calibration and result summarization

USGS Publications Warehouse

Westenbroek, Stephen M.; Doherty, John; Walker, John F.; Kelson, Victor A.; Hunt, Randall J.; Cera, Timothy B.

2012-01-01

The TSPROC (Time Series PROCessor) computer software uses a simple scripting language to process and analyze time series. It was developed primarily to assist in the calibration of environmental models. The software is designed to perform calculations on time-series data commonly associated with surface-water models, including calculation of flow volumes, transformation by means of basic arithmetic operations, and generation of seasonal and annual statistics and hydrologic indices. TSPROC can also be used to generate some of the key input files required to perform parameter optimization by means of the PEST (Parameter ESTimation) computer software. Through the use of TSPROC, the objective function for use in the model-calibration process can be focused on specific components of a hydrograph.

[Development of opened instrument for generating and measuring physiological signal].

PubMed

Chen, Longcong; Hu, Guohu; Gao, Bin

2004-12-01

An opened instrument with liquid crystal display (LCD) for generating and measuring physiological signal is introduced in this paper. Based on a single-chip microcomputer. the instrument uses the technique of LCD screen to display signal wave and information, and it realizes man-machine interaction by keyboard. This instrument can produce not only defined signal in common use by utilizing important saved data and relevant arithmetic, but also user-defined signal. Therefore, it is open to produce signal. In addition, this instrument has strong extension because of its modularized design as computer, which has much function such as displaying, measuring and saving physiological signal, and many features such as low power consumption, small volume, low cost and portability. Hence this instrument is convenient for experiment teaching, clinic examining, maintaining of medical instrument.

Regionalizing nonparametric models of precipitation amounts on different temporal scales

NASA Astrophysics Data System (ADS)

Mosthaf, Tobias; Bárdossy, András

2017-05-01

Parametric distribution functions are commonly used to model precipitation amounts corresponding to different durations. The precipitation amounts themselves are crucial for stochastic rainfall generators and weather generators. Nonparametric kernel density estimates (KDEs) offer a more flexible way to model precipitation amounts. As already stated in their name, these models do not exhibit parameters that can be easily regionalized to run rainfall generators at ungauged locations as well as at gauged locations. To overcome this deficiency, we present a new interpolation scheme for nonparametric models and evaluate it for different temporal resolutions ranging from hourly to monthly. During the evaluation, the nonparametric methods are compared to commonly used parametric models like the two-parameter gamma and the mixed-exponential distribution. As water volume is considered to be an essential parameter for applications like flood modeling, a Lorenz-curve-based criterion is also introduced. To add value to the estimation of data at sub-daily resolutions, we incorporated the plentiful daily measurements in the interpolation scheme, and this idea was evaluated. The study region is the federal state of Baden-Württemberg in the southwest of Germany with more than 500 rain gauges. The validation results show that the newly proposed nonparametric interpolation scheme provides reasonable results and that the incorporation of daily values in the regionalization of sub-daily models is very beneficial.

Assessing the genetic overlap between BMI and cognitive function

PubMed Central

Marioni, R E; Yang, J; Dykiert, D; Mõttus, R; Campbell, A; Ibrahim-Verbaas, Carla A; Bressler, Jan; Debette, Stephanie; Schuur, Maaike; Smith, Albert V; Davies, Gail; Bennett, David A; Deary, Ian J; Ikram, M Arfan; Launer, Lenore J; Fitzpatrick, Annette L; Seshadri, Sudha; van Duijn, Cornelia M; Mosely Jr, Thomas H; Davies, G; Hayward, C; Porteous, D J; Visscher, P M; Deary, I J

2016-01-01

Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r=−0.11; high body mass index (BMI)−low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)–GREML; independent samples bivariate GCTA–GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA–GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA–GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 × 10−7) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at P<5 × 10−5, which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function. PMID:26857597

Local vs. volume conductance activity of field potentials in the human subthalamic nucleus

PubMed Central

Marmor, Odeya; Valsky, Dan; Joshua, Mati; Bick, Atira S; Arkadir, David; Tamir, Idit; Bergman, Hagai; Israel, Zvi

2017-01-01

Subthalamic nucleus field potentials have attracted growing research and clinical interest over the last few decades. However, it is unclear whether subthalamic field potentials represent locally generated neuronal subthreshold activity or volume conductance of the organized neuronal activity generated in the cortex. This study aimed at understanding of the physiological origin of subthalamic field potentials and determining the most accurate method for recording them. We compared different methods of recordings in the human subthalamic nucleus: spikes (300–9,000 Hz) and field potentials (3–100 Hz) recorded by monopolar micro- and macroelectrodes, as well as by differential-bipolar macroelectrodes. The recordings were done outside and inside the subthalamic nucleus during electrophysiological navigation for deep brain stimulation procedures (150 electrode trajectories) in 41 Parkinson’s disease patients. We modeled the signal and estimated the contribution of nearby/independent vs. remote/common activity in each recording configuration and area. Monopolar micro- and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity. However, bipolar macroelectrode recordings inside the subthalamic nucleus can detect locally generated potentials. These results are confirmed by high correspondence between the model predictions and actual correlation of neuronal activity recorded by electrode pairs. Differential bipolar macroelectrode subthalamic field potentials can overcome volume conductance effects and reflect locally generated neuronal activity. Bipolar macroelectrode local field potential recordings might be used as a biological marker of normal and pathological brain functions for future electrophysiological studies and navigation systems as well as for closed-loop deep brain stimulation paradigms. NEW & NOTEWORTHY Our results integrate a new method for human subthalamic recordings with a development of an advanced mathematical model. We found that while monopolar microelectrode and macroelectrode recordings detect field potentials that are considerably affected by common (probably cortical) activity, bipolar macroelectrode recordings inside the subthalamic nucleus (STN) detect locally generated potentials that are significantly different than those recorded outside the STN. Differential bipolar subthalamic field potentials can be used in navigation and closed-loop deep brain stimulation paradigms. PMID:28202569

ROC-ing along: Evaluation and interpretation of receiver operating characteristic curves.

PubMed

Carter, Jane V; Pan, Jianmin; Rai, Shesh N; Galandiuk, Susan

2016-06-01

It is vital for clinicians to understand and interpret correctly medical statistics as used in clinical studies. In this review, we address current issues and focus on delivering a simple, yet comprehensive, explanation of common research methodology involving receiver operating characteristic (ROC) curves. ROC curves are used most commonly in medicine as a means of evaluating diagnostic tests. Sample data from a plasma test for the diagnosis of colorectal cancer were used to generate a prediction model. These are actual, unpublished data that have been used to describe the calculation of sensitivity, specificity, positive predictive and negative predictive values, and accuracy. The ROC curves were generated to determine the accuracy of this plasma test. These curves are generated by plotting the sensitivity (true-positive rate) on the y axis and 1 - specificity (false-positive rate) on the x axis. Curves that approach closest to the coordinate (x = 0, y = 1) are more highly predictive, whereas ROC curves that lie close to the line of equality indicate that the result is no better than that obtained by chance. The optimum sensitivity and specificity can be determined from the graph as the point where the minimum distance line crosses the ROC curve. This point corresponds to the Youden index (J), a function of sensitivity and specificity used commonly to rate diagnostic tests. The area under the curve is used to quantify the overall ability of a test to discriminate between 2 outcomes. By following these simple guidelines, interpretation of ROC curves will be less difficult and they can then be interpreted more reliably when writing, reviewing, or analyzing scientific papers. Copyright © 2016 Elsevier Inc. All rights reserved.

From movement to thought: executive function, embodied cognition, and the cerebellum.

PubMed

Koziol, Leonard F; Budding, Deborah Ely; Chidekel, Dana

2012-06-01

This paper posits that the brain evolved for the control of action rather than for the development of cognition per se. We note that the terms commonly used to describe brain-behavior relationships define, and in many ways limit, how we conceptualize and investigate them and may therefore constrain the questions we ask and the utility of the "answers" we generate. Many constructs are so nonspecific and over-inclusive as to be scientifically meaningless. "Executive function" is one such term in common usage. As the construct is increasingly focal in neuroscience research, defining it clearly is critical. We propose a definition that places executive function within a model of continuous sensorimotor interaction with the environment. We posit that control of behavior is the essence of "executive function," and we explore the evolutionary advantage conferred by being able to anticipate and control behavior with both implicit and explicit mechanisms. We focus on the cerebellum's critical role in these control processes. We then hypothesize about the ways in which procedural (skill) learning contributes to the acquisition of declarative (semantic) knowledge. We hypothesize how these systems might interact in the process of grounding knowledge in sensorimotor anticipation, thereby directly linking movement to thought and "embodied cognition." We close with a discussion of ways in which the cerebellum instructs frontal systems how to think ahead by providing anticipatory control mechanisms, and we briefly review this model's potential applications.

Dual-Phase Lock-In Amplifier Based on FPGA for Low-Frequencies Experiments

PubMed Central

Macias-Bobadilla, Gonzalo; Rodríguez-Reséndiz, Juvenal; Mota-Valtierra, Georgina; Soto-Zarazúa, Genaro; Méndez-Loyola, Maurino; Garduño-Aparicio, Mariano

2016-01-01

Photothermal techniques allow the detection of characteristics of material without invading it. Researchers have developed hardware for some specific Phase and Amplitude detection (Lock-In Function) applications, eliminating space and unnecessary electronic functions, among others. This work shows the development of a Digital Lock-In Amplifier based on a Field Programmable Gate Array (FPGA) for low-frequency applications. This system allows selecting and generating the appropriated frequency depending on the kind of experiment or material studied. The results show good frequency stability in the order of 1.0 × 10−9 Hz, which is considered good linearity and repeatability response for the most common Laboratory Amplitude and Phase Shift detection devices, with a low error and standard deviation. PMID:26999138

Dual-Phase Lock-In Amplifier Based on FPGA for Low-Frequencies Experiments.

PubMed

Macias-Bobadilla, Gonzalo; Rodríguez-Reséndiz, Juvenal; Mota-Valtierra, Georgina; Soto-Zarazúa, Genaro; Méndez-Loyola, Maurino; Garduño-Aparicio, Mariano

2016-03-16

Photothermal techniques allow the detection of characteristics of material without invading it. Researchers have developed hardware for some specific Phase and Amplitude detection (Lock-In Function) applications, eliminating space and unnecessary electronic functions, among others. This work shows the development of a Digital Lock-In Amplifier based on a Field Programmable Gate Array (FPGA) for low-frequency applications. This system allows selecting and generating the appropriated frequency depending on the kind of experiment or material studied. The results show good frequency stability in the order of 1.0 × 10(-9) Hz, which is considered good linearity and repeatability response for the most common Laboratory Amplitude and Phase Shift detection devices, with a low error and standard deviation.

Epigenetic memory: the Lamarckian brain

PubMed Central

Fischer, Andre

2014-01-01

Recent data support the view that epigenetic processes play a role in memory consolidation and help to transmit acquired memories even across generations in a Lamarckian manner. Drugs that target the epigenetic machinery were found to enhance memory function in rodents and ameliorate disease phenotypes in models for brain diseases such as Alzheimer's disease, Chorea Huntington, Depression or Schizophrenia. In this review, I will give an overview on the current knowledge of epigenetic processes in memory function and brain disease with a focus on Morbus Alzheimer as the most common neurodegenerative disease. I will address the question whether an epigenetic therapy could indeed be a suitable therapeutic avenue to treat brain diseases and discuss the necessary steps that should help to take neuroepigenetic research to the next level. PMID:24719207

Exploring the distinction between experimental resonant modes and theoretical eigenmodes: from vibrating plates to laser cavities.

PubMed

Tuan, P H; Wen, C P; Yu, Y T; Liang, H C; Huang, K F; Chen, Y F

2014-02-01

Experimentally resonant modes are commonly presumed to correspond to eigenmodes in the same bounded domain. However, the one-to-one correspondence between theoretical eigenmodes and experimental observations is never reached. Theoretically, eigenmodes in numerous classical and quantum systems are the solutions of the homogeneous Helmholtz equation, whereas resonant modes should be solved from the inhomogeneous Helmholtz equation. In the present paper we employ the eigenmode expansion method to derive the wave functions for manifesting the distinction between eigenmodes and resonant modes. The derived wave functions are successfully used to reconstruct a variety of experimental results including Chladni figures generated from the vibrating plate, resonant patterns excited from microwave cavities, and lasing modes emitted from the vertical cavity.

Transcriptome Analysis of Salt Tolerant Common Bean (Phaseolus vulgaris L.) under Saline Conditions

PubMed Central

Hiz, Mahmut Can; Canher, Balkan; Niron, Harun; Turet, Muge

2014-01-01

Salinity is one of the important abiotic stress factors that limit crop production. Common bean, Phaseolus vulgaris L., a major protein source in developing countries, is highly affected by soil salinity and the information on genes that play a role in salt tolerance is scarce. We aimed to identify differentially expressed genes (DEGs) and related pathways by comprehensive analysis of transcriptomes of both root and leaf tissues of the tolerant genotype grown under saline and control conditions in hydroponic system. We have generated a total of 158 million high-quality reads which were assembled into 83,774 all-unigenes with a mean length of 813 bp and N50 of 1,449 bp. Among the all-unigenes, 58,171 were assigned with Nr annotations after homology analyses. It was revealed that 6,422 and 4,555 all-unigenes were differentially expressed upon salt stress in leaf and root tissues respectively. Validation of the RNA-seq quantifications (RPKM values) was performed by qRT-PCR (Quantitative Reverse Transcription PCR) analyses. Enrichment analyses of DEGs based on GO and KEGG databases have shown that both leaf and root tissues regulate energy metabolism, transmembrane transport activity, and secondary metabolites to cope with salinity. A total of 2,678 putative common bean transcription factors were identified and classified under 59 transcription factor families; among them 441 were salt responsive. The data generated in this study will help in understanding the fundamentals of salt tolerance in common bean and will provide resources for functional genomic studies. PMID:24651267

Common variants of the vitamin D binding protein gene and adverse health outcomes.

PubMed

Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y L; Gozdzik, Agnes; Cole, David E C

2013-01-01

The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene - rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys - change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged.

Biophysical force regulation in 3D tumor cell invasion

NASA Astrophysics Data System (ADS)

Wu, Mingming

When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

Modeling discrete and rhythmic movements through motor primitives: a review.

PubMed

Degallier, Sarah; Ijspeert, Auke

2010-10-01

Rhythmic and discrete movements are frequently considered separately in motor control, probably because different techniques are commonly used to study and model them. Yet the increasing interest in finding a comprehensive model for movement generation requires bridging the different perspectives arising from the study of those two types of movements. In this article, we consider discrete and rhythmic movements within the framework of motor primitives, i.e., of modular generation of movements. In this way we hope to gain an insight into the functional relationships between discrete and rhythmic movements and thus into a suitable representation for both of them. Within this framework we can define four possible categories of modeling for discrete and rhythmic movements depending on the required command signals and on the spinal processes involved in the generation of the movements. These categories are first discussed in terms of biological concepts such as force fields and central pattern generators and then illustrated by several mathematical models based on dynamical system theory. A discussion on the plausibility of theses models concludes the work.

Examining the benefits of combining two learning strategies on recall of functional information in persons with multiple sclerosis.

PubMed

Goverover, Yael; Basso, Michael; Wood, Hali; Chiaravalloti, Nancy; DeLuca, John

2011-12-01

Forgetfulness occurs commonly in people with multiple sclerosis (MS), but few treatments alleviate this problem. This study examined the combined effect of two cognitive rehabilitation strategies to improve learning and memory in MS: self-generation and spaced learning. The hypothesis was that the combination of spaced learning and self-generation would yield better learning and memory recall performance than spaced learning alone. Using a within groups design, 20 participants with MS and 18 healthy controls (HC) were presented with three tasks (learning names, appointment, and object location), each in three learning conditions (Massed, Spaced Learning, and combination of spaced and generated information). Participants were required to recall the information they learned in each of these conditions immediately and 30 min following the initial presentation. The combination of spaced learning and self-generation yielded better recall than did spaced learning alone. In turn, spaced learning resulted in better recall than the massed rehearsal condition. These findings reveal that the combination of these two learning strategies may possess utility as a cognitive rehabilitation strategy.

Simplified Novel Application (SNApp) framework: a guide to developing and implementing second-generation mobile applications for behavioral health research.

PubMed

Fillo, Jennifer; Staplefoote-Boynton, B Lynette; Martinez, Angel; Sontag-Padilla, Lisa; Shadel, William G; Martino, Steven C; Setodji, Claude M; Meeker, Daniella; Scharf, Deborah

2016-12-01

Advances in mobile technology and mobile applications (apps) have opened up an exciting new frontier for behavioral health researchers, with a "second generation" of apps allowing for the simultaneous collection of multiple streams of data in real time. With this comes a host of technical decisions and ethical considerations unique to this evolving approach to research. Drawing on our experience developing a second-generation app for the simultaneous collection of text message, voice, and self-report data, we provide a framework for researchers interested in developing and using second-generation mobile apps to study health behaviors. Our Simplified Novel Application (SNApp) framework breaks the app development process into four phases: (1) information and resource gathering, (2) software and hardware decisions, (3) software development and testing, and (4) study start-up and implementation. At each phase, we address common challenges and ethical issues and make suggestions for effective and efficient app development. Our goal is to help researchers effectively balance priorities related to the function of the app with the realities of app development, human subjects issues, and project resource constraints.

The situation of generation, treatment and supervision of common industrial solid wastes in China

NASA Astrophysics Data System (ADS)

Xu, Shumin

2018-02-01

From the point of view of location and sources, an analysis is done for the generation, utilization, treatment and storage of common industrial solid wastes in China. Based on the current situations, suggestions are given to the treatment and supervision polices in China for the utilization of common industrial solid wastes.

Common theme for drugs effective in overactive bladder treatment: Inhibition of afferent signaling from the bladder

PubMed Central

Hood, Brandy; Andersson, Karl-Erik

2013-01-01

The overactive bladder syndrome and detrusor overactivity are conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are still first-line treatment. These drugs often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium/suburothelium, the autonomous detrusor muscle activity during bladder filling and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of overactive bladder syndrome/detrusor overactivity pathophysiology. Three drugs recently approved for treatment of overactive bladder syndrome/detrusor overactivity (mirabegron, tadalafil and onabotulinum toxin A), representing different pharmacological mechanisms; that is, β-adrenoceptor agonism, phosphodiesterase type 5 inhibition, and inhibition of nerve release of efferent and afferent transmitters, all seem to have one effect in common: inhibition of the afferent nervous activity generated by the bladder during filling. In the present review, the different mechanisms forming the pharmacological basis for the use of these drugs are discussed. PMID:23072271

A Model Independent S/W Framework for Search-Based Software Testing

PubMed Central

Baik, Jongmoon

2014-01-01

In Model-Based Testing (MBT) area, Search-Based Software Testing (SBST) has been employed to generate test cases from the model of a system under test. However, many types of models have been used in MBT. If the type of a model has changed from one to another, all functions of a search technique must be reimplemented because the types of models are different even if the same search technique has been applied. It requires too much time and effort to implement the same algorithm over and over again. We propose a model-independent software framework for SBST, which can reduce redundant works. The framework provides a reusable common software platform to reduce time and effort. The software framework not only presents design patterns to find test cases for a target model but also reduces development time by using common functions provided in the framework. We show the effectiveness and efficiency of the proposed framework with two case studies. The framework improves the productivity by about 50% when changing the type of a model. PMID:25302314

Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells.

PubMed

Zhang, Yancong; Li, Yongliang; Shi, Ruirui; Zhang, Siqi; Liu, Hao; Zheng, Yunfei; Li, Yan; Cai, Jinglei; Pei, Duanqing; Wei, Shicheng

2017-06-08

A number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth-periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth-periodontium complex structures in vivo. First, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth-periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining. Our study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth-periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth-periodontium complex structures shared a similar histological structure with normal mouse teeth. An optimized induction method was established to promote the differentiation of mES cells into dental epithelium by temporally controlling the function of BMP4. A novel tooth-periodontium complex structure was generated using the epithelium.

Rotor Noise due to Blade-Turbulence Interaction.

NASA Astrophysics Data System (ADS)

Ishimaru, Kiyoto

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)(.)(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function. The acoustic intensity density function is not necessarily stationary even if the inflow turbulence is homogeneous and isotropic. The time variation of the propagation path due to the rotation should be considered in the computation of the intensity density function; for instance, in the present rotor specification, the rotor radius is about 0.3 m and the rotational speed Mach number is about 0.2.

Duration of Tsunami Generation Longer than Duration of Seismic Wave Generation in the 2011 Mw 9.0 Tohoku-Oki Earthquake

NASA Astrophysics Data System (ADS)

Fujihara, S.; Korenaga, M.; Kawaji, K.; Akiyama, S.

2013-12-01

We try to compare and evaluate the nature of tsunami generation and seismic wave generation in occurrence of the 2011 Tohoku-Oki earthquake (hereafter, called as TOH11), in terms of two type of moment rate functions, inferred from finite source imaging of tsunami waveforms and seismic waveforms. Since 1970's, the nature of "tsunami earthquakes" has been discussed in many researches (e.g. Kanamori, 1972; Kanamori and Kikuchi, 1993; Kikuchi and Kanamori, 1995; Ide et al., 1993; Satake, 1994) mostly based on analysis of seismic waveform data , in terms of the "slow" nature of tsunami earthquakes (e.g., the 1992 Nicaragura earthquake). Although TOH11 is not necessarily understood as a tsunami earthquake, TOH11 is one of historical earthquakes that simultaneously generated large seismic waves and tsunami. Also, TOH11 is one of earthquakes which was observed both by seismic observation network and tsunami observation network around the Japanese islands. Therefore, for the purpose of analyzing the nature of tsunami generation, we try to utilize tsunami waveform data as much as possible. In our previous studies of TOH11 (Fujihara et al., 2012a; Fujihara et al., 2012b), we inverted tsunami waveforms at GPS wave gauges of NOWPHAS to image the spatio-temporal slip distribution. The "temporal" nature of our tsunami source model is generally consistent with the other tsunami source models (e.g., Satake et al, 2013). For seismic waveform inversion based on 1-D structure, here we inverted broadband seismograms at GSN stations based on the teleseismic body-wave inversion scheme (Kikuchi and Kanamori, 2003). Also, for seismic waveform inversion considering the inhomogeneous internal structure, we inverted strong motion seismograms at K-NET and KiK-net stations, based on 3-D Green's functions (Fujihara et al., 2013a; Fujihara et al., 2013b). The gross "temporal" nature of our seismic source models are generally consistent with the other seismic source models (e.g., Yoshida et al., 2011; Ide at al., 2011; Yagi and Fukahata, 2011; Suzuki et al., 2011). The comparison of two type of moment rate functions, inferred from finite source imaging of tsunami waveforms and seismic waveforms, suggested that there was the time period common to both seismic wave generation and tsunami generation followed by the time period unique to tsunami generation. At this point, we think that comparison of the absolute values of moment rates is not so meaningful between tsunami waveform inversion and seismic waveform inversion, because of general ambiguity of rigidity values of each subfault in the fault region (assuming the rigidity value of 30 GPa of Yoshida et al (2011)). Considering this, the normalized value of moment rate function was also evaluated and it does not change the general feature of two moment rate functions in terms of duration property. Furthermore, the results suggested that tsunami generation process apparently took more time than seismic wave generation process did. Tsunami can be generated even by "extra" motions resulting from many suggested abnormal mechanisms. These extra motions may be attribute to the relatively larger-scale tsunami generation than expected from the magnitude level from seismic ground motion, and attribute to the longer duration of tsunami generation process.

A model for phase noise generation in amplifiers.

PubMed

Tomlin, T D; Fynn, K; Cantoni, A

2001-11-01

In this paper, a model is presented for predicting the phase modulation (PM) and amplitude modulation (AM) noise in bipolar junction transistor (BJT) amplifiers. The model correctly predicts the dependence of phase noise on the signal frequency (at a particular carrier offset frequency), explains the noise shaping of the phase noise about the signal frequency, and shows the functional dependence on the transistor parameters and the circuit parameters. Experimental studies on common emitter (CE) amplifiers have been used to validate the PM noise model at carrier frequencies between 10 and 100 MHz.

Gene-network inference by message passing

NASA Astrophysics Data System (ADS)

Braunstein, A.; Pagnani, A.; Weigt, M.; Zecchina, R.

2008-01-01

The inference of gene-regulatory processes from gene-expression data belongs to the major challenges of computational systems biology. Here we address the problem from a statistical-physics perspective and develop a message-passing algorithm which is able to infer sparse, directed and combinatorial regulatory mechanisms. Using the replica technique, the algorithmic performance can be characterized analytically for artificially generated data. The algorithm is applied to genome-wide expression data of baker's yeast under various environmental conditions. We find clear cases of combinatorial control, and enrichment in common functional annotations of regulated genes and their regulators.

Thermotropic Liquid Crystal-Assisted Chemical and Biological Sensors

PubMed Central

Honaker, Lawrence W.; Usol’tseva, Nadezhda; Mann, Elizabeth K.

2017-01-01

In this review article, we analyze recent progress in the application of liquid crystal-assisted advanced functional materials for sensing biological and chemical analytes. Multiple research groups demonstrate substantial interest in liquid crystal (LC) sensing platforms, generating an increasing number of scientific articles. We review trends in implementing LC sensing techniques and identify common problems related to the stability and reliability of the sensing materials as well as to experimental set-ups. Finally, we suggest possible means of bridging scientific findings to viable and attractive LC sensor platforms. PMID:29295530

The neighbourhood polynomial of some families of dendrimers

NASA Astrophysics Data System (ADS)

Nazri Husin, Mohamad; Hasni, Roslan

2018-04-01

The neighbourhood polynomial N(G,x) is generating function for the number of faces of each cardinality in the neighbourhood complex of a graph and it is defined as (G,x)={\\sum }U\\in N(G){x}|U|, where N(G) is neighbourhood complex of a graph, whose vertices of the graph and faces are subsets of vertices that have a common neighbour. A dendrimers is an artificially manufactured or synthesized molecule built up from branched units called monomers. In this paper, we compute this polynomial for some families of dendrimer.

A Simple Primary Amine Catalyst for Enantioselective α-Hydroxylations and α-Fluorinations of Branched Aldehydes.

PubMed

Witten, Michael R; Jacobsen, Eric N

2015-06-05

A new primary amine catalyst for the asymmetric α-hydroxylation and α-fluorination of α-branched aldehydes is described. The products of the title transformations are generated in excellent yields with high enantioselectivities. Both processes can be performed within short reaction times and on gram scale. The similarity in results obtained in both reactions, combined with computational evidence, implies a common basis for stereoinduction and the possibility of a general catalytic mechanism for α-functionalizations. Promising initial results in α-amination and α-chlorination reactions support this hypothesis.

Analysis of crackling noise using the maximum-likelihood method: Power-law mixing and exponential damping.

PubMed

Salje, Ekhard K H; Planes, Antoni; Vives, Eduard

2017-10-01

Crackling noise can be initiated by competing or coexisting mechanisms. These mechanisms can combine to generate an approximate scale invariant distribution that contains two or more contributions. The overall distribution function can be analyzed, to a good approximation, using maximum-likelihood methods and assuming that it follows a power law although with nonuniversal exponents depending on a varying lower cutoff. We propose that such distributions are rather common and originate from a simple superposition of crackling noise distributions or exponential damping.

A genetic-algorithm approach for assessing the liquefaction potential of sandy soils

NASA Astrophysics Data System (ADS)

Sen, G.; Akyol, E.

2010-04-01

The determination of liquefaction potential is required to take into account a large number of parameters, which creates a complex nonlinear structure of the liquefaction phenomenon. The conventional methods rely on simple statistical and empirical relations or charts. However, they cannot characterise these complexities. Genetic algorithms are suited to solve these types of problems. A genetic algorithm-based model has been developed to determine the liquefaction potential by confirming Cone Penetration Test datasets derived from case studies of sandy soils. Software has been developed that uses genetic algorithms for the parameter selection and assessment of liquefaction potential. Then several estimation functions for the assessment of a Liquefaction Index have been generated from the dataset. The generated Liquefaction Index estimation functions were evaluated by assessing the training and test data. The suggested formulation estimates the liquefaction occurrence with significant accuracy. Besides, the parametric study on the liquefaction index curves shows a good relation with the physical behaviour. The total number of misestimated cases was only 7.8% for the proposed method, which is quite low when compared to another commonly used method.

Optical fiber sensor technique for strain measurement

DOEpatents

Butler, Michael A.; Ginley, David S.

1989-01-01

Laser light from a common source is split and conveyed through two similar optical fibers and emitted at their respective ends to form an interference pattern, one of the optical fibers having a portion thereof subjected to a strain. Changes in the strain cause changes in the optical path length of the strain fiber, and generate corresponding changes in the interference pattern. The interference pattern is received and transduced into signals representative of fringe shifts corresponding to changes in the strain experienced by the strained one of the optical fibers. These signals are then processed to evaluate strain as a function of time, typical examples of the application of the apparatus including electrodeposition of a metallic film on a conductive surface provided on the outside of the optical fiber being strained, so that strains generated in the optical fiber during the course of the electrodeposition are measurable as a function of time. In one aspect of the invention, signals relating to the fringe shift are stored for subsequent processing and analysis, whereas in another aspect of the invention the signals are processed for real-time display of the strain changes under study.

Leak Isolation in Pressurized Pipelines using an Interpolation Function to approximate the Fitting Losses

NASA Astrophysics Data System (ADS)

Badillo-Olvera, A.; Begovich, O.; Peréz-González, A.

2017-01-01

The present paper is motivated by the purpose of detection and isolation of a single leak considering the Fault Model Approach (FMA) focused on pipelines with changes in their geometry. These changes generate a different pressure drop that those produced by the friction, this phenomenon is a common scenario in real pipeline systems. The problem arises, since the dynamical model of the fluid in a pipeline only considers straight geometries without fittings. In order to address this situation, several papers work with a virtual model of a pipeline that generates a equivalent straight length, thus, friction produced by the fittings is taking into account. However, when this method is applied, the leak is isolated in a virtual length, which for practical reasons does not represent a complete solution. This research proposes as a solution to the problem of leak isolation in a virtual length, the use of a polynomial interpolation function in order to approximate the conversion of the virtual position to a real-coordinates value. Experimental results in a real prototype are shown, concluding that the proposed methodology has a good performance.

Use of Phage Display to Generate Conformation-Sensor Recombinant Antibodies

PubMed Central

Haque, Aftabul; Tonks, Nicholas K.

2013-01-01

We describe a phage display approach that we have previously used to generate conformation-sensor antibodies that recognize specifically and stabilize the oxidized, inactive conformation of protein tyrosine phosphatase 1B (PTP1B). We use a solution-based panning and screening strategy conducted in the presence of reduced active PTP1B, which enriches antibodies to epitopes unique to the oxidized form, while excluding antibodies that recognize epitopes common to oxidized and reduced forms of PTP1B. This strategy avoids conventional solid-phase immobilization, with its inherent potential for denaturation of the antigen. In addition, a functional screening strategy selects scFvs directly for their capacity for both specific binding and stabilization of the target enzyme in its inactive conformation. These conformation-specific scFvs illustrate that stabilization of oxidized PTP1B is an effective strategy to inhibit PTP1B function; it is possible that this approach may be applicable to the PTP family as a whole. Using this protocol, isolation and characterization of specific scFvs from immune responsive animals should take ~6 weeks. PMID:23154784

The Black Queen Hypothesis: evolution of dependencies through adaptive gene loss.

PubMed

Morris, J Jeffrey; Lenski, Richard E; Zinser, Erik R

2012-01-01

Reductive genomic evolution, driven by genetic drift, is common in endosymbiotic bacteria. Genome reduction is less common in free-living organisms, but it has occurred in the numerically dominant open-ocean bacterioplankton Prochlorococcus and "Candidatus Pelagibacter," and in these cases the reduction appears to be driven by natural selection rather than drift. Gene loss in free-living organisms may leave them dependent on cooccurring microbes for lost metabolic functions. We present the Black Queen Hypothesis (BQH), a novel theory of reductive evolution that explains how selection leads to such dependencies; its name refers to the queen of spades in the game Hearts, where the usual strategy is to avoid taking this card. Gene loss can provide a selective advantage by conserving an organism's limiting resources, provided the gene's function is dispensable. Many vital genetic functions are leaky, thereby unavoidably producing public goods that are available to the entire community. Such leaky functions are thus dispensable for individuals, provided they are not lost entirely from the community. The BQH predicts that the loss of a costly, leaky function is selectively favored at the individual level and will proceed until the production of public goods is just sufficient to support the equilibrium community; at that point, the benefit of any further loss would be offset by the cost. Evolution in accordance with the BQH thus generates "beneficiaries" of reduced genomic content that are dependent on leaky "helpers," and it may explain the observed nonuniversality of prototrophy, stress resistance, and other cellular functions in the microbial world.

Standardised assessment of functioning in ADHD: consensus on the ICF Core Sets for ADHD.

PubMed

Bölte, Sven; Mahdi, Soheil; Coghill, David; Gau, Susan Shur-Fen; Granlund, Mats; Holtmann, Martin; Karande, Sunil; Levy, Florence; Rohde, Luis A; Segerer, Wolfgang; de Vries, Petrus J; Selb, Melissa

2018-02-12

Attention-deficit/hyperactivity disorder (ADHD) is associated with significant impairments in social, educational, and occupational functioning, as well as specific strengths. Currently, there is no internationally accepted standard to assess the functioning of individuals with ADHD. WHO's International Classification of Functioning, Disability and Health-child and youth version (ICF) can serve as a conceptual basis for such a standard. The objective of this study is to develop a comprehensive, a common brief, and three age-appropriate brief ICF Core Sets for ADHD. Using a standardised methodology, four international preparatory studies generated 132 second-level ICF candidate categories that served as the basis for developing ADHD Core Sets. Using these categories and following an iterative consensus process, 20 ADHD experts from nine professional disciplines and representing all six WHO regions selected the most relevant categories to constitute the ADHD Core Sets. The consensus process resulted in 72 second-level ICF categories forming the comprehensive ICF Core Set-these represented 8 body functions, 35 activities and participation, and 29 environmental categories. A Common Brief Core Set that included 38 categories was also defined. Age-specific brief Core Sets included a 47 category preschool version for 0-5 years old, a 55 category school-age version for 6-16 years old, and a 52 category version for older adolescents and adults 17 years old and above. The ICF Core Sets for ADHD mark a milestone toward an internationally standardised functional assessment of ADHD across the lifespan, and across educational, administrative, clinical, and research settings.

Forthergillian Lecture. Imaging human brain function.

PubMed

Frackowiak, R S

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Generation of terahertz from ZnGeP2 crystal and its application to record the time-resolved photoacoustic spectra of nitromethane

NASA Astrophysics Data System (ADS)

Rao, K. S.; Ganesh, D.; Chaudhary, A. K.

