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Sample records for human mtdna control

  1. Human mitochondrial DNA (mtDNA) types in Malaysia

    International Nuclear Information System (INIS)

    Lian, L.H.; Koh, C.L.; Lim, M.E.

    2000-01-01

    Each human cell contains hundreds of mitochondria and thousands of double-stranded circular mtDNA. The delineation of human mtDNA variation and genetics over the past decade has provided unique and often startling insights into human evolution, degenerative diseases, and aging. Each mtDNA of 16,569 base pairs, encodes 13 polypeptides essential to the enzymes of the mitochondrial energy generating pathway, plus the necessary tRNAs and rRNAs. The highly polymorphic noncoding D-(displacement) loop region, also called the control region, is approximately 1.2 kb long. It contains two well-characterized hypervariable (HV-) regions, HV1 and HV2. MtDNA identification is usually based on these sequence differences. According to the TWTGDAM (Technical Working Group for DNA Analysis Methods), the minimum requirement for a mtDNA database for HV1 is from positions 16024 to 16365 and for HV2, from positions 00073 to 00340. The targeted Malaysian population subgroups for this study were mainly the Malays, Chinese, Indians, and indigenous Ibans, Bidayuhs, Kadazan-Dusuns, and Bajaus. Research methodologies undertaken included DNA extraction of samples from unrelated individuals, amplification of the specific regions via the polymerase chain reaction (PCR), and preparation of template DNA for sequencing by using an automated DNA sequencer. Sufficient nucleotide sequence data were generated from the mtDNA analysis. When the sequences were analyzed, sequence variations were found to be caused by nucleotide substitutions, insertions, and deletions. Of the three causes of the sequence variations, nucleotide substitutions (86.1%) accounted for the vast majority of polymorphism. It is noted that transitions (83.5%) were predominant when compared to the significantly lower frequencies of transversions (2.6%). Insertions (0.9%) and deletions (13.0%) were rather rare and found only in HV2. The data generated will also form the basis of a Malaysian DNA sequence database of mtDNA D

  2. Capillary electrophoresis of Big-Dye terminator sequencing reactions for human mtDNA Control Region haplotyping in the identification of human remains.

    Science.gov (United States)

    Montesino, Marta; Prieto, Lourdes

    2012-01-01

    Cycle sequencing reaction with Big-Dye terminators provides the methodology to analyze mtDNA Control Region amplicons by means of capillary electrophoresis. DNA sequencing with ddNTPs or terminators was developed by (1). The progressive automation of the method by combining the use of fluorescent-dye terminators with cycle sequencing has made it possible to increase the sensibility and efficiency of the method and hence has allowed its introduction into the forensic field. PCR-generated mitochondrial DNA products are the templates for sequencing reactions. Different set of primers can be used to generate amplicons with different sizes according to the quality and quantity of the DNA extract providing sequence data for different ranges inside the Control Region.

  3. Does aerobic exercises induce mtDNA mutation in human blood ...

    African Journals Online (AJOL)

    The aim of this study was to determine the effect of eight weeks aerobic training on mitochondrial DNA (mtDNA) mutation in human blood leucocytes. Twenty untrained healthy students (training group: n =10, age = 20.7±1.5 yrs, weight = 67.7±10 kg, BF% = 17.5±7.35 & control group: n =10, age = 21±1.3 yrs, weight ...

  4. [Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGM™ Platform].

    Science.gov (United States)

    Cao, Y; Zou, K N; Huang, J P; Ma, K; Ping, Y

    2017-08-01

    To analyze and detect the whole genome sequence of human mitochondrial DNA (mtDNA) by Ion Torrent PGM™ platform and to study the differences of mtDNA sequence in different tissues. Samples were collected from 6 unrelated individuals by forensic postmortem examination, including chest blood, hair, costicartilage, nail, skeletal muscle and oral epithelium. Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer. Libraries were constructed with Ion Shear™ Plus Reagents kit and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed using Ion Torrent PGM™ platform. Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HVⅠ region. The whole genome sequence of mtDNA from all samples were amplified successfully. Six unrelated individuals belonged to 6 different haplotypes. Different tissues in one individual had heteroplasmy difference. The heteroplasmy positions and the mutation positions on HVⅠ region were verified by Sanger sequencing. After a consistency check by the Kappa method, it was found that the results of mtDNA sequence had a high consistency in different tissues. The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues, which have good consistency. The results provide guidance for the further applications of mtDNA in forensic science. Copyright© by the Editorial Department of Journal of Forensic Medicine

  5. Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells

    International Nuclear Information System (INIS)

    Akimoto, Miho; Niikura, Mamoru; Ichikawa, Masami; Yonekawa, Hiromichi; Nakada, Kazuto; Honma, Yoshio; Hayashi, Jun-Ichi

    2005-01-01

    Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (ρ 0 ) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties

  6. No evidence of Neandertal mtDNA contribution to early modern humans.

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    David Serre

    2004-03-01

    Full Text Available The retrieval of mitochondrial DNA (mtDNA sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution.