2018-07-01

This paper reports the generation of THz radiation through the optical rectification process from type-I cut Zinc germanium phosphate (ZnGeP2or ZGP) crystal using optical parametric amplifier pulses (tunable between 1.15-1.6 μm range, at 60 fs pulse duration and 1 kHz repetition rate) as pump wavelengths at an average power of 50 mW. Also, we have ascertained the conversion efficiency of the generated THz signal, which is of the order of 0.62% at 1.5 THz. Further, the generated radiation is employed for the recording of absorption bands (in terms of PA spectra) of nitromethane and methanol vapor at room temperature using bandpass filters having central frequencies of 0.5 and 1.5 THz. In addition, we have employed the UV-266 nm as an excitation wavelength to record the time domain photoacoustic (PA) spectra of nitromethane (CH3NO2). In case of UV and THz radiations, the excitation mechanisms follow strong electronic (π∗ ← n) and weak vibrational-rotational due to ultrafast transition, respectively. In case of UV-266 nm the characteristic PA spectra has been also presented as a function of vapor pressure and data acquisition time with two different PA cells. The current study reveals the effect of the nanoseconds and the ultrafast pulses on some of the common excited acoustic modes (due to similar functional group), which follow two different types of excitation mechanism.

Identification of uncommon objects in containers

DOEpatents

Bremer, Peer-Timo; Kim, Hyojin; Thiagarajan, Jayaraman J.

2017-09-12

A system for identifying in an image an object that is commonly found in a collection of images and for identifying a portion of an image that represents an object based on a consensus analysis of segmentations of the image. The system collects images of containers that contain objects for generating a collection of common objects within the containers. To process the images, the system generates a segmentation of each image. The image analysis system may also generate multiple segmentations for each image by introducing variations in the selection of voxels to be merged into a segment. The system then generates clusters of the segments based on similarity among the segments. Each cluster represents a common object found in the containers. Once the clustering is complete, the system may be used to identify common objects in images of new containers based on similarity between segments of images and the clusters.

Influence of the exchange and correlation functional on the structure of amorphous InSb and In{sub 3}SbTe{sub 2} compounds

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

Gabardi, Silvia; Caravati, Sebastiano; Bernasconi, Marco, E-mail: marco.bernasconi@mater.unimib.it

2016-05-28

We have investigated the structural, vibrational, and electronic properties of the amorphous phase of InSb and In{sub 3}SbTe{sub 2} compounds of interest for applications in phase change non-volatile memories. Models of the amorphous phase have been generated by quenching from the melt by molecular dynamics simulations based on density functional theory. In particular, we have studied the dependence of the structural properties on the choice of the exchange-correlation functional. It turns out that the use of the Becke-Lee-Yang-Parr functional provides models with a much larger fraction of In atoms in a tetrahedral bonding geometry with respect to previous results obtainedmore » with the most commonly used Perdew-Becke-Ernzerhof functional. This outcome is at odd with the properties of Ge{sub 2}Sb{sub 2}Te{sub 5} phase change compound for which the two exchange-correlation functionals yield very similar results on the structure of the amorphous phase.« less

ASIC Readout Circuit Architecture for Large Geiger Photodiode Arrays

NASA Technical Reports Server (NTRS)

Vasile, Stefan; Lipson, Jerold

2012-01-01

The objective of this work was to develop a new class of readout integrated circuit (ROIC) arrays to be operated with Geiger avalanche photodiode (GPD) arrays, by integrating multiple functions at the pixel level (smart-pixel or active pixel technology) in 250-nm CMOS (complementary metal oxide semiconductor) processes. In order to pack a maximum of functions within a minimum pixel size, the ROIC array is a full, custom application-specific integrated circuit (ASIC) design using a mixed-signal CMOS process with compact primitive layout cells. The ROIC array was processed to allow assembly in bump-bonding technology with photon-counting infrared detector arrays into 3-D imaging cameras (LADAR). The ROIC architecture was designed to work with either common- anode Si GPD arrays or common-cathode InGaAs GPD arrays. The current ROIC pixel design is hardwired prior to processing one of the two GPD array configurations, and it has the provision to allow soft reconfiguration to either array (to be implemented into the next ROIC array generation). The ROIC pixel architecture implements the Geiger avalanche quenching, bias, reset, and time to digital conversion (TDC) functions in full-digital design, and uses time domain over-sampling (vernier) to allow high temporal resolution at low clock rates, increased data yield, and improved utilization of the laser beam.

Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.

PubMed

Jacobo, Sarah Melissa P; Deangelis, Margaret M; Kim, Ivana K; Kazlauskas, Andrius

2013-05-01

Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD.

Motor Neurons Tune Premotor Activity in a Vertebrate Central Pattern Generator

PubMed Central

2017-01-01

Central patterns generators (CPGs) are neural circuits that drive rhythmic motor output without sensory feedback. Vertebrate CPGs are generally believed to operate in a top-down manner in which premotor interneurons activate motor neurons that in turn drive muscles. In contrast, the frog (Xenopus laevis) vocal CPG contains a functionally unexplored neuronal projection from the motor nucleus to the premotor nucleus, indicating a recurrent pathway that may contribute to rhythm generation. In this study, we characterized the function of this bottom-up connection. The X. laevis vocal CPG produces a 50–60 Hz “fast trill” song used by males during courtship. We recorded “fictive vocalizations” in the in vitro CPG from the laryngeal nerve while simultaneously recording premotor activity at the population and single-cell level. We show that transecting the motor-to-premotor projection eliminated the characteristic firing rate of premotor neurons. Silencing motor neurons with the intracellular sodium channel blocker QX-314 also disrupted premotor rhythms, as did blockade of nicotinic synapses in the motor nucleus (the putative location of motor neuron-to-interneuron connections). Electrically stimulating the laryngeal nerve elicited primarily IPSPs in premotor neurons that could be blocked by a nicotinic receptor antagonist. Our results indicate that an inhibitory signal, activated by motor neurons, is required for proper CPG function. To our knowledge, these findings represent the first example of a CPG in which precise premotor rhythms are tuned by motor neuron activity. SIGNIFICANCE STATEMENT Central pattern generators (CPGs) are neural circuits that produce rhythmic behaviors. In vertebrates, motor neurons are not commonly known to contribute to CPG function, with the exception of a few spinal circuits where the functional significance of motor neuron feedback is still poorly understood. The frog hindbrain vocal circuit contains a previously unexplored connection from the motor to premotor region. Our results indicate that motor neurons activate this bottom-up connection, and blocking this signal eliminates normal premotor activity. These findings may promote increased awareness of potential involvement of motor neurons in a wider range of CPGs, perhaps clarifying our understanding of network principles underlying motor behaviors in numerous organisms, including humans. PMID:28219984

Comparison of Bootstrapping and Markov Chain Monte Carlo for Copula Analysis of Hydrological Droughts

NASA Astrophysics Data System (ADS)

Yang, P.; Ng, T. L.; Yang, W.

2015-12-01

Effective water resources management depends on the reliable estimation of the uncertainty of drought events. Confidence intervals (CIs) are commonly applied to quantify this uncertainty. A CI seeks to be at the minimal length necessary to cover the true value of the estimated variable with the desired probability. In drought analysis where two or more variables (e.g., duration and severity) are often used to describe a drought, copulas have been found suitable for representing the joint probability behavior of these variables. However, the comprehensive assessment of the parameter uncertainties of copulas of droughts has been largely ignored, and the few studies that have recognized this issue have not explicitly compared the various methods to produce the best CIs. Thus, the objective of this study to compare the CIs generated using two widely applied uncertainty estimation methods, bootstrapping and Markov Chain Monte Carlo (MCMC). To achieve this objective, (1) the marginal distributions lognormal, Gamma, and Generalized Extreme Value, and the copula functions Clayton, Frank, and Plackett are selected to construct joint probability functions of two drought related variables. (2) The resulting joint functions are then fitted to 200 sets of simulated realizations of drought events with known distribution and extreme parameters and (3) from there, using bootstrapping and MCMC, CIs of the parameters are generated and compared. The effect of an informative prior on the CIs generated by MCMC is also evaluated. CIs are produced for different sample sizes (50, 100, and 200) of the simulated drought events for fitting the joint probability functions. Preliminary results assuming lognormal marginal distributions and the Clayton copula function suggest that for cases with small or medium sample sizes (~50-100), MCMC to be superior method if an informative prior exists. Where an informative prior is unavailable, for small sample sizes (~50), both bootstrapping and MCMC yield the same level of performance, and for medium sample sizes (~100), bootstrapping is better. For cases with a large sample size (~200), there is little difference between the CIs generated using bootstrapping and MCMC regardless of whether or not an informative prior exists.

An Artificial Functional Family Filter in Homolog Searching in Next-generation Sequencing Metagenomics

PubMed Central

Du, Ruofei; Mercante, Donald; Fang, Zhide

2013-01-01

In functional metagenomics, BLAST homology search is a common method to classify metagenomic reads into protein/domain sequence families such as Clusters of Orthologous Groups of proteins (COGs) in order to quantify the abundance of each COG in the community. The resulting functional profile of the community is then used in downstream analysis to correlate the change in abundance to environmental perturbation, clinical variation, and so on. However, the short read length coupled with next-generation sequencing technologies poses a barrier in this approach, essentially because similarity significance cannot be discerned by searching with short reads. Consequently, artificial functional families are produced, in which those with a large number of reads assigned decreases the accuracy of functional profile dramatically. There is no method available to address this problem. We intended to fill this gap in this paper. We revealed that BLAST similarity scores of homologues for short reads from COG protein members coding sequences are distributed differently from the scores of those derived elsewhere. We showed that, by choosing an appropriate score cut-off, we are able to filter out most artificial families and simultaneously to preserve sufficient information in order to build the functional profile. We also showed that, by incorporated application of BLAST and RPS-BLAST, some artificial families with large read counts can be further identified after the score cutoff filtration. Evaluated on three experimental metagenomic datasets with different coverages, we found that the proposed method is robust against read coverage and consistently outperforms the other E-value cutoff methods currently used in literatures. PMID:23516532

NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

PubMed

Sun, Duanchen; Liu, Yinliang; Zhang, Xiang-Sun; Wu, Ling-Yun

2017-09-21

High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies. The GO terms identified via current functional enrichment analysis tools often contain direct parent or descendant terms in the GO hierarchical structure. Highly redundant terms make users difficult to analyze the underlying biological processes. In this paper, a novel network-based probabilistic generative model, NetGen, was proposed to perform the functional enrichment analysis. An additional protein-protein interaction (PPI) network was explicitly used to assist the identification of significantly enriched GO terms. NetGen achieved a superior performance than the existing methods in the simulation studies. The effectiveness of NetGen was explored further on four real datasets. Notably, several GO terms which were not directly linked with the active gene list for each disease were identified. These terms were closely related to the corresponding diseases when accessed to the curated literatures. NetGen has been implemented in the R package CopTea publicly available at GitHub ( http://github.com/wulingyun/CopTea/ ). Our procedure leads to a more reasonable and interpretable result of the functional enrichment analysis. As a novel term combination-based functional enrichment analysis method, NetGen is complementary to current individual term-based methods, and can help to explore the underlying pathogenesis of complex diseases.

Observation of Neutron Skyshine from an Accelerator Based Neutron Source

NASA Astrophysics Data System (ADS)

Franklyn, C. B.

2011-12-01

A key feature of neutron based interrogation systems is the need for adequate provision of shielding around the facility. Accelerator facilities adapted for fast neutron generation are not necessarily suitably equipped to ensure complete containment of the vast quantity of neutrons generated, typically >1011 nṡs-1. Simulating the neutron leakage from a facility is not a simple exercise since the energy and directional distribution can only be approximated. Although adequate horizontal, planar shielding provision is made for a neutron generator facility, it is sometimes the case that vertical shielding is minimized, due to structural and economic constraints. It is further justified by assuming the atmosphere above a facility functions as an adequate radiation shield. It has become apparent that multiple neutron scattering within the atmosphere can result in a measurable dose of neutrons reaching ground level some distance from a facility, an effect commonly known as skyshine. This paper describes a neutron detection system developed to monitor neutrons detected several hundred metres from a neutron source due to the effect of skyshine.

Global impact of RNA splicing on transcriptome remodeling in the heart.

PubMed

Gao, Chen; Wang, Yibin

2012-08-01

In the eukaryotic transcriptome, both the numbers of genes and different RNA species produced by each gene contribute to the overall complexity. These RNA species are generated by the utilization of different transcriptional initiation or termination sites, or more commonly, from different messenger RNA (mRNA) splicing events. Among the 30,000+ genes in human genome, it is estimated that more than 95% of them can generate more than one gene product via alternative RNA splicing. The protein products generated from different RNA splicing variants can have different intracellular localization, activity, or tissue-distribution. Therefore, alternative RNA splicing is an important molecular process that contributes to the overall complexity of the genome and the functional specificity and diversity among different cell types. In this review, we will discuss current efforts to unravel the full complexity of the cardiac transcriptome using a deep-sequencing approach, and highlight the potential of this technology to uncover the global impact of RNA splicing on the transcriptome during development and diseases of the heart.

A frontal cortex event-related potential driven by the basal forebrain

PubMed Central

Nguyen, David P; Lin, Shih-Chieh

2014-01-01

Event-related potentials (ERPs) are widely used in both healthy and neuropsychiatric conditions as physiological indices of cognitive functions. Contrary to the common belief that cognitive ERPs are generated by local activity within the cerebral cortex, here we show that an attention-related ERP in the frontal cortex is correlated with, and likely generated by, subcortical inputs from the basal forebrain (BF). In rats performing an auditory oddball task, both the amplitude and timing of the frontal ERP were coupled with BF neuronal activity in single trials. The local field potentials (LFPs) associated with the frontal ERP, concentrated in deep cortical layers corresponding to the zone of BF input, were similarly coupled with BF activity and consistently triggered by BF electrical stimulation within 5–10 msec. These results highlight the important and previously unrecognized role of long-range subcortical inputs from the BF in the generation of cognitive ERPs. DOI: http://dx.doi.org/10.7554/eLife.02148.001 PMID:24714497

Emergence of a Novel Chimeric Gene Underlying Grain Number in Rice

PubMed Central

Chen, Hao; Tang, Yanyan; Liu, Jianfeng; Tan, Lubin; Jiang, Jiahuan; Wang, Mumu; Zhu, Zuofeng; Sun, Xianyou; Sun, Chuanqing

2017-01-01

Grain number is an important factor in determining grain production of rice (Oryza sativa L.). The molecular genetic basis for grain number is complex. Discovering new genes involved in regulating rice grain number increases our knowledge regarding its molecular mechanisms and aids breeding programs. Here, we identified GRAINS NUMBER 2 (GN2), a novel gene that is responsible for rice grain number, from “Yuanjiang” common wild rice (O. rufipogon Griff.). Transgenic plants overexpressing GN2 showed less grain number, reduced plant height, and later heading date than control plants. Interestingly, GN2 arose through the insertion of a 1094-bp sequence from LOC_Os02g45150 into the third exon of LOC_Os02g56630, and the inserted sequence recruited its nearby sequence to generate the chimeric GN2. The gene structure and expression pattern of GN2 were distinct from those of LOC_Os02g45150 and LOC_Os02g56630. Sequence analysis showed that GN2 may be generated in the natural population of Yuanjiang common wild rice. In this study, we identified a novel functional chimeric gene and also provided information regarding the molecular mechanisms regulating rice grain number. PMID:27986805

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Indirect pacemaker generator function analyzer... Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an electrically powered device that is used to determine pacemaker function or...

Characterizing visible and invisible cell wall mutant phenotypes

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

Carpita, Nicholas C.; McCann, Maureen C.

2015-04-06

About 10% of a plant's genome is devoted to generating the protein machinery to synthesize, remodel, and deconstruct the cell wall. High-throughput genome sequencing technologies have enabled a reasonably complete inventory of wall-related genes that can be assembled into families of common evolutionary origin. Assigning function to each gene family member has been aided immensely by identification of mutants with visible phenotypes or by chemical and spectroscopic analysis of mutants with ‘invisible’ phenotypes of modified cell wall composition and architecture that do not otherwise affect plant growth or development. This review connects the inference of gene function on the basismore » of deviation from the wild type in genetic functional analyses to insights provided by modern analytical techniques that have brought us ever closer to elucidating the sequence structures of the major polysaccharide components of the plant cell wall.« less

Monitoring patients with continuous-flow ventricular assist devices outside of the intensive care unit: novel challenges to bedside nursing.

PubMed

O'Shea, Genevieve; Teuteberg, Jeffrey J; Severyn, Donald A

2013-03-01

Ventricular assist devices provide therapeutic options for patients with severe heart failure who have exhausted available medical therapies. With restoration of organ perfusion with ventricular assist devices, the heart failure resolves and quality of life and functional status improve. The current generation of continuous-flow devices present novel challenges to the clinical assessment of patients by substantially reducing or nearly eliminating any palpable pulse. Patients therefore generally have inadequate arterial pulsatility for most noninvasive monitoring devices such as pulse oximeters or automated blood pressure cuffs to work accurately. This article describes the function of continuous-flow devices and how this function affects common monitoring options, as well as how to clinically assess recipients of continuous-flow devices to promptly identify those whose condition may be deteriorating or who may be receiving inadequate perfusion.

Searching for a 4 α linear-chain structure in excited states of 16O with covariant density functional theory

NASA Astrophysics Data System (ADS)

Yao, J. M.; Itagaki, N.; Meng, J.

2014-11-01

A study of the 4 α linear-chain structure in high-lying collective excitation states of 16O with covariant density functional theory is presented. The low-spin states are obtained by configuration mixing of particle-number and angular-momentum projected quadrupole deformed mean-field states with the generator coordinate method. The high-spin states are determined by cranking calculations. These two calculations are based on the same energy density functional PC-PK1. We have found a rotational band at low spin with the dominant intrinsic configuration considered to be the one whereby 4 α clusters stay along a common axis. The strongly deformed rod shape also appears in the high-spin region with the angular momentum 13 ℏ to18 ℏ ; however, whether the state is a pure 4 α linear chain is less obvious than for the low-spin states.

Isolation and Characterization of Precise Dye/Dendrimer Ratios

PubMed Central

Dougherty, Casey A.; Furgal, Joseph C.; van Dongen, Mallory A.; Goodson, Theodore; Banaszak Holl, Mark M.; Manono, Janet; DiMaggio, Stassi

2014-01-01

Fluorescent dyes are commonly conjugated to nanomaterials for imaging applications using stochastic synthesis conditions that result in a Poisson distribution of dye/particle ratios and therefore a broad range of photophysical and biodistribution properties. We report the isolation and characterization of generation 5 poly(amidoamine) (G5 PAMAM) dendrimer samples containing 1, 2, 3, and 4 fluorescein (FC) or 6-carboxytetramethylrhodamine succinimidyl ester (TAMRA) dyes per polymer particle. For the fluorescein case, this was achieved by stochastically functionalizing dendrimer with a cyclooctyne `click' ligand, separation into sample containing precisely defined `click' ligand/particle ratios using reverse-phase high performance liquid chromatography (rp-HPLC), followed by reaction with excess azide-functionalized fluorescein dye. For the TAMRA samples, stochastically functionalized dendrimer was directly separated into precise dye/particle ratios using rp-HPLC. These materials were characterized using 1H and 19F NMR, rp-HPLC, UV-Vis and fluorescence spectroscopy, lifetime measurements, and MALDI. PMID:24604830

Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke.

PubMed

Khodaparast, N; Hays, S A; Sloan, A M; Hulsey, D R; Ruiz, A; Pantoja, M; Rennaker, R L; Kilgard, M P

2013-12-01

Upper limb impairment is a common debilitating consequence of ischemic stroke. Physical rehabilitation after stroke enhances neuroplasticity and improves limb function, but does not typically restore normal movement. We have recently developed a novel method that uses vagus nerve stimulation (VNS) paired with forelimb movements to drive specific, long-lasting map plasticity in rat primary motor cortex. Here we report that VNS paired with rehabilitative training can enhance recovery of forelimb force generation following infarction of primary motor cortex in rats. Quantitative measures of forelimb function returned to pre-lesion levels when VNS was delivered during rehab training. Intensive rehab training without VNS failed to restore function back to pre-lesion levels. Animals that received VNS during rehab improved twice as much as rats that received the same rehabilitation without VNS. VNS delivered during physical rehabilitation represents a novel method that may provide long-lasting benefits towards stroke recovery. © 2013.

Biomedical Applications of Functionalized Hollow Mesoporous Silica Nanoparticles: Focusing on Molecular Imaging

PubMed Central

Shi, Sixiang; Chen, Feng; Cai, Weibo

2013-01-01

Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle (MSN), have recently gained increasing interest due to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in engineering of functionalized HMSNs (i.e. f-HMSNs) with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this review article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, positron emission tomography, magnetic resonance, and ultrasound imaging in preclinical studies. Lastly, we also discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy. PMID:24279491

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

PubMed Central

Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

2015-01-01

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation. PMID:26528968

Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome.

PubMed

Villate, Olatz; Ibarluzea, Nekane; Fraile-Bethencourt, Eugenia; Valenzuela, Alberto; Velasco, Eladio A; Grozeva, Detelina; Raymond, F L; Botella, María P; Tejada, María-Isabel

2018-01-01

Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS) of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T) was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD ® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG) 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

Familial hypertrophic cardiomyopathy: functional variance among individual cardiomyocytes as a trigger of FHC-phenotype development

PubMed Central

Brenner, Bernhard; Seebohm, Benjamin; Tripathi, Snigdha; Montag, Judith; Kraft, Theresia

2014-01-01

Familial hypertrophic cardiomyopathy (FHC) is the most frequent inherited cardiac disease. It has been related to numerous mutations in many sarcomeric and even some non-sarcomeric proteins. So far, however, no common mechanism has been identified by which the many different mutations in different sarcomeric and non-sarcomeric proteins trigger development of the FHC phenotype. Here we show for different MYH7 mutations variance in force pCa-relations from normal to highly abnormal as a feature common to all mutations we studied, while direct functional effects of the different FHC-mutations, e.g., on force generation, ATPase or calcium sensitivity of the contractile system, can be quite different. The functional variation among individual M. soleus fibers of FHC-patients is accompanied by large variation in mutant vs. wildtype β-MyHC-mRNA. Preliminary results show a similar variation in mutant vs. wildtype β-MyHC-mRNA among individual cardiomyocytes. We discuss our previously proposed concept as to how different mutations in the β-MyHC and possibly other sarcomeric and non-sarcomeric proteins may initiate an FHC-phenotype by functional variation among individual cardiomyocytes that results in structural distortions within the myocardium, leading to cellular and myofibrillar disarray. In addition, distortions can activate stretch-sensitive signaling in cardiomyocytes and non-myocyte cells which is known to induce cardiac remodeling with interstitial fibrosis and hypertrophy. Such a mechanism will have major implications for therapeutic strategies to prevent FHC-development, e.g., by reducing functional imbalances among individual cardiomyocytes or by inhibition of their triggering of signaling paths initiating remodeling. Targeting increased or decreased contractile function would require selective targeting of mutant or wildtype protein to reduce functional imbalances. PMID:25346696

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

PubMed

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

PubMed Central

May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M. Arfan; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G.; Cilio, Maria Roberta; Kunz, Wolfram S.; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R.; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A.

2016-01-01

Objective The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10−4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions. PMID:26990884

Correlation between 25-hydroxyvitamin D levels and latitude in Brazilian postmenopausal women: from the Arzoxifene Generations Trial.

PubMed

Arantes, H P; Kulak, C A M; Fernandes, C E; Zerbini, C; Bandeira, F; Barbosa, I C; Brenol, J C T; Russo, L A; Borba, V C; Chiang, A Y; Bilezikian, J P; Lazaretti-Castro, M

2013-10-01

We investigated vitamin D status in Brazilian cities located at different latitudes. Insufficiency (<50 nmol/L) was common (17 %), even in those living in a tropical climate. Vitamin D insufficiency increased as a function of latitude. Mean 25-hydroxyvitamin D (25(OH)D) levels in each site and latitude correlation were very high (r = -0.88; p=0.02). [corrected]. Inadequate vitamin D, determined by low levels of 25(OH)D, has become very common despite the availability of sunlight at some latitudes. National data from a country that spans a wide range of latitudes would help to determine to what extent latitude or other factors are responsible for vitamin D deficiency. We investigated vitamin D status in cities located at different latitudes in Brazil, a large continental country. The source is the Brazilian database from the Generations Trial (1,933 osteopenic or osteoporotic postmenopausal women (60 to 85 years old) with 25(OH)D measurements). 25(OH)D below 25 nmol/L (10 ng/mL) was an exclusion criterion. Baseline values were between fall and winter. The sites included Recife, Salvador, Rio de Janeiro, São Paulo, Curitiba, and Porto Alegre. Mean and standard deviation of 25(OH)D, age, spine and femoral neck T-score, calcium, creatinine, and alkaline phosphatase were calculated for each city. Pearson correlation was used for 25(OH)D and latitude. Insufficiency (<50 or <20 ng/mL) was common (329 subjects, 17 %). Vitamin D insufficiency increased as a function of latitude, reaching 24.5 % in the southernmost city, Porto Alegre. The correlation between mean 25(OH)D levels in each site and latitude was very high (r = -0.88, p < 0.0001). There is a high percentage of individuals with vitamin D insufficiency in Brazil, even in cities near the equator, and this percentage progressively increases with more southern latitudes.

Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT.

PubMed

Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

2016-04-05

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial-mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.

Development of FuGO: An Ontology for Functional Genomics Investigations

PubMed Central

Whetzel, Patricia L.; Brinkman, Ryan R.; Causton, Helen C.; Fan, Liju; Field, Dawn; Fostel, Jennifer; Fragoso, Gilberto; Gray, Tanya; Heiskanen, Mervi; Hernandez-Boussard, Tina; Morrison, Norman; Parkinson, Helen; Rocca-Serra, Philippe; Sansone, Susanna-Assunta; Schober, Daniel; Smith, Barry; Stevens, Robert; Stoeckert, Christian J.; Taylor, Chris; White, Joe; Wood, Andrew

2009-01-01

The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the “semantic glue” to provide a common understanding of data from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans. PMID:16901226

Large deviation principle at work: Computation of the statistical properties of the exact one-point aperture mass

NASA Astrophysics Data System (ADS)

Reimberg, Paulo; Bernardeau, Francis

2018-01-01

We present a formalism based on the large deviation principle (LDP) applied to cosmological density fields, and more specifically to the arbitrary functional of density profiles, and we apply it to the derivation of the cumulant generating function and one-point probability distribution function (PDF) of the aperture mass (Map ), a common observable for cosmic shear observations. We show that the LDP can indeed be used in practice for a much larger family of observables than previously envisioned, such as those built from continuous and nonlinear functionals of density profiles. Taking advantage of this formalism, we can extend previous results, which were based on crude definitions of the aperture mass, with top-hat windows and the use of the reduced shear approximation (replacing the reduced shear with the shear itself). We were precisely able to quantify how this latter approximation affects the Map statistical properties. In particular, we derive the corrective term for the skewness of the Map and reconstruct its one-point PDF.

Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT

PubMed Central

Zhu, Jianjian; Kwan, Kin Ming; Mackem, Susan

2016-01-01

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial–mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers. PMID:27006501

Characterization of neutrophils and macrophages from ex vivo cultured murine bone marrow for morphologic maturation and functional responses by imaging flow cytometry

PubMed Central

Pelletier, Margery G. H.; Szymczak, Klaudia; Barbeau, Anna M.; Prata, Gianna N.; O’Fallon, Kevin S.; Gaines, Peter

2016-01-01

Neutrophils and macrophages differentiate from common myeloid progenitors in the bone marrow, where they undergo nuclear morphologic changes during maturation. During this process, both cell types acquire critical innate immune functions that include phagocytosis of pathogens, and for neutrophils the release of nuclear material called nuclear extracellular traps (NETs). Primary cells used to study these functions are typically purified from mature mouse tissues, but bone marrow-derived ex vivo cultures provide more abundant numbers of progenitors and functionally mature cells. Routine analyses of these cells use conventional microscopy and flow cytometry, which present limitations; microscopy is laborious and subjective, whereas flow cytometry lacks spatial resolution. Here we describe methods to generate enriched populations of neutrophils or macrophages from cryopreserved mouse bone marrow cultured ex vivo, and to use imaging flow cytometry that combines the resolution of microscopy with flow cytometry to analyze cells for morphologic features, phagocytosis, and NETosis. PMID:27663441

The impact of Moore's Law and loss of Dennard scaling: Are DSP SoCs an energy efficient alternative to x86 SoCs?

NASA Astrophysics Data System (ADS)

Johnsson, L.; Netzer, G.

2016-10-01

Moore's law, the doubling of transistors per unit area for each CMOS technology generation, is expected to continue throughout the decade, while Dennard voltage scaling resulting in constant power per unit area stopped about a decade ago. The semiconductor industry's response to the loss of Dennard scaling and the consequent challenges in managing power distribution and dissipation has been leveled off clock rates, a die performance gain reduced from about a factor of 2.8 to 1.4 per technology generation, and multi-core processor dies with increased cache sizes. Increased caches sizes offers performance benefits for many applications as well as energy savings. Accessing data in cache is considerably more energy efficient than main memory accesses. Further, caches consume less power than a corresponding amount of functional logic. As feature sizes continue to be scaled down an increasing fraction of the die must be “underutilized” or “dark” due to power constraints. With power being a prime design constraint there is a concerted effort to find significantly more energy efficient chip architectures than dominant in servers today, with chips potentially incorporating several types of cores to cover a range of applications, or different functions in an application, as is already common for the mobile processor market. Digital Signal Processors (DSPs), largely targeting the embedded and mobile processor markets, typically have been designed for a power consumption of 10% or less of a typical x86 CPU, yet with much more than 10% of the floating-point capability of the same technology generation x86 CPUs. Thus, DSPs could potentially offer an energy efficient alternative to x86 CPUs. Here we report an assessment of the Texas Instruments TMS320C6678 DSP in regards to its energy efficiency for two common HPC benchmarks: STREAM (memory system benchmark) and HPL (CPU benchmark)

The Design-To-Cost Manifold

NASA Technical Reports Server (NTRS)

Dean, Edwin B.

1990-01-01

Design-to-cost is a popular technique for controlling costs. Although qualitative techniques exist for implementing design to cost, quantitative methods are sparse. In the launch vehicle and spacecraft engineering process, the question whether to minimize mass is usually an issue. The lack of quantification in this issue leads to arguments on both sides. This paper presents a mathematical technique which both quantifies the design-to-cost process and the mass/complexity issue. Parametric cost analysis generates and applies mathematical formulas called cost estimating relationships. In their most common forms, they are continuous and differentiable. This property permits the application of the mathematics of differentiable manifolds. Although the terminology sounds formidable, the application of the techniques requires only a knowledge of linear algebra and ordinary differential equations, common subjects in undergraduate scientific and engineering curricula. When the cost c is expressed as a differentiable function of n system metrics, setting the cost c to be a constant generates an n-1 dimensional subspace of the space of system metrics such that any set of metric values in that space satisfies the constant design-to-cost criterion. This space is a differentiable manifold upon which all mathematical properties of a differentiable manifold may be applied. One important property is that an easily implemented system of ordinary differential equations exists which permits optimization of any function of the system metrics, mass for example, over the design-to-cost manifold. A dual set of equations defines the directions of maximum and minimum cost change. A simplified approximation of the PRICE H(TM) production-production cost is used to generate this set of differential equations over [mass, complexity] space. The equations are solved in closed form to obtain the one dimensional design-to-cost trade and design-for-cost spaces. Preliminary results indicate that cost is relatively insensitive to changes in mass and that the reduction of complexity, both in the manufacturing process and of the spacecraft, is dominant in reducing cost.

Uridine Nucleoside Thiation: Gas-Phase Structures and Energetics

NASA Astrophysics Data System (ADS)

Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

2016-06-01

The naturally occurring thiated uridine nucleosides, 4-thiouridine (s4Urd) and 2-thiouridine (s2Urd), play important roles in the function and analysis of a variety of RNAs. 2-Thiouridine and its C5 modified analogues are commonly found in tRNAs and are believed to play an important role in codon recognition possibly due to their different structure, which has been shown by NMR to be predominantly C3'-endo. 2-Thiouridine may also play an important role in facilitating nonenzymatic RNA replication and transcription. 4-Thiouridine is a commonly used photoactivatable crosslinker that is often used to study RNA-RNA and RNA-protein cross-linking behavior. Differences in the base pairing between uracil and 4-thiouracil with adenine and guanine are an important factor in their role as a cross linker. The photoactivity of s4Urd may also aid in preventing near-UV lethality in cells. An understanding of their intrinsic structure in the gas-phase may help further elucidate the roles these modified nucleosides play in the regulation of RNAs. In this work, infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of s2Urd and s4Urd were collected in the IR fingerprint region. Structural information is determined by comparison with theoretical linear IR spectra generated from density functional theory calculations using molecular modeling to generate low-energy candidate structures. Present results are compared with analogous results for the protonated forms of uridine and 2'-deoxyuridine as well as solution phase NMR data and crystal structures.

A comparative study of linear and nonlinear anomaly detectors for hyperspectral imagery

NASA Astrophysics Data System (ADS)

Goldberg, Hirsh; Nasrabadi, Nasser M.

2007-04-01

In this paper we implement various linear and nonlinear subspace-based anomaly detectors for hyperspectral imagery. First, a dual window technique is used to separate the local area around each pixel into two regions - an inner-window region (IWR) and an outer-window region (OWR). Pixel spectra from each region are projected onto a subspace which is defined by projection bases that can be generated in several ways. Here we use three common pattern classification techniques (Principal Component Analysis (PCA), Fisher Linear Discriminant (FLD) Analysis, and the Eigenspace Separation Transform (EST)) to generate projection vectors. In addition to these three algorithms, the well-known Reed-Xiaoli (RX) anomaly detector is also implemented. Each of the four linear methods is then implicitly defined in a high- (possibly infinite-) dimensional feature space by using a nonlinear mapping associated with a kernel function. Using a common machine-learning technique known as the kernel trick all dot products in the feature space are replaced with a Mercer kernel function defined in terms of the original input data space. To determine how anomalous a given pixel is, we then project the current test pixel spectra and the spectral mean vector of the OWR onto the linear and nonlinear projection vectors in order to exploit the statistical differences between the IWR and OWR pixels. Anomalies are detected if the separation of the projection of the current test pixel spectra and the OWR mean spectra are greater than a certain threshold. Comparisons are made using receiver operating characteristics (ROC) curves.

Generation of a new Gateway-compatible inducible lentiviral vector platform allowing easy derivation of co-transduced cells.