  7. Optimized mtDNA Control Region Primer Extension Capture Analysis for Forensically Relevant Samples and Highly Compromised mtDNA of Different Age and Origin

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    Mayra Eduardoff

    2017-09-01

    Full Text Available The analysis of mitochondrial DNA (mtDNA has proven useful in forensic genetics and ancient DNA (aDNA studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR is commonly sequenced using established Sanger-type Sequencing (STS protocols involving fragment sizes down to approximately 150 base pairs (bp. Recent developments include Massively Parallel Sequencing (MPS of (multiplex PCR-generated libraries using the same amplicon sizes. Molecular genetic studies on archaeological remains that harbor more degraded aDNA have pioneered alternative approaches to target mtDNA, such as capture hybridization and primer extension capture (PEC methods followed by MPS. These assays target smaller mtDNA fragment sizes (down to 50 bp or less, and have proven to be substantially more successful in obtaining useful mtDNA sequences from these samples compared to electrophoretic methods. Here, we present the modification and optimization of a PEC method, earlier developed for sequencing the Neanderthal mitochondrial genome, with forensic applications in mind. Our approach was designed for a more sensitive enrichment of the mtDNA CR in a single tube assay and short laboratory turnaround times, thus complying with forensic practices. We characterized the method using sheared, high quantity mtDNA (six samples, and tested challenging forensic samples (n = 2 as well as compromised solid tissue samples (n = 15 up to 8 kyrs of age. The PEC MPS method produced reliable and plausible mtDNA haplotypes that were useful in the forensic context. It yielded plausible data in samples that did not provide results with STS and other MPS techniques. We addressed the issue of contamination by including four generations of negative controls, and discuss the results in the forensic context. We finally offer perspectives for future research to enable the validation and accreditation of the PEC MPS

  8. mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

    Science.gov (United States)

    Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

    2008-02-01

    The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

  9. Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans

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    Mastana Sarabjit

    2004-08-01

    Full Text Available Abstract Background Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia. Results Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades. Conclusions Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.

  10. Somatic mtDNA mutation spectra in the aging human putamen.

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    Siôn L Williams

    Full Text Available The accumulation of heteroplasmic mitochondrial DNA (mtDNA deletions and single nucleotide variants (SNVs is a well-accepted facet of the biology of aging, yet comprehensive mutation spectra have not been described. To address this, we have used next generation sequencing of mtDNA-enriched libraries (Mito-Seq to investigate mtDNA mutation spectra of putamen from young and aged donors. Frequencies of the "common" deletion and other "major arc" deletions were significantly increased in the aged cohort with the fold increase in the frequency of the common deletion exceeding that of major arc deletions. SNVs also increased with age with the highest rate of accumulation in the non-coding control region which contains elements necessary for translation and replication. Examination of predicted amino acid changes revealed a skew towards pathogenic SNVs in the coding region driven by mutation bias. Levels of the pathogenic m.3243A>G tRNA mutation were also found to increase with age. Novel multimeric tandem duplications that resemble murine control region multimers and yeast ρ(- mtDNAs, were identified in both young and aged specimens. Clonal ∼50 bp deletions in the control region were found at high frequencies in aged specimens. Our results reveal the complex manner in which the mitochondrial genome alters with age and provides a foundation for studies of other tissues and disease states.

  11. A Signal, from Human mtDNA, of Postglacial Recolonization in Europe

    Science.gov (United States)

    Torroni, Antonio; Bandelt, Hans-Jürgen; Macaulay, Vincent; Richards, Martin; Cruciani, Fulvio; Rengo, Chiara; Martinez-Cabrera, Vicente; Villems, Richard; Kivisild, Toomas; Metspalu, Ene; Parik, Jüri; Tolk, Helle-Viivi; Tambets, Kristiina; Forster, Peter; Karger, Bernd; Francalacci, Paolo; Rudan, Pavao; Janicijevic, Branka; Rickards, Olga; Savontaus, Marja-Liisa; Huoponen, Kirsi; Laitinen, Virpi; Koivumäki, Satu; Sykes, Bryan; Hickey, Eileen; Novelletto, Andrea; Moral, Pedro; Sellitto, Daniele; Coppa, Alfredo; Al-Zaheri, Nadia; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Scozzari, Rosaria

    2001-01-01

    Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T→C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed “pre*V,” since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory. PMID:11517423

  12. Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing.

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    Coon, Keith D; Valla, Jon; Szelinger, Szabolics; Schneider, Lonnie E; Niedzielko, Tracy L; Brown, Kevin M; Pearson, John V; Halperin, Rebecca; Dunckley, Travis; Papassotiropoulos, Andreas; Caselli, Richard J; Reiman, Eric M; Stephan, Dietrich A

    2006-08-01

    The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease (AD) has been well documented. Though evidence for the role of mitochondria in AD seems incontrovertible, the impact of mitochondrial DNA (mtDNA) mutations in AD etiology remains controversial. Though mutations in mitochondrially encoded genes have repeatedly been implicated in the pathogenesis of AD, many of these studies have been plagued by lack of replication as well as potential contamination of nuclear-encoded mitochondrial pseudogenes. To assess the role of mtDNA mutations in the pathogenesis of AD, while avoiding the pitfalls of nuclear-encoded mitochondrial pseudogenes encountered in previous investigations and showcasing the benefits of a novel resequencing technology, we sequenced the entire coding region (15,452 bp) of mtDNA from 19 extremely well-characterized AD patients and 18 age-matched, unaffected controls utilizing a new, reliable, high-throughput array-based resequencing technique, the Human MitoChip. High-throughput, array-based DNA resequencing of the entire mtDNA coding region from platelets of 37 subjects revealed the presence of 208 loci displaying a total of 917 sequence variants. There were no statistically significant differences in overall mutational burden between cases and controls, however, 265 independent sites of statistically significant change between cases and controls were identified. Changed sites were found in genes associated with complexes I (30.2%), III (3.0%), IV (33.2%), and V (9.1%) as well as tRNA (10.6%) and rRNA (14.0%). Despite their statistical significance, the subtle nature of the observed changes makes it difficult to determine whether they represent true functional variants involved in AD etiology or merely naturally occurring dissimilarity. Regardless, this study demonstrates the tremendous value of this novel mtDNA resequencing platform, which avoids the pitfalls of erroneously amplifying nuclear-encoded mtDNA pseudogenes, and

  13. Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

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    Lorenz, Carmen; Lesimple, Pierre; Bukowiecki, Raul; Zink, Annika; Inak, Gizem; Mlody, Barbara; Singh, Manvendra; Semtner, Marcus; Mah, Nancy; Auré, Karine; Leong, Megan; Zabiegalov, Oleksandr; Lyras, Ekaterini-Maria; Pfiffer, Vanessa; Fauler, Beatrix; Eichhorst, Jenny; Wiesner, Burkhard; Huebner, Norbert; Priller, Josef; Mielke, Thorsten; Meierhofer, David; Izsvák, Zsuzsanna; Meier, Jochen C; Bouillaud, Frédéric; Adjaye, James; Schuelke, Markus; Wanker, Erich E; Lombès, Anne; Prigione, Alessandro

    2017-05-04

    Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Primary quantitative analysis of the mtDNA4977bp deletion induced by lonizing radiation in human peripheral blood u-sing real-time PCR

    International Nuclear Information System (INIS)

    Duan Zhikai; Liu Jiangong; Guo Wanlong; Zhang Shuxian

    2011-01-01

    Objective: To observe the influence of mtDNA4977bp deletion induced by different dose of γ ray in human peripheral blood in order to explore the feasibility of mtDNA4977bp deletion as biodosimeter. Methods: Human peripheral blood samples were collected from three healthy donors and irradiated by γ ray, MtDNA4977bp deletion was detected by real-time PCR. Results: It indicated that that from the range of 0 ∼ 8 Gy, the relationship between mtDNA4977bp deletion and irradiation dose represents certain curvilinear correlation (Y=1.2693+1.0660X+0.0198X 2 ). Conclusion: We find that γ ray has influence on the mtDNA4977bp deletion, so it may be an important biodosmeter in future. (authors)

  15. 'Mitominis': multiplex PCR analysis of reduced size amplicons for compound sequence analysis of the entire mtDNA control region in highly degraded samples.

    Science.gov (United States)

    Eichmann, Cordula; Parson, Walther

    2008-09-01

    The traditional protocol for forensic mitochondrial DNA (mtDNA) analyses involves the amplification and sequencing of the two hypervariable segments HVS-I and HVS-II of the mtDNA control region. The primers usually span fragment sizes of 300-400 bp each region, which may result in weak or failed amplification in highly degraded samples. Here we introduce an improved and more stable approach using shortened amplicons in the fragment range between 144 and 237 bp. Ten such amplicons were required to produce overlapping fragments that cover the entire human mtDNA control region. These were co-amplified in two multiplex polymerase chain reactions and sequenced with the individual amplification primers. The primers were carefully selected to minimize binding on homoplasic and haplogroup-specific sites that would otherwise result in loss of amplification due to mis-priming. The multiplexes have successfully been applied to ancient and forensic samples such as bones and teeth that showed a high degree of degradation.

  16. Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA study

    DEFF Research Database (Denmark)

    Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena

    2010-01-01

    and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions....

  17. The mitochondrial DNA makeup of Romanians: A forensic mtDNA control region database and phylogenetic characterization.