PubMed

De Groote, Philippe; Grootjans, Sasker; Lippens, Saskia; Eichperger, Chantal; Leurs, Kirsten; Kahr, Irene; Tanghe, Giel; Bruggeman, Inge; De Schamphelaire, Wouter; Urwyler, Corinne; Vandenabeele, Peter; Haustraete, Jurgen; Declercq, Wim

2016-01-01

In contrast to most common gene delivery techniques, lentiviral vectors allow targeting of almost any mammalian cell type, even non-dividing cells, and they stably integrate in the genome. Therefore, these vectors are a very powerful tool for biomedical research. Here we report the generation of a versatile new set of 22 lentiviral vectors with broad applicability in multiple research areas. In contrast to previous systems, our platform provides a choice between constitutive and/or conditional expression and six different C-terminal fusions. Furthermore, two compatible selection markers enable the easy derivation of stable cell lines co-expressing differently tagged transgenes in a constitutive or inducible manner. We show that all of the vector features are functional and that they contribute to transgene overexpression in proof-of-principle experiments.

Generation and the role of dislocations in single-crystalline phase-change In 2 Se 3 nanowires under electrical pulses

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

Mafi, Elham; Tao, Xin; Zhu, Wenguang

2016-07-08

Using single crystalline In2Se3 nanowires as a platform, we have studied the RESET switching (from low to high electrical resistance) in this phase-change material under electric pulses. Particularly, we correlated the atomic-scale structural evolutions with local electrical resistance variations, by performing transmission electron microscopy and scanning Kelvin probe microscopy on the same nanowires. By coupling the experimental results with density functional theory calculations, we show that the immobile dislocations generated via vacancy condensations are responsible for the RESET switching and that the material maintains the single crystallinity during the process. This new mechanism is fundamentally different from the crystalline-amorphous transition,more » which is commonly understood as the underlying process for the RESET switching in similar phase-change materials.« less

Rapamycin has suppressive and stimulatory effects on human plasmacytoid dendritic cell functions

PubMed Central

Boor, P P C; Metselaar, H J; Mancham, S; van der Laan, L J W; Kwekkeboom, J

2013-01-01

Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon (IFN)-α production, and in adaptive immunity by stimulating T cells and inducing generation of regulatory T cells (Treg). In this study we studied the effects of mammalian target of rapamycin (mTOR) inhibition by rapamycin, a commonly used immunosuppressive and anti-cancer drug, on innate and adaptive immune functions of human PDC. A clinically relevant concentration of rapamycin inhibited Toll-like receptor (TLR)-7-induced IFN-α secretion potently (−64%) but TLR-9-induced IFN-α secretion only slightly (−20%), while the same concentration suppressed proinflammatory cytokine production by TLR-7-activated and TLR-9-activated PDC with similar efficacy. Rapamycin inhibited the ability of both TLR-7-activated and TLR-9-activated PDC to stimulate production of IFN-γ and interleukin (IL)-10 by allogeneic T cells. Surprisingly, mTOR-inhibition enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T helper cell proliferation, which was caused by rapamycin-induced up-regulation of CD80 expression on PDC. Finally, rapamycin treatment of TLR-7-activated PDC enhanced their capacity to induce CD4+forkhead box protein 3 (FoxP3)+ regulatory T cells, but did not affect the generation of suppressive CD8+CD38+lymphocyte activation gene (LAG)-3+ Treg. In general, rapamycin inhibits innate and adaptive immune functions of TLR-stimulated human PDC, but enhances the ability of TLR-7-stimulated PDC to stimulate CD4+ T cell proliferation and induce CD4+FoxP3+ regulatory T cell generation. PMID:23968562

Towards an improved ensemble precipitation forecast: A probabilistic post-processing approach

NASA Astrophysics Data System (ADS)

Khajehei, Sepideh; Moradkhani, Hamid

2017-03-01

Recently, ensemble post-processing (EPP) has become a commonly used approach for reducing the uncertainty in forcing data and hence hydrologic simulation. The procedure was introduced to build ensemble precipitation forecasts based on the statistical relationship between observations and forecasts. More specifically, the approach relies on a transfer function that is developed based on a bivariate joint distribution between the observations and the simulations in the historical period. The transfer function is used to post-process the forecast. In this study, we propose a Bayesian EPP approach based on copula functions (COP-EPP) to improve the reliability of the precipitation ensemble forecast. Evaluation of the copula-based method is carried out by comparing the performance of the generated ensemble precipitation with the outputs from an existing procedure, i.e. mixed type meta-Gaussian distribution. Monthly precipitation from Climate Forecast System Reanalysis (CFS) and gridded observation from Parameter-Elevation Relationships on Independent Slopes Model (PRISM) have been employed to generate the post-processed ensemble precipitation. Deterministic and probabilistic verification frameworks are utilized in order to evaluate the outputs from the proposed technique. Distribution of seasonal precipitation for the generated ensemble from the copula-based technique is compared to the observation and raw forecasts for three sub-basins located in the Western United States. Results show that both techniques are successful in producing reliable and unbiased ensemble forecast, however, the COP-EPP demonstrates considerable improvement in the ensemble forecast in both deterministic and probabilistic verification, in particular in characterizing the extreme events in wet seasons.

Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study.

PubMed

Lavigne, Katie M; Woodward, Todd S

2018-04-01

Hypercoupling of activity in speech-perception-specific brain networks has been proposed to play a role in the generation of auditory-verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task-based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI-CPCA), which allowed for comparison of task-related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory-motor, (b) language processing, and (c) default-mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory-motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non-AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech-perception-related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation. © 2017 Wiley Periodicals, Inc.

Functional approach to exploring climatic and landscape controls of runoff generation: 1. Behavioral constraints on runoff volume

NASA Astrophysics Data System (ADS)

Li, Hong-Yi; Sivapalan, Murugesu; Tian, Fuqiang; Harman, Ciaran

2014-12-01

Inspired by the Dunne diagram, the climatic and landscape controls on the partitioning of annual runoff into its various components (Hortonian and Dunne overland flow and subsurface stormflow) are assessed quantitatively, from a purely theoretical perspective. A simple distributed hydrologic model has been built sufficient to simulate the effects of different combinations of climate, soil, and topography on the runoff generation processes. The model is driven by a sequence of simple hypothetical precipitation events, for a large combination of climate and landscape properties, and hydrologic responses at the catchment scale are obtained through aggregation of grid-scale responses. It is found, first, that the water balance responses, including relative contributions of different runoff generation mechanisms, could be related to a small set of dimensionless similarity parameters. These capture the competition between the wetting, drying, storage, and drainage functions underlying the catchment responses, and in this way, provide a quantitative approximation of the conceptual Dunne diagram. Second, only a subset of all hypothetical catchment/climate combinations is found to be "behavioral," in terms of falling sufficiently close to the Budyko curve, describing mean annual runoff as a function of climate aridity. Furthermore, these behavioral combinations are mostly consistent with the qualitative picture presented in the Dunne diagram, indicating clearly the commonality between the Budyko curve and the Dunne diagram. These analyses also suggest clear interrelationships amongst the "behavioral" climate, soil, and topography parameter combinations, implying these catchment properties may be constrained to be codependent in order to satisfy the Budyko curve.

Functional overlap of top-down emotion regulation and generation: an fMRI study identifying common neural substrates between cognitive reappraisal and cognitively generated emotions.

PubMed

Otto, Benjamin; Misra, Supriya; Prasad, Aditya; McRae, Kateri

2014-09-01

One factor that influences the success of emotion regulation is the manner in which the regulated emotion was generated. Recent research has suggested that reappraisal, a top-down emotion regulation strategy, is more effective in decreasing self-reported negative affect when emotions were generated from the top-down, versus the bottom-up. On the basis of a process overlap framework, we hypothesized that the neural regions active during reappraisal would overlap more with emotions that were generated from the top-down, rather than from the bottom-up. In addition, we hypothesized that increased neural overlap between reappraisal and the history effects of top-down emotion generation would be associated with increased reappraisal success. The results of several analyses suggested that reappraisal and emotions that were generated from the top-down share a core network of prefrontal, temporal, and cingulate regions. This overlap is specific; no such overlap was observed between reappraisal and emotions that were generated in a bottom-up fashion. This network consists of regions previously implicated in linguistic processing, cognitive control, and self-relevant appraisals, which are processes thought to be crucial to both reappraisal and top-down emotion generation. Furthermore, individuals with high reappraisal success demonstrated greater neural overlap between reappraisal and the history of top-down emotion generation than did those with low reappraisal success. The overlap of these key regions, reflecting overlapping processes, provides an initial insight into the mechanism by which generation history may facilitate emotion regulation.

Diversity Generator Mechanisms Are Essential Components of Biological Systems: The Two Queen Hypothesis

PubMed Central

Muraille, Eric

2018-01-01

Diversity is widely known to fuel adaptation and evolutionary processes and increase robustness at the population, species and ecosystem levels. The Neo-Darwinian paradigm proposes that the diversity of biological entities is the consequence of genetic changes arising spontaneously and randomly, without regard for their usefulness. However, a growing body of evidence demonstrates that the evolutionary process has shaped mechanisms, such as horizontal gene transfer mechanisms, meiosis and the adaptive immune system, which has resulted in the regulated generation of diversity among populations. Though their origins are unrelated, these diversity generator (DG) mechanisms share common functional properties. They (i) contribute to the great unpredictability of the composition and/or behavior of biological systems, (ii) favor robustness and collectivism among populations and (iii) operate mainly by manipulating the systems that control the interaction of living beings with their environment. The definition proposed here for DGs is based on these properties and can be used to identify them according to function. Interestingly, prokaryotic DGs appear to be mainly reactive, as they generate diversity in response to environmental stress. They are involved in the widely described Red Queen/arms race/Cairnsian dynamic. The emergence of multicellular organisms harboring K selection traits (longer reproductive life cycle and smaller population size) has led to the acquisition of a new class of DGs that act anticipatively to stress pressures and generate a distinct dynamic called the “White Queen” here. The existence of DGs leads to the view of evolution as a more “intelligent” and Lamarckian-like process. Their repeated selection during evolution could be a neglected example of convergent evolution and suggests that some parts of the evolutionary process are tightly constrained by ecological factors, such as the population size, the generation time and the intensity of selective pressure. The ubiquity of DGs also suggests that regulated auto-generation of diversity is a fundamental property of life. PMID:29487592

Systematic Evaluation of the Efficacy of Chlorine Dioxide in Decontamination of Building Interior Surfaces Contaminated with Anthrax Spores▿

PubMed Central

Rastogi, Vipin K.; Ryan, Shawn P.; Wallace, Lalena; Smith, Lisa S.; Shah, Saumil S.; Martin, G. Blair

2010-01-01

Efficacy of chlorine dioxide (CD) gas generated by two distinct generation systems, Sabre (wet system with gas generated in water) and ClorDiSys (dry system with gas generated in air), was evaluated for inactivation of Bacillus anthracis spores on six building interior surfaces. The six building materials included carpet, acoustic ceiling tile, unpainted cinder block, painted I-beam steel, painted wallboard, and unpainted pinewood. There was no statistically significant difference in the data due to the CD generation technology at a 95% confidence level. Note that a common method of CD gas measurement was used for both wet and dry CD generation types. Doses generated by combinations of different concentrations of CD gas (500, 1,000, 1,500, or 3,000 parts per million of volume [ppmv]) and exposure times (ranging between 0.5 and 12 h) were used to evaluate the relative role of fumigant exposure period and total dose in the decontamination of building surfaces. The results showed that the time required to achieve at least a 6-log reduction in viable spores is clearly a function of the material type on which the spores are inoculated. The wood and cinder block coupons required a longer exposure time to achieve a 6-log reduction. The only material showing a clear statistical difference in rate of decay of viable spores as a function of concentration was cinder block. For all other materials, the profile of spore kill (i.e., change in number of viable spores with exposure time) was not dependent upon fumigant concentration (500 to 3,000 ppmv). The CD dose required for complete spore kill on biological indicators (typically, 1E6 spores of Bacillus atrophaeus on stainless steel) was significantly less than that required for decontamination of most of the building materials tested. PMID:20305025

Systematic evaluation of the efficacy of chlorine dioxide in decontamination of building interior surfaces contaminated with anthrax spores.

PubMed

Rastogi, Vipin K; Ryan, Shawn P; Wallace, Lalena; Smith, Lisa S; Shah, Saumil S; Martin, G Blair

2010-05-01

Efficacy of chlorine dioxide (CD) gas generated by two distinct generation systems, Sabre (wet system with gas generated in water) and ClorDiSys (dry system with gas generated in air), was evaluated for inactivation of Bacillus anthracis spores on six building interior surfaces. The six building materials included carpet, acoustic ceiling tile, unpainted cinder block, painted I-beam steel, painted wallboard, and unpainted pinewood. There was no statistically significant difference in the data due to the CD generation technology at a 95% confidence level. Note that a common method of CD gas measurement was used for both wet and dry CD generation types. Doses generated by combinations of different concentrations of CD gas (500, 1,000, 1,500, or 3,000 parts per million of volume [ppmv]) and exposure times (ranging between 0.5 and 12 h) were used to evaluate the relative role of fumigant exposure period and total dose in the decontamination of building surfaces. The results showed that the time required to achieve at least a 6-log reduction in viable spores is clearly a function of the material type on which the spores are inoculated. The wood and cinder block coupons required a longer exposure time to achieve a 6-log reduction. The only material showing a clear statistical difference in rate of decay of viable spores as a function of concentration was cinder block. For all other materials, the profile of spore kill (i.e., change in number of viable spores with exposure time) was not dependent upon fumigant concentration (500 to 3,000 ppmv). The CD dose required for complete spore kill on biological indicators (typically, 1E6 spores of Bacillus atrophaeus on stainless steel) was significantly less than that required for decontamination of most of the building materials tested.

Functional acclimation across microgeographic scales in Dodonaea viscosa

PubMed Central

Baruch, Zdravko; Jones, Alice R; Hill, Kathryn E; McInerney, Francesca A; Blyth, Colette; Caddy-Retalic, Stefan; Christmas, Matthew J; Gellie, Nicholas J C; Lowe, Andrew J; Martin-Fores, Irene; Nielson, Kristine E

2018-01-01

Abstract Intraspecific plant functional trait variation provides mechanistic insight into persistence and can infer population adaptive capacity. However, most studies explore intraspecific trait variation in systems where geographic and environmental distances co-vary. Such a design reduces the certainty of trait–environment associations, and it is imperative for studies that make trait–environment associations be conducted in systems where environmental distance varies independently of geographic distance. Here we explored trait variation in such a system, and aimed to: (i) quantify trait variation of parent and offspring generations, and associate this variation to parental environments; (ii) determine the traits which best explain population differences; (iii) compare parent and offspring trait–trait relationships. We characterized 15 plant functional traits in eight populations of a shrub with a maximum separation ca. 100 km. Populations differed markedly in aridity and elevation, and environmental distance varied independently of geographic distance. We measured traits in parent populations collected in the field, as well as their offspring reared in greenhouse conditions. Parent traits regularly associated with their environment. These associations were largely lost in the offspring generation, indicating considerable phenotypic plasticity. An ordination of parent traits showed clear structure with strong influence of leaf area, specific leaf area, stomatal traits, isotope δ13C and δ15N ratios, and Narea, whereas the offspring ordination was less structured. Parent trait–trait correlations were in line with expectations from the leaf economic spectrum. We show considerable trait plasticity in the woody shrub over microgeographic scales (<100 km), indicating it has the adaptive potential within a generation to functionally acclimate to a range of abiotic conditions. Since our study shrub is commonly used for restoration in southern Australia and local populations do not show strong genetic differentiation in functional traits, the potential risks of transferring seed across the broad environmental conditions are not likely to be a significant issue.

Annual research review: Current limitations and future directions in MRI studies of child- and adult-onset developmental psychopathologies.

PubMed

Horga, Guillermo; Kaur, Tejal; Peterson, Bradley S

2014-06-01

The widespread use of Magnetic Resonance Imaging (MRI) in the study of child- and adult-onset developmental psychopathologies has generated many investigations that have measured brain structure and function in vivo throughout development, often generating great excitement over our ability to visualize the living, developing brain using the attractive, even seductive images that these studies produce. Often lost in this excitement is the recognition that brain imaging generally, and MRI in particular, is simply a technology, one that does not fundamentally differ from any other technology, be it a blood test, a genotyping assay, a biochemical assay, or behavioral test. No technology alone can generate valid scientific findings. Rather, it is only technology coupled with a strong experimental design that can generate valid and reproducible findings that lead to new insights into the mechanisms of disease and therapeutic response. In this review we discuss selected studies to illustrate the most common and important limitations of MRI study designs as most commonly implemented thus far, as well as the misunderstanding that the interpretations of findings from those studies can create for our theories of developmental psychopathologies. Common limitations of MRI study designs are in large part responsible thus far for the generally poor reproducibility of findings across studies, poor generalizability to the larger population, failure to identify developmental trajectories, inability to distinguish causes from effects of illness, and poor ability to infer causal mechanisms in most MRI studies of developmental psychopathologies. For each of these limitations in study design and the difficulties they entail for the interpretation of findings, we discuss various approaches that numerous laboratories are now taking to address those difficulties, which have in common the yoking of brain imaging technologies to studies with inherently stronger designs that permit more valid and more powerful causal inferences. Those study designs include epidemiological, longitudinal, high-risk, clinical trials, and multimodal imaging studies. We highlight several studies that have yoked brain imaging technologies to these stronger designs to illustrate how doing so can aid our understanding of disease mechanisms and in the foreseeable future can improve clinical diagnosis, prevention, and treatment planning for developmental psychopathologies. © 2014 The Authors. Journal of Child Psychology and Psychiatry © 2014 Association for Child and Adolescent Mental Health.

Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.

PubMed

Schlitzer, Andreas; Heiseke, Alexander F; Einwächter, Henrik; Reindl, Wolfgang; Schiemann, Matthias; Manta, Calin-Petru; See, Peter; Niess, Jan-Hendrik; Suter, Tobias; Ginhoux, Florent; Krug, Anne B

2012-06-21

The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.

Combining a weed traits database with a population dynamics model predicts shifts in weed communities.

PubMed

Storkey, J; Holst, N; Bøjer, O Q; Bigongiali, F; Bocci, G; Colbach, N; Dorner, Z; Riemens, M M; Sartorato, I; Sønderskov, M; Verschwele, A

2015-04-01

A functional approach to predicting shifts in weed floras in response to management or environmental change requires the combination of data on weed traits with analytical frameworks that capture the filtering effect of selection pressures on traits. A weed traits database (WTDB) was designed, populated and analysed, initially using data for 19 common European weeds, to begin to consolidate trait data in a single repository. The initial choice of traits was driven by the requirements of empirical models of weed population dynamics to identify correlations between traits and model parameters. These relationships were used to build a generic model, operating at the level of functional traits, to simulate the impact of increasing herbicide and fertiliser use on virtual weeds along gradients of seed weight and maximum height. The model generated 'fitness contours' (defined as population growth rates) within this trait space in different scenarios, onto which two sets of weed species, defined as common or declining in the UK, were mapped. The effect of increasing inputs on the weed flora was successfully simulated; 77% of common species were predicted to have stable or increasing populations under high fertiliser and herbicide use, in contrast with only 29% of the species that have declined. Future development of the WTDB will aim to increase the number of species covered, incorporate a wider range of traits and analyse intraspecific variability under contrasting management and environments.

Solution Structures of Highly Active Molecular Ir Water-Oxidation Catalysts from Density Functional Theory Combined with High-Energy X-ray Scattering and EXAFS Spectroscopy.

PubMed

Yang, Ke R; Matula, Adam J; Kwon, Gihan; Hong, Jiyun; Sheehan, Stafford W; Thomsen, Julianne M; Brudvig, Gary W; Crabtree, Robert H; Tiede, David M; Chen, Lin X; Batista, Victor S

2016-05-04

The solution structures of highly active Ir water-oxidation catalysts are elucidated by combining density functional theory, high-energy X-ray scattering (HEXS), and extended X-ray absorption fine structure (EXAFS) spectroscopy. We find that the catalysts are Ir dimers with mono-μ-O cores and terminal anionic ligands, generated in situ through partial oxidation of a common catalyst precursor. The proposed structures are supported by (1)H and (17)O NMR, EPR, resonance Raman and UV-vis spectra, electrophoresis, etc. Our findings are particularly valuable to understand the mechanism of water oxidation by highly reactive Ir catalysts. Importantly, our DFT-EXAFS-HEXS methodology provides a new in situ technique for characterization of active species in catalytic systems.

Identification, characterization and isolation of a common progenitor for osteoclasts, macrophages and dendritic cells from murine bone marrow and periphery

PubMed Central

Jacome-Galarza, Christian E.; Lee, Sun-Kyeong; Lorenzo, Joseph A.; LeonardoAguila, Hector

2012-01-01

Osteoclasts are specialized bone resorbing cells that derive from monocyte precursors. We have identified three populations of cells with high osteoclastogenic potential in murine bone marrow, which expressed the phenotype: B220−CD3−CD11b−/low CD115+ and either CD117hi, CD117intermediate or CD117low. We have evaluated these populations for their ability to also generate macrophages and dendritic cells. At a single cell level, the population expressing higher CD117 levels was able to generate bone-resorbing osteoclasts, phagocytic macrophages and antigen-presenting dendritic cells in vitro with efficiencies of over 90 percent, indicating that there exists a common developmental pathway for these cell types. Cells with osteoclastogenic potential also exist in blood and peripheral hematopoietic organs. Their functional meaning and/or their relationship with bone marrow progenitors is not well established. Hence, we characterized murine peripheral cell populations for their ability to form osteoclasts, macrophages and dendritic cells in vitro. The spleen and peripheral blood monocyte progenitors share phenotypic markers with bone marrow progenitors, but differ in their expression of CD11b, which was low in bone marrow but high in periphery. We propose that circulating monocyte progenitors are derived from a common bone marrow osteoclasts/macrophage/dendritic cell progenitor (OcMDC), which we have now characterized at a clonal level. However, the lineage relationship between the bone marrow and peripheral monocyte progenitors has yet to be defined. PMID:23165930

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

21 CFR 870.3630 - Pacemaker generator function analyzer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Pacemaker generator function analyzer. 870.3630... (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device that is...

Developmental and Functional Control of Natural Killer Cells by Cytokines

PubMed Central

Wu, Yang; Tian, Zhigang; Wei, Haiming

2017-01-01

Natural killer (NK) cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tissues. The development and functions of such NK cells are controlled by various cytokines, such as fms-like tyrosine kinase 3 ligand (FL), kit ligand (KL), interleukin (IL)-3, IL-10, IL-12, IL-18, transforming growth factor-β, and common-γ chain family cytokines, which operate at different stages by regulating distinct signaling pathways. Nevertheless, the specific roles of each cytokine that regulates NK cell development or that shapes different NK cell functions remain unclear. In this review, we attempt to describe the characteristics of each cytokine and the existing protocols to expand NK cells using different combinations of cytokines and feeder cells. A comprehensive understanding of the role of cytokines in NK cell development and function will aid the generation of better efficacy for adoptive NK cell treatment. PMID:28824650

Evaluating gambles using dynamics

NASA Astrophysics Data System (ADS)

Peters, O.; Gell-Mann, M.

2016-02-01

Gambles are random variables that model possible changes in wealth. Classic decision theory transforms money into utility through a utility function and defines the value of a gamble as the expectation value of utility changes. Utility functions aim to capture individual psychological characteristics, but their generality limits predictive power. Expectation value maximizers are defined as rational in economics, but expectation values are only meaningful in the presence of ensembles or in systems with ergodic properties, whereas decision-makers have no access to ensembles, and the variables representing wealth in the usual growth models do not have the relevant ergodic properties. Simultaneously addressing the shortcomings of utility and those of expectations, we propose to evaluate gambles by averaging wealth growth over time. No utility function is needed, but a dynamic must be specified to compute time averages. Linear and logarithmic "utility functions" appear as transformations that generate ergodic observables for purely additive and purely multiplicative dynamics, respectively. We highlight inconsistencies throughout the development of decision theory, whose correction clarifies that our perspective is legitimate. These invalidate a commonly cited argument for bounded utility functions.

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism

PubMed Central

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G

2017-01-01

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability. PMID:28634279

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

PubMed

Salvatori, Roberto; Radian, Serban; Diekmann, Yoan; Iacovazzo, Donato; David, Alessia; Gabrovska, Plamena; Grassi, Giorgia; Bussell, Anna-Marie; Stals, Karen; Weber, Astrid; Quinton, Richard; Crowne, Elizabeth C; Corazzini, Valentina; Metherell, Lou; Kearney, Tara; Du Plessis, Daniel; Sinha, Ajay Kumar; Baborie, Atik; Lecoq, Anne-Lise; Chanson, Philippe; Ansorge, Olaf; Ellard, Sian; Trainer, Peter J; Balding, David; Thomas, Mark G; Korbonits, Márta

2017-09-01

Mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP -region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability. © 2017 The authors.

Next generation interatomic potentials for condensed systems

NASA Astrophysics Data System (ADS)

Handley, Christopher Michael; Behler, Jörg

2014-07-01

The computer simulation of condensed systems is a challenging task. While electronic structure methods like density-functional theory (DFT) usually provide a good compromise between accuracy and efficiency, they are computationally very demanding and thus applicable only to systems containing up to a few hundred atoms. Unfortunately, many interesting problems require simulations to be performed on much larger systems involving thousands of atoms or more. Consequently, more efficient methods are urgently needed, and a lot of effort has been spent on the development of a large variety of potentials enabling simulations with significantly extended time and length scales. Most commonly, these potentials are based on physically motivated functional forms and thus perform very well for the applications they have been designed for. On the other hand, they are often highly system-specific and thus cannot easily be transferred from one system to another. Moreover, their numerical accuracy is restricted by the intrinsic limitations of the imposed functional forms. In recent years, several novel types of potentials have emerged, which are not based on physical considerations. Instead, they aim to reproduce a set of reference electronic structure data as accurately as possible by using very general and flexible functional forms. In this review we will survey a number of these methods. While they differ in the choice of the employed mathematical functions, they all have in common that they provide high-quality potential-energy surfaces, while the efficiency is comparable to conventional empirical potentials. It has been demonstrated that in many cases these potentials now offer a very interesting new approach to study complex systems with hitherto unreached accuracy.

TERA-MIR radiation: materials, generation, detection and applications III (Conference Presentation)

NASA Astrophysics Data System (ADS)

Pereira, Mauro F.

2016-10-01

This talk summarizes the achievements of COST ACTION MP1204 during the last four years. [M.F. Pereira, Opt Quant Electron 47, 815-820 (2015).]. TERA-MIR main objectives are to advance novel materials, concepts and device designs for generating and detecting THz and Mid Infrared radiation using semiconductor, superconductor, metamaterials and lasers and to beneficially exploit their common aspects within a synergetic approach. We used the unique networking and capacity-building capabilities provided by the COST framework to unify these two spectral domains from their common aspects of sources, detectors, materials and applications. We created a platform to investigate interdisciplinary topics in Physics, Electrical Engineering and Technology, Applied Chemistry, Materials Sciences and Biology and Radio Astronomy. The main emphasis has been on new fundamental material properties, concepts and device designs that are likely to open the way to new products or to the exploitation of new technologies in the fields of sensing, healthcare, biology, and industrial applications. End users are: research centres, academic, well-established and start-up Companies and hospitals. Results are presented along our main lines of research: Intersubband materials and devices with applications to fingerprint spectroscopy; Metamaterials, photonic crystals and new functionalities; Nonlinearities and interaction of radiation with matter including biomaterials; Generation and Detection based on Nitrides and Bismides. The talk is closed by indicating the future direction of the network that will remain active beyond the funding period and our expectations for future joint research.

Pollution level and reusability of the waste soil generated from demolition of a rural railway.

PubMed

Han, Il; Wee, Gui Nam; No, Jee Hyun; Lee, Tae Kwon

2018-09-01

Railways are typically considered polluted from years of train operation. However, the pollution level of railway in a rural area, which is less exposed to hazardous material from trains and freights, is rarely assessed. This study evaluated common railway pollutants such as heavy metals, total petroleum hydrocarbons (TPHs) and polycyclic aromatic hydrocarbons (PAHs) and their chemical properties in the waste soil generated from the renovation of an old railway in rural area of Wonju, South Korea. Furthermore, lab-scale cultivation tests of peas (Pisum sativum) were performed to assess reusability of the waste soil as a soil amendment. Carbonaceous materials were found in the upper layer of the railway (0 to -40 cm) and the concentration of common railway pollutants was comparable to those of the agricultural land nearby. Specifically, total aromatic and aliphatic TPHs were below detection limit; and total PAHs < 1.0 mg kg -1 was 1000-times less than railway functional parts. Applying the carbonaceous waste soil improved the water holding capacity of soil by approximately 10% and sprouts formed on the soil with 10% waste soil composition had greater fresh weight, stem length, and root length than the control. Although this investigation was confined to a small length of the railway route, the results confirm environmental safety and the potential value of the waste generated from rural railways for the first time. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intrapersonal and interpersonal functions of non suicidal self-injury: associations with emotional and social functioning.

PubMed

Turner, Brianna J; Chapman, Alexander L; Layden, Brianne K

2012-02-01

Understanding the functions of nonsuicidal self-injury (NSSI) has important implications for the development and refinement of theoretical models and treatments of NSSI. Emotional and social vulnerabilities associated with five common functions of NSSI-emotion relief (ER), feeling generation (FG), self-punishment (SP), interpersonal influence (II), and interpersonal communication (IC)-were investigated to clarify why individuals use this behavior in the service of different purposes. Female participants (n = 162) with a history of NSSI completed online measures of self-injury, emotion regulation strategies and abilities, trait affectivity, social problem-solving styles, and interpersonal problems. ER functions were associated with more intense affectivity, expressive suppression, and limited access to emotion regulation strategies. FG functions were associated with a lack of emotional clarity. Similar to ER functions, SP functions were associated with greater affective intensity and expressive suppression. II functions were negatively associated with expressive suppression and positively associated with domineering/controlling and intrusive/needy interpersonal styles. IC functions were negatively associated with expressive suppression and positively associated with a vindictive or self-centered interpersonal style. These findings highlight the specific affective traits, emotional and social skill deficits, and interpersonal styles that may render a person more likely to engage in NSSI to achieve specific goals. © 2012 The American Association of Suicidology.

Synchronization of motor unit firings: an epiphenomenon of firing rate characteristics not common inputs

PubMed Central

Kline, Joshua C.

2015-01-01

Synchronous motor unit firing instances have been attributed to anatomical inputs shared by motoneurons. Yet, there is a lack of empirical evidence confirming the notion that common inputs elicit synchronization under voluntary conditions. We tested this notion by measuring synchronization between motor unit action potential trains (MUAPTs) as their firing rates progressed within a contraction from a relatively low force level to a higher one. On average, the degree of synchronization decreased as the force increased. The common input notion provides no empirically supported explanation for the observed synchronization behavior. Therefore, we investigated a more probable explanation for synchronization. Our data set of 17,546 paired MUAPTs revealed that the degree of synchronization varies as a function of two characteristics of the motor unit firing rate: the similarity and the slope as a function of force. Both are measures of the excitation of the motoneurons. As the force generated by the muscle increases, the firing rate slope decreases, and the synchronization correspondingly decreases. Different muscles have motor units with different firing rate characteristics and display different amounts of synchronization. Although this association is not proof of causality, it consistently explains our observations and strongly suggests further investigation. So viewed, synchronization is likely an epiphenomenon, subject to countless unknown neural interactions. As such, synchronous firing instances may not be the product of a specific design and may not serve a specific physiological purpose. Our explanation for synchronization has the advantage of being supported by empirical evidence, whereas the common input does not. PMID:26490288

Common variants of the vitamin D binding protein gene and adverse health outcomes

PubMed Central

Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes

2013-01-01

The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene – rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys – change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD). Whether these variants also influence the role of vitamin D in an immunologic milieu is not known. However, the issue is relevant, given the immunomodulatory effects of DBP and the role of protracted innate immune-related inflammation in response to tissue injury or repeated infection. Indeed, DBP and vitamin D may jointly or independently contribute to a variety of adverse health outcomes unrelated to classical notions of their function in bone and mineral metabolism. This review summarizes the reports to date of associations between DBP variants, and various chronic and infectious diseases. The available information leads us to conclude that DBP variants are a significant and common genetic factor in some common disorders, and therefore, are worthy of closer attention. In view of the heightened interest in vitamin D as a public health target, well-designed studies that look simultaneously at vitamin D and its carrier in relation to genotypes and adverse health outcome should be encouraged. PMID:23427793

Synchronization of motor unit firings: an epiphenomenon of firing rate characteristics not common inputs.

PubMed

Kline, Joshua C; De Luca, Carlo J

2016-01-01

Synchronous motor unit firing instances have been attributed to anatomical inputs shared by motoneurons. Yet, there is a lack of empirical evidence confirming the notion that common inputs elicit synchronization under voluntary conditions. We tested this notion by measuring synchronization between motor unit action potential trains (MUAPTs) as their firing rates progressed within a contraction from a relatively low force level to a higher one. On average, the degree of synchronization decreased as the force increased. The common input notion provides no empirically supported explanation for the observed synchronization behavior. Therefore, we investigated a more probable explanation for synchronization. Our data set of 17,546 paired MUAPTs revealed that the degree of synchronization varies as a function of two characteristics of the motor unit firing rate: the similarity and the slope as a function of force. Both are measures of the excitation of the motoneurons. As the force generated by the muscle increases, the firing rate slope decreases, and the synchronization correspondingly decreases. Different muscles have motor units with different firing rate characteristics and display different amounts of synchronization. Although this association is not proof of causality, it consistently explains our observations and strongly suggests further investigation. So viewed, synchronization is likely an epiphenomenon, subject to countless unknown neural interactions. As such, synchronous firing instances may not be the product of a specific design and may not serve a specific physiological purpose. Our explanation for synchronization has the advantage of being supported by empirical evidence, whereas the common input does not. Copyright © 2016 the American Physiological Society.

Improving insight and non-insight problem solving with brief interventions.

PubMed

Wen, Ming-Ching; Butler, Laurie T; Koutstaal, Wilma

2013-02-01

Developing brief training interventions that benefit different forms of problem solving is challenging. In earlier research, Chrysikou (2006) showed that engaging in a task requiring generation of alternative uses of common objects improved subsequent insight problem solving. These benefits were attributed to a form of implicit transfer of processing involving enhanced construction of impromptu, on-the-spot or 'ad hoc' goal-directed categorizations of the problem elements. Following this, it is predicted that the alternative uses exercise should benefit abilities that govern goal-directed behaviour, such as fluid intelligence and executive functions. Similarly, an indirect intervention - self-affirmation (SA) - that has been shown to enhance cognitive and executive performance after self-regulation challenge and when under stereotype threat, may also increase adaptive goal-directed thinking and likewise should bolster problem-solving performance. In Experiment 1, brief single-session interventions, involving either alternative uses generation or SA, significantly enhanced both subsequent insight and visual-spatial fluid reasoning problem solving. In Experiment 2, we replicated the finding of benefits of both alternative uses generation and SA on subsequent insight problem-solving performance, and demonstrated that the underlying mechanism likely involves improved executive functioning. Even brief cognitive- and social-psychological interventions may substantially bolster different types of problem solving and may exert largely similar facilitatory effects on goal-directed behaviours. © 2012 The British Psychological Society.