    Science.gov (United States)

    Turchi, Chiara; Stanciu, Florin; Paselli, Giorgia; Buscemi, Loredana; Parson, Walther; Tagliabracci, Adriano

    2016-09-01

    To evaluate the pattern of Romanian population from a mitochondrial perspective and to establish an appropriate mtDNA forensic database, we generated a high-quality mtDNA control region dataset from 407 Romanian subjects belonging to four major historical regions: Moldavia, Transylvania, Wallachia and Dobruja. The entire control region (CR) was analyzed by Sanger-type sequencing assays and the resulting 306 different haplotypes were classified into haplogroups according to the most updated mtDNA phylogeny. The Romanian gene pool is mainly composed of West Eurasian lineages H (31.7%), U (12.8%), J (10.8%), R (10.1%), T (9.1%), N (8.1%), HV (5.4%),K (3.7%), HV0 (4.2%), with exceptions of East Asian haplogroup M (3.4%) and African haplogroup L (0.7%). The pattern of mtDNA variation observed in this study indicates that the mitochondrial DNA pool is geographically homogeneous across Romania and that the haplogroup composition reveals signals of admixture of populations of different origin. The PCA scatterplot supported this scenario, with Romania located in southeastern Europe area, close to Bulgaria and Hungary, and as a borderland with respect to east Mediterranean and other eastern European countries. High haplotype diversity (0.993) and nucleotide diversity indices (0.00838±0.00426), together with low random match probability (0.0087) suggest the usefulness of this control region dataset as a forensic database in routine forensic mtDNA analysis and in the investigation of maternal genetic lineages in the Romanian population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Pleistocene-Holocene boundary in Southern Arabia from the perspective of human mtDNA variation

    Czech Academy of Sciences Publication Activity Database

    Al-Abri, A.-R.; Podgorná, E.; Rose, J. I.; Pereira, L.; Mulligan, C. J.; Silva, N. M.; Bayoumi, R.; Soares, P.; Černý, Viktor

    2012-01-01

    Roč. 149, č. 2 (2012), s. 291-298 ISSN 0002-9483 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.481, year: 2012

  19. Identification of a new human mtDNA polymorphism (A14290G in the NADH dehydrogenase subunit 6 gene

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    M. Houshmand

    2006-06-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity. The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid. We looked for base conservation using DNA star software (MEGALIGN program as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4%. This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

  20. Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

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    Sarit Suissa

    2009-05-01

    Full Text Available Although the functional consequences of mitochondrial DNA (mtDNA genetic backgrounds (haplotypes, haplogroups have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74% and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%. The variant defining Caucasian haplogroup J (C295T increased the binding of TFAM (Electro Mobility Shift Assay and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1, a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mtDNA

  1. Minding the gap: Frequency of indels in mtDNA control region sequence data and influence on population genetic analyses

    Science.gov (United States)

    Pearce, J.M.

    2006-01-01

    Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.

  2. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

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    Lygia T Budnik

    Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

  3. Integration of mtDNA pseudogenes into the nuclear genome coincides with speciation of the human genus. A hypothesis.

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    Gunbin, Konstantin; Peshkin, Leonid; Popadin, Konstantin; Annis, Sofia; Ackermann, Rebecca R; Khrapko, Konstantin

    2017-05-01

    Fragments of mitochondrial DNA are known to get inserted into nuclear DNA to form NUMTs, i.e. nuclear pseudogenes of the mtDNA. The insertion of a NUMT is a rare event. Hundreds of pseudogenes have been cataloged in the human genome. NUMTs are, in essence, a special type of mutation with their own internal timer, which is synchronized with an established molecular clock, the mtDNA. Thus insertion of NUMTs can be timed with respect to evolution milestones such as the emergence of new species. We asked whether NUMTs were inserted uniformly over time or preferentially during certain periods of evolution, as implied by the "punctuated evolution" model. To our surprise, the NUMT insertion times do appear nonrandom with at least one cluster positioned at around 2.8 million years ago (Ma). Interestingly, 2.8Ma closely corresponds to the time of emergence of the genus Homo, and to a well-documented period of major climate change ca. 2.9-2.5Ma. It is tempting to hypothesize that the insertion of NUMTs is related to the speciation process. NUMTs could be either "riders", i.e., their insertion could be facilitated by the overall higher genome rearrangement activity during speciation, or "drivers", i.e. they may more readily get fixed in the population due to positive selection associated with speciation. If correct, the hypothesis would support the idea that evolution of our genus may have happened in a rapid, punctuated manner. Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  4. The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific

    DEFF Research Database (Denmark)

    Raule, Nicola; Sevini, Federica; Li, Shengting

    2014-01-01

    To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification...

  5. Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens.

    Science.gov (United States)

    Penny, D; Steel, M; Waddell, P J; Hendy, M D

    1995-09-01

    New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers

  6. Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

    Science.gov (United States)

    Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

    2005-01-01

    We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

  7. Human aging and somatic point mutations in mtDNA: a comparative study of generational differences (grandparents and grandchildren

    Directory of Open Access Journals (Sweden)

    Anderson Nonato do Rosário Marinho

    2011-01-01

    Full Text Available The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years and their 62 grandchildren (mean age: 15 ± 4.1 years, the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old mutations (homoplasia and heteroplasmy. It is possible that both of these situations (homoplasia and heteroplasmy were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life.