Natural and Genetically Engineered Proteins for Tissue Engineering

PubMed Central

Gomes, Sílvia; Leonor, Isabel B.; Mano, João F.; Reis, Rui L.

2011-01-01

To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio-resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials. In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein-based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification. PMID:22058578

Quercitrin protects skin from UVB-induced oxidative damage

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

Yin, Yuanqin; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY; Li, Wenqi

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidativemore » damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.« less

Electrode channel selection based on backtracking search optimization in motor imagery brain-computer interfaces.

PubMed

Dai, Shengfa; Wei, Qingguo

2017-01-01

Common spatial pattern algorithm is widely used to estimate spatial filters in motor imagery based brain-computer interfaces. However, use of a large number of channels will make common spatial pattern tend to over-fitting and the classification of electroencephalographic signals time-consuming. To overcome these problems, it is necessary to choose an optimal subset of the whole channels to save computational time and improve the classification accuracy. In this paper, a novel method named backtracking search optimization algorithm is proposed to automatically select the optimal channel set for common spatial pattern. Each individual in the population is a N-dimensional vector, with each component representing one channel. A population of binary codes generate randomly in the beginning, and then channels are selected according to the evolution of these codes. The number and positions of 1's in the code denote the number and positions of chosen channels. The objective function of backtracking search optimization algorithm is defined as the combination of classification error rate and relative number of channels. Experimental results suggest that higher classification accuracy can be achieved with much fewer channels compared to standard common spatial pattern with whole channels.

Defining recovery in chronic fatigue syndrome: a critical review.

PubMed

Adamowicz, Jenna L; Caikauskaite, Indre; Friedberg, Fred

2014-11-01

In chronic fatigue syndrome (CFS), the lack of consensus on how recovery should be defined or interpreted has generated controversy and confusion. The purpose of this paper was to systematically review, compare, and evaluate the definitions of recovery reported in the CFS literature and to make recommendations about the scope of recovery assessments. A search was done using the MEDLINE, PubMed, PsycINFO, CINAHL, and Cochrane databases for peer review papers that contained the search terms "chronic fatigue syndrome" and "recovery," "reversal," "remission," and/or "treatment response." From the 22 extracted studies, recovery was operationally defined by reference with one or more of these domains: (1) pre-morbid functioning; (2) both fatigue and function; (3) fatigue (or related symptoms) alone; (4) function alone; and/or (5) brief global assessment. Almost all of the studies measuring recovery in CFS did so differently. The brief global assessment was the most common outcome measure used to define recovery. Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies. Given that the term "recovery" was often based on limited assessments and less than full restoration of health, other more precise and accurate labels (e.g., clinically significant improvement) may be more appropriate and informative. In keeping with common understandings of the term recovery, we recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status.

Functional and structural mapping of human cerebral cortex: Solutions are in the surfaces

PubMed Central

Van Essen, David C.; Drury, Heather A.; Joshi, Sarang; Miller, Michael I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex. PMID:9448242

Functional and structural mapping of human cerebral cortex: solutions are in the surfaces

NASA Technical Reports Server (NTRS)

Van Essen, D. C.; Drury, H. A.; Joshi, S.; Miller, M. I.

1998-01-01

The human cerebral cortex is notorious for the depth and irregularity of its convolutions and for its variability from one individual to the next. These complexities of cortical geography have been a chronic impediment to studies of functional specialization in the cortex. In this report, we discuss ways to compensate for the convolutions by using a combination of strategies whose common denominator involves explicit reconstructions of the cortical surface. Surface-based visualization involves reconstructing cortical surfaces and displaying them, along with associated experimental data, in various complementary formats (including three-dimensional native configurations, two-dimensional slices, extensively smoothed surfaces, ellipsoidal representations, and cortical flat maps). Generating these representations for the cortex of the Visible Man leads to a surface-based atlas that has important advantages over conventional stereotaxic atlases as a substrate for displaying and analyzing large amounts of experimental data. We illustrate this by showing the relationship between functionally specialized regions and topographically organized areas in human visual cortex. Surface-based warping allows data to be mapped from individual hemispheres to a surface-based atlas while respecting surface topology, improving registration of identifiable landmarks, and minimizing unwanted distortions. Surface-based warping also can aid in comparisons between species, which we illustrate by warping a macaque flat map to match the shape of a human flat map. Collectively, these approaches will allow more refined analyses of commonalities as well as individual differences in the functional organization of primate cerebral cortex.

Developing CORBA-Based Distributed Scientific Applications from Legacy Fortran Programs

NASA Technical Reports Server (NTRS)

Sang, Janche; Kim, Chan; Lopez, Isaac

2000-01-01

Recent progress in distributed object technology has enabled software applications to be developed and deployed easily such that objects or components can work together across the boundaries of the network, different operating systems, and different languages. A distributed object is not necessarily a complete application but rather a reusable, self-contained piece of software that co-operates with other objects in a plug-and-play fashion via a well-defined interface. The Common Object Request Broker Architecture (CORBA), a middleware standard defined by the Object Management Group (OMG), uses the Interface Definition Language (IDL) to specify such an interface for transparent communication between distributed objects. Since IDL can be mapped to any programming language, such as C++, Java, Smalltalk, etc., existing applications can be integrated into a new application and hence the tasks of code re-writing and software maintenance can be reduced. Many scientific applications in aerodynamics and solid mechanics are written in Fortran. Refitting these legacy Fortran codes with CORBA objects can increase the codes reusability. For example, scientists could link their scientific applications to vintage Fortran programs such as Partial Differential Equation(PDE) solvers in a plug-and-play fashion. Unfortunately, CORBA IDL to Fortran mapping has not been proposed and there seems to be no direct method of generating CORBA objects from Fortran without having to resort to manually writing C/C++ wrappers. In this paper, we present an efficient methodology to integrate Fortran legacy programs into a distributed object framework. Issues and strategies regarding the conversion and decomposition of Fortran codes into CORBA objects are discussed. The following diagram shows the conversion and decomposition mechanism we proposed. Our goal is to keep the Fortran codes unmodified. The conversion- aided tool takes the Fortran application program as input and helps programmers generate C/C++ header file and IDL file for wrapping the Fortran code. Programmers need to determine by themselves how to decompose the legacy application into several reusable components based on the cohesion and coupling factors among the functions and subroutines. However, programming effort still can be greatly reduced because function headings and types have been converted to C++ and IDL styles. Most Fortran applications use the COMMON block to facilitate the transfer of large amount of variables among several functions. The COMMON block plays the similar role of global variables used in C. In the CORBA-compliant programming environment, global variables can not be used to pass values between objects. One approach to dealing with this problem is to put the COMMON variables into the parameter list. We do not adopt this approach because it requires modification of the Fortran source code which violates our design consideration. Our approach is to extract the COMMON blocks and convert them into a structure-typed attribute in C++. Through attributes, each component can initialize the variables and return the computation result back to the client. We have tested successfully the proposed conversion methodology based on the f2c converter. Since f2c only translates Fortran to C, we still needed to edit the converted code to meet the C++ and IDL syntax. For example, C++/IDL requires a tag in the structure type, while C does not. In this paper, we identify the necessary changes to the f2c converter in order to directly generate the C++ header and the IDL file. Our future work is to add GUI interface to ease the decomposition task by simply dragging and dropping icons.

Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search.

PubMed

Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

2014-03-01

Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI.

Brain-computer interface controlled functional electrical stimulation device for foot drop due to stroke.

PubMed

Do, An H; Wang, Po T; King, Christine E; Schombs, Andrew; Cramer, Steven C; Nenadic, Zoran

2012-01-01

Gait impairment due to foot drop is a common outcome of stroke, and current physiotherapy provides only limited restoration of gait function. Gait function can also be aided by orthoses, but these devices may be cumbersome and their benefits disappear upon removal. Hence, new neuro-rehabilitative therapies are being sought to generate permanent improvements in motor function beyond those of conventional physiotherapies through positive neural plasticity processes. Here, the authors describe an electroencephalogram (EEG) based brain-computer interface (BCI) controlled functional electrical stimulation (FES) system that enabled a stroke subject with foot drop to re-establish foot dorsiflexion. To this end, a prediction model was generated from EEG data collected as the subject alternated between periods of idling and attempted foot dorsiflexion. This prediction model was then used to classify online EEG data into either "idling" or "dorsiflexion" states, and this information was subsequently used to control an FES device to elicit effective foot dorsiflexion. The performance of the system was assessed in online sessions, where the subject was prompted by a computer to alternate between periods of idling and dorsiflexion. The subject demonstrated purposeful operation of the BCI-FES system, with an average cross-correlation between instructional cues and BCI-FES response of 0.60 over 3 sessions. In addition, analysis of the prediction model indicated that non-classical brain areas were activated in the process, suggesting post-stroke cortical re-organization. In the future, these systems may be explored as a potential therapeutic tool that can help promote positive plasticity and neural repair in chronic stroke patients.

Electromiography comparison of distal and proximal lower limb muscle activity patterns during external perturbation in subjects with and without functional ankle instability.

PubMed

Kazemi, Khadijeh; Arab, Amir Massoud; Abdollahi, Iraj; López-López, Daniel; Calvo-Lobo, César

2017-10-01

Ankle sprain is one of the most common injuries among athletes and the general population. Most ankle injuries commonly affect the lateral ligament complex. Changes in postural sway and hip abductor muscle strength may be generated after inversion ankle sprain. Therefore, the consequences of ankle injury may affect proximal structures of the lower limb. The aim is to describe and compare the activity patterns of distal and proximal lower limb muscles following external perturbation in individuals with and without functional ankle instability. The sample consisted of 16 women with functional ankle instability and 18 healthy women were recruited to participate in this research. The external perturbation via body jacket using surface electromyography, amplitude and onset of muscle activity of gluteus maximums, gluteus medius, tibialis anterior, and peroneus longus was recorded and analyzed during external perturbation. There were differences between the onset of muscles activity due to perturbation direction in the two groups (healthy and functional ankle instability). In the healthy group, there were statistically significant differences in amplitude of proximal muscle activity with distal muscle activity during front perturbation with eyes open and closed. In the functional ankle instability group; there were statistically significant differences in amplitude of proximal muscle activity with distal muscle activity during perturbation of the front and back with eyes open. There were statistically significant differences in the onset of muscle activity and amplitude of muscle activity, with-in and between groups (P<0.05). Therefore, in the presence of functional ankle instability, activation patterns of the lower limb proximal muscles may be altered. Copyright © 2017 Elsevier B.V. All rights reserved.

TrawlerWeb: an online de novo motif discovery tool for next-generation sequencing datasets.

PubMed

Dang, Louis T; Tondl, Markus; Chiu, Man Ho H; Revote, Jerico; Paten, Benedict; Tano, Vincent; Tokolyi, Alex; Besse, Florence; Quaife-Ryan, Greg; Cumming, Helen; Drvodelic, Mark J; Eichenlaub, Michael P; Hallab, Jeannette C; Stolper, Julian S; Rossello, Fernando J; Bogoyevitch, Marie A; Jans, David A; Nim, Hieu T; Porrello, Enzo R; Hudson, James E; Ramialison, Mirana

2018-04-05

A strong focus of the post-genomic era is mining of the non-coding regulatory genome in order to unravel the function of regulatory elements that coordinate gene expression (Nat 489:57-74, 2012; Nat 507:462-70, 2014; Nat 507:455-61, 2014; Nat 518:317-30, 2015). Whole-genome approaches based on next-generation sequencing (NGS) have provided insight into the genomic location of regulatory elements throughout different cell types, organs and organisms. These technologies are now widespread and commonly used in laboratories from various fields of research. This highlights the need for fast and user-friendly software tools dedicated to extracting cis-regulatory information contained in these regulatory regions; for instance transcription factor binding site (TFBS) composition. Ideally, such tools should not require prior programming knowledge to ensure they are accessible for all users. We present TrawlerWeb, a web-based version of the Trawler_standalone tool (Nat Methods 4:563-5, 2007; Nat Protoc 5:323-34, 2010), to allow for the identification of enriched motifs in DNA sequences obtained from next-generation sequencing experiments in order to predict their TFBS composition. TrawlerWeb is designed for online queries with standard options common to web-based motif discovery tools. In addition, TrawlerWeb provides three unique new features: 1) TrawlerWeb allows the input of BED files directly generated from NGS experiments, 2) it automatically generates an input-matched biologically relevant background, and 3) it displays resulting conservation scores for each instance of the motif found in the input sequences, which assists the researcher in prioritising the motifs to validate experimentally. Finally, to date, this web-based version of Trawler_standalone remains the fastest online de novo motif discovery tool compared to other popular web-based software, while generating predictions with high accuracy. TrawlerWeb provides users with a fast, simple and easy-to-use web interface for de novo motif discovery. This will assist in rapidly analysing NGS datasets that are now being routinely generated. TrawlerWeb is freely available and accessible at: http://trawler.erc.monash.edu.au .

Generation, characterization and potential therapeutic applications of mature and functional hepatocytes from stem cells.

PubMed

Zhang, Zhenzhen; Liu, Jianfang; Liu, Yang; Li, Zheng; Gao, Wei-Qiang; He, Zuping

2013-02-01

Liver cancer is the sixth most common tumor in the world and the majority of patients with this disease usually die within 1 year. The effective treatment for end-stage liver disease (also known as liver failure), including liver cancer or cirrhosis, is liver transplantation. However, there is a severe shortage of liver donors worldwide, which is the major handicap for the treatment of patients with liver failure. Scarcity of liver donors underscores the urgent need of using stem cell therapy to the end-stage liver disease. Notably, hepatocytes have recently been generated from hepatic and extra-hepatic stem cells. We have obtained mature and functional hepatocytes from rat hepatic stem cells. Here, we review the advancements on hepatic differentiation from various stem cells, including hepatic stem cells, embryonic stem cells, the induced pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, and probably spermatogonial stem cells. The advantages, disadvantages, and concerns on differentiation of these stem cells into hepatic cells are highlighted. We further address the methodologies, phenotypes, and functional characterization on the differentiation of numerous stem cells into hepatic cells. Differentiation of stem cells into mature and functional hepatocytes, especially from an extra-hepatic stem cell source, would circumvent the scarcity of liver donors and human hepatocytes, and most importantly it would offer an ideal and promising source of hepatocytes for cell therapy and tissue engineering in treating liver disease. Copyright © 2012 Wiley Periodicals, Inc.

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika

2017-01-01

Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061

A Simple Primary Amine Catalyst for Enantioselective α-Hydroxylations and α-Fluorinations of Branched Aldehydes

PubMed Central

Witten, Michael R.; Jacobsen, Eric N.

2016-01-01

A new primary amine catalyst for the asymmetric α-hydroxylation and α-fluorination of α-branched aldehydes is described. The products of the title transformations are generated in excellent yields and with high enantioselectivities. Both processes can be performed within short reaction times and on gram scale. The similarity in the results obtained in both reactions, combined with computational evidence, implies a common basis for stereoinduction and the possibility of a general catalytic mechanism for α-functionalizations. Promising initial results in α-amination and α-chlorination reactions support this hypothesis. PMID:25952578

Silicon photonic transceiver circuit for high-speed polarization-based discrete variable quantum key distribution

DOE PAGES

Cai, Hong; Long, Christopher M.; DeRose, Christopher T.; ...

2017-01-01

We demonstrate a silicon photonic transceiver circuit for high-speed discrete variable quantum key distribution that employs a common structure for transmit and receive functions. The device is intended for use in polarization-based quantum cryptographic protocols, such as BB84. Our characterization indicates that the circuit can generate the four BB84 states (TE/TM/45°/135° linear polarizations) with >30 dB polarization extinction ratios and gigabit per second modulation speed, and is capable of decoding any polarization bases differing by 90° with high extinction ratios.

Silicon photonic transceiver circuit for high-speed polarization-based discrete variable quantum key distribution.

PubMed

Cai, Hong; Long, Christopher M; DeRose, Christopher T; Boynton, Nicholas; Urayama, Junji; Camacho, Ryan; Pomerene, Andrew; Starbuck, Andrew L; Trotter, Douglas C; Davids, Paul S; Lentine, Anthony L

2017-05-29

We demonstrate a silicon photonic transceiver circuit for high-speed discrete variable quantum key distribution that employs a common structure for transmit and receive functions. The device is intended for use in polarization-based quantum cryptographic protocols, such as BB84. Our characterization indicates that the circuit can generate the four BB84 states (TE/TM/45°/135° linear polarizations) with >30 dB polarization extinction ratios and gigabit per second modulation speed, and is capable of decoding any polarization bases differing by 90° with high extinction ratios.

Silicon photonic transceiver circuit for high-speed polarization-based discrete variable quantum key distribution

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

Cai, Hong; Long, Christopher M.; DeRose, Christopher T.

We demonstrate a silicon photonic transceiver circuit for high-speed discrete variable quantum key distribution that employs a common structure for transmit and receive functions. The device is intended for use in polarization-based quantum cryptographic protocols, such as BB84. Our characterization indicates that the circuit can generate the four BB84 states (TE/TM/45°/135° linear polarizations) with >30 dB polarization extinction ratios and gigabit per second modulation speed, and is capable of decoding any polarization bases differing by 90° with high extinction ratios.

Most common problems across health conditions as described by the International Classification of Functioning, Disability, and Health.

PubMed

Ptyushkin, Pavel; Cieza, Alarcos; Stucki, Gerold

2015-09-01

Health conditions are associated with a variety of functional outcomes. Even though functional outcomes are diverse for different health conditions, they can have important commonalities. The aim of this study was to identify the most common problems in functioning across the wide range of health conditions using the International Classification of Functioning (ICF). Existing databases created for the 21 ICF Core Sets studies were descriptively analyzed. These included data collected in 44 countries on 9978 patients with one of 21 health conditions as the main diagnosis. A frequency cutoff of 50% was used to identify the most common problems in functioning when looking at single health conditions and across them. No category was identified as common to all health conditions included in the study. Fifteen most frequent categories were common in 10 to 13 health conditions out of 21. Eleven categories correspond to the list of activities and participation, and four to the list of body functions. These are related to mobility, daily routine, mental functions, intimate relations, employment, and leisure. Some health conditions have more commonalities between each other. The most common problems across health conditions are therefore related to mental functions, mobility, daily life, intimate relations, employment, and leisure. The results contribute toward the identification of the universal set of ICF categories that can be used in clinical practice for the general assessment of functioning.

Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition

PubMed Central

D'Angelo, Egidio; Casali, Stefano

2013-01-01

Following the fundamental recognition of its involvement in sensory-motor coordination and learning, the cerebellum is now also believed to take part in the processing of cognition and emotion. This hypothesis is recurrent in numerous papers reporting anatomical and functional observations, and it requires an explanation. We argue that a similar circuit structure in all cerebellar areas may carry out various operations using a common computational scheme. On the basis of a broad review of anatomical data, it is conceivable that the different roles of the cerebellum lie in the specific connectivity of the cerebellar modules, with motor, cognitive, and emotional functions (at least partially) segregated into different cerebro-cerebellar loops. We here develop a conceptual and operational framework based on multiple interconnected levels (a meta-levels hypothesis): from cellular/molecular to network mechanisms leading to generation of computational primitives, thence to high-level cognitive/emotional processing, and finally to the sphere of mental function and dysfunction. The main concept explored is that of intimate interplay between timing and learning (reminiscent of the “timing and learning machine” capabilities long attributed to the cerebellum), which reverberates from cellular to circuit mechanisms. Subsequently, integration within large-scale brain loops could generate the disparate cognitive/emotional and mental functions in which the cerebellum has been implicated. We propose, therefore, that the cerebellum operates as a general-purpose co-processor, whose effects depend on the specific brain centers to which individual modules are connected. Abnormal functioning in these loops could eventually contribute to the pathogenesis of major brain pathologies including not just ataxia but also dyslexia, autism, schizophrenia, and depression. PMID:23335884

Intellectual function evaluation of first generation immigrant children with sickle cell disease: the role of language and sociodemographic factors.

PubMed

Montanaro, Maria; Colombatti, Raffaella; Pugliese, Marisa; Migliozzi, Camilla; Zani, Fabiana; Guerzoni, Maria Elena; Manoli, Sheila; Manara, Renzo; Meneghetti, Giorgio; Rampazzo, Patrizia; Cavalleri, Francesca; Giordan, Marco; Paolucci, Paolo; Basso, Giuseppe; Palazzi, Giovanni; Sainati, Laura

2013-06-04

Sickle Cell Disease (SCD) is the most common genetic disease worldwide. Neurological events are among the most worrisome clinical complications of SCD and are frequently accompanied by cognitive impairment. Intellectual function in SCD may vary according to genetic and environmental factors. Immigrant children with SCD are increasing at a global level and display specific health care needs. The aim of our multicenter study was to describe the intellectual function of first generation African immigrants with SCD and the influence of sociodemographic factors on its characteristics. The Wechsler Intelligence Scales were administered to evaluate broad intellectual functions in children with SCD and in age-matched healthy siblings. Patients' clinical, socio-demographic, Magnetic Resonance Imaging (MRI) and Angiography (MRA) data were correlated to intellectual function scores. 68 children, mean age 8.95 years were evaluated. 72% spoke three languages, 21% two. FSIQ was <75 in 25% of the children. Mean VIQ was lower than PIQ in 75%. Mean verbal subtest scores were lower than performance scores. Female gender, number of languages spoken at home and mother's employment were associated with single subtest performances (p < 0.05). MRA was abnormal in 73.4% and MRI in 35.9%. No significant correlation was established between silent lesions and intellectual function, even if patients with lesions performed worse. Fifteen siblings performed better than patients on cognitive domains, including language (p < 0.05). Immigrant bilingual children with SCD seem to display a rate of cognitive impairment similar to their monolingual counterparts but a more pronounced and precocious onset of language difficulties. Adjunctive tests need to be considered in this group of patients to better define their specific deficits.

Transcriptomics Provide Insight Into Mussel (Mytilus galloprovincialis) Mantle Function And Its Role In Biomineralization

NASA Astrophysics Data System (ADS)

Zaghdoudi-Allan, N.; Yarra, T.; Churcher, A.; Felix, R. C.; Cardoso, J.; Clark, M.; Power, D. M.

2016-02-01

With over 90,000 extant species, the Mollusca is one of the most successful and species-rich phyla, comprising 23% of known marine fauna. Common to all molluscs, the mantle is a multi-functional highly muscular tissue that contacts the shell and envelops vital organs. In bivalves, the epithelial cells of the mantle secrete the external shell by a complex network of mechanisms that remain poorly understood. To date, the bulk of the work on Mytilus mantle has focused on two of its features: the mantle edge and the pallial mantle and relatively little is known about the factors regulating its function. We hypothesize that the mantle edge in Mytilus species is heterogeneous in cellular structure and function and use next generation sequencing to mine for receptors involved in biomineralization. The mantle edge of the Mediterranean mussel (Mytilus galloprovincialis) was sectioned into three parts and sequenced using the Illumina platform. The transcriptome sequences generated assembled into 179,879 transcripts with a 34% GC content, congruent with other bivalve asssemblies. The transcriptome was annotated and String analysis (http://www.string-db.org) was used for a preliminary characterisation of biological processes. To test our hypothesis, we compared the transcripts from the 3 mantle segments and the expression levels of putative receptors such as the G -protein coupled receptors (GPCRs) in the sectioned mantle of 6 individuals using qPCR. Candidates were chosen based on their regulatory function and potential involvement in shell formation. Our results show differences in transcript abundance and cellular function amongst the three mantle sections. Combining our transcriptomic study with histological studies of the mantle tissue, we present evidence of both molecular and structural heterogeneity of the mussel mantle and identify several putative regulatory networks.

Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions.

PubMed

Swee, Lee Kim; Tan, Zhen Wei; Sanecka, Anna; Yoshida, Nagisa; Patel, Harshil; Grotenbreg, Gijsbert; Frickel, Eva-Maria; Ploegh, Hidde L

2016-11-01

T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR identity-hence reactivity to self-and effector function(s) remains to be fully understood and has rarely been explored outside of the H-2 b haplotype. We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs that recognize the identical H-2 L d -restricted epitope, derived from the Rop7 protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by somatic cell nuclear transfer as the closest approximation of primary T cells with physiological TCR rearrangements and TCR expression levels. First, we demonstrate the common occurrence of secondary rearrangements in endogenously rearranged loci. Furthermore, we characterized and compared the response of Rop7-specific CD8 T-cell clones upon Toxoplasma gondii infection as well as effector function and TCR signalling upon antigenic stimulation in vitro Antigen-independent TCR cross-linking in vitro uncovered profound intrinsic differences in the effector functions between T-cell clones. Finally, by assessing the degree of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we show that lower self-reactivity correlates with lower effector capacity, whereas higher self-reactivity is associated with enhanced effector function as well as cell cycle entry under physiological conditions. Altogether, our data show that potential effector functions and basal proliferation of CD8 T cells are set by self-reactivity thresholds. © 2016 The Authors.

Assessing the effects of common variation in the FOXP2 gene on human brain structure.

PubMed

Hoogman, Martine; Guadalupe, Tulio; Zwiers, Marcel P; Klarenbeek, Patricia; Francks, Clyde; Fisher, Simon E

2014-01-01

The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus, and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry (VBM) and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than 10 times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques.

A generating function approach to HIV transmission with dynamic contact rates

DOE PAGES

Romero-Severson, Ethan O.; Meadors, Grant D.; Volz, Erik M.

2014-04-24

The basic reproduction number, R 0, is often defined as the average number of infections generated by a newly infected individual in a fully susceptible population. The interpretation, meaning, and derivation of R 0 are controversial. However, in the context of mean field models, R 0 demarcates the epidemic threshold below which the infected population approaches zero in the limit of time. In this manner, R 0 has been proposed as a method for understanding the relative impact of public health interventions with respect to disease eliminations from a theoretical perspective. The use of R 0 is made more complexmore » by both the strong dependency of R 0 on the model form and the stochastic nature of transmission. A common assumption in models of HIV transmission that have closed form expressions for R 0 is that a single individual’s behavior is constant over time. For this research, we derive expressions for both R 0 and probability of an epidemic in a finite population under the assumption that people periodically change their sexual behavior over time. We illustrate the use of generating functions as a general framework to model the effects of potentially complex assumptions on the number of transmissions generated by a newly infected person in a susceptible population. In conclusion, we find that the relationship between the probability of an epidemic and R 0 is not straightforward, but, that as the rate of change in sexual behavior increases both R 0 and the probability of an epidemic also decrease.« less

A generating function approach to HIV transmission with dynamic contact rates

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

Romero-Severson, Ethan O.; Meadors, Grant D.; Volz, Erik M.

The basic reproduction number, R 0, is often defined as the average number of infections generated by a newly infected individual in a fully susceptible population. The interpretation, meaning, and derivation of R 0 are controversial. However, in the context of mean field models, R 0 demarcates the epidemic threshold below which the infected population approaches zero in the limit of time. In this manner, R 0 has been proposed as a method for understanding the relative impact of public health interventions with respect to disease eliminations from a theoretical perspective. The use of R 0 is made more complexmore » by both the strong dependency of R 0 on the model form and the stochastic nature of transmission. A common assumption in models of HIV transmission that have closed form expressions for R 0 is that a single individual’s behavior is constant over time. For this research, we derive expressions for both R 0 and probability of an epidemic in a finite population under the assumption that people periodically change their sexual behavior over time. We illustrate the use of generating functions as a general framework to model the effects of potentially complex assumptions on the number of transmissions generated by a newly infected person in a susceptible population. In conclusion, we find that the relationship between the probability of an epidemic and R 0 is not straightforward, but, that as the rate of change in sexual behavior increases both R 0 and the probability of an epidemic also decrease.« less

Generating short-term probabilistic wind power scenarios via nonparametric forecast error density estimators: Generating short-term probabilistic wind power scenarios via nonparametric forecast error density estimators

DOE PAGES

Staid, Andrea; Watson, Jean -Paul; Wets, Roger J. -B.; ...

2017-07-11

Forecasts of available wind power are critical in key electric power systems operations planning problems, including economic dispatch and unit commitment. Such forecasts are necessarily uncertain, limiting the reliability and cost effectiveness of operations planning models based on a single deterministic or “point” forecast. A common approach to address this limitation involves the use of a number of probabilistic scenarios, each specifying a possible trajectory of wind power production, with associated probability. We present and analyze a novel method for generating probabilistic wind power scenarios, leveraging available historical information in the form of forecasted and corresponding observed wind power timemore » series. We estimate non-parametric forecast error densities, specifically using epi-spline basis functions, allowing us to capture the skewed and non-parametric nature of error densities observed in real-world data. We then describe a method to generate probabilistic scenarios from these basis functions that allows users to control for the degree to which extreme errors are captured.We compare the performance of our approach to the current state-of-the-art considering publicly available data associated with the Bonneville Power Administration, analyzing aggregate production of a number of wind farms over a large geographic region. Finally, we discuss the advantages of our approach in the context of specific power systems operations planning problems: stochastic unit commitment and economic dispatch. Here, our methodology is embodied in the joint Sandia – University of California Davis Prescient software package for assessing and analyzing stochastic operations strategies.« less

Generating short-term probabilistic wind power scenarios via nonparametric forecast error density estimators: Generating short-term probabilistic wind power scenarios via nonparametric forecast error density estimators

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

Staid, Andrea; Watson, Jean -Paul; Wets, Roger J. -B.

Forecasts of available wind power are critical in key electric power systems operations planning problems, including economic dispatch and unit commitment. Such forecasts are necessarily uncertain, limiting the reliability and cost effectiveness of operations planning models based on a single deterministic or “point” forecast. A common approach to address this limitation involves the use of a number of probabilistic scenarios, each specifying a possible trajectory of wind power production, with associated probability. We present and analyze a novel method for generating probabilistic wind power scenarios, leveraging available historical information in the form of forecasted and corresponding observed wind power timemore » series. We estimate non-parametric forecast error densities, specifically using epi-spline basis functions, allowing us to capture the skewed and non-parametric nature of error densities observed in real-world data. We then describe a method to generate probabilistic scenarios from these basis functions that allows users to control for the degree to which extreme errors are captured.We compare the performance of our approach to the current state-of-the-art considering publicly available data associated with the Bonneville Power Administration, analyzing aggregate production of a number of wind farms over a large geographic region. Finally, we discuss the advantages of our approach in the context of specific power systems operations planning problems: stochastic unit commitment and economic dispatch. Here, our methodology is embodied in the joint Sandia – University of California Davis Prescient software package for assessing and analyzing stochastic operations strategies.« less

Are Rab Proteins the Link Between Golgi Organization and Membrane Trafficking?

PubMed Central

Liu, Shijie; Storrie, Brian

2014-01-01

The fundamental separation of Golgi function between subcompartments termed cisternae is conserved across all eukaryotes. Likewise, Rab proteins, small GTPases of the Ras superfamily, are putative common coordinators of Golgi organization and protein transport. However, despite sequence conservation, e.g., Rab6 and Ypt6 are conserved proteins between humans and yeast, the fundamental organization of the organelle can vary profoundly. In the yeast Sacchromyces cerevisiae, the Golgi cisternae are physically separated from one another while, in mammalian cells, the cisternae are stacked one upon the other. Moreover, in mammalian cells many Golgi stacks are typically linked together to generate a ribbon structure. Do evolutionarily conserved Rab proteins regulate secretory membrane trafficking and diverse Golgi organization in a common manner? In mammalian cells, some Golgi associated Rab proteins function in coordination of protein transport and maintenance of Golgi organization. These include Rab6, Rab33B, Rab1, Rab2, Rab18 and Rab43. In yeast, these include Ypt1, Ypt32 and Ypt6. Here, based on evidence from both yeast and mammalian cells, we speculate on the essential role of Rab proteins in Golgi organization and protein transport. PMID:22581368

Easy access to nucleophilic boron through diborane to magnesium boryl metathesis

NASA Astrophysics Data System (ADS)

Pécharman, Anne-Frédérique; Colebatch, Annie L.; Hill, Michael S.; McMullin, Claire L.; Mahon, Mary F.; Weetman, Catherine

2017-04-01

Organoboranes are some of the most synthetically valuable and widely used intermediates in organic and pharmaceutical chemistry. Their synthesis, however, is limited by the behaviour of common boron starting materials as archetypal Lewis acids such that common routes to organoboranes rely on the reactivity of boron as an electrophile. While the realization of convenient sources of nucleophilic boryl anions would open up a wealth of opportunity for the development of new routes to organoboranes, the synthesis of current candidates is generally limited by a need for highly reducing reaction conditions. Here, we report a simple synthesis of a magnesium boryl through the heterolytic activation of the B-B bond of bis(pinacolato)diboron, which is achieved by treatment of an easily generated magnesium diboranate complex with 4-dimethylaminopyridine. The magnesium boryl is shown to act as an unambiguous nucleophile through its reactions with iodomethane, benzophenone and N,N'-di-isopropyl carbodiimide and by density functional theory.

Quantum mechanics as classical statistical mechanics with an ontic extension and an epistemic restriction.

PubMed

Budiyono, Agung; Rohrlich, Daniel

2017-11-03

Where does quantum mechanics part ways with classical mechanics? How does quantum randomness differ fundamentally from classical randomness? We cannot fully explain how the theories differ until we can derive them within a single axiomatic framework, allowing an unambiguous account of how one theory is the limit of the other. Here we derive non-relativistic quantum mechanics and classical statistical mechanics within a common framework. The common axioms include conservation of average energy and conservation of probability current. But two axioms distinguish quantum mechanics from classical statistical mechanics: an "ontic extension" defines a nonseparable (global) random variable that generates physical correlations, and an "epistemic restriction" constrains allowed phase space distributions. The ontic extension and epistemic restriction, with strength on the order of Planck's constant, imply quantum entanglement and uncertainty relations. This framework suggests that the wave function is epistemic, yet it does not provide an ontic dynamics for individual systems.

3D printing of tissue-simulating phantoms as a traceable standard for biomedical optical measurement

NASA Astrophysics Data System (ADS)

Dong, Erbao; Wang, Minjie; Shen, Shuwei; Han, Yilin; Wu, Qiang; Xu, Ronald

2016-01-01

Optical phantoms are commonly used to validate and calibrate biomedical optical devices in order to ensure accurate measurement of optical properties in biological tissue. However, commonly used optical phantoms are based on homogenous materials that reflect neither optical properties nor multi-layer heterogeneities of biological tissue. Using these phantoms for optical calibration may result in significant bias in biological measurement. We propose to characterize and fabricate tissue simulating phantoms that simulate not only the multi-layer heterogeneities but also optical properties of biological tissue. The tissue characterization module detects tissue structural and functional properties in vivo. The phantom printing module generates 3D tissue structures at different scales by layer-by-layer deposition of phantom materials with different optical properties. The ultimate goal is to fabricate multi-layer tissue simulating phantoms as a traceable standard for optimal calibration of biomedical optical spectral devices.

Control of adaptive immunity by the innate immune system.

PubMed

Iwasaki, Akiko; Medzhitov, Ruslan

2015-04-01

Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.