  8. Geographic structure and demographic history of Iranian brown bear (Ursus arctos based on mtDNA control region sequences

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    Mohammad Reza Ashrafzadeh

    2015-12-01

    Full Text Available In recent years, the brown bear's range has declined and its populations in some areas have faced extinction. Therefore, to have a comprehensive picture of genetic diversity and geographic structure of populations is essential for effective conservation strategies. In this research, we sequenced a 271bp segment of mtDNA control region of seven Iranian brown bears, where a total dataset of 467 sequences (brown and polar bears were used in analyses. Overall, 113 different haplotypes and 77 polymorphic sites were identified within the segment. Based on phylogenetic analyses, Iranian brown bears were not nested in any other clades. The low values of Nm (range=0.014-0.187 and high values of Fst (range=0.728-0.972 among Iranian bears and others revealed a genetically significant differentiation. We aren't found any significant signal of demographic reduction in Iranian bears. The time to the most recent common ancestor of Iranian brown bears (Northern Iran was found to be around 19000 BP.

  9. Tandemly repeated sequence in 5'end of mtDNA control region of ...

    African Journals Online (AJOL)

    Extensive length variability was observed in 5' end sequence of the mitochondrial DNA control region of the Japanese Spanish mackerel (Scomberomorus niphonius). This length variability was due to the presence of varying numbers of a 56-bp tandemly repeated sequence and a 46-bp insertion/deletion (indel).

  10. Anthropology. Response to Comment on "Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans".

    Science.gov (United States)

    Kemp, Brian M; Lindo, John; Bolnick, Deborah A; Malhi, Ripan S; Chatters, James C

    2015-02-20

    Prüfer and Meyer raise concerns over the mitochondrial DNA (mtDNA) results we reported for the Hoyo Negro individual, citing failure of a portion of these data to conform to their expectations of ancient DNA (aDNA). Because damage patterns in aDNA vary, outright rejection of our findings on this basis is unwarranted, especially in light of our other observations. Copyright © 2015, American Association for the Advancement of Science.

  11. Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response

    Science.gov (United States)

    Wan, Xianxiu; Gupta, Shivali; Zago, Maria P.; Davidson, Mercy M.; Dousset, Pierre; Amoroso, Alejandro; Garg, Nisha Jain

    2012-01-01

    Background Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for

  12. Tracing the phylogeography of human populations in Britain based on 4th-11th century mtDNA genotypes.

    Science.gov (United States)

    Töpf, A L; Gilbert, M T P; Dumbacher, J P; Hoelzel, A R

    2006-01-01

    Some of the transitional periods of Britain during the first millennium A.D. are traditionally associated with the movement of people from continental Europe, composed largely of invading armies (e.g., the Roman, Saxon, and Viking invasions). However, the extent to which these were migrations (as opposed to cultural exchange) remains controversial. We investigated the history of migration by women by amplifying mitochondrial DNA (mtDNA) from ancient Britons who lived between approximately A.D. 300-1,000 and compared these with 3,549 modern mtDNA database genotypes from England, Europe, and the Middle East. The objective was to assess the dynamics of the historical population composition by comparing genotypes in a temporal context. Towards this objective we test and calibrate the use of rho statistics to identify relationships between founder and source populations. We find evidence for shared ancestry between the earliest sites (predating Viking invasions) with modern populations across the north of Europe from Norway to Estonia, possibly reflecting common ancestors dating back to the last glacial epoch. This is in contrast with a late Saxon site in Norwich, where the genetic signature is consistent with more recent immigrations from the south, possibly as part of the Saxon invasions.

  13. Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

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    Martyn A. Sharpe

    2012-01-01

    Full Text Available Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

  14. Keeping mtDNA in shape between generations.

    Directory of Open Access Journals (Sweden)

    James B Stewart

    2014-10-01

    Full Text Available Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing.

  15. Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region.