Flavonoids and Melanins: A Common Strategy across Two Kingdoms

PubMed Central

Carletti, Giorgia; Nervo, Giuseppe; Cattivelli, Luigi

2014-01-01

Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2-). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant. PMID:25516714

Flavonoids and Melanins: a common strategy across two kingdoms.

PubMed

Carletti, Giorgia; Nervo, Giuseppe; Cattivelli, Luigi

2014-01-01

Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.

Capture, Learning, and Classification of Upper Extremity Movement Primitives in Healthy Controls and Stroke Patients

PubMed Central

Guerra, Jorge; Uddin, Jasim; Nilsen, Dawn; Mclnerney, James; Fadoo, Ammarah; Omofuma, Isirame B.; Hughes, Shatif; Agrawal, Sunil; Allen, Peter; Schambra, Heidi M.

2017-01-01

There currently exist no practical tools to identify functional movements in the upper extremities (UEs). This absence has limited the precise therapeutic dosing of patients recovering from stroke. In this proof-of-principle study, we aimed to develop an accurate approach for classifying UE functional movement primitives, which comprise functional movements. Data were generated from inertial measurement units (IMUs) placed on upper body segments of older healthy individuals and chronic stroke patients. Subjects performed activities commonly trained during rehabilitation after stroke. Data processing involved the use of a sliding window to obtain statistical descriptors, and resulting features were processed by a Hidden Markov Model (HMM). The likelihoods of the states, resulting from the HMM, were segmented by a second sliding window and their averages were calculated. The final predictions were mapped to human functional movement primitives using a Logistic Regression algorithm. Algorithm performance was assessed with a leave-one-out analysis, which determined its sensitivity, specificity, and positive and negative predictive values for all classified primitives. In healthy control and stroke participants, our approach identified functional movement primitives embedded in training activities with, on average, 80% precision. This approach may support functional movement dosing in stroke rehabilitation. PMID:28813877

Development of ICF Core Sets to standardize assessment of functioning and impairment in ADHD: the path ahead.

PubMed

Bölte, Sven; de Schipper, Elles; Holtmann, Martin; Karande, Sunil; de Vries, Petrus J; Selb, Melissa; Tannock, Rosemary

2014-12-01

In the study of health and quality of life in attention deficit/hyperactivity disorder (ADHD), it is of paramount importance to include assessment of functioning. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive, universally accepted framework for the description of functioning in relation to health conditions. In this paper, the authors outline the process to develop ICF Core Sets for ADHD. ICF Core Sets are subgroups of ICF categories selected to capture the aspects of functioning that are most likely to be affected in specific disorders. The ICF categories that will be included in the ICF Core Sets for ADHD will be determined at an ICF Core Set Consensus Conference, wherein evidence from four preliminary studies (a systematic review, an expert survey, a patient and caregiver qualitative study, and a clinical cross-sectional study) will be integrated. Comprehensive and Brief ICF Core Sets for ADHD will be developed with the goal of providing useful standards for research and clinical practice, and to generate a common language for the description of functioning in ADHD in different areas of life and across the lifespan.

On compensatory strategies and computational models: the case of pure alexia.

PubMed

Shallice, Tim

2014-01-01

The article is concerned with inferences from the behaviour of neurological patients to models of normal function. It takes the letter-by-letter reading strategy common in pure alexic patients as an example of the methodological problems involved in making such inferences that compensatory strategies produce. The evidence is discussed on the possible use of three ways the letter-by-letter reading process might operate: "reversed spelling"; the use of the phonological input buffer as a temporary holding store during word building; and the use of serial input to the visual word-form system entirely within the visual-orthographic domain such as in the model of Plaut [1999. A connectionist approach to word reading and acquired dyslexia: Extension to sequential processing. Cognitive Science, 23, 543-568]. The compensatory strategy used by, at least, one pure alexic patient does not fit with the third of these possibilities. On the more general question, it is argued that even if compensatory strategies are being used, the behaviour of neurological patients can be useful for the development and assessment of first-generation information-processing models of normal function, but they are not likely to be useful for the development and assessment of second-generation computational models.

RSEQtools: a modular framework to analyze RNA-Seq data using compact, anonymized data summaries.

PubMed

Habegger, Lukas; Sboner, Andrea; Gianoulis, Tara A; Rozowsky, Joel; Agarwal, Ashish; Snyder, Michael; Gerstein, Mark

2011-01-15

The advent of next-generation sequencing for functional genomics has given rise to quantities of sequence information that are often so large that they are difficult to handle. Moreover, sequence reads from a specific individual can contain sufficient information to potentially identify and genetically characterize that person, raising privacy concerns. In order to address these issues, we have developed the Mapped Read Format (MRF), a compact data summary format for both short and long read alignments that enables the anonymization of confidential sequence information, while allowing one to still carry out many functional genomics studies. We have developed a suite of tools (RSEQtools) that use this format for the analysis of RNA-Seq experiments. These tools consist of a set of modules that perform common tasks such as calculating gene expression values, generating signal tracks of mapped reads and segmenting that signal into actively transcribed regions. Moreover, the tools can readily be used to build customizable RNA-Seq workflows. In addition to the anonymization afforded by MRF, this format also facilitates the decoupling of the alignment of reads from downstream analyses. RSEQtools is implemented in C and the source code is available at http://rseqtools.gersteinlab.org/.

Epigenetics of sex determination and gonadogenesis.

PubMed

Piferrer, Francesc

2013-04-01

Epigenetics is commonly defined as the study of heritable changes in gene function that cannot be explained by changes in DNA sequence. The three major epigenetic mechanisms for gene expression regulation include DNA methylation, histone modifications, and non-coding RNAs. Epigenetic mechanisms provide organisms with the ability to integrate genomic and environmental information to modify the activity of their genes for generating a particular phenotype. During development, cells differentiate, acquire, and maintain identity through changes in gene expression. This is crucial for sex determination and differentiation, which are among the most important developmental processes for the proper functioning and perpetuation of species. This review summarizes studies showing how epigenetic regulatory mechanisms contribute to sex determination and reproductive organ formation in plants, invertebrates, and vertebrates. Further progress will be made by integrating several approaches, including genomics and Next Generation Sequencing to create epigenetic maps related to different aspects of sex determination and gonadogenesis. Epigenetics will also contribute to understand the etiology of several disorders of sexual development. It also might play a significant role in the control of reproduction in animal farm production and will aid in recognizing the environmental versus genetic influences on sex determination of sensitive species in a global change scenario. Copyright © 2013 Wiley Periodicals, Inc.

Optical fiber sensor technique for strain measurement during materials deposition, chemical reaction, and relaxation

DOEpatents

Butler, M.A.; Ginley, D.S.

1988-01-21

Laser light from a common source is split and conveyed through two similar optical fibers and emitted at their respective ends to form an interference pattern, one of the optical fibers having a portion thereof subjected to a strain. Changes in the strain cause changes in the optical path length of the strain fiber, and generate corresponding changes in the interference pattern. The interference pattern is received and transduced into signals representative of fringe shifts corresponding to changes in the strain experienced by the strained one of the optical fibers. These signals are then processed to evaluate strain as a function of time, typical examples of the application of the apparatus including electrodeposition of a metallic film on a conductive surface provided on the outside of the optical fiber being strained, so that strains generated in the optical fiber during the course of the electrodeposition are measurable as a function of time. In one aspect of the invention, signals relating to the fringe shift are stored for subsequent processing and analysis, whereas in another aspect of the invention the signals are processed for real-time display of the strain changes under study. 9 figs.

Shared brain lateralization patterns in language and Acheulean stone tool production: a functional transcranial Doppler ultrasound study.

PubMed

Uomini, Natalie Thaïs; Meyer, Georg Friedrich

2013-01-01

The popular theory that complex tool-making and language co-evolved in the human lineage rests on the hypothesis that both skills share underlying brain processes and systems. However, language and stone tool-making have so far only been studied separately using a range of neuroimaging techniques and diverse paradigms. We present the first-ever study of brain activation that directly compares active Acheulean tool-making and language. Using functional transcranial Doppler ultrasonography (fTCD), we measured brain blood flow lateralization patterns (hemodynamics) in subjects who performed two tasks designed to isolate the planning component of Acheulean stone tool-making and cued word generation as a language task. We show highly correlated hemodynamics in the initial 10 seconds of task execution. Stone tool-making and cued word generation cause common cerebral blood flow lateralization signatures in our participants. This is consistent with a shared neural substrate for prehistoric stone tool-making and language, and is compatible with language evolution theories that posit a co-evolution of language and manual praxis. In turn, our results support the hypothesis that aspects of language might have emerged as early as 1.75 million years ago, with the start of Acheulean technology.

The association between scalp hair-whorl direction, handedness and hemispheric language dominance: is there a common genetic basis of lateralization?

PubMed

Jansen, Andreas; Lohmann, Hubertus; Scharfe, Stefanie; Sehlmeyer, Christina; Deppe, Michael; Knecht, Stefan

2007-04-01

The hemispheres of the human brain are functionally asymmetric. The left hemisphere tends to be dominant for language and superior in the control of manual dexterity. The mechanisms underlying these asymmetries are not known. Genetic as well as environmental factors are discussed. Recently, atypical anticlockwise hair-whorl direction has been related to an increased probability for non-right-handedness and atypical hemispheric language dominance. These findings are fascinating and important since hair-whorl direction is a structural marker of lateralization and could provide a readily observable anatomical clue to functional brain lateralization. Based on data on handedness and hair-whorl direction, Amar Klar proposed a genetic model ("random-recessive model") in that a single gene with two alleles controls both handedness and hair-whorl orientation (Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 165, 269-276). The present study was designed to further investigate the relationship between scalp hair-whorl direction with handedness and hemispheric language dominance. 1212 subjects were investigated for scalp hair-whorl direction and handedness. Additionally, we determined hemispheric language dominance (as assessed by a word generation task) in a subgroup of 212 subjects using functional transcranial Doppler sonography (fTCD). As for the single attributes - hair-whorl direction, handedness, and language dominance - we reproduced previously published results. However, we found no association between hair-whorl direction and either language dominance or handedness. These results strongly argue against a common genetic basis of handedness or language lateralization with scalp hair-whorl direction. Inspection of hair patterns will not help us to determine language dominance.

Comparison of Ground-Based and Airborne Function Allocation Concepts for NextGen Using Human-In-The-Loop Simulations

NASA Technical Reports Server (NTRS)

Wing, David J.; Prevot, Thomas; Murdoch, Jennifer L.; Cabrall, Christopher D.; Homola, Jeffrey R.; Martin, Lynne H.; Mercer, Joey S.; Hoadley, Sherwood T.; Wilson, Sara R.; Hubbs, Clay E.;

Statistics of Shared Components in Complex Component Systems

NASA Astrophysics Data System (ADS)

Mazzolini, Andrea; Gherardi, Marco; Caselle, Michele; Cosentino Lagomarsino, Marco; Osella, Matteo

2018-04-01

Many complex systems are modular. Such systems can be represented as "component systems," i.e., sets of elementary components, such as LEGO bricks in LEGO sets. The bricks found in a LEGO set reflect a target architecture, which can be built following a set-specific list of instructions. In other component systems, instead, the underlying functional design and constraints are not obvious a priori, and their detection is often a challenge of both scientific and practical importance, requiring a clear understanding of component statistics. Importantly, some quantitative invariants appear to be common to many component systems, most notably a common broad distribution of component abundances, which often resembles the well-known Zipf's law. Such "laws" affect in a general and nontrivial way the component statistics, potentially hindering the identification of system-specific functional constraints or generative processes. Here, we specifically focus on the statistics of shared components, i.e., the distribution of the number of components shared by different system realizations, such as the common bricks found in different LEGO sets. To account for the effects of component heterogeneity, we consider a simple null model, which builds system realizations by random draws from a universe of possible components. Under general assumptions on abundance heterogeneity, we provide analytical estimates of component occurrence, which quantify exhaustively the statistics of shared components. Surprisingly, this simple null model can positively explain important features of empirical component-occurrence distributions obtained from large-scale data on bacterial genomes, LEGO sets, and book chapters. Specific architectural features and functional constraints can be detected from occurrence patterns as deviations from these null predictions, as we show for the illustrative case of the "core" genome in bacteria.

Predicting Gene Structure Changes Resulting from Genetic Variants via Exon Definition Features.

PubMed

Majoros, William H; Holt, Carson; Campbell, Michael S; Ware, Doreen; Yandell, Mark; Reddy, Timothy E

2018-04-25

Genetic variation that disrupts gene function by altering gene splicing between individuals can substantially influence traits and disease. In those cases, accurately predicting the effects of genetic variation on splicing can be highly valuable for investigating the mechanisms underlying those traits and diseases. While methods have been developed to generate high quality computational predictions of gene structures in reference genomes, the same methods perform poorly when used to predict the potentially deleterious effects of genetic changes that alter gene splicing between individuals. Underlying that discrepancy in predictive ability are the common assumptions by reference gene finding algorithms that genes are conserved, well-formed, and produce functional proteins. We describe a probabilistic approach for predicting recent changes to gene structure that may or may not conserve function. The model is applicable to both coding and noncoding genes, and can be trained on existing gene annotations without requiring curated examples of aberrant splicing. We apply this model to the problem of predicting altered splicing patterns in the genomes of individual humans, and we demonstrate that performing gene-structure prediction without relying on conserved coding features is feasible. The model predicts an unexpected abundance of variants that create de novo splice sites, an observation supported by both simulations and empirical data from RNA-seq experiments. While these de novo splice variants are commonly misinterpreted by other tools as coding or noncoding variants of little or no effect, we find that in some cases they can have large effects on splicing activity and protein products, and we propose that they may commonly act as cryptic factors in disease. The software is available from geneprediction.org/SGRF. bmajoros@duke.edu. Supplementary information is available at Bioinformatics online.

Optical Peaking Enhancement in High-Speed Ring Modulators

PubMed Central

Müller, J.; Merget, F.; Azadeh, S. Sharif; Hauck, J.; García, S. Romero; Shen, B.; Witzens, J.

2014-01-01

Ring resonator modulators (RRM) combine extreme compactness, low power consumption and wavelength division multiplexing functionality, making them a frontrunner for addressing the scalability requirements of short distance optical links. To extend data rates beyond the classically assumed bandwidth capability, we derive and experimentally verify closed form equations of the electro-optic response and asymmetric side band generation resulting from inherent transient time dynamics and leverage these to significantly improve device performance. An equivalent circuit description with a commonly used peaking amplifier model allows straightforward assessment of the effect on existing communication system architectures. A small signal analytical expression of peaking in the electro-optic response of RRMs is derived and used to extend the electro-optic bandwidth of the device above 40 GHz as well as to open eye diagrams penalized by intersymbol interference at 32, 40 and 44 Gbps. Predicted peaking and asymmetric side band generation are in excellent agreement with experiments. PMID:25209255

De novo active sites for resurrected Precambrian enzymes

NASA Astrophysics Data System (ADS)

Risso, Valeria A.; Martinez-Rodriguez, Sergio; Candel, Adela M.; Krüger, Dennis M.; Pantoja-Uceda, David; Ortega-Muñoz, Mariano; Santoyo-Gonzalez, Francisco; Gaucher, Eric A.; Kamerlin, Shina C. L.; Bruix, Marta; Gavira, Jose A.; Sanchez-Ruiz, Jose M.

2017-07-01

Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.

Evolution in the Cycles of Life.

PubMed

Bowman, John L; Sakakibara, Keiko; Furumizu, Chihiro; Dierschke, Tom

2016-11-23

The life cycles of eukaryotes alternate between haploid and diploid phases, which are initiated by meiosis and gamete fusion, respectively. In both ascomycete and basidiomycete fungi and chlorophyte algae, the haploid-to-diploid transition is regulated by a pair of paralogous homeodomain protein encoding genes. That a common genetic program controls the haploid-to-diploid transition in phylogenetically disparate eukaryotic lineages suggests this may be the ancestral function for homeodomain proteins. Multicellularity has evolved independently in many eukaryotic lineages in either one or both phases of the life cycle. Organisms, such as land plants, exhibiting a life cycle whereby multicellular bodies develop in both the haploid and diploid phases are often referred to as possessing an alternation of generations. We review recent progress on understanding the genetic basis for the land plant alternation of generations and highlight the roles that homeodomain-encoding genes may have played in the evolution of complex multicellularity in this lineage.

An Interpolation Method for Obtaining Thermodynamic Properties Near Saturated Liquid and Saturated Vapor Lines

NASA Technical Reports Server (NTRS)

Nguyen, Huy H.; Martin, Michael A.

2004-01-01

The two most common approaches used to formulate thermodynamic properties of pure substances are fundamental (or characteristic) equations of state (Helmholtz and Gibbs functions) and a piecemeal approach that is described in Adebiyi and Russell (1992). This paper neither presents a different method to formulate thermodynamic properties of pure substances nor validates the aforementioned approaches. Rather its purpose is to present a method to generate property tables from existing property packages and a method to facilitate the accurate interpretation of fluid thermodynamic property data from those tables. There are two parts to this paper. The first part of the paper shows how efficient and usable property tables were generated, with the minimum number of data points, using an aerospace industry standard property package. The second part describes an innovative interpolation technique that has been developed to properly obtain thermodynamic properties near the saturated liquid and saturated vapor lines.

The piriform, perirhinal, and entorhinal cortex in seizure generation

PubMed Central

Vismer, Marta S.; Forcelli, Patrick A.; Skopin, Mark D.; Gale, Karen; Koubeissi, Mohamad Z.

2015-01-01

Understanding neural network behavior is essential to shed light on epileptogenesis and seizure propagation. The interconnectivity and plasticity of mammalian limbic and neocortical brain regions provide the substrate for the hypersynchrony and hyperexcitability associated with seizure activity. Recurrent unprovoked seizures are the hallmark of epilepsy, and limbic epilepsy is the most common type of medically-intractable focal epilepsy in adolescents and adults that necessitates surgical evaluation. In this review, we describe the role and relationships among the piriform (PIRC), perirhinal (PRC), and entorhinal cortex (ERC) in seizure-generation and epilepsy. The inherent function, anatomy, and histological composition of these cortical regions are discussed. In addition, the neurotransmitters, intrinsic and extrinsic connections, and the interaction of these regions are described. Furthermore, we provide evidence based on clinical research and animal models that suggest that these cortical regions may act as key seizure-trigger zones and, even, epileptogenesis. PMID:26074779

BGen: A UML Behavior Network Generator Tool

NASA Technical Reports Server (NTRS)

Huntsberger, Terry; Reder, Leonard J.; Balian, Harry

2010-01-01

BGen software was designed for autogeneration of code based on a graphical representation of a behavior network used for controlling automatic vehicles. A common format used for describing a behavior network, such as that used in the JPL-developed behavior-based control system, CARACaS ["Control Architecture for Robotic Agent Command and Sensing" (NPO-43635), NASA Tech Briefs, Vol. 32, No. 10 (October 2008), page 40] includes a graph with sensory inputs flowing through the behaviors in order to generate the signals for the actuators that drive and steer the vehicle. A computer program to translate Unified Modeling Language (UML) Freeform Implementation Diagrams into a legacy C implementation of Behavior Network has been developed in order to simplify the development of C-code for behavior-based control systems. UML is a popular standard developed by the Object Management Group (OMG) to model software architectures graphically. The C implementation of a Behavior Network is functioning as a decision tree.

An ultraviolet-visible spectrophotometer automation system. Part 3: Program documentation

NASA Astrophysics Data System (ADS)

Roth, G. S.; Teuschler, J. M.; Budde, W. L.

1982-07-01

The Ultraviolet-Visible Spectrophotometer (UVVIS) automation system accomplishes 'on-line' spectrophotometric quality assurance determinations, report generations, plot generations and data reduction for chlorophyll or color analysis. This system also has the capability to process manually entered data for the analysis of chlorophyll or color. For each program of the UVVIS system, this document contains a program description, flowchart, variable dictionary, code listing, and symbol cross-reference table. Also included are descriptions of file structures and of routines common to all automated analyses. The programs are written in Data General extended BASIC, Revision 4.3, under the RDOS operating systems, Revision 6.2. The BASIC code has been enhanced for real-time data acquisition, which is accomplished by CALLS to assembly language subroutines. Two other related publications are 'An Ultraviolet-Visible Spectrophotometer Automation System - Part I Functional Specifications,' and 'An Ultraviolet-Visible Spectrophotometer Automation System - Part II User's Guide.'

Osmotic pressure induced tensile forces in tendon collagen

NASA Astrophysics Data System (ADS)

Masic, Admir; Bertinetti, Luca; Schuetz, Roman; Chang, Shu-Wei; Metzger, Till Hartmut; Buehler, Markus J.; Fratzl, Peter

2015-01-01

Water is an important component of collagen in tendons, but its role for the function of this load-carrying protein structure is poorly understood. Here we use a combination of multi-scale experimentation and computation to show that water is an integral part of the collagen molecule, which changes conformation upon water removal. The consequence is a shortening of the molecule that translates into tensile stresses in the range of several to almost 100 MPa, largely surpassing those of about 0.3 MPa generated by contractile muscles. Although a complete drying of collagen would be relevant for technical applications, such as the fabrication of leather or parchment, stresses comparable to muscle contraction already occur at small osmotic pressures common in biological environments. We suggest, therefore, that water-generated tensile stresses may play a role in living collagen-based materials such as tendon or bone.

Pearls and pitfalls in genetic studies of migraine.

PubMed

Eising, Else; de Vries, Boukje; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M

2013-06-01

Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

Toolsets for Airborne Data (TAD): Customized Data Merging Function

NASA Astrophysics Data System (ADS)

Benson, A.; Peeters, M. C.; Perez, J.; Parker, L.; Chen, G.

2013-12-01

NASA has conducted airborne tropospheric chemistry studies for about three decades. These field campaigns have generated a great wealth of observations, including a wide range of the trace gases and aerosol properties. The ASDC Toolset for Airborne Data (TAD) is being designed to meet the user community needs for manipulating aircraft data for scientific research on climate change and air quality relevant issues. Prior to the actual toolset development, a comprehensive metadata database was created to compensate for the absence of standardization of the ICARTT data format in which the data is stored. This database tracks the Principal Investigator-provided metadata, and links the measurement variables to a common naming system that was developed as a part of this project. This database is used by the data merging module. Most aircraft data reported during a single flight is not on a consistent time base and is difficult to intercompare. This module provides the user with the ability to merge original data measurements from multiple data providers into a specified time interval or common time base. The database development, common naming scheme and data merge module development will be presented.

Performance and Architecture Lab Modeling Tool

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

2014-06-19

Analytical application performance models are critical for diagnosing performance-limiting resources, optimizing systems, and designing machines. Creating models, however, is difficult. Furthermore, models are frequently expressed in forms that are hard to distribute and validate. The Performance and Architecture Lab Modeling tool, or Palm, is a modeling tool designed to make application modeling easier. Palm provides a source code modeling annotation language. Not only does the modeling language divide the modeling task into sub problems, it formally links an application's source code with its model. This link is important because a model's purpose is to capture application behavior. Furthermore, this linkmore » makes it possible to define rules for generating models according to source code organization. Palm generates hierarchical models according to well-defined rules. Given an application, a set of annotations, and a representative execution environment, Palm will generate the same model. A generated model is a an executable program whose constituent parts directly correspond to the modeled application. Palm generates models by combining top-down (human-provided) semantic insight with bottom-up static and dynamic analysis. A model's hierarchy is defined by static and dynamic source code structure. Because Palm coordinates models and source code, Palm's models are 'first-class' and reproducible. Palm automates common modeling tasks. For instance, Palm incorporates measurements to focus attention, represent constant behavior, and validate models. Palm's workflow is as follows. The workflow's input is source code annotated with Palm modeling annotations. The most important annotation models an instance of a block of code. Given annotated source code, the Palm Compiler produces executables and the Palm Monitor collects a representative performance profile. The Palm Generator synthesizes a model based on the static and dynamic mapping of annotations to program behavior. The model -- an executable program -- is a hierarchical composition of annotation functions, synthesized functions, statistics for runtime values, and performance measurements.« less

State Transition Matrix for Perturbed Orbital Motion Using Modified Chebyshev Picard Iteration

NASA Astrophysics Data System (ADS)

Read, Julie L.; Younes, Ahmad Bani; Macomber, Brent; Turner, James; Junkins, John L.

2015-06-01

The Modified Chebyshev Picard Iteration (MCPI) method has recently proven to be highly efficient for a given accuracy compared to several commonly adopted numerical integration methods, as a means to solve for perturbed orbital motion. This method utilizes Picard iteration, which generates a sequence of path approximations, and Chebyshev Polynomials, which are orthogonal and also enable both efficient and accurate function approximation. The nodes consistent with discrete Chebyshev orthogonality are generated using cosine sampling; this strategy also reduces the Runge effect and as a consequence of orthogonality, there is no matrix inversion required to find the basis function coefficients. The MCPI algorithms considered herein are parallel-structured so that they are immediately well-suited for massively parallel implementation with additional speedup. MCPI has a wide range of applications beyond ephemeris propagation, including the propagation of the State Transition Matrix (STM) for perturbed two-body motion. A solution is achieved for a spherical harmonic series representation of earth gravity (EGM2008), although the methodology is suitable for application to any gravity model. Included in this representation the normalized, Associated Legendre Functions are given and verified numerically. Modifications of the classical algorithm techniques, such as rewriting the STM equations in a second-order cascade formulation, gives rise to additional speedup. Timing results for the baseline formulation and this second-order formulation are given.

Trypanosome RNA Editing Mediator Complex proteins have distinct functions in gRNA utilization.

PubMed

Simpson, Rachel M; Bruno, Andrew E; Chen, Runpu; Lott, Kaylen; Tylec, Brianna L; Bard, Jonathan E; Sun, Yijun; Buck, Michael J; Read, Laurie K

2017-07-27

Uridine insertion/deletion RNA editing is an essential process in kinetoplastid parasites whereby mitochondrial mRNAs are modified through the specific insertion and deletion of uridines to generate functional open reading frames, many of which encode components of the mitochondrial respiratory chain. The roles of numerous non-enzymatic editing factors have remained opaque given the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus roles of individual proteins. Here, we examined whole populations of partially edited sequences using high throughput sequencing and a novel bioinformatic platform, the Trypanosome RNA Editing Alignment Tool (TREAT), to elucidate the roles of three proteins in the RNA Editing Mediator Complex (REMC). We determined that the factors examined function in the progression of editing through a gRNA; however, they have distinct roles and REMC is likely heterogeneous in composition. We provide the first evidence that editing can proceed through numerous paths within a single gRNA and that non-linear modifications are essential, generating commonly observed junction regions. Our data support a model in which RNA editing is executed via multiple paths that necessitate successive re-modification of junction regions facilitated, in part, by the REMC variant containing TbRGG2 and MRB8180. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Expert system development for commonality analysis in space programs

NASA Technical Reports Server (NTRS)

Yeager, Dorian P.

1987-01-01

This report is a combination of foundational mathematics and software design. A mathematical model of the Commonality Analysis problem was developed and some important properties discovered. The complexity of the problem is described herein and techniques, both deterministic and heuristic, for reducing that complexity are presented. Weaknesses are pointed out in the existing software (System Commonality Analysis Tool) and several improvements are recommended. It is recommended that: (1) an expert system for guiding the design of new databases be developed; (2) a distributed knowledge base be created and maintained for the purpose of encoding the commonality relationships between design items in commonality databases; (3) a software module be produced which automatically generates commonality alternative sets from commonality databases using the knowledge associated with those databases; and (4) a more complete commonality analysis module be written which is capable of generating any type of feasible solution.

Computational and informatics strategies for identification of specific protein interaction partners in affinity purification mass spectrometry experiments

PubMed Central

Nesvizhskii, Alexey I.

2013-01-01

Analysis of protein interaction networks and protein complexes using affinity purification and mass spectrometry (AP/MS) is among most commonly used and successful applications of proteomics technologies. One of the foremost challenges of AP/MS data is a large number of false positive protein interactions present in unfiltered datasets. Here we review computational and informatics strategies for detecting specific protein interaction partners in AP/MS experiments, with a focus on incomplete (as opposite to genome-wide) interactome mapping studies. These strategies range from standard statistical approaches, to empirical scoring schemes optimized for a particular type of data, to advanced computational frameworks. The common denominator among these methods is the use of label-free quantitative information such as spectral counts or integrated peptide intensities that can be extracted from AP/MS data. We also discuss related issues such as combining multiple biological or technical replicates, and dealing with data generated using different tagging strategies. Computational approaches for benchmarking of scoring methods are discussed, and the need for generation of reference AP/MS datasets is highlighted. Finally, we discuss the possibility of more extended modeling of experimental AP/MS data, including integration with external information such as protein interaction predictions based on functional genomics data. PMID:22611043

Lay perspectives on the social and psychological functions of heroes

PubMed Central

Kinsella, Elaine L.; Ritchie, Timothy D.; Igou, Eric R.

2015-01-01

Declaring and thinking about heroes are common human preoccupations but surprisingly aspects of heroism that reinforce these behaviors are not well-understood. In four thematically consistent studies, we attempt to identify lay perspectives about the psychological functions served by heroes. In Study 1, participants (n = 189) freely generated open-ended descriptions of hero functions, which were then sorted by independent coders into 14 categories (e.g., instill hope, guide others). In Study 2, in an attempt to identify the most important functions associated with heroes, participants (n = 249) rated how each function corresponded with their personal views about heroes. Results from a confirmatory factor analysis suggested that a three-factor model of hero functions fit the data well: participants thought that heroes enhanced the lives of others, promoted morals, and protected individuals from threats. In Study 3 (n = 242), participants rated heroes as more likely to fulfill a protecting function than either leaders or role models. In Studies 4A (n = 38) and 4B (n = 102), participants indicated that thinking about a hero (relative to a leader or an acquaintance) during psychological threat fulfilled personal enhancement, moral modeling, and protection needs. In all, these findings provide an empirical basis to spur additional research about the social and psychological functions that heroes offer. PMID:25741302

Lay perspectives on the social and psychological functions of heroes.

PubMed

Kinsella, Elaine L; Ritchie, Timothy D; Igou, Eric R

2015-01-01

Declaring and thinking about heroes are common human preoccupations but surprisingly aspects of heroism that reinforce these behaviors are not well-understood. In four thematically consistent studies, we attempt to identify lay perspectives about the psychological functions served by heroes. In Study 1, participants (n = 189) freely generated open-ended descriptions of hero functions, which were then sorted by independent coders into 14 categories (e.g., instill hope, guide others). In Study 2, in an attempt to identify the most important functions associated with heroes, participants (n = 249) rated how each function corresponded with their personal views about heroes. Results from a confirmatory factor analysis suggested that a three-factor model of hero functions fit the data well: participants thought that heroes enhanced the lives of others, promoted morals, and protected individuals from threats. In Study 3 (n = 242), participants rated heroes as more likely to fulfill a protecting function than either leaders or role models. In Studies 4A (n = 38) and 4B (n = 102), participants indicated that thinking about a hero (relative to a leader or an acquaintance) during psychological threat fulfilled personal enhancement, moral modeling, and protection needs. In all, these findings provide an empirical basis to spur additional research about the social and psychological functions that heroes offer.

Human germline and pan-cancer variomes and their distinct functional profiles

PubMed Central

Pan, Yang; Karagiannis, Konstantinos; Zhang, Haichen; Dingerdissen, Hayley; Shamsaddini, Amirhossein; Wan, Quan; Simonyan, Vahan; Mazumder, Raja

2014-01-01

Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 549 variations that significantly affect 10 major functional sites. Furthermore, we found distinct patterns of site disruptions due to germline and somatic nsSNVs. Pan-cancer analysis across 12 different cancer types led to the identification of 51 genes with 106 nsSNV affected functional sites found in 3 or more cancer types. 13 of the 51 genes overlap with previously identified Significantly Mutated Genes (Nature. 2013 Oct 17;502(7471)). 62 mutations in these 13 genes affecting functional sites such as DNA, ATP binding and various PTM sites occur across several cancers and can be prioritized for additional validation and investigations. PMID:25232094

Advances in Parallelization for Large Scale Oct-Tree Mesh Generation

NASA Technical Reports Server (NTRS)

O'Connell, Matthew; Karman, Steve L.

2015-01-01

Despite great advancements in the parallelization of numerical simulation codes over the last 20 years, it is still common to perform grid generation in serial. Generating large scale grids in serial often requires using special "grid generation" compute machines that can have more than ten times the memory of average machines. While some parallel mesh generation techniques have been proposed, generating very large meshes for LES or aeroacoustic simulations is still a challenging problem. An automated method for the parallel generation of very large scale off-body hierarchical meshes is presented here. This work enables large scale parallel generation of off-body meshes by using a novel combination of parallel grid generation techniques and a hybrid "top down" and "bottom up" oct-tree method. Meshes are generated using hardware commonly found in parallel compute clusters. The capability to generate very large meshes is demonstrated by the generation of off-body meshes surrounding complex aerospace geometries. Results are shown including a one billion cell mesh generated around a Predator Unmanned Aerial Vehicle geometry, which was generated on 64 processors in under 45 minutes.

Studies of aggregated nanoparticles steering during magnetic-guided drug delivery in the blood vessels

NASA Astrophysics Data System (ADS)

Hoshiar, Ali Kafash; Le, Tuan-Anh; Amin, Faiz Ul; Kim, Myeong Ok; Yoon, Jungwon

2017-04-01

Magnetic-guided targeted drug delivery (TDD) systems can enhance the treatment of diverse diseases. Despite the potential and promising results of nanoparticles, aggregation prevents precise particle guidance in the vasculature. In this study, we developed a simulation platform to investigate aggregation during steering of nanoparticles using a magnetic field function. The magnetic field function (MFF) comprises a positive and negative pulsed magnetic field generated by electromagnetic coils, which prevents adherence of particles to the vessel wall during magnetic guidance. A commonly used Y-shaped vessel was simulated and the performance of the MFF analyzed; the experimental data were in agreement with the simulation results. Moreover, the effects of various parameters on magnetic guidance were evaluated and the most influential identified. The simulation results presented herein will facilitate more precise guidance of nanoparticles in vivo.

Optimal population size and endogenous growth.

PubMed

Palivos, T; Yip, C K

1993-01-01

"Many applications in economics require the selection of an objective function which enables the comparison of allocations involving different population sizes. The two most commonly used criteria are the Benthamite and the Millian welfare functions, also known as classical and average utilitarianism, respectively. The former maximizes total utility of the society and thus represents individuals, while the latter maximizes average utility and so represents generations. Edgeworth (1925) was the first to conjecture, that the Benthamite principle leads to a larger population size and a lower standard of living.... The purpose of this paper is to examine Edgeworth's conjecture in an endogenous growth framework in which there are interactions between output and population growth rates. It is shown that, under conditions that ensure an optimum, the Benthamite criterion leads to smaller population and higher output growth rates than the Millian." excerpt

Migration of legacy mumps applications to relational database servers.