    Science.gov (United States)

    Hernández, Candela L; Reales, Guillermo; Dugoujon, Jean-Michel; Novelletto, Andrea; Rodríguez, Juan Nicolás; Cuesta, Pedro; Calderón, Rosario

    2014-01-24

    The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to those terrestrial movements

  16. Inspecting close maternal relatedness: Towards better mtDNA population samples in forensic databases.

    Science.gov (United States)

    Bodner, Martin; Irwin, Jodi A; Coble, Michael D; Parson, Walther

    2011-03-01

    Reliable data are crucial for all research fields applying mitochondrial DNA (mtDNA) as a genetic marker. Quality control measures have been introduced to ensure the highest standards in sequence data generation, validation and a posteriori inspection. A phylogenetic alignment strategy has been widely accepted as a prerequisite for data comparability and database searches, for forensic applications, for reconstructions of human migrations and for correct interpretation of mtDNA mutations in medical genetics. There is continuing effort to enhance the number of worldwide population samples in order to contribute to a better understanding of human mtDNA variation. This has often lead to the analysis of convenience samples collected for other purposes, which might not meet the quality requirement of random sampling for mtDNA data sets. Here, we introduce an additional quality control means that deals with one aspect of this limitation: by combining autosomal short tandem repeat (STR) marker with mtDNA information, it helps to avoid the bias introduced by related individuals included in the same (small) sample. By STR analysis of individuals sharing their mitochondrial haplotype, pedigree construction and subsequent software-assisted calculation of likelihood ratios based on the allele frequencies found in the population, closely maternally related individuals can be identified and excluded. We also discuss scenarios that allow related individuals in the same set. An ideal population sample would be representative for its population: this new approach represents another contribution towards this goal. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Green turtles (Chelonia mydas foraging at Arvoredo Island in Southern Brazil: genetic characterization and mixed stock analysis through mtDNA control region haplotypes

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    Maíra Carneiro Proietti

    2009-01-01

    Full Text Available We analyzed mtDNA control region sequences of green turtles (Chelonia mydas from Arvoredo Island, a foraging ground in southern Brazil, and identified eight haplotypes. Of these, CM-A8 (64% and CM-A5 (22% were dominant, the remainder presenting low frequencies ( 0.05. Mixed Stock Analysis, incorporating eleven Atlantic and one Mediterranean rookery as possible sources of individuals, indicated Ascension and Aves islands as the main contributing stocks to the Arvoredo aggregation (68.01% and 22.96%, respectively. These results demonstrate the extensive relationships between Arvoredo Island and other Atlantic foraging and breeding areas. Such an understanding provides a framework for establishing adequate management and conservation strategies for this endangered species.

  18. Human settlement history between Sunda and Sahul: a focus on East Timor (Timor-Leste) and the Pleistocenic mtDNA diversity.

    Science.gov (United States)

    Gomes, Sibylle M; Bodner, Martin; Souto, Luis; Zimmermann, Bettina; Huber, Gabriela; Strobl, Christina; Röck, Alexander W; Achilli, Alessandro; Olivieri, Anna; Torroni, Antonio; Côrte-Real, Francisco; Parson, Walther

    2015-02-14

    Distinct, partly competing, "waves" have been proposed to explain human migration in(to) today's Island Southeast Asia and Australia based on genetic (and other) evidence. The paucity of high quality and high resolution data has impeded insights so far. In this study, one of the first in a forensic environment, we used the Ion Torrent Personal Genome Machine (PGM) for generating complete mitogenome sequences via stand-alone massively parallel sequencing and describe a standard data validation practice. In this first representative investigation on the mitochondrial DNA (mtDNA) variation of East Timor (Timor-Leste) population including >300 individuals, we put special emphasis on the reconstruction of the initial settlement, in particular on the previously poorly resolved haplogroup P1, an indigenous lineage of the Southwest Pacific region. Our results suggest a colonization of southern Sahul (Australia) >37 kya, limited subsequent exchange, and a parallel incubation of initial settlers in northern Sahul (New Guinea) followed by westward migrations <28 kya. The temporal proximity and possible coincidence of these latter dispersals, which encompassed autochthonous haplogroups, with the postulated "later" events of (South) East Asian origin pinpoints a highly dynamic migratory phase.

  19. Possible conservation units of the sun bear (Helarctos malayanus) in Sarawak based on variation of mtDNA control region.

    Science.gov (United States)

    Onuma, Manabu; Suzuki, Masatsugu; Ohtaishi, Noriyuki

    2006-11-01

    The mitochondrial DNA control region of the sun bear (Helarctos malayanus) was sequenced using 21 DNA samples collected from confiscated sun bears to identify conservation units, such as evolutionarily significant units and management units, in Sarawak, Borneo Island. A total of 10 haplotypes were observed, indicating the presence of at least two lineages in the sun bear population in Sarawak. Presumably, these two lineages could represent evolutionarily significant units. However, the geographical distributions of the two lineages remained unknown due to the lack of information regarding the exact capture locations of the confiscated sun bears. It is essential to elucidate the geographical distributions of these lineages in order to create a proper conservation plan for the sun bears in Sarawak. Therefore, further studies examining the haplotype distributions using DNA samples from known localities are essential.