PubMed

O'Kane, K C

2001-07-01

An extended implementation of the Mumps language is described that facilitates vendor neutral migration of legacy Mumps applications to SQL-based relational database servers. Implemented as a compiler, this system translates Mumps programs to operating system independent, standard C code for subsequent compilation to fully stand-alone, binary executables. Added built-in functions and support modules extend the native hierarchical Mumps database with access to industry standard, networked, relational database management servers (RDBMS) thus freeing Mumps applications from dependence upon vendor specific, proprietary, unstandardized database models. Unlike Mumps systems that have added captive, proprietary RDMBS access, the programs generated by this development environment can be used with any RDBMS system that supports common network access protocols. Additional features include a built-in web server interface and the ability to interoperate directly with programs and functions written in other languages.

Following in Real Time the Two-Step Assembly of Nanoparticles into Mesocrystals in Levitating Drops.

PubMed

Agthe, Michael; Plivelic, Tomás S; Labrador, Ana; Bergström, Lennart; Salazar-Alvarez, German

2016-11-09

Mesocrystals composed of crystallographically aligned nanocrystals are present in biominerals and assembled materials which show strongly directional properties of importance for mechanical protection and functional devices. Mesocrystals are commonly formed by complex biomineralization processes and can also be generated by assembly of anisotropic nanocrystals. Here, we follow the evaporation-induced assembly of maghemite nanocubes into mesocrystals in real time in levitating drops. Analysis of time-resolved small-angle X-ray scattering data and ex situ scanning electron microscopy together with interparticle potential calculations show that the substrate-free, particle-mediated crystallization process proceeds in two stages involving the formation and rapid transformation of a dense, structurally disordered phase into ordered mesocrystals. Controlling and tailoring the particle-mediated formation of mesocrystals could be utilized to assemble designed nanoparticles into new materials with unique functions.

The Highly Adaptive Lasso Estimator

PubMed Central

Benkeser, David; van der Laan, Mark

2017-01-01

Estimation of a regression functions is a common goal of statistical learning. We propose a novel nonparametric regression estimator that, in contrast to many existing methods, does not rely on local smoothness assumptions nor is it constructed using local smoothing techniques. Instead, our estimator respects global smoothness constraints by virtue of falling in a class of right-hand continuous functions with left-hand limits that have variation norm bounded by a constant. Using empirical process theory, we establish a fast minimal rate of convergence of our proposed estimator and illustrate how such an estimator can be constructed using standard software. In simulations, we show that the finite-sample performance of our estimator is competitive with other popular machine learning techniques across a variety of data generating mechanisms. We also illustrate competitive performance in real data examples using several publicly available data sets. PMID:29094111

A trait-based approach for examining microbial community assembly

NASA Astrophysics Data System (ADS)

Prest, T. L.; Nemergut, D.

2015-12-01

Microorganisms regulate all of Earth's major biogeochemical cycles and an understanding of how microbial communities assemble is a key part in evaluating controls over many types of ecosystem processes. Rapid advances in technology and bioinformatics have led to a better appreciation for the variation in microbial community structure in time and space. Yet, advances in theory are necessary to make sense of these data and allow us to generate unifying hypotheses about the causes and consequences of patterns in microbial biodiversity and what they mean for ecosystem function. Here, I will present a metaanalysis of microbial community assembly from a variety of successional and post-disturbance systems. Our analysis shows various distinct patterns in community assembly, and the potential importance of nutrients and dispersal in shaping microbial community beta diversity in these systems. We also used a trait-based approach to generate hypotheses about the mechanisms driving patterns of microbial community assembly and the implications for function. Our work reveals the importance of rRNA operon copy number as a community aggregated trait in helping to reconcile differences in community dynamics between distinct types of successional and disturbed systems. Specifically, our results demonstrate that decreases in average copy number can be a common feature of communities across various drivers of ecological succession, supporting a transition from an r-selected to a K-selected community. Importantly, our work supports the scaling of the copy number trait over multiple levels of biological organization, from cells to populations and communities, and has implications for both ecology and evolution. Trait-based approaches are an important next step to generate and test hypotheses about the forces structuring microbial communities and the subsequent consequences for ecosystem function.

R package to estimate intracluster correlation coefficient with confidence interval for binary data.

PubMed

Chakraborty, Hrishikesh; Hossain, Akhtar

2018-03-01

The Intracluster Correlation Coefficient (ICC) is a major parameter of interest in cluster randomized trials that measures the degree to which responses within the same cluster are correlated. There are several types of ICC estimators and its confidence intervals (CI) suggested in the literature for binary data. Studies have compared relative weaknesses and advantages of ICC estimators as well as its CI for binary data and suggested situations where one is advantageous in practical research. The commonly used statistical computing systems currently facilitate estimation of only a very few variants of ICC and its CI. To address the limitations of current statistical packages, we developed an R package, ICCbin, to facilitate estimating ICC and its CI for binary responses using different methods. The ICCbin package is designed to provide estimates of ICC in 16 different ways including analysis of variance methods, moments based estimation, direct probabilistic methods, correlation based estimation, and resampling method. CI of ICC is estimated using 5 different methods. It also generates cluster binary data using exchangeable correlation structure. ICCbin package provides two functions for users. The function rcbin() generates cluster binary data and the function iccbin() estimates ICC and it's CI. The users can choose appropriate ICC and its CI estimate from the wide selection of estimates from the outputs. The R package ICCbin presents very flexible and easy to use ways to generate cluster binary data and to estimate ICC and it's CI for binary response using different methods. The package ICCbin is freely available for use with R from the CRAN repository (https://cran.r-project.org/package=ICCbin). We believe that this package can be a very useful tool for researchers to design cluster randomized trials with binary outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatial prediction of near surface soil water retention functions using hydrogeophysics and empirical orthogonal functions

NASA Astrophysics Data System (ADS)

Gibson, Justin; Franz, Trenton E.

2018-06-01

The hydrological community often turns to widely available spatial datasets such as the NRCS Soil Survey Geographic database (SSURGO) to characterize the spatial variability of soil properties. When used to spatially characterize and parameterize watershed models, this has served as a reasonable first approximation when lacking localized or incomplete soil data. Within agriculture, soil data has been left relatively coarse when compared to numerous other data sources measured. This is because localized soil sampling is both expensive and time intense, thus a need exists in better connecting spatial datasets with ground observations. Given that hydrogeophysics is data-dense, rapid, non-invasive, and relatively easy to adopt, it is a promising technique to help dovetail localized soil sampling with spatially exhaustive datasets. In this work, we utilize two common near surface geophysical methods, cosmic-ray neutron probe and electromagnetic induction, to identify temporally stable spatial patterns of measured geophysical properties in three 65 ha agricultural fields in western Nebraska. This is achieved by repeat geophysical observations of the same study area across a range of wet to dry field conditions in order to evaluate with an empirical orthogonal function. Shallow cores were then extracted within each identified zone and water retention functions were generated in the laboratory. Using EOF patterns as a covariate, we quantify the predictive skill of estimating soil hydraulic properties in areas without measurement using a bootstrap validation analysis. Results indicate that sampling locations informed via repeat hydrogeophysical surveys, required only five cores to reduce the cross-validation root mean squared error by an average of 64% as compared to soil parameters predicted by a commonly used benchmark, SSURGO and ROSETTA. The reduction to five strategically located samples within the 65 ha fields reduces sampling efforts by up to ∼90% as compared to the common practice of soil grid sampling every 1 ha.

An agent-oriented approach to automated mission operations

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Odubiyi, Jide

1994-01-01

As we plan for the next generation of Mission Operations Control Center (MOCC) systems, there are many opportunities for the increased utilization of innovative knowledge-based technologies. The innovative technology discussed is an advanced use of agent-oriented approaches to the automation of mission operations. The paper presents an overview of this technology and discusses applied operational scenarios currently being investigated and prototyped. A major focus of the current work is the development of a simple user mechanism that would empower operations staff members to create, in real time, software agents to assist them in common, labor intensive operations tasks. These operational tasks would include: handling routine data and information management functions; amplifying the capabilities of a spacecraft analyst/operator to rapidly identify, analyze, and correct spacecraft anomalies by correlating complex data/information sets and filtering error messages; improving routine monitoring and trend analysis by detecting common failure signatures; and serving as a sentinel for spacecraft changes during critical maneuvers enhancing the system's capabilities to support nonroutine operational conditions with minimum additional staff. An agent-based testbed is under development. This testbed will allow us to: (1) more clearly understand the intricacies of applying agent-based technology in support of the advanced automation of mission operations and (2) access the full set of benefits that can be realized by the proper application of agent-oriented technology in a mission operations environment. The testbed under development addresses some of the data management and report generation functions for the Explorer Platform (EP)/Extreme UltraViolet Explorer (EUVE) Flight Operations Team (FOT). We present an overview of agent-oriented technology and a detailed report on the operation's concept for the testbed.

High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli.

PubMed

Zhao, Min; Qu, Hong

2011-11-30

The phylogenetic profile is widely used to characterize functional linkage and conservation between proteins without amino acid sequence similarity. To survey the conservative regulatory properties of rate-limiting enzymes (RLEs) in metabolic inhibitory network across different species, we define the enzyme inhibiting pair as: where the first enzyme in a pair is the inhibitor provider and the second is the target of the inhibitor. Phylogenetic profiles of enzymes in the inhibiting pairs are further generated to measure the functional linkage of these enzymes during evolutionary history. We find that the RLEs generate, on average, over half of all in vivo inhibitors in each surveyed model organism. And these inhibitors inhibit on average over 85% targets in metabolic inhibitory network and cover the majority of targets of cross-pathway inhibiting relations. Furthermore, we demonstrate that the phylogenetic profiles of the enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often show higher similarities than those in common inhibiting enzyme pairs. In addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP instead of AMP in conservative inhibitory networks. Combined with the conservative roles of RLEs in their efficiency in sensing metabolic signals and transmitting regulatory signals to the rest of the metabolic system, the RLEs may be important molecules in balancing energy homeostasis via maintaining the ratio of ATP to ADP in living cells. Furthermore, our results indicate that similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs are not only correlated with enzyme topological importance, but also related with roles of the enzymes in metabolic inhibitory network.

High similarity of phylogenetic profiles of rate-limiting enzymes with inhibitory relation in Human, Mouse, Rat, budding Yeast and E. coli

PubMed Central

2011-01-01

Background The phylogenetic profile is widely used to characterize functional linkage and conservation between proteins without amino acid sequence similarity. To survey the conservative regulatory properties of rate-limiting enzymes (RLEs) in metabolic inhibitory network across different species, we define the enzyme inhibiting pair as: where the first enzyme in a pair is the inhibitor provider and the second is the target of the inhibitor. Phylogenetic profiles of enzymes in the inhibiting pairs are further generated to measure the functional linkage of these enzymes during evolutionary history. Results We find that the RLEs generate, on average, over half of all in vivo inhibitors in each surveyed model organism. And these inhibitors inhibit on average over 85% targets in metabolic inhibitory network and cover the majority of targets of cross-pathway inhibiting relations. Furthermore, we demonstrate that the phylogenetic profiles of the enzymes in inhibiting pairs in which at least one enzyme is rate-limiting often show higher similarities than those in common inhibiting enzyme pairs. In addition, RLEs, compared to common metabolic enzymes, often tend to produce ADP instead of AMP in conservative inhibitory networks. Conclusions Combined with the conservative roles of RLEs in their efficiency in sensing metabolic signals and transmitting regulatory signals to the rest of the metabolic system, the RLEs may be important molecules in balancing energy homeostasis via maintaining the ratio of ATP to ADP in living cells. Furthermore, our results indicate that similarities of phylogenetic profiles of enzymes in the inhibiting enzyme pairs are not only correlated with enzyme topological importance, but also related with roles of the enzymes in metabolic inhibitory network. PMID:22369203

Observation of Neutron Skyshine from an Accelerator Based Neutron Source

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

Franklyn, C. B.

2011-12-13

A key feature of neutron based interrogation systems is the need for adequate provision of shielding around the facility. Accelerator facilities adapted for fast neutron generation are not necessarily suitably equipped to ensure complete containment of the vast quantity of neutrons generated, typically >10{sup 11} n{center_dot}s{sup -1}. Simulating the neutron leakage from a facility is not a simple exercise since the energy and directional distribution can only be approximated. Although adequate horizontal, planar shielding provision is made for a neutron generator facility, it is sometimes the case that vertical shielding is minimized, due to structural and economic constraints. It ismore » further justified by assuming the atmosphere above a facility functions as an adequate radiation shield. It has become apparent that multiple neutron scattering within the atmosphere can result in a measurable dose of neutrons reaching ground level some distance from a facility, an effect commonly known as skyshine. This paper describes a neutron detection system developed to monitor neutrons detected several hundred metres from a neutron source due to the effect of skyshine.« less

[Patient reported outcome of tyrosine kinase inhibitor related side effects and their impact on daily life in Chinese patients with chronic myeloid leukemia in the chronic phase].

PubMed

Yu, L; Wang, H B; Jiang, Q

2016-11-14

Objective: To explore the impact of patient reported outcome of tyrosine kinase inhibitor (TKI) related side effects on daily life in Chinese patients with chronic myeloid leukemia (CML) in the chronic phase (CP). Methods: From May to November in 2014, anonymous questionnaires were distributed to adult CML patients who were receiving TKI treatment in China. The impact of TKI-related side effects on daily life were assessed by the score of 1 (no impact) to 5 (high impact) from patient self-report. Results: Data from 731 respondents in the CP who reported the score of the impact of TKI-related side effects on daily life were collected. 407 (56%) were male. The median age was 41 years (range, 18 to 88 years). 560 (77%) started TKI treatment within 1 year after diagnosis. With a median treatment duration of 3 years (range, <1 to 13 years), 549 (75% ) respondents achieved a complete cytogenetic response (CCyR) and 301 (41%) achieved a complete molecular response (CMR). The most common TKI-related adverse effects were edema ( n =323, 44% ), fatigue ( n =277, 38% ), gastrointestinal disorders ( n =235, 32% ), skin color changes ( n =142, 19% ), muscle cramps ( n =137, 19% ), rash ( n =105, 14% ), hepatic function abnormalities ( n =91, 12%), weight gain ( n =86, 12%), and cytopenia ( n =59, 8%). Multivariate analyses showed that TKI treatment duration <4 years was the factor associated with fatigue; Edema was more observed in female, ≥40 years old and use of 1st generation TKI; Gastrointestinal disorders in use of 1st generation TKI; Hepatic function abnormalities and rash in use of 2nd generation TKI; Weight gain in female; Muscle cramps in long-term interval from diagnosis to therapy and use of 1st generation TKI; Low blood counts in use of generic TKI. There was no impact of TKI-related side effects on daily life in 218 (30%)respondents (1 score). 375 (51%)respondents reported their daily life were slightly or moderately decreased (2 or 3 score), while 138 (19%) significantly decreased (4 or 5 score). Multivariate analyses showed that female, ≥40 years old, use of generic TKI, TKI treatment duration <4 years were factors associated with negative effect on their daily life. When taking TKI related side-effects into considderation, secondary school and below, use of generic TKI, TKI treatment duration <4 years, edema, fatigue, gastrointestinal disorders, skin color changes, rash and hepatic function abnormalities, were factors associated with negative effect on their daily life. Conclusion: Edema, fatigue, gastrointestinal disorders, rash, skin color changes and hepatic function abnormalities were common TKI-related side effects and influenced CML patients' daily life in China. In addition, female, older age, lower education level, use of generic TKI and shorter TKI treatment duration were associated with negative impact on quality of life.

GO-based functional dissimilarity of gene sets.

PubMed

Díaz-Díaz, Norberto; Aguilar-Ruiz, Jesús S

2011-09-01

The Gene Ontology (GO) provides a controlled vocabulary for describing the functions of genes and can be used to evaluate the functional coherence of gene sets. Many functional coherence measures consider each pair of gene functions in a set and produce an output based on all pairwise distances. A single gene can encode multiple proteins that may differ in function. For each functionality, other proteins that exhibit the same activity may also participate. Therefore, an identification of the most common function for all of the genes involved in a biological process is important in evaluating the functional similarity of groups of genes and a quantification of functional coherence can helps to clarify the role of a group of genes working together. To implement this approach to functional assessment, we present GFD (GO-based Functional Dissimilarity), a novel dissimilarity measure for evaluating groups of genes based on the most relevant functions of the whole set. The measure assigns a numerical value to the gene set for each of the three GO sub-ontologies. Results show that GFD performs robustly when applied to gene set of known functionality (extracted from KEGG). It performs particularly well on randomly generated gene sets. An ROC analysis reveals that the performance of GFD in evaluating the functional dissimilarity of gene sets is very satisfactory. A comparative analysis against other functional measures, such as GS2 and those presented by Resnik and Wang, also demonstrates the robustness of GFD.

Intersecting transcriptomic profiling technologies and long non-coding RNA function in lung adenocarcinoma: discovery, mechanisms, and therapeutic applications

PubMed Central

Castillo, Jonathan; Stueve, Theresa R.; Marconett, Crystal N.

2017-01-01

Previously thought of as junk transcripts and pseudogene remnants, long non-coding RNAs (lncRNAs) have come into their own over the last decade as an essential component of cellular activity, regulating a plethora of functions within multicellular organisms. lncRNAs are now known to participate in development, cellular homeostasis, immunological processes, and the development of disease. With the advent of next generation sequencing technology, hundreds of thousands of lncRNAs have been identified. However, movement beyond mere discovery to the understanding of molecular processes has been stymied by the complicated genomic structure, tissue-restricted expression, and diverse regulatory roles lncRNAs play. In this review, we will focus on lncRNAs involved in lung cancer, the most common cause of cancer-related death in the United States and worldwide. We will summarize their various methods of discovery, provide consensus rankings of deregulated lncRNAs in lung cancer, and describe in detail the limited functional analysis that has been undertaken so far. PMID:29113413

Calcium signaling in smooth muscle.

PubMed

Hill-Eubanks, David C; Werner, Matthias E; Heppner, Thomas J; Nelson, Mark T

2011-09-01

Changes in intracellular Ca(2+) are central to the function of smooth muscle, which lines the walls of all hollow organs. These changes take a variety of forms, from sustained, cell-wide increases to temporally varying, localized changes. The nature of the Ca(2+) signal is a reflection of the source of Ca(2+) (extracellular or intracellular) and the molecular entity responsible for generating it. Depending on the specific channel involved and the detection technology employed, extracellular Ca(2+) entry may be detected optically as graded elevations in intracellular Ca(2+), junctional Ca(2+) transients, Ca(2+) flashes, or Ca(2+) sparklets, whereas release of Ca(2+) from intracellular stores may manifest as Ca(2+) sparks, Ca(2+) puffs, or Ca(2+) waves. These diverse Ca(2+) signals collectively regulate a variety of functions. Some functions, such as contractility, are unique to smooth muscle; others are common to other excitable cells (e.g., modulation of membrane potential) and nonexcitable cells (e.g., regulation of gene expression).

Functional expression and characterization of recombinant NADPH-P450 reductase from Malassezia globosa.

PubMed

Lee, Hwayoun; Park, Hyoung-Goo; Lim, Young-Ran; Lee, Im-Soon; Kim, Beom Joon; Seong, Cheul-Hun; Chun, Young-Jin; Kim, Donghak

2012-01-01

Malassezia globosa is a common pathogenic fungus that causes skin diseases including dandruff and seborrheic dermatitis in humans. Analysis of its genome identified a gene (MGL_1677) coding for a putative NADPH-P450 reductase (NPR) to support the fungal cytochrome P450 enzymes. The heterologously expressed recombinant M. globosa NPR protein was purified, and its functional features were characterized. The purified protein generated a single band on SDS-PAGE at 80.74 kDa and had an absorption maximum at 452 nm, indicating its possible function as an oxidized flavin cofactor. It evidenced NADPH-dependent reducing activity for cytochrome c or nitroblue tetrazolium. Human P450 1A2 and 2A6 were able to successfully catalyze the O-deethylation of 7- ethoxyresorufin and the 7-hydroxylation of coumarin, respectively, with the support of the purified NPR. These results demonstrate that purified NPR is an orthologous reductase protein that supports cytochrome P450 enzymes in M. globosa.

Nonconvex Sparse Logistic Regression With Weakly Convex Regularization

NASA Astrophysics Data System (ADS)

Shen, Xinyue; Gu, Yuantao

2018-06-01

In this work we propose to fit a sparse logistic regression model by a weakly convex regularized nonconvex optimization problem. The idea is based on the finding that a weakly convex function as an approximation of the $\\ell_0$ pseudo norm is able to better induce sparsity than the commonly used $\\ell_1$ norm. For a class of weakly convex sparsity inducing functions, we prove the nonconvexity of the corresponding sparse logistic regression problem, and study its local optimality conditions and the choice of the regularization parameter to exclude trivial solutions. Despite the nonconvexity, a method based on proximal gradient descent is used to solve the general weakly convex sparse logistic regression, and its convergence behavior is studied theoretically. Then the general framework is applied to a specific weakly convex function, and a necessary and sufficient local optimality condition is provided. The solution method is instantiated in this case as an iterative firm-shrinkage algorithm, and its effectiveness is demonstrated in numerical experiments by both randomly generated and real datasets.

Computational Studies of pH Sensing Design Principles in Proteins

NASA Astrophysics Data System (ADS)

Garrido Ruiz, Diego

Changes in pH are important regulatory signals for biological function, under physiological and pathological conditions. Recent advances in computer simulations strategies have made the exploration of the effects of charge titrations on protein function possible. In this work, I make use of these strategies to investigate the thermodynamic coupling between conformation and protonation states that give rise to pH-dependent function. As motivation for the rest of the work, I start by presenting a collaborative investigation on a pH-sensing mutant of the EGFR tyrosine kinase common to a set of distinct cancers. From then, I reduce the complexity of the systems under study to build models where exact enumeration of states is possible to inquire about the nature of the couplings between protonation states and conformation. Finally, I discuss detailed simulations of pH-sensing proteins for which I use the expectations and insights generated with simple models to identify and interpret couplings of interest for pH-dependent behavior.

The transcription factors Thpok and LRF are necessary and partly redundant for T helper cell differentiation

PubMed Central

Carpenter, Andrea C.; Grainger, John R.; Xiong, Yumei; Kanno, Yuka; Chu, H. Hamlet; Wang, Lie; Naik, Shruti; dos Santos, Liliane; Wei, Lai; Jenkins, Marc K.; O’Shea, John J.; Belkaid, Yasmine; Bosselut, Rémy

2014-01-01

Summary T helper (Th) cells are critical for defenses against infection and recognize peptides bound to Class II Major Histocompatibility Complex (MHC-II) molecules. Although transcription factors have been identified that direct helper cells into specific effector fates, whether a ‘master’ regulator controls the developmental program common to all Th cells remains unclear. Here we showed that the two transcription factors Thpok and LRF share this function. Although disruption of both factors did not prevent the generation of MHC II-specific T cells, these cells failed to express Th cell genes or undergo Th cell differentiation in vivo. In contrast, T cells lacking Thpok only displayed LRF-dependent functions and contributed to multiple effector responses, both in vitro and in vivo, with the notable exception of Th2 cell responses that control extra-cellular parasites. These findings identify the Thpok-LRF pair as a core node of Th cell differentiation and function. PMID:23041065

Characterizing visible and invisible cell wall mutant phenotypes.

PubMed

Carpita, Nicholas C; McCann, Maureen C

2015-07-01

About 10% of a plant's genome is devoted to generating the protein machinery to synthesize, remodel, and deconstruct the cell wall. High-throughput genome sequencing technologies have enabled a reasonably complete inventory of wall-related genes that can be assembled into families of common evolutionary origin. Assigning function to each gene family member has been aided immensely by identification of mutants with visible phenotypes or by chemical and spectroscopic analysis of mutants with 'invisible' phenotypes of modified cell wall composition and architecture that do not otherwise affect plant growth or development. This review connects the inference of gene function on the basis of deviation from the wild type in genetic functional analyses to insights provided by modern analytical techniques that have brought us ever closer to elucidating the sequence structures of the major polysaccharide components of the plant cell wall. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effective Design of Multifunctional Peptides by Combining Compatible Functions

PubMed Central

Diener, Christian; Garza Ramos Martínez, Georgina; Moreno Blas, Daniel; Castillo González, David A.; Corzo, Gerardo; Castro-Obregon, Susana; Del Rio, Gabriel

2016-01-01

Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf. PMID:27096600

Executive Functions and Adaptive Behaviour in Autism Spectrum Disorders with and without Intellectual Disability

PubMed Central

Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Genitori D'Arrigo, Valentina; Elia, Maurizio

2014-01-01

Executive functions (EF) in autism spectrum disorders (ASD) have been often investigated, although results seem to be rather inconsistent. The first aim of this study was to detect which EF components are common to the ASD continuum (from high- to low-functioning ASD) and identify a possible EF profile for ASD people. Planning, mental flexibility, inhibition of response, generativity, and ecologic EF were investigated. This study was extended not only to high-functioning ASD, but also to ASD with intellectual disability (ID). The second aim was to find EF aspects correlating with adaptive skills in ASD. A total of 61 children participated in the study (27 ASD with and without ID and 34 controls). Results highlight an executive profile characterised by impaired flexibility and deficient planning; these deficits are associated with decreased adaptive ability, particularly socialization, and a deficient shifting in ecologic conditions. These features are present in all ASD subgroups with and without ID; for this reason, they might be assumed as being specific features in ASD. PMID:24829905

Identification and characterization of novel NuMA isoforms

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

Wu, Jin, E-mail: petersdu2112@hotmail.com; Xu, Zhe; Core Laboratory for Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing

2014-11-21

Highlights: • Seven NuMA isoforms generated by alternative splicing were categorized into 3 groups: long, middle and short. • Both exons 15 and 16 in long NuMA were “hotspot” for alternative splicing. • Lower expression of short NuMA was observed in cancer cells compared with nonneoplastic controls. • Distinct localization pattern of short isoforms indicated different function from that of long and middle NuMA. - Abstract: The large nuclear mitotic apparatus (NuMA) has been investigated for over 30 years with functions related to the formation and maintenance of mitotic spindle poles during mitosis. However, the existence and functions of NuMAmore » isoforms generated by alternative splicing remains unclear. In the present work, we show that at least seven NuMA isoforms (categorized into long, middle and short groups) generated by alternative splicing from a common NuMA mRNA precursor were discovered in HeLa cells and these isoforms differ mainly at the carboxyl terminus and the coiled-coil domains. Two “hotspot” exons with molecular mass of 3366-nt and 42-nt tend to be spliced during alternative splicing in long and middle groups. Furthermore, full-length coding sequences of long and middle NuMA obtained by using fusion PCR were constructed into GFP-tagged vector to illustrate their cellular localization. Long NuMA mainly localized in the nucleus with absence from nucleoli during interphase and translocated to the spindle poles in mitosis. Middle NuMA displayed the similar cell cycle-dependent distribution pattern as long NuMA. However, expression of NuMA short isoforms revealed a distinct subcellular localization. Short NuMA were present in the cytosol during the whole cycle, without colocalization with mitotic apparatus. These results have allowed us tentatively to explore a new research direction for NuMA’s various functions.« less

Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation.

PubMed

Moazamian, Ryan; Polhemus, Ashley; Connaughton, Haley; Fraser, Barbara; Whiting, Sara; Gharagozloo, Parviz; Aitken, Robert John

2015-06-01

Oxidative stress is known to compromise human sperm function and to activate the intrinsic apoptotic cascade in these cells. One of the key features of oxidatively stressed spermatozoa is the induction of a lipid peroxidation process that results in the formation of aldehydes potentially capable of disrupting sperm function through the formation of adducts with DNA and key proteins. In this study, we have examined the impact of a range of small molecular mass aldehydes generated as a consequence of lipid peroxidation on human sperm function and also compared the two most commonly formed compounds, 4-hydroxynonenal (4HNE) and malondialdehyde (MDA), for their relative ability to reflect a state of oxidative stress in these cells. Dramatic differences in the bioactivity of individual aldehydes were observed, that generally correlated with the second order rate constants describing their interaction with the model nucleophile, glutathione. Our results demonstrate that acrolein and 4HNE were the most reactive lipid aldehydes, inhibiting sperm motility while augmenting reactive oxygen species production, lipid peroxidation, oxidative DNA damage and caspase activation, in a dose-dependent manner (P < 0.001). In contrast, a variety of saturated aldehydes and the well-known marker of oxidative stress, MDA, were without effect on this cell type. While MDA was not cytotoxic per se, its generation did reflect the induction of oxidative stress in vivo and in vitro in a manner that was highly correlated with the bioactive lipid aldehyde, 4HNE. Despite such overall correlations, individual patient samples were observed in which either MDA or 4HNE predominated. Given the relative cytotoxicity of 4HNE, we propose that this aldehyde should be the preferred criterion for diagnosing oxidative stress in the male germ line. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identification and Functional Characterization of N-Terminally Acetylated Proteins in Drosophila melanogaster

PubMed Central

Gerrits, Bertran; Roschitzki, Bernd; Mohanty, Sonali; Niederer, Eva M.; Laczko, Endre; Timmerman, Evy; Lange, Vinzenz; Hafen, Ernst; Aebersold, Ruedi; Vandekerckhove, Joël; Basler, Konrad; Ahrens, Christian H.; Gevaert, Kris; Brunner, Erich

2009-01-01

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X)PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X)PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species. PMID:19885390

FANCB is essential in the male germline and regulates H3K9 methylation on the sex chromosomes during meiosis

PubMed Central

Kato, Yasuko; Alavattam, Kris G.; Sin, Ho-Su; Meetei, Amom Ruhikanta; Pang, Qishen; Andreassen, Paul R.; Namekawa, Satoshi H.

2015-01-01

Fanconi anemia (FA) is a recessive X-linked and autosomal genetic disease associated with bone marrow failure and increased cancer, as well as severe germline defects such as hypogonadism and germ cell depletion. Although deficiencies in FA factors are commonly associated with germ cell defects, it remains unknown whether the FA pathway is involved in unique epigenetic events in germ cells. In this study, we generated Fancb mutant mice, the first mouse model of X-linked FA, and identified a novel function of the FA pathway in epigenetic regulation during mammalian gametogenesis. Fancb mutant mice were infertile and exhibited primordial germ cell (PGC) defects during embryogenesis. Further, Fancb mutation resulted in the reduction of undifferentiated spermatogonia in spermatogenesis, suggesting that FANCB regulates the maintenance of undifferentiated spermatogonia. Additionally, based on functional studies, we dissected the pathway in which FANCB functions during meiosis. The localization of FANCB on sex chromosomes is dependent on MDC1, a binding partner of H2AX phosphorylated at serine 139 (γH2AX), which initiates chromosome-wide silencing. Also, FANCB is required for FANCD2 localization during meiosis, suggesting that the role of FANCB in the activation of the FA pathway is common to both meiosis and somatic DNA damage responses. H3K9me2, a silent epigenetic mark, was decreased on sex chromosomes, whereas H3K9me3 was increased on sex chromosomes in Fancb mutant spermatocytes. Taken together, these results indicate that FANCB functions at critical stages of germ cell development and reveal a novel function of the FA pathway in the regulation of H3K9 methylation in the germline. PMID:26123487

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-06-01

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

Pathway analysis with next-generation sequencing data.

PubMed

Zhao, Jinying; Zhu, Yun; Boerwinkle, Eric; Xiong, Momiao

2015-04-01

Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods.

Decomposing Multifractal Crossovers

PubMed Central

Nagy, Zoltan; Mukli, Peter; Herman, Peter; Eke, Andras

2017-01-01

Physiological processes—such as, the brain's resting-state electrical activity or hemodynamic fluctuations—exhibit scale-free temporal structuring. However, impacts common in biological systems such as, noise, multiple signal generators, or filtering by transport function, result in multimodal scaling that cannot be reliably assessed by standard analytical tools that assume unimodal scaling. Here, we present two methods to identify breakpoints or crossovers in multimodal multifractal scaling functions. These methods incorporate the robust iterative fitting approach of the focus-based multifractal formalism (FMF). The first approach (moment-wise scaling range adaptivity) allows for a breakpoint-based adaptive treatment that analyzes segregated scale-invariant ranges. The second method (scaling function decomposition method, SFD) is a crossover-based design aimed at decomposing signal constituents from multimodal scaling functions resulting from signal addition or co-sampling, such as, contamination by uncorrelated fractals. We demonstrated that these methods could handle multimodal, mono- or multifractal, and exact or empirical signals alike. Their precision was numerically characterized on ideal signals, and a robust performance was demonstrated on exemplary empirical signals capturing resting-state brain dynamics by near infrared spectroscopy (NIRS), electroencephalography (EEG), and blood oxygen level-dependent functional magnetic resonance imaging (fMRI-BOLD). The NIRS and fMRI-BOLD low-frequency fluctuations were dominated by a multifractal component over an underlying biologically relevant random noise, thus forming a bimodal signal. The crossover between the EEG signal components was found at the boundary between the δ and θ bands, suggesting an independent generator for the multifractal δ rhythm. The robust implementation of the SFD method should be regarded as essential in the seamless processing of large volumes of bimodal fMRI-BOLD imaging data for the topology of multifractal metrics free of the masking effect of the underlying random noise. PMID:28798694

Degeneration of Phrenic Motor Neurons Induces Long-Term Diaphragm Deficits following Mid-Cervical Spinal Contusion in Mice

PubMed Central

Nicaise, Charles; Putatunda, Rajarshi; Hala, Tamara J.; Regan, Kathleen A.; Frank, David M.; Brion, Jean-Pierre; Leroy, Karelle; Pochet, Roland; Wright, Megan C.

2012-01-01

Abstract A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle of inspiration. Contusion-type trauma to the cervical spinal cord is one of the most common forms of human SCI; however, few studies have evaluated mid-cervical contusion in animal models or characterized consequent histopathological and functional effects of degeneration of phrenic motor neuron–diaphragm circuitry. We have generated a mouse model of cervical contusion SCI that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and have examined histological and functional outcomes for up to 6 weeks post-injury. We report that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and denervation at diaphragm neuromuscular junctions (NMJ) resulted in compromised ipsilateral diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle action potential amplitudes following phrenic nerve stimulation and abnormalities in spontaneous diaphragm electromyography (EMG) recordings. This injury paradigm is reproducible, does not require ventilatory assistance, and provides proof-of-principle that generation of unilateral cervical contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This study and its accompanying analyses pave the way for using transgenic mouse technology to explore the function of specific genes in the pathophysiology of phrenic motor neuron degeneration and respiratory dysfunction following cervical SCI. PMID:23176637

Functional connectivity studies of patients with auditory verbal hallucinations.