  20. Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

    Science.gov (United States)

    Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

    2014-01-01

    Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

  1. Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

    Science.gov (United States)

    Boucret, L; Bris, C; Seegers, V; Goudenège, D; Desquiret-Dumas, V; Domin-Bernhard, M; Ferré-L'Hotellier, V; Bouet, P E; Descamps, P; Reynier, P; Procaccio, V; May-Panloup, P

    2017-10-01

    Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being

  2. Metabolic rescue in pluripotent cells from patients with mtDNA disease.

    Science.gov (United States)

    Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

    2015-08-13

    Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

  3. Melanesian mtDNA complexity.

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    Jonathan S Friedlaender

    Full Text Available Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA sequences from hypervariable regions 1 and 2 (HVR1 and HVR2 from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups. Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at approximately 30-50,000 years before present (YBP, and a second important expansion from Island Southeast Asia/Taiwan during the interval approximately 3,500-8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal Austronesian influence in this region remains unresolved.

  4. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  5. Hypervariable region polymorphism of mtDNA of recurrent oral ulceration in Chinese.

    Directory of Open Access Journals (Sweden)

    Mao Sun

    Full Text Available BACKGROUND: MtDNA haplogroups could have important implication for understanding of the relationship between the mutations of the mitochondrial genome and diseases. Distribution of a variety of diseases among these haplogroups showed that some of the mitochondrial haplogroups are predisposed to disease. To examine the susceptibility of mtDNA haplogroups to ROU, we sequenced the mtDNA HV1, HV2 and HV3 in Chinese ROU. METHODOLOGY/PRINCIPAL FINDINGS: MtDNA haplogroups were analyzed in the 249 cases of ROU patients and the 237 cases of healthy controls respectively by means of primer extension analysis and DNA sequencing. Haplogroups G1 and H were found significantly more abundant in ROU patients than in healthy persons, while haplogroups D5 and R showed a trend toward a higher frequency in control as compared to those in patients. The distribution of C-stretch sequences polymorphism in mtDNA HV1, HV2 and HV3 regions was found in diversity. CONCLUSIONS/SIGNIFICANCE: For the first time, the relationship of mtDNA haplogroups and ROU in Chinese was investigated. Our results indicated that mtDNA haplogroups G1 and H might constitute a risk factor for ROU, which possibly increasing the susceptibility of ROU. Meanwhile, haplogroups D5 and R were indicated as protective factors for ROU. The polymorphisms of C-stretch sequences might being unstable and influence the mtDNA replication fidelity.

  6. Data on haplotype diversity in the hypervariable region I, II and III of mtDNA amongst the Brahmin population of Haryana

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    Kapil Verma

    2018-04-01

    Full Text Available Human mitochondrial DNA (mtDNA is routinely analysed for pathogenic mutations, evolutionary studies, estimation of time of divergence within or between species, phylogenetic studies and identification of degraded remains. The data on various regions of human mtDNA has added enormously to the knowledge pool of population genetics as well as forensic genetics. The displacement-loop (D-loop in the control region of mtDNA is rated as the most rapidly evolving part, due to the presence of variations in this region. The control region consists of three hypervariable regions. These hypervariable regions (HVI, HVII and HVIII tend to mutate 5–10 times faster than nuclear DNA. The high mutation rate of these hypervariable regions is used in population genetic studies and human identity testing. In the present data, potentially informative hypervariable regions of mitochondrial DNA (mtDNA i.e. HVI (np 16024–16365, HVII (np 73–340 and HVIII (np 438–576 were estimated to understand the genetic diversity amongst Brahmin population of Haryana. Blood samples had been collected from maternally unrelated individuals from the different districts of Haryana. An array of parameters comprising of polymorphic sites, transitions, transversions, deletions, gene diversity, nucleotide diversity, pairwise differences, Tajima's D test, Fu's Fs test, mismatch observed variance and expected heterozygosity were estimated. The observed polymorphisms with their respective haplogroups in comparison to rCRS were assigned. Keywords: Mitochondrial DNA, D-loop, Hypervariable regions, Forensic genetics

  7. Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

    Science.gov (United States)

    Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

    2015-01-01

    The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

  8. Mitochondrial DNA copy number threshold in mtDNA depletion myopathy.

    Science.gov (United States)

    Durham, S E; Bonilla, E; Samuels, D C; DiMauro, S; Chinnery, P F

    2005-08-09

    The authors measured the absolute amount of mitochondrial DNA (mtDNA) within single muscle fibers from two patients with thymidine kinase 2 (TK2) deficiency and two healthy controls. TK2 deficient fibers containing more than 0.01 mtDNA/microm3 had residual cytochrome c oxidase (COX) activity. This defines the minimum amount of wild-type mtDNA molecules required to maintain COX activity in skeletal muscle and provides an explanation for the mosaic histochemical pattern seen in patients with mtDNA depletion syndrome.

  9. Multiplexed SNP Typing of Ancient DNA Clarifies the Origin of Andaman mtDNA Haplogroups amongst South Asian Tribal Populations

    Science.gov (United States)

    Endicott, Phillip; Metspalu, Mait; Stringer, Chris; Macaulay, Vincent; Cooper, Alan; Sanchez, Juan J.

    2006-01-01

    The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently under-exploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups ∼30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity. PMID:17218991

  10. Reduced Mtdna Diversity in the Ngobe Amerinds of Panama

    Science.gov (United States)

    Kolman, C. J.; Bermingham, E.; Cooke, R.; Ward, R. H.; Arias, T. D.; Guionneau-Sinclair, F.

    1995-01-01

    Mitochondrial DNA (mtDNA) haplotype diversity was determined for 46 Ngobe Amerinds sampled widely across their geographic range in western Panama. The Ngobe data were compared with mtDNA control region I sequences from two additional Amerind groups located at the northern and southern extremes of Amerind distribution, the Nuu-Chah-Nulth of the Pacific Northwest and the Chilean Mapuche and from one Na-Dene group, the Haida of the Pacific Northwest. The Ngobe exhibit the lowest mtDNA control region sequence diversity yet reported for an Amerind group. Moreover, they carry only two of the four Amerind founding lineages first described by Wallace and coworkers. We posit that the Ngobe passed through a population bottleneck caused by ethnogenesis from a small founding population and/or European conquest and colonization. Dating of the Ngobe population expansion using the HARPENDING et al. approach to the analysis of pairwise genetic differences indicates a Ngobe expansion at roughly 6800 years before present (range: 1850-14,000 years before present), a date more consistent with a bottleneck at Chibcha ethnogenesis than a conquest-based event. PMID:7635293

  11. mtDNA point and length heteroplasmy in high- and low radiation areas of Kerala

    International Nuclear Information System (INIS)

    Forster, L.; Forster, P.; Gurney, S.M.; Spencer, M.; Huang, C.; Röhl, A.; Brinkmann, B.

    2010-01-01

    A coastal peninsula in Kerala (India) contains the world's highest level of natural radioactivity in a densely populated area, offering an opportunity to characterize radiation-associated DNA mutations. Here, we focus on mitochondrial DNA (mtDNA) mutations, which are passed exclusively from the mother to her children. To analyse point mutations, we sampled 248 pedigrees (988 individuals) in the high-radiation peninsula and in nearby low-radiation islands as a control population. Then, in an extended sample of 1,172 mtDNA sequences (containing some non-Indians for comparison), we also analysed length mutations, which in mtDNA can lead to the phenomenon of length heteroplasmy, i.e. the existence of different DNA types in the same cell. We wished to find out how fast mtDNA mutates between generations, and whether the mutation rate is increased in radioactive conditions compared to the low-irradiation sample

  12. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  13. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    International Nuclear Information System (INIS)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee

    2009-01-01

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with 137 Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H 2 O 2 -treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H 2 O 2 -treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells

  14. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-06-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with {sup 137}Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H{sub 2}O{sub 2}-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H{sub 2}O{sub 2}-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

  15. Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA.

    Science.gov (United States)

    Karavaeva, Iuliia E; Golyshev, Sergey A; Smirnova, Ekaterina A; Sokolov, Svyatoslav S; Severin, Fedor F; Knorre, Dmitry A

    2017-04-01

    Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8 , ATG32 or ATG33 , implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes. © 2017. Published by The Company of Biologists Ltd.

  16. [New data on the phylogeography and genetic diversity of the brown bear Ursus arctos Linnaeus, 1758 of northeastern Eurasia (mtDNA control region polymorphism analysis)].

    Science.gov (United States)

    Salomashkina, V V; Kholodova, M V; Tiuten'kov, O Iu; Moskvitina, N S; Erokhin, N G

    2014-01-01

    An analysis of polymorphism of the fragment of the control region of mitochondrial DNA of 53 tissue samples of the brown bear Ursus arctos from several regions of the eastern part of Russia was carried out. It was found that most of the described haplotypes belong to cluster 3a, the most common in Eurasia, and do not form regionally specific haplogroups. However, among the bears from Western and Eastern Siberia, as well as the island of Kunashir, three haplotypes were identified, which are close to the haplogroup typical of Eastern Hokkaido bears. The assumption was made of the existence in Siberia and the Far East of one or more Pleistocene refugia.

  17. Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect beta-Oxidation

    OpenAIRE

    Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Dobeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

    2013-01-01

    Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathologica...

  18. The Trojan female technique: a novel, effective and humane approach for pest population control.

    Science.gov (United States)

    Gemmell, Neil J; Jalilzadeh, Aidin; Didham, Raphael K; Soboleva, Tanya; Tompkins, Daniel M

    2013-12-22

    Humankind's ongoing battle with pest species spans millennia. Pests cause or carry disease, damage or consume food crops and other resources, and drive global environmental change. Conventional approaches to pest management usually involve lethal control, but such approaches are costly, of varying efficiency and often have ethical issues. Thus, pest management via control of reproductive output is increasingly considered an optimal solution. One of the most successful such 'fertility control' strategies developed to date is the sterile male technique (SMT), in which large numbers of sterile males are released into a population each generation. However, this approach is time-consuming, labour