PubMed

Hoffman, Ralph E; Hampson, Michelle

2011-12-02

Functional connectivity (FC) studies of brain mechanisms leading to auditory verbal hallucinations (AVHs) utilizing functional magnetic resonance imaging (fMRI) data are reviewed. Initial FC studies utilized fMRI data collected during performance of various tasks, which suggested frontotemporal disconnection and/or source-monitoring disturbances. Later FC studies have utilized resting (no-task) fMRI data. These studies have produced a mixed picture of disconnection and hyperconnectivity involving different pathways associated with AVHs. Results of our most recent FC study of AVHs are reviewed in detail. This study suggests that the core mechanism producing AVHs involves not a single pathway, but a more complex functional loop. Components of this loop include Wernicke's area and its right homologue, the left inferior frontal cortex, and the putamen. It is noteworthy that the putamen appears to play a critical role in the generation of spontaneous language, and in determining whether auditory stimuli are registered consciously as percepts. Excessive functional coordination linking this region with the Wernicke's seed region in patients with schizophrenia could, therefore, generate an overabundance of potentially conscious language representations. In our model, intact FC in the other two legs of corticostriatal loop (Wernicke's with left IFG, and left IFG with putamen) appeared to allow hyperconnectivity linking the putamen and Wernicke's area (common to schizophrenia overall) to be expressed as conscious hallucinations of speech. Recommendations for future studies are discussed, including inclusion of multiple methodologies applied to the same subjects in order to compare and contrast different mechanistic hypotheses, utilizing EEG to better parse time-course of neural synchronization leading to AVHs, and ascertaining experiential subtypes of AVHs that may reflect distinct mechanisms.

Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

PubMed Central

Rabiller, Gratianne; He, Ji-Wei; Nishijima, Yasuo; Wong, Aaron; Liu, Jialing

2015-01-01

Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG) in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV), θ (4–8 Hz, 10 μV), α (8–12 Hz, 20–200 μV), β (12–30 Hz, 5–10 μV), and γ (30–80 Hz, low amplitude). Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy. PMID:26516838

Functional MRI mapping of visual function and selective attention for performance assessment and presurgical planning using conjunctive visual search

PubMed Central

Parker, Jason G; Zalusky, Eric J; Kirbas, Cemil

2014-01-01

Background Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes. Aims The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors as well as an optimized contrast condition. Materials and methods Images from 10 healthy volunteers were analyzed and brain regions of greatest activation and deactivation were determined using a nonbiased decomposition of the results at the hemisphere, lobe, and gyrus levels. The results were quantified in terms of activation and deactivation extent and mean z-statistic. Results The proposed CVS was found to generate robust activation of the occipital lobe, as well as regions in the middle frontal gyrus associated with coordinating eye movements and in regions of the insula associated with task-level control and focal attention. As expected, the task demonstrated deactivation patterns commonly implicated in the default-mode network. Further deactivation was noted in the posterior region of the cerebellum, most likely associated with the formation of optimal search strategy. Conclusion We believe the task will be useful in studies of visual and selective attention in the neuroscience community as well as in mapping visual function in clinical fMRI. PMID:24683515

Differential Expression and Functional Analysis of High-Throughput -Omics Data Using Open Source Tools.

PubMed

Kebschull, Moritz; Fittler, Melanie Julia; Demmer, Ryan T; Papapanou, Panos N

2017-01-01

Today, -omics analyses, including the systematic cataloging of messenger RNA and microRNA sequences or DNA methylation patterns in a cell population, organ, or tissue sample, allow for an unbiased, comprehensive genome-level analysis of complex diseases, offering a large advantage over earlier "candidate" gene or pathway analyses. A primary goal in the analysis of these high-throughput assays is the detection of those features among several thousand that differ between different groups of samples. In the context of oral biology, our group has successfully utilized -omics technology to identify key molecules and pathways in different diagnostic entities of periodontal disease.A major issue when inferring biological information from high-throughput -omics studies is the fact that the sheer volume of high-dimensional data generated by contemporary technology is not appropriately analyzed using common statistical methods employed in the biomedical sciences.In this chapter, we outline a robust and well-accepted bioinformatics workflow for the initial analysis of -omics data generated using microarrays or next-generation sequencing technology using open-source tools. Starting with quality control measures and necessary preprocessing steps for data originating from different -omics technologies, we next outline a differential expression analysis pipeline that can be used for data from both microarray and sequencing experiments, and offers the possibility to account for random or fixed effects. Finally, we present an overview of the possibilities for a functional analysis of the obtained data.

Bioinactivation: Software for modelling dynamic microbial inactivation.

PubMed

Garre, Alberto; Fernández, Pablo S; Lindqvist, Roland; Egea, Jose A

2017-03-01

This contribution presents the bioinactivation software, which implements functions for the modelling of isothermal and non-isothermal microbial inactivation. This software offers features such as user-friendliness, modelling of dynamic conditions, possibility to choose the fitting algorithm and generation of prediction intervals. The software is offered in two different formats: Bioinactivation core and Bioinactivation SE. Bioinactivation core is a package for the R programming language, which includes features for the generation of predictions and for the fitting of models to inactivation experiments using non-linear regression or a Markov Chain Monte Carlo algorithm (MCMC). The calculations are based on inactivation models common in academia and industry (Bigelow, Peleg, Mafart and Geeraerd). Bioinactivation SE supplies a user-friendly interface to selected functions of Bioinactivation core, namely the model fitting of non-isothermal experiments and the generation of prediction intervals. The capabilities of bioinactivation are presented in this paper through a case study, modelling the non-isothermal inactivation of Bacillus sporothermodurans. This study has provided a full characterization of the response of the bacteria to dynamic temperature conditions, including confidence intervals for the model parameters and a prediction interval of the survivor curve. We conclude that the MCMC algorithm produces a better characterization of the biological uncertainty and variability than non-linear regression. The bioinactivation software can be relevant to the food and pharmaceutical industry, as well as to regulatory agencies, as part of a (quantitative) microbial risk assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Munc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles

PubMed Central

Woo, Sang Su; James, Declan J.; Martin, Thomas F. J.

2017-01-01

Munc13-4 is a Ca2+-dependent SNARE (soluble N-ethylmaleimide–sensitive factor attachment protein receptor)- and phospholipid-binding protein that localizes to and primes secretory granules (SGs) for Ca2+-evoked secretion in various secretory cells. Studies in mast cell–like RBL-2H3 cells provide direct evidence that Munc13–4 with its two Ca2+-binding C2 domains functions as a Ca2+ sensor for SG exocytosis. Unexpectedly, Ca2+ stimulation also generated large (>2.4 μm in diameter) Munc13-4+/Rab7+/Rab11+ endosomal vacuoles. Vacuole generation involved the homotypic fusion of Munc13-4+/Rab7+ SGs, followed by a merge with Rab11+ endosomes, and depended on Ca2+ binding to Munc13-4. Munc13-4 promoted the Ca2+-stimulated fusion of VAMP8-containing liposomes with liposomes containing exocytic or endosomal Q-SNAREs and directly interacted with late endosomal SNARE complexes. Thus Munc13-4 is a tethering/priming factor and Ca2+ sensor for both heterotypic SG-plasma membrane and homotypic SG-SG fusion. Total internal reflection fluorescence microscopy imaging revealed that vacuoles were exocytic and mediated secretion of β-hexosaminidase and cytokines accompanied by Munc13-4 diffusion onto the plasma membrane. The results provide new molecular insights into the mechanism of multigranular compound exocytosis commonly observed in various secretory cells. PMID:28100639

An Efficient Functional Test Generation Method For Processors Using Genetic Algorithms

NASA Astrophysics Data System (ADS)

Hudec, Ján; Gramatová, Elena

2015-07-01

The paper presents a new functional test generation method for processors testing based on genetic algorithms and evolutionary strategies. The tests are generated over an instruction set architecture and a processor description. Such functional tests belong to the software-oriented testing. Quality of the tests is evaluated by code coverage of the processor description using simulation. The presented test generation method uses VHDL models of processors and the professional simulator ModelSim. The rules, parameters and fitness functions were defined for various genetic algorithms used in automatic test generation. Functionality and effectiveness were evaluated using the RISC type processor DP32.

PTMScout, a Web Resource for Analysis of High Throughput Post-translational Proteomics Studies*

PubMed Central

Naegle, Kristen M.; Gymrek, Melissa; Joughin, Brian A.; Wagner, Joel P.; Welsch, Roy E.; Yaffe, Michael B.; Lauffenburger, Douglas A.; White, Forest M.

2010-01-01

The rate of discovery of post-translational modification (PTM) sites is increasing rapidly and is significantly outpacing our biological understanding of the function and regulation of those modifications. To help meet this challenge, we have created PTMScout, a web-based interface for viewing, manipulating, and analyzing high throughput experimental measurements of PTMs in an effort to facilitate biological understanding of protein modifications in signaling networks. PTMScout is constructed around a custom database of PTM experiments and contains information from external protein and post-translational resources, including gene ontology annotations, Pfam domains, and Scansite predictions of kinase and phosphopeptide binding domain interactions. PTMScout functionality comprises data set comparison tools, data set summary views, and tools for protein assignments of peptides identified by mass spectrometry. Analysis tools in PTMScout focus on informed subset selection via common criteria and on automated hypothesis generation through subset labeling derived from identification of statistically significant enrichment of other annotations in the experiment. Subset selection can be applied through the PTMScout flexible query interface available for quantitative data measurements and data annotations as well as an interface for importing data set groupings by external means, such as unsupervised learning. We exemplify the various functions of PTMScout in application to data sets that contain relative quantitative measurements as well as data sets lacking quantitative measurements, producing a set of interesting biological hypotheses. PTMScout is designed to be a widely accessible tool, enabling generation of multiple types of biological hypotheses from high throughput PTM experiments and advancing functional assignment of novel PTM sites. PTMScout is available at http://ptmscout.mit.edu. PMID:20631208

Comparative toxicities of organophosphate and pyrethroid insecticides to aquatic macroarthropods.

PubMed

Halstead, Neal T; Civitello, David J; Rohr, Jason R

2015-09-01

As agricultural expansion and intensification increase to meet the growing global food demand, so too will insecticide use and thus the risk of non-target effects. Insecticide pollution poses a particular threat to aquatic macroarthropods, which play important functional roles in freshwater ecosystems. Thus, understanding the relative toxicities of insecticides to non-target functional groups is critical for predicting effects on ecosystem functions. We exposed two common macroarthropod predators, the crayfish Procambarus alleni and the water bug Belostoma flumineum, to three insecticides in each of two insecticide classes (three organophosphates: chlorpyrifos, malathion, and terbufos; and three pyrethroids: esfenvalerate, λ-cyhalothrin, and permethrin) to assess their toxicities. We generated 150 simulated environmental exposures using the US EPA Surface Water Contamination Calculator to determine the proportion of estimated peak environmental concentrations (EECs) that exceeded the US EPA level of concern (0.5×LC50) for non-endangered aquatic invertebrates. Organophosphate insecticides generated consistently low-risk exposure scenarios (EECs<0.5×LC50) for both P. alleni and B. flumineum. Pyrethroid exposure scenarios presented consistently high risk (EECs>0.5×LC50) to P. alleni, but not to B. flumineum, where only λ-cyhalothrin produced consistently high-risk exposures. Survival analyses demonstrated that insecticide class accounted for 55.7% and 91.1% of explained variance in P. alleni and B. flumineum survival, respectively. Thus, risk to non-target organisms is well predicted by pesticide class. Identifying insecticides that pose low risk to aquatic macroarthropods might help meet increased demands for food while mitigating against potential negative effects on ecosystem functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Titanium Dioxide Nanoparticle Ingestion Alters Nutrient Absorption in an In Vitro Model of the Small Intestine

PubMed Central

Guo, Zhongyuan; Martucci, Nicole J.; Moreno-Olivas, Fabiola; Tako, Elad; Mahler, Gretchen J.

2017-01-01

Ingestion of titanium dioxide (TiO2) nanoparticles from products such as agricultural chemicals, processed food, and nutritional supplements is nearly unavoidable. The gastrointestinal tract serves as a critical interface between the body and the external environment, and is the site of essential nutrient absorption. The goal of this study was to examine the effects of ingesting the 30 nm TiO2 nanoparticles with an in vitro cell culture model of the small intestinal epithelium, and to determine how acute or chronic exposure to nano-TiO2 influences intestinal barrier function, reactive oxygen species generation, proinflammatory signaling, nutrient absorption (iron, zinc, fatty acids), and brush border membrane enzyme function (intestinal alkaline phosphatase). A Caco-2/HT29-MTX cell culture model was exposed to physiologically relevant doses of TiO2 nanoparticles for acute (four hours) or chronic (five days) time periods. Exposure to TiO2 nanoparticles significantly decreased intestinal barrier function following chronic exposure. Reactive oxygen species (ROS) generation, proinflammatory signaling, and intestinal alkaline phosphatase activity all showed increases in response to nano-TiO2. Iron, zinc, and fatty acid transport were significantly decreased following exposure to TiO2 nanoparticles. This is because nanoparticle exposure induced a decrease in absorptive microvilli in the intestinal epithelial cells. Nutrient transporter protein gene expression was also altered, suggesting that cells are working to regulate the transport mechanisms disturbed by nanoparticle ingestion. Overall, these results show that intestinal epithelial cells are affected at a functional level by physiologically relevant exposure to nanoparticles commonly ingested from food. PMID:28944308

Snake River Plain Geothermal Play Fairway Analysis - Phase 1 Raster Files

DOE Data Explorer

John Shervais

2015-10-09

Snake River Plain Play Fairway Analysis - Phase 1 CRS Raster Files. This dataset contains raster files created in ArcGIS. These raster images depict Common Risk Segment (CRS) maps for HEAT, PERMEABILITY, AND SEAL, as well as selected maps of Evidence Layers. These evidence layers consist of either Bayesian krige functions or kernel density functions, and include: (1) HEAT: Heat flow (Bayesian krige map), Heat flow standard error on the krige function (data confidence), volcanic vent distribution as function of age and size, groundwater temperature (equivalue interval and natural breaks bins), and groundwater T standard error. (2) PERMEABILTY: Fault and lineament maps, both as mapped and as kernel density functions, processed for both dilational tendency (TD) and slip tendency (ST), along with data confidence maps for each data type. Data types include mapped surface faults from USGS and Idaho Geological Survey data bases, as well as unpublished mapping; lineations derived from maximum gradients in magnetic, deep gravity, and intermediate depth gravity anomalies. (3) SEAL: Seal maps based on presence and thickness of lacustrine sediments and base of SRP aquifer. Raster size is 2 km. All files generated in ArcGIS.

Impaired Spermatogenesis, Muscle, and Erythrocyte Function in U12 Intron Splicing-Defective Zrsr1 Mutant Mice.

PubMed

Horiuchi, Keiko; Perez-Cerezales, Serafín; Papasaikas, Panagiotis; Ramos-Ibeas, Priscila; López-Cardona, Angela Patricia; Laguna-Barraza, Ricardo; Fonseca Balvís, Noelia; Pericuesta, Eva; Fernández-González, Raul; Planells, Benjamín; Viera, Alberto; Suja, Jose Angel; Ross, Pablo Juan; Alén, Francisco; Orio, Laura; Rodriguez de Fonseca, Fernando; Pintado, Belén; Valcárcel, Juan; Gutiérrez-Adán, Alfonso

2018-04-03

The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility. Testis RNA sequencing (RNA-seq) analyses revealed increased intron retention of both U2- and U12-type introns, including U12-type intron events in genes with key functions in spermatogenesis and spermatid development. Affected U2 introns were commonly found flanking U12 introns, suggesting functional cross-talk between the two spliceosomes. The splicing and tissue defects observed in mutant mice attributed to ZRSR1 loss of function suggest a physiological role for this factor in U12 intron splicing. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Detection of CFTR function and modulation in primary human nasal cell spheroids.

PubMed

Brewington, John J; Filbrandt, Erin T; LaRosa, F J; Ostmann, Alicia J; Strecker, Lauren M; Szczesniak, Rhonda D; Clancy, John P

2018-01-01

Expansion of CFTR modulators to patients with rare/undescribed mutations will be facilitated by patient-derived models quantifying CFTR function and restoration. We aimed to generate a personalized model system of CFTR function and modulation using non-surgically obtained nasal epithelial cells (NECs). NECs obtained by curettage from healthy volunteers and CF patients were expanded and grown in 3-dimensional culture as spheroids, characterized, and stimulated with cAMP-inducing agents to activate CFTR. Spheroid swelling was quantified as a proxy for CFTR function. NEC spheroids recapitulated characteristics of pseudostratified respiratory epithelia. When stimulated with forskolin/IBMX, spheroids swelled in the presence of functional CFTR, and shrank in its absence. Spheroid swelling quantified mutant CFTR restoration in F508del homozygous cells using clinically available CFTR modulators. NEC spheroids hold promise for understanding rare CFTR mutations and personalized modulator testing to drive evaluation for CF patients with common, rare or undescribed mutations. Portions of this data have previously been presented in abstract form at the 2016 meetings of the American Thoracic Society and the 2016 North American Cystic Fibrosis Conference. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

PubMed

Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

2018-03-30

Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

APP Function and Lipids: A Bidirectional Link

PubMed Central

Grimm, Marcus O. W.; Mett, Janine; Grimm, Heike S.; Hartmann, Tobias

2017-01-01

Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer’s disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals. Interestingly, the observed lipid changes in the brain seem not only to be a consequence of the disease but also modulate Aβ generation. In line with these observations, protective lipids being able to decrease Aβ generation and also potential negative lipids in respect to AD were identified. Mechanistically, Aβ peptides are generated by sequential proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. The α-secretase appears to compete with β-secretase for the initial cleavage of APP, preventing Aβ production. All APP-cleaving secretases as well as APP are transmembrane proteins, further illustrating the impact of lipids on Aβ generation. Beside the pathological impact of Aβ, accumulating evidence suggests that Aβ and the APP intracellular domain (AICD) play an important role in regulating lipid homeostasis, either by direct effects or by affecting gene expression or protein stability of enzymes involved in the de novo synthesis of different lipid classes. This review summarizes the current literature addressing the complex bidirectional link between lipids and AD and APP processing including lipid alterations found in AD post mortem brains, lipids that alter APP processing and the physiological functions of Aβ and AICD in the regulation of several lipid metabolism pathways. PMID:28344547

A New Multivariate Approach in Generating Ensemble Meteorological Forcings for Hydrological Forecasting

NASA Astrophysics Data System (ADS)

Khajehei, Sepideh; Moradkhani, Hamid

2015-04-01

Producing reliable and accurate hydrologic ensemble forecasts are subject to various sources of uncertainty, including meteorological forcing, initial conditions, model structure, and model parameters. Producing reliable and skillful precipitation ensemble forecasts is one approach to reduce the total uncertainty in hydrological applications. Currently, National Weather Prediction (NWP) models are developing ensemble forecasts for various temporal ranges. It is proven that raw products from NWP models are biased in mean and spread. Given the above state, there is a need for methods that are able to generate reliable ensemble forecasts for hydrological applications. One of the common techniques is to apply statistical procedures in order to generate ensemble forecast from NWP-generated single-value forecasts. The procedure is based on the bivariate probability distribution between the observation and single-value precipitation forecast. However, one of the assumptions of the current method is fitting Gaussian distribution to the marginal distributions of observed and modeled climate variable. Here, we have described and evaluated a Bayesian approach based on Copula functions to develop an ensemble precipitation forecast from the conditional distribution of single-value precipitation forecasts. Copula functions are known as the multivariate joint distribution of univariate marginal distributions, which are presented as an alternative procedure in capturing the uncertainties related to meteorological forcing. Copulas are capable of modeling the joint distribution of two variables with any level of correlation and dependency. This study is conducted over a sub-basin in the Columbia River Basin in USA using the monthly precipitation forecasts from Climate Forecast System (CFS) with 0.5x0.5 Deg. spatial resolution to reproduce the observations. The verification is conducted on a different period and the superiority of the procedure is compared with Ensemble Pre-Processor approach currently used by National Weather Service River Forecast Centers in USA.

Common sense reasoning about petroleum flow

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

Rosenberg, S.

1981-02-01

This paper describes an expert system for understanding and Reasoning in a petroleum resources domain. A basic model is implemented in FRL (Frame Representation Language). Expertise is encoded as rule frames. The model consists of a set of episodic contexts which are sequentially generated over time. Reasoning occurs in separate reasoning contexts consisting of a buffer frame and packets of rules. These function similar to small production systems. reasoning is linked to the model through an interface of Sentinels (instance driven demons) which notice anomalous conditions. Heuristics and metaknowledge are used through the creation of further reasoning contexts which overlaymore » the simpler ones.« less

Distribution of oxygen in silicon and its effects on electronic characteristics on a microscale

NASA Technical Reports Server (NTRS)

Gatos, H. C.; Rava, P.; Lagowski, J. J.

1980-01-01

The microdistribution of oxygen in silicon was obtained by scanning IR absorption in as grown Czochralski crystals. The crystals were subsequently submitted to various heat treatments. The profiles of the generated thermal donors were determined by spreading resistance measurements. Contrary to the prevailing views, it was found that the concentration of the activated thermal donors is not strictly a function of the oxygen concentration, but depends strongly on an additional factor, which was shown to be associated with vacancy concentration. These conclusions could only be reached on the basis of microscale characterization. In fact, commonly employed macroscale analysis has led to erroneous conclusions.

The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

PubMed Central

2016-01-01

Conspectus Redox-neutral methods for the functionalization of amine α-C–H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C–H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet–Spengler, and Kabachnik–Fields reactions, Friedel–Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C–H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been identified as common intermediates. Extension of this chemistry to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) saturated cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chemistry of amines and carbonyl compounds than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions. PMID:25560649

The azomethine ylide route to amine C-H functionalization: redox-versions of classic reactions and a pathway to new transformations.

PubMed

Seidel, Daniel

2015-02-17

Conspectus Redox-neutral methods for the functionalization of amine α-C-H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C-H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel-Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C-H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been identified as common intermediates. Extension of this chemistry to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) saturated cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chemistry of amines and carbonyl compounds than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions.

Temperature modulates dengue virus epidemic growth rates through its effects on reproduction numbers and generation intervals

PubMed Central

Oidtman, Rachel J.; Huber, John H.; Kraemer, Moritz U. G.; Brady, Oliver J.; Johansson, Michael A.; Perkins, T. Alex

2017-01-01

Epidemic growth rate, r, provides a more complete description of the potential for epidemics than the more commonly studied basic reproduction number, R0, yet the former has never been described as a function of temperature for dengue virus or other pathogens with temperature-sensitive transmission. The need to understand the drivers of epidemics of these pathogens is acute, with arthropod-borne virus epidemics becoming increasingly problematic. We addressed this need by developing temperature-dependent descriptions of the two components of r—R0 and the generation interval—to obtain a temperature-dependent description of r. Our results show that the generation interval is highly sensitive to temperature, decreasing twofold between 25 and 35°C and suggesting that dengue virus epidemics may accelerate as temperatures increase, not only because of more infections per generation but also because of faster generations. Under the empirical temperature relationships that we considered, we found that r peaked at a temperature threshold that was robust to uncertainty in model parameters that do not depend on temperature. Although the precise value of this temperature threshold could be refined following future studies of empirical temperature relationships, the framework we present for identifying such temperature thresholds offers a new way to classify regions in which dengue virus epidemic intensity could either increase or decrease under future climate change. PMID:28723920

AMPX: a modular code system for generating coupled multigroup neutron-gamma libraries from ENDF/B

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

Greene, N.M.; Lucius, J.L.; Petrie, L.M.

1976-03-01

AMPX is a modular system for producing coupled multigroup neutron-gamma cross section sets. Basic neutron and gamma cross-section data for AMPX are obtained from ENDF/B libraries. Most commonly used operations required to generate and collapse multigroup cross-section sets are provided in the system. AMPX is flexibly dimensioned; neutron group structures, and gamma group structures, and expansion orders to represent anisotropic processes are all arbitrary and limited only by available computer core and budget. The basic processes provided will (1) generate multigroup neutron cross sections; (2) generate multigroup gamma cross sections; (3) generate gamma yields for gamma-producing neutron interactions; (4) combinemore » neutron cross sections, gamma cross sections, and gamma yields into final ''coupled sets''; (5) perform one-dimensional discrete ordinates transport or diffusion theory calculations for neutrons and gammas and, on option, collapse the cross sections to a broad-group structure, using the one-dimensional results as weighting functions; (6) plot cross sections, on option, to facilitate the ''evaluation'' of a particular multigroup set of data; (7) update and maintain multigroup cross section libraries in such a manner as to make it not only easy to combine new data with previously processed data but also to do it in a single pass on the computer; and (8) output multigroup cross sections in convenient formats for other codes. (auth)« less

Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta.

PubMed

Bamba, Yohei; Nonaka, Masahiro; Sasaki, Natsu; Shofuda, Tomoko; Kanematsu, Daisuke; Suemizu, Hiroshi; Higuchi, Yuichiro; Pooh, Ritsuko K; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-12-01

We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods. We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use. SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues. Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology. We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology. We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.

Temperature modulates dengue virus epidemic growth rates through its effects on reproduction numbers and generation intervals.

NASA Astrophysics Data System (ADS)

Siraj, A. S.; Oidtman, R. J.; Huber, J. H.; Kraemer, M. U.; Brady, O. J.; Johansson, M. A.; Perkins, T. A.

2017-12-01

Epidemic growth rate, r, provides a more complete description of the potential for epidemics than the more commonly studied basic reproduction number, R0, yet the former has never been described as a function of temperature for dengue virus or other pathogens with temperature-sensitive transmission. The need to understand the drivers of epidemics of these pathogens is acute, with arthropod-borne virus epidemics becoming increasingly problematic. We addressed this need by developing temperature-dependent descriptions of the two components of r—R0 and the generation interval—to obtain a temperature-dependent description of r. Our results show that the generation interval is highly sensitive to temperature, decreasing twofold between 25 and 35 °C and suggesting that dengue virus epidemics may accelerate as temperatures increase, not only because of more infections per generation but also because of faster generations. Under the empirical temperature relationships that we considered, we found that r peaked at a temperature threshold that was robust to uncertainty in model parameters that do not depend on temperature. Although the precise value of this temperature threshold could be refined following future studies of empirical temperature relationships, the framework we present for identifying such temperature thresholds offers a new way to classify regions in which dengue virus epidemic intensity could either increase or decrease under future climate change.

Biophysical characterization of a de novo elastin

NASA Astrophysics Data System (ADS)

Greenland, Kelly Nicole

Natural human elastin is found in tissue such as the lungs, arteries, and skin. This protein is formed at birth with no mechanism present to repair or supplement the initial quantity formed. As a result, the functionality and durability of elastin's elasticity is critically important. To date, the mechanics of this ability to stretch and recoil is not fully understood. This study utilizes de novo protein design to create a small library of simplistic versions of elastin-like proteins, demonstrate the elastin-like proteins, maintain elastin's functionality, and inquire into its structure using solution nuclear magnetic resonance (NMR). Elastin is formed from cross-linked tropoelastin. Therefore, the first generation of designed proteins consisted of one protein that utilized homogony of interspecies tropoelastin by using three common domains, two hydrophobic and one cross-linking domains. Basic modifications were made to open the hydrophobic region and also to make the protein easier to purify and characterize. The designed protein maintained its functionality, self-aggregating as the temperature increased. Uniquely, the protein remained self-aggregated as the temperature returned below the critical transition temperature. Self-aggregation was additionally induced by increasing salt concentrations and by modifying the pH. The protein appeared to have little secondary structure when studied with solution NMR. These results fueled a second generation of designed elastin-like proteins. This generation contained variations designed to study the cross-linking domain, one specific hydrophobic domain, and the effect of the length of the elastin-like protein. The cross-linking domain in one variation has been significantly modified while the flanking hydrophobic domains have remained unchanged. This characterization of this protein will answer questions regarding the specificity of the homologous nature of the cross-linking domain of tropoelastin across species. A second protein has additional hydrophobic domains flanking the originally designed elastin-like protein. The characterization of this protein will answer questions regarding the functionality of longer or more hydrophobic elastin-like proteins. The final variation designed is one hydrophobic domain and the new cross-linking domain repeating several times. The characterization of this protein will answer questions regarding the specific hydrophobic domain and its functionality.

Genomic insight into the common carp (Cyprinus carpio) genome by sequencing analysis of BAC-end sequences

PubMed Central

2011-01-01

Background Common carp is one of the most important aquaculture teleost fish in the world. Common carp and other closely related Cyprinidae species provide over 30% aquaculture production in the world. However, common carp genomic resources are still relatively underdeveloped. BAC end sequences (BES) are important resources for genome research on BAC-anchored genetic marker development, linkage map and physical map integration, and whole genome sequence assembling and scaffolding. Result To develop such valuable resources in common carp (Cyprinus carpio), a total of 40,224 BAC clones were sequenced on both ends, generating 65,720 clean BES with an average read length of 647 bp after sequence processing, representing 42,522,168 bp or 2.5% of common carp genome. The first survey of common carp genome was conducted with various bioinformatics tools. The common carp genome contains over 17.3% of repetitive elements with GC content of 36.8% and 518 transposon ORFs. To identify and develop BAC-anchored microsatellite markers, a total of 13,581 microsatellites were detected from 10,355 BES. The coding region of 7,127 genes were recognized from 9,443 BES on 7,453 BACs, with 1,990 BACs have genes on both ends. To evaluate the similarity to the genome of closely related zebrafish, BES of common carp were aligned against zebrafish genome. A total of 39,335 BES of common carp have conserved homologs on zebrafish genome which demonstrated the high similarity between zebrafish and common carp genomes, indicating the feasibility of comparative mapping between zebrafish and common carp once we have physical map of common carp. Conclusion BAC end sequences are great resources for the first genome wide survey of common carp. The repetitive DNA was estimated to be approximate 28% of common carp genome, indicating the higher complexity of the genome. Comparative analysis had mapped around 40,000 BES to zebrafish genome and established over 3,100 microsyntenies, covering over 50% of the zebrafish genome. BES of common carp are tremendous tools for comparative mapping between the two closely related species, zebrafish and common carp, which should facilitate both structural and functional genome analysis in common carp. PMID:21492448

Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART.

PubMed

Brown, Elliot G

2002-01-01

To support signal generation a terminology should facilitate recognition of medical conditions by using terms which represent unique concepts, providing appropriate, homogeneous grouping of related terms. It should allow intuitive or mathematical identification of adverse events reaching a threshold frequency or with disproportionate incidence, permit identification of important events which are commonly drug-related, and support recognition of new syndromes. It is probable that the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) or high level terms (HLTs) will be used to represent adverse events for the purposes of signal generation. A comparison with 315 WHO Adverse Reaction Terminology (WHO-ART) PTs showed that for about 72% of WHO-ART PTs, there were one or two corresponding MedDRA PTs. However, there were instances where there were many MedDRA PTs corresponding to single WHO-ART PTs. In many cases, MedDRA HLTs grouped large numbers of PTs and sometimes there could be problems when a single HLT comprises PTs which represent very different medical concepts, or conditions which differ greatly in their clinical importance. Further studies are needed to compare the way in which identical data sets coded with MedDRA and with other terminologies actually function in generating and exploring signals using the same methods of detection and evaluation.

A Sociocognitive Perspective on Assessing EL Students in the Age of Common Core and Next Generation Science Standards

ERIC Educational Resources Information Center

Mislevy, Robert J.; Durán, Richard P.

2014-01-01

Subject-area standards such as Common Core State Standards for Language Arts and Mathematics and Next Generation Science Standards offer deeper, richer views of subject-area proficiency. In science, they underscore doing things with facts and concepts, such as explaining, planning, and investigating--activities that are intertwined with language,…

Next Generation MODTRAN for Improved Atmospheric Correction of Spectral Imagery

DTIC Science & Technology

2016-01-29

DoD operational and research sensor and data processing systems, particularly those involving the removal of atmospheric effects, commonly referred...atmospheric correction process. Given the ever increasing capabilities of spectral sensors to quickly generate enormous quantities of data, combined...many DoD operational and research sensor and data processing systems, particularly those involving the removal of atmospheric effects, commonly

Common Core State Standards for ELA/Literacy and Next Generation Science Standards: Convergences and Discrepancies Using Argument as an Example

ERIC Educational Resources Information Center

Lee, Okhee

2017-01-01

As the Common Core State Standards (CCSS) for English language arts (ELA)/literacy and the Next Generation Science Standards (NGSS) highlight connections across subject areas, convergences and discrepancies come into view. As a prominent example, this article focuses on how the CCSS and the NGSS treat "argument," especially in Grades…

Managing intergenerational differences in academic anesthesiology.

PubMed

Shangraw, Robert E; Whitten, Charles W

2007-12-01

Common definitions for workplace generations are the silent generation (born 1925-1945), the baby boomer generation (1946-1962), generation X (1963-1981), and generation Y (1982-2000). Distinct motivational and value perceptions stereotype generations. This review defines the characteristics of workplace generations today and provides insight into how differences influence the workplace environment. Senior faculty members are mostly boomers, whereas residents and junior faculty members tend to belong to generation X. Medical students and incoming interns are from generation Y. When compared with boomers, generation X is more savvy with technology, more independent, less loyal to the institution, and seeks balance between work and lifestyle. The 80-h resident working week restriction has reinforced differences between older and younger physicians. Generation Y exhibits traits that are similar to those of generation X. Their increased interest in anesthesiology may reflect, in part, their assumption that it affords better control of lifestyle. Understanding, improved communication strategies, mentorship, and flexibility in methods employed to achieve common goals are most likely to capture the interest and cooperation of members of generation X and possibly Y. Future studies should test effects of particular interventions on outcome in terms of recruitment and performance milestones.

The evolutionary ecology of decorating behaviour

PubMed Central

Ruxton, Graeme D.; Stevens, Martin

2015-01-01

Many animals decorate themselves through the accumulation of environmental material on their exterior. Decoration has been studied across a range of different taxa, but there are substantial limits to current understanding. Decoration in non-humans appears to function predominantly in defence against predators and parasites, although an adaptive function is often assumed rather than comprehensively demonstrated. It seems predominantly an aquatic phenomenon—presumably because buoyancy helps reduce energetic costs associated with carrying the decorative material. In terrestrial examples, decorating is relatively common in the larval stages of insects. Insects are small and thus able to generate the power to carry a greater mass of material relative to their own body weight. In adult forms, the need to be lightweight for flight probably rules out decoration. We emphasize that both benefits and costs to decoration are rarely quantified, and that costs should include those associated with collecting as well as carrying the material. PMID:26041868

What imitation tells us about social cognition: a rapprochement between developmental psychology and cognitive neuroscience.

PubMed Central

Meltzoff, Andrew N; Decety, Jean

2003-01-01

Both developmental and neurophysiological research suggest a common coding between perceived and generated actions. This shared representational network is innately wired in humans. We review psychological evidence concerning the imitative behaviour of newborn human infants. We suggest that the mechanisms involved in infant imitation provide the foundation for understanding that others are 'like me' and underlie the development of theory of mind and empathy for others. We also analyse functional neuroimaging studies that explore the neurophysiological substrate of imitation in adults. We marshal evidence that imitation recruits not only shared neural representations between the self and the other but also cortical regions in the parietal cortex that are crucial for distinguishing between the perspective of self and other. Imitation is doubly revealing: it is used by infants to learn about adults, and by scientists to understand the organization and functioning of the brain. PMID:12689375

Anterior Insular Cortex and Emotional Awareness

PubMed Central

Gu, Xiaosi; Hof, Patrick R.; Friston, Karl J.; Fan, Jin

2014-01-01

This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people’s emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness. PMID:23749500

Developmental mechanisms facilitating the evolution of bills and quills

PubMed Central

Schneider, Richard A

2005-01-01

Beaks and feathers epitomize inimitable avian traits. Within individuals and across species there exists astounding diversity in the size, shape, arrangement, and colour of beaks and feathers in association with various functional adaptations. What has enabled the concomitantly divergent evolution of beaks and feathers? The common denominator may lie in their developmental programmes. As revealed through recent transplant experiments using quail and duck embryos, the developmental programme for each structure utilizes mesenchyme as a dominant source of species-specific patterning information, acts as a module of closely coupled molecular and histogenic events, and operates with a high degree of spatial and temporal plasticity. By synergizing these three features, the developmental programmes underlying beaks and feathers likely have the essential potential to react spontaneously to novel conditions and new gene functions, and as a consequence are well equipped to generate and accommodate innovative phenotypes during the course of evolution. PMID:16313392

Au nanoparticles films used in biological sensing

NASA Astrophysics Data System (ADS)

Rosales Pérez, M.; Delgado Macuil, R.; Rojas López, M.; Gayou, V. L.; Sánchez Ramírez, J. F.

2009-05-01

Lactobacillus para paracasei are used commonly as functional food and probiotic substances. In this work Au nanoparticles self-assembled films were used for Lactobacillus para paracasei determination at five different concentrations. Functionalized substrates were immersed in a colloidal solution for one and a half hour at room temperature and dried at room temperature during four hours. After that, drops of Lactobacillus para paracasei in aqueous solution were put into the Au nanoparticles film and let dry at room temperature for another two hours. Infrared spectroscopy in attenuated total reflectance sampling mode was used to observe generation peaks due to substrate silanization, enhancement of Si-O band intensity due to the Au colloids added to silanized substrate and also to observe the enhancement of Lactobacillus para paracasei infrared intensity of the characteristic frequencies at 1650, 1534 and 1450 cm-1 due to surface enhancement infrared absorption.

Mechanistic Role of Thioredoxin 2 in Heart Failure.

PubMed

Chen, Chaofei; Chen, Haixuan; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2017-01-01

Thioredoxin 2 (Trx2) is a pivotal mitochondrial protein that regulates redox signaling. The mitochondrial Trx2 is expressed ubiquitously, but it is found at the highest levels in metabolically active tissues like the heart. Global gene knockout of Trx2 results in embryonic lethality, likely due to the increased cellular oxidative stress. Moreover, mice with cardiac-specific Trx2 deletion develop spontaneous dilated cardiomyopathy (DCM), correlating with increased apoptosis stress kinase-1 (ASK1) signaling and increased cardiomyocyte apoptosis. Cardiomyocyte apoptosis is a common mechanism in the pathogenesis of heart failure. Our results show that Trx2 is essential for maintaining cardiac function. In this chapter, we summarize the key mechanistic role of Trx2 in preserving cardiac function by suppressing mitochondrial reactive oxygen species (ROS) generation and by inhibiting ASK1-dependent apoptosis in heart failure. Trx2 and ASK1 represent promising targets to develop therapeutic strategies for the treatment of DCM and heart failure.

Identification of genetic elements in metabolism by high-throughput mouse phenotyping.

PubMed

Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A; Schütt, Christine; Ravindranath, Aakash Chavan; Leuchtenberger, Stefanie; Sharma, Sapna; Kistler, Martin; Willershäuser, Monja; Brommage, Robert; Meehan, Terrence F; Mason, Jeremy; Haselimashhadi, Hamed; Hough, Tertius; Mallon, Ann-Marie; Wells, Sara; Santos, Luis; Lelliott, Christopher J; White, Jacqueline K; Sorg, Tania; Champy, Marie-France; Bower, Lynette R; Reynolds, Corey L; Flenniken, Ann M; Murray, Stephen A; Nutter, Lauryl M J; Svenson, Karen L; West, David; Tocchini-Valentini, Glauco P; Beaudet, Arthur L; Bosch, Fatima; Braun, Robert B; Dobbie, Michael S; Gao, Xiang; Herault, Yann; Moshiri, Ala; Moore, Bret A; Kent Lloyd, K C; McKerlie, Colin; Masuya, Hiroshi; Tanaka, Nobuhiko; Flicek, Paul; Parkinson, Helen E; Sedlacek, Radislav; Seong, Je Kyung; Wang, Chi-Kuang Leo; Moore, Mark; Brown, Steve D; Tschöp, Matthias H; Wurst, Wolfgang; Klingenspor, Martin; Wolf, Eckhard; Beckers, Johannes; Machicao, Fausto; Peter, Andreas; Staiger, Harald; Häring, Hans-Ulrich; Grallert, Harald; Campillos, Monica; Maier, Holger; Fuchs, Helmut; Gailus-Durner, Valerie; Werner, Thomas; Hrabe de Angelis, Martin

2018-01-18

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

The Drosophila homolog of Down's syndrome critical region 1 gene regulates learning: Implications for mental retardation

PubMed Central

Chang, Karen T.; Shi, Yi-Jun; Min, Kyung-Tai

2003-01-01

Mental retardation is the most common phenotypic abnormality seen in Down's syndrome (DS) patients, yet the underlying mechanism remains mysterious. DS critical region 1 (DSCR1), located on chromosome 21, is overexpressed in the brain of DS fetus and encodes an inhibitor of calcineurin, but its physiological significance is unknown. To study its functional importance and role in mental retardation in DS, we generated Drosophila mutants of nebula, an ortholog of human DSCR1. Here, we report that both nebula loss-of-function and overexpression mutants exhibit severe learning defects that are attributed by biochemical perturbations rather than maldevelopment of the brain. These results, combined with our data showing that the same biochemical signaling pathway is altered in human DS fetal brain tissue overexpressing DSCR1, suggest that alteration of DSCR1 expression could contribute to mental retardation in DS. PMID:14668437

[Atopy and interleukin-4 receptor].

PubMed

Izuhara, K

1999-06-01

Both IL-4 and IL-13 induce IgE synthesis in B cells by binding to their functional receptors on target cells. These receptors are considered to be composed of heterodimers and both share the IL-4R alpha chain (IL-4R alpha) as a component. Atopy is an inherited tendency, underlying asthma, rhinitis and eczema, and generating high nonspecific IgE and/or high specific IgE against common antigens. Based on findings concerning the molecular mechanism of the signal transduction of IL-4 and IL-13, IL-4R alpha was considered a gene that gave rise to atopy. One polymorphism in the IL-4R alpha gene, Ile50Val, has been correlated with atopy by both genetic and functional assessment. The strategy used in these studies should lead to identification of other genes involved in atopy. Furthermore, these studies should be useful for gene diagnosis of atopy and development of new therapies for atopy in the future.

Concepts and Categories: A Cognitive Neuropsychological Perspective

PubMed Central

Mahon, Bradford Z.; Caramazza, Alfonso

2010-01-01

One of the most provocative and exciting issues in cognitive science is how neural specificity for semantic categories of common objects arises in the functional architecture of the brain. More than two decades of research on the neuropsychological phenomenon of category-specific semantic deficits has generated detailed claims about the organization and representation of conceptual knowledge. More recently, researchers have sought to test hypotheses developed on the basis of neuropsychological evidence with functional imaging. From those two fields, the empirical generalization emerges that object domain and sensory modality jointly constrain the organization of knowledge in the brain. At the same time, research within the embodied cognition framework has highlighted the need to articulate how information is communicated between the sensory and motor systems, and processes that represent and generalize abstract information. Those developments point toward a new approach for understanding category specificity in terms of the coordinated influences of diverse regions and cognitive systems. PMID:18767921

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

PubMed Central

Miller, David C.; Tarantino, Kyle T.; Knowles, Robert R.

2016-01-01

Proton-coupled electron transfers (PCETs) are unconventional redox processes in which both protons and electrons are exchanged, often in a concerted elementary step. While PCET is now recognized to play a central a role in biological redox catalysis and inorganic energy conversion technologies, its applications in organic synthesis are only beginning to be explored. In this chapter we aim to highlight the origins, development and evolution of PCET processes most relevant to applications in organic synthesis. Particular emphasis is given to the ability of PCET to serve as a non-classical mechanism for homolytic bond activation that is complimentary to more traditional hydrogen atom transfer processes, enabling the direct generation of valuable organic radical intermediates directly from their native functional group precursors under comparatively mild catalytic conditions. The synthetically advantageous features of PCET reactivity are described in detail, along with examples from the literature describing the PCET activation of common organic functional groups. PMID:27573270

Identifying thematic roles from neural representations measured by functional magnetic resonance imaging.

PubMed

Wang, Jing; Cherkassky, Vladimir L; Yang, Ying; Chang, Kai-Min Kevin; Vargas, Robert; Diana, Nicholas; Just, Marcel Adam

2016-01-01

The generativity and complexity of human thought stem in large part from the ability to represent relations among concepts and form propositions. The current study reveals how a given object such as rabbit is neurally encoded differently and identifiably depending on whether it is an agent ("the rabbit punches the monkey") or a patient ("the monkey punches the rabbit"). Machine-learning classifiers were trained on functional magnetic resonance imaging (fMRI) data evoked by a set of short videos that conveyed agent-verb-patient propositions. When tested on a held-out video, the classifiers were able to reliably identify the thematic role of an object from its associated fMRI activation pattern. Moreover, when trained on one subset of the study participants, classifiers reliably identified the thematic roles in the data of a left-out participant (mean accuracy = .66), indicating that the neural representations of thematic roles were common across individuals.

Printed batteries and conductive patterns in technical textiles

NASA Astrophysics Data System (ADS)

Willert, Andreas; Meuser, Carmen; Baumann, Reinhard R.

2018-05-01

Various applications of functional devices need a tailored and reliable supply of electrical energy. Batteries are electrochemical systems that deliver energy for functional devices and applications. Due to the common use, several rigid types of batteries have been standardized. To fully integrate the battery into a product that is bendable, free in geometry and less than 1 mm thick, printing of power adaptable batteries is a challenging area of research. Therefore, the well-known zinc-manganese system, which is very promising due to its environmental sustainability and its simplicity, has been used to manufacture battery solutions on a new kind of substrate: technical textiles. Another challenge is the deposition of conductive patterns. At present, embroidery with metallic yarn is the only possibility to provide conducting paths on technical textiles, a time-consuming and elaborate process. Screen printed conductive pathways will generate a new momentum in the manufacturing of conductivity on textiles.

Amnion: a potent graft source for cell therapy in stroke.

PubMed

Yu, Seong Jin; Soncini, Maddalena; Kaneko, Yuji; Hess, David C; Parolini, Ornella; Borlongan, Cesar V

2009-01-01

Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

Pathway analysis from lists of microRNAs: common pitfalls and alternative strategy

PubMed Central

Godard, Patrice; van Eyll, Jonathan

2015-01-01

MicroRNAs (miRNAs) are involved in the regulation of gene expression at a post-transcriptional level. As such, monitoring miRNA expression has been increasingly used to assess their role in regulatory mechanisms of biological processes. In large scale studies, once miRNAs of interest have been identified, the target genes they regulate are often inferred using algorithms or databases. A pathway analysis is then often performed in order to generate hypotheses about the relevant biological functions controlled by the miRNA signature. Here we show that the method widely used in scientific literature to identify these pathways is biased and leads to inaccurate results. In addition to describing the bias and its origin we present an alternative strategy to identify potential biological functions specifically impacted by a miRNA signature. More generally, our study exemplifies the crucial need of relevant negative controls when developing, and using, bioinformatics methods. PMID:25800743

Genetic Determinants of Thrombin Generation and Their Relation to Venous Thrombosis: Results from the GAIT-2 Project

PubMed Central

Martin-Fernandez, Laura; Ziyatdinov, Andrey; Carrasco, Marina; Millon, Juan Antonio; Martinez-Perez, Angel; Vilalta, Noelia; Brunel, Helena; Font, Montserrat; Hamsten, Anders; Souto, Juan Carlos; Soria, José Manuel

2016-01-01

Background Venous thromboembolism (VTE) is a common disease where known genetic risk factors explain only a small portion of the genetic variance. Then, the analysis of intermediate phenotypes, such as thrombin generation assay, can be used to identify novel genetic risk factors that contribute to VTE. Objectives To investigate the genetic basis of distinct quantitative phenotypes of thrombin generation and its relationship to the risk of VTE. Patients/Methods Lag time, thrombin peak and endogenous thrombin potential (ETP) were measured in the families of the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT-2) Project. This sample consisted of 935 individuals in 35 extended families selected through a proband with idiopathic thrombophilia. We performed also genome wide association studies (GWAS) with thrombin generation phenotypes. Results The results showed that 67% of the variation in the risk of VTE is attributable to genetic factors. The heritabilities of lag time, thrombin peak and ETP were 49%, 54% and 52%, respectively. More importantly, we demonstrated also the existence of positive genetic correlations between thrombin peak or ETP and the risk of VTE. Moreover, the major genetic determinant of thrombin generation was the F2 gene. However, other suggestive signals were observed. Conclusions The thrombin generation phenotypes are strongly genetically determined. The thrombin peak and ETP are significantly genetically correlated with the risk of VTE. In addition, F2 was identified as a major determinant of thrombin generation. We reported suggestive signals that might increase our knowledge to explain the variability of this important phenotype. Validation and functional studies are required to confirm GWAS results. PMID:26784699

tDCS polarity effects in motor and cognitive domains: a meta-analytical review.

PubMed

Jacobson, Liron; Koslowsky, Meni; Lavidor, Michal

2012-01-01

In vivo effects of transcranial direct current stimulation (tDCS) have attracted much attention nowadays as this area of research spreads to both the motor and cognitive domains. The common assumption is that the anode electrode causes an enhancement of cortical excitability during stimulation, which then lasts for a few minutes thereafter, while the cathode electrode generates the opposite effect, i.e., anodal-excitation and cathodal-inhibition effects (AeCi). Yet, this dual-polarity effect has not been observed in all tDCS studies. Here, we conducted a meta-analytical review aimed to investigate the homogeneity/heterogeneity of the effect sizes of the AeCi dichotomy in both motor and cognitive functions. The AeCi effect was found to occur quite commonly with motor investigations and rarely in cognitive studies. When the anode electrode is applied over a non-motor area, in most cases, it will cause an excitation as measured by a relevant cognitive or perceptual task; however, the cathode electrode rarely causes an inhibition. We found homogeneity in motor studies and heterogeneity in cognitive studies with the electrode's polarity serving as a moderator that can explain the source of heterogeneity in cognitive studies. The lack of inhibitory cathodal effects might reflect compensation processes as cognitive functions are typically supported by rich brain networks. Further insights as to the polarity and domain interaction are offered, including subdivision to different classes of cognitive functions according to their likelihood of being affected by stimulation.

Piezoelectrically Initiated Pyrotechnic Igniter

NASA Technical Reports Server (NTRS)

Quince, Asia; Dutton, Maureen; Hicks, Robert; Burnham, Karen

2013-01-01

This innovation consists of a pyrotechnic initiator and piezoelectric initiation system. The device will be capable of being initiated mechanically; resisting initiation by EMF, RF, and EMI (electromagnetic field, radio frequency, and electromagnetic interference, respectively); and initiating in water environments and space environments. Current devices of this nature are initiated by the mechanical action of a firing pin against a primer. Primers historically are prone to failure. These failures are commonly known as misfires or hang-fires. In many cases, the primer shows the dent where the firing pin struck the primer, but the primer failed to fire. In devices such as "T" handles, which are commonly used to initiate the blowout of canopies, loss of function of the device may result in loss of crew. In devices such as flares or smoke generators, failure can result in failure to spot a downed pilot. The piezoelectrically initiated ignition system consists of a pyrotechnic device that plugs into a mechanical system (activator), which on activation, generates a high-voltage spark. The activator, when released, will strike a stack of electrically linked piezo crystals, generating a high-voltage, low-amperage current that is then conducted to the pyro-initiator. Within the initiator, an electrode releases a spark that passes through a pyrotechnic first-fire mixture, causing it to combust. The combustion of the first-fire initiates a primary pyrotechnic or explosive powder. If used in a "T" handle, the primary would ramp the speed of burn up to the speed of sound, generating a shock wave that would cause a high explosive to go "high order." In a flare or smoke generator, the secondary would produce the heat necessary to ignite the pyrotechnic mixture. The piezo activator subsystem is redundant in that a second stack of crystals would be struck at the same time with the same activation force, doubling the probability of a first strike spark generation. If the first activation fails to ignite, the device is capable of multiple attempts. Another unique aspect is in the design of the pyrotechnic device. There is an electrode that aids the generation of a directed spark and the use of a conductive matrix to support the first-fire material so that the spark will penetrate to the second electrode.

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum☆

PubMed Central

Verly, Marjolein; Verhoeven, Judith; Zink, Inge; Mantini, Dante; Peeters, Ronald; Deprez, Sabine; Emsell, Louise; Boets, Bart; Noens, Ilse; Steyaert, Jean; Lagae, Lieven; De Cock, Paul; Rommel, Nathalie; Sunaert, Stefan

2014-01-01

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI. PMID:24567909

Probability distribution functions for intermittent scrape-off layer plasma fluctuations

NASA Astrophysics Data System (ADS)

Theodorsen, A.; Garcia, O. E.

2018-03-01

A stochastic model for intermittent fluctuations in the scrape-off layer of magnetically confined plasmas has been constructed based on a super-position of uncorrelated pulses arriving according to a Poisson process. In the most common applications of the model, the pulse amplitudes are assumed exponentially distributed, supported by conditional averaging of large-amplitude fluctuations in experimental measurement data. This basic assumption has two potential limitations. First, statistical analysis of measurement data using conditional averaging only reveals the tail of the amplitude distribution to be exponentially distributed. Second, exponentially distributed amplitudes leads to a positive definite signal which cannot capture fluctuations in for example electric potential and radial velocity. Assuming pulse amplitudes which are not positive definite often make finding a closed form for the probability density function (PDF) difficult, even if the characteristic function remains relatively simple. Thus estimating model parameters requires an approach based on the characteristic function, not the PDF. In this contribution, the effect of changing the amplitude distribution on the moments, PDF and characteristic function of the process is investigated and a parameter estimation method using the empirical characteristic function is presented and tested on synthetically generated data. This proves valuable for describing intermittent fluctuations of all plasma parameters in the boundary region of magnetized plasmas.

Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis.

PubMed

Nicholas, Dequina; Proctor, Elizabeth A; Raval, Forum M; Ip, Blanche C; Habib, Chloe; Ritou, Eleni; Grammatopoulos, Tom N; Steenkamp, Devin; Dooms, Hans; Apovian, Caroline M; Lauffenburger, Douglas A; Nikolajczyk, Barbara S

2017-01-01

Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96) analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

Efficient exon skipping of SGCG mutations mediated by phosphorodiamidate morpholino oligomers.

PubMed

Wyatt, Eugene J; Demonbreun, Alexis R; Kim, Ellis Y; Puckelwartz, Megan J; Vo, Andy H; Dellefave-Castillo, Lisa M; Gao, Quan Q; Vainzof, Mariz; Pavanello, Rita C M; Zatz, Mayana; McNally, Elizabeth M

2018-05-03

Exon skipping uses chemically modified antisense oligonucleotides to modulate RNA splicing. Therapeutically, exon skipping can bypass mutations and restore reading frame disruption by generating internally truncated, functional proteins to rescue the loss of native gene expression. Limb-girdle muscular dystrophy type 2C is caused by autosomal recessive mutations in the SGCG gene, which encodes the dystrophin-associated protein γ-sarcoglycan. The most common SGCG mutations disrupt the transcript reading frame abrogating γ-sarcoglycan protein expression. In order to treat most SGCG gene mutations, it is necessary to skip 4 exons in order to restore the SGCG transcript reading frame, creating an internally truncated protein referred to as Mini-Gamma. Using direct reprogramming of human cells with MyoD, myogenic cells were tested with 2 antisense oligonucleotide chemistries, 2'-O-methyl phosphorothioate oligonucleotides and vivo-phosphorodiamidate morpholino oligomers, to induce exon skipping. Treatment with vivo-phosphorodiamidate morpholino oligomers demonstrated efficient skipping of the targeted exons and corrected the mutant reading frame, resulting in the expression of a functional Mini-Gamma protein. Antisense-induced exon skipping of SGCG occurred in normal cells and those with multiple distinct SGCG mutations, including the most common 521ΔT mutation. These findings demonstrate a multiexon-skipping strategy applicable to the majority of limb-girdle muscular dystrophy 2C patients.

Patient-Specific Induced Pluripotent Stem Cell as a Model for Familial Dilated Cardiomyopathy

PubMed Central

Sun, Ning; Yazawa, Masayuki; Liu, Jianwei; Han, Leng; Sanchez-Freire, Veronica; Abilez, Oscar J.; Navarrete, Enrique G.; Hu, Shijun; Wang, Li; Lee, Andrew; Pavlovic, Aleksandra; Lin, Shin; Chen, Rui; Hajjar, Roger J.; Snyder, Michael P.; Dolmetsch, Ricardo E.; Butte, Manish J.; Ashley, Euan A.; Longaker, Michael T.; Robbins, Robert C.; Wu, Joseph C.

2013-01-01

Dilated cardiomyopathy (DCM) is the most common cardiomyopathy, characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific models, investigating underlying mechanisms, and optimizing therapy. Here we generated cardiomyocytes (CMs) from iPSCs derived from patients of a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to the control healthy individuals in the same family cohort, DCM iPSC-CMs exhibited altered Ca2+ handling, decreased contractility, and abnormal sarcomeric α-actinin distribution. When stimulated with β-adrenergic agonist, DCM iPSC-CMs showed characteristics of failure such as reduced beating rates, compromised contraction, and significantly more cells with abnormal sarcomeric α-actinin distribution. β-adrenergic blocker treatment and over-expression of sarcoplasmic reticulum Ca2+ ATPase (Serca2a) improved DCM iPSC-CMs function. Our study demonstrated that human DCM iPSC-CMs recapitulated to some extent the disease phenotypes morphologically and functionally, and thus can serve as a useful platform for exploring molecular and cellular mechanisms and optimizing treatment of this particular disease. PMID:22517884

Time-dependent resilience assessment and improvement of urban infrastructure systems

NASA Astrophysics Data System (ADS)

Ouyang, Min; Dueñas-Osorio, Leonardo

2012-09-01

This paper introduces an approach to assess and improve the time-dependent resilience of urban infrastructure systems, where resilience is defined as the systems' ability to resist various possible hazards, absorb the initial damage from hazards, and recover to normal operation one or multiple times during a time period T. For different values of T and its position relative to current time, there are three forms of resilience: previous resilience, current potential resilience, and future potential resilience. This paper mainly discusses the third form that takes into account the systems' future evolving processes. Taking the power transmission grid in Harris County, Texas, USA as an example, the time-dependent features of resilience and the effectiveness of some resilience-inspired strategies, including enhancement of situational awareness, management of consumer demand, and integration of distributed generators, are all simulated and discussed. Results show a nonlinear nature of resilience as a function of T, which may exhibit a transition from an increasing function to a decreasing function at either a threshold of post-blackout improvement rate, a threshold of load profile with consumer demand management, or a threshold number of integrated distributed generators. These results are further confirmed by studying a typical benchmark system such as the IEEE RTS-96. Such common trends indicate that some resilience strategies may enhance infrastructure system resilience in the short term, but if not managed well, they may compromise practical utility system resilience in the long run.

Time-dependent resilience assessment and improvement of urban infrastructure systems.

PubMed

Ouyang, Min; Dueñas-Osorio, Leonardo

2012-09-01

This paper introduces an approach to assess and improve the time-dependent resilience of urban infrastructure systems, where resilience is defined as the systems' ability to resist various possible hazards, absorb the initial damage from hazards, and recover to normal operation one or multiple times during a time period T. For different values of T and its position relative to current time, there are three forms of resilience: previous resilience, current potential resilience, and future potential resilience. This paper mainly discusses the third form that takes into account the systems' future evolving processes. Taking the power transmission grid in Harris County, Texas, USA as an example, the time-dependent features of resilience and the effectiveness of some resilience-inspired strategies, including enhancement of situational awareness, management of consumer demand, and integration of distributed generators, are all simulated and discussed. Results show a nonlinear nature of resilience as a function of T, which may exhibit a transition from an increasing function to a decreasing function at either a threshold of post-blackout improvement rate, a threshold of load profile with consumer demand management, or a threshold number of integrated distributed generators. These results are further confirmed by studying a typical benchmark system such as the IEEE RTS-96. Such common trends indicate that some resilience strategies may enhance infrastructure system resilience in the short term, but if not managed well, they may compromise practical utility system resilience in the long run.

Time Reversal Mirrors and Cross Correlation Functions in Acoustic Wave Propagation

NASA Astrophysics Data System (ADS)

Fishman, Louis; Jonsson, B. Lars G.; de Hoop, Maarten V.

2009-03-01

In time reversal acoustics (TRA), a signal is recorded by an array of transducers, time reversed, and then retransmitted into the configuration. The retransmitted signal propagates back through the same medium and retrofocuses on the source that generated the signal. If the transducer array is a single, planar (flat) surface, then this configuration is referred to as a planar, one-sided, time reversal mirror (TRM). In signal processing, for example, in active-source seismic interferometry, the measurement of the wave field at two distinct receivers, generated by a common source, is considered. Cross correlating these two observations and integrating the result over the sources yield the cross correlation function (CCF). Adopting the TRM experiments as the basic starting point and identifying the kinematically correct correspondences, it is established that the associated CCF signal processing constructions follow in a specific, infinite recording time limit. This perspective also provides for a natural rationale for selecting the Green's function components in the TRM and CCF expressions. For a planar, one-sided, TRM experiment and the corresponding CCF signal processing construction, in a three-dimensional homogeneous medium, the exact expressions are explicitly calculated, and the connecting limiting relationship verified. Finally, the TRM and CCF results are understood in terms of the underlying, governing, two-way wave equation, its corresponding time reversal invariance (TRI) symmetry, and the absence of TRI symmetry in the associated one-way wave equations, highlighting the role played by the evanescent modal contributions.

Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia.

PubMed

Ward, C; Lucas, M; Piris, J; Collier, J; Chapel, H

2008-09-01

Patients with common variable immunodeficiency disorders are monitored for liver function test abnormalities. A proportion of patients develop deranged liver function and some also develop hepatomegaly. We investigated the prevalence of abnormalities and types of liver disease, aiming to identify those at risk and determine outcomes. The local primary immunodeficiency database was searched for patients with a common variable immunodeficiency disorder and abnormal liver function and/or a liver biopsy. Patterns of liver dysfunction were determined and biopsies reviewed. A total of 47 of 108 patients had deranged liver function, most commonly raised alkaline phosphatase levels. Twenty-three patients had liver biopsies. Nodular regenerative hyperplasia was found in 13 of 16 with unexplained pathology. These patients were more likely to have other disease-related complications of common variable immunodeficiency disorders, in particular non-coeliac (gluten insensitive) lymphocytic enteropathy. However, five had no symptoms of liver disease and only one died of liver complications. Nodular regenerative hyperplasia is a common complication of common variable immunodeficiency disorders but was rarely complicated by portal hypertension.

Generation and characterization of Atoh1-Cre knock-in mouse line

PubMed Central

Yang, Hua; Xie, Xiaoling; Deng, Min; Chen, Xiaowei; Gan, Lin

2010-01-01

Summary Atoh1 encodes a basic helix-loop-helix (bHLH) transcription factor required for the development of the inner ear sensory epithelia, the dorsal spinal cord, brainstem, cerebellum, and intestinal secretory cells. In this study to create a genetic tool for the research on gene function in the ear sensory organs, we generated an Atoh1-Cre knock-in mouse line by replacing the entire Atoh1 coding sequences with the Cre coding sequences. Atoh1Cre/+mice were viable, fertile, and displayed no visible defects whereas the Atoh1Cre/Cremice died perinatally. The spatiotemporal activities of Cre recombinase were examined by crossing Atoh1-Cre mice with the R26R-lacZ conditional reporter mice. Atoh1-Cre activities were detected in the developing inner ear, the hindbrain, the spinal cord, and the intestine. In the inner ear, Atoh1-Cre activities were confined to the sensory organs in which lacZ expression is detected in nearly all of the hair cells and in many supporting cells. Thus, Atoh1-Cre mouse line serves as a useful tool for the functional study of genes in the inner ear. In addition, our results demonstrate that Atoh1 is expressed in the common progenitors destined for both hair and supporting cells. PMID:20533400

Vehicular road influence areas

NASA Astrophysics Data System (ADS)

Huertas, María E.; Huertas, José I.; Valencia, Alexander

2017-02-01

Vehicle operation over paved and unpaved roads is an emission source that significantly contributes to air pollution. Emissions are derived from vehicle exhaust pipes and re-suspension of particulate matter generated by wind erosion and tire to road surface interactions. Environmental authorities require a methodology to evaluate road impact areas, which enable managers to initiate counter-measures, particularly under circumstances where historic meteorological and/or air quality data is unavailable. The present study describes an analytical and experimental work developed to establish a simplified methodology to estimate the area influenced by vehicular roads. AERMOD was chosen to model pollutant dispersion generated by two roads of common attributes (straight road over flat terrain) under the effects of several arbitrary chosen weather conditions. The resulting pollutant concentration vs. Distance curves collapsed into a single curve when concentration and distance were expressed as dimensionless numbers and this curve can be described by a beta distribution function. This result implied that average concentration at a given distance was proportional to emission intensity and that it showed minor sensitivity to meteorological conditions. Therefore, road influence was defined by the area adjacent to the road limited by distance at which the beta distribution function equaled the limiting value specified by the national air quality standard for the pollutant under consideration.

Nonsense-mediated mRNA decay: inter-individual variability and human disease

PubMed Central

Nguyen, Lam Son; Wilkinson, Miles; Gecz, Jozef

2013-01-01

Nonsense-Mediated mRNA Decay (NMD) is a regulatory pathway that functions to degrade transcripts containing premature termination codons (PTCs) and to maintain normal transcriptome homeostasis. Nonsense and frameshift mutations that generate PTCs cause approximately one-third of all known human genetic diseases and thus NMD has a potentially important role in human disease. In genetic disorders in which the affected genes carry PTC-generating mutations, NMD acts as a double-edge sword. While it can benefit the patient by degrading PTC-containing mRNAs that encode detrimental, dominant-negative truncated proteins, it can also make the disease worse when a PTC-containing mRNA is degraded that encodes a mutant but still functional protein. There is evidence that the magnitude of NMD varies between individuals, which, in turn, has been shown to correlate with both clinical presentations and the patients’ responses to drugs that promote read-through of PTCs. In this review, we examine the evidence supporting the existence of inter-individual variability in NMD efficiency and discuss the genetic factors that underlie this variability. We propose that inter-individual variability in NMD efficiency is a common phenomenon in human populations and that an individual’s NMD efficiency should be taken into consideration when testing, developing, and making therapeutic decisions for diseases caused by genes harboring PTCs. PMID:24239855

Chemical copatterning strategies using azlactone-based block copolymers

DOE PAGES

Masigol, Mohammadali; Barua, Niloy; Retterer, Scott T.; ...

2017-09-01

Interfaces can be modified with azlactone-functional polymers in order to manipulate the chemical surface reactivity. Azlactone groups are highly reactive toward amine, thiol, and alcohol nucleophiles, providing a versatile coupling chemistry for secondary surface modification. Azlactone-based surface polymers have been explored in numerous applications, including chemical and biological capture, sensing, and cell culture. These applications often require that the polymer is copatterned within a chemically or biologically inert background; however, common fabrication methods degrade azlactone groups during processing steps or result in polymer films with poorly controlled thicknesses. Here, the authors develop fabrication strategies using parylene lift-off and interface-directed assemblymore » methods to generate microscale patterns of azlactone-based block copolymer in chemically or biologically inert backgrounds. The functionality of azlactone groups was preserved during fabrication, and patterned films appeared as uniform, 80–120nm brushlike films. The authors also develop a patterning approach that uses a novel microcontact stamping method to generate cross-linked, three-dimensional structures of azlactone-based polymers with controllable, microscale thicknesses. The authors identify the benefits of each approach and expect these polymers and patterning strategies to provide a versatile toolbox for developing synthetic interfaces with tuned chemical and physical features for sensing, cell culture, or material capture applications.« less

Chemical copatterning strategies using azlactone-based block copolymers

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

Masigol, Mohammadali; Barua, Niloy; Retterer, Scott T.

Interfaces can be modified with azlactone-functional polymers in order to manipulate the chemical surface reactivity. Azlactone groups are highly reactive toward amine, thiol, and alcohol nucleophiles, providing a versatile coupling chemistry for secondary surface modification. Azlactone-based surface polymers have been explored in numerous applications, including chemical and biological capture, sensing, and cell culture. These applications often require that the polymer is copatterned within a chemically or biologically inert background; however, common fabrication methods degrade azlactone groups during processing steps or result in polymer films with poorly controlled thicknesses. Here, the authors develop fabrication strategies using parylene lift-off and interface-directed assemblymore » methods to generate microscale patterns of azlactone-based block copolymer in chemically or biologically inert backgrounds. The functionality of azlactone groups was preserved during fabrication, and patterned films appeared as uniform, 80–120nm brushlike films. The authors also develop a patterning approach that uses a novel microcontact stamping method to generate cross-linked, three-dimensional structures of azlactone-based polymers with controllable, microscale thicknesses. The authors identify the benefits of each approach and expect these polymers and patterning strategies to provide a versatile toolbox for developing synthetic interfaces with tuned chemical and physical features for sensing, cell culture, or material capture applications.« less

On the composition of an arbitrary collection of SU(2) spins: an enumerative combinatoric approach

NASA Astrophysics Data System (ADS)

Gyamfi, J. A.; Barone, V.

2018-03-01

The whole enterprise of spin compositions can be recast as simple enumerative combinatoric problems. We show here that enumerative combinatorics (Stanley 2011 Enumerative Combinatorics (Cambridge Studies in Advanced Mathematics vol 1) (Cambridge: Cambridge University Press)) is a natural setting for spin composition, and easily leads to very general analytic formulae—many of which hitherto not present in the literature. Based on it, we propose three general methods for computing spin multiplicities; namely, (1) the multi-restricted composition, (2) the generalized binomial and (3) the generating function methods. Symmetric and anti-symmetric compositions of SU(2) spins are also discussed, using generating functions. Of particular importance is the observation that while the common Clebsch-Gordan decomposition—which considers the spins as distinguishable—is related to integer compositions, the symmetric and anti-symmetric compositions (where one considers the spins as indistinguishable) are obtained considering integer partitions. The integers in question here are none other than the occupation numbers of the Holstein-Primakoff bosons. The pervasiveness of q-analogues in our approach is a testament to the fundamental role they play in spin compositions. In the appendix, some new results in the power series representation of Gaussian polynomials (or q-binomial coefficients)—relevant to symmetric and antisymmetric compositions—are presented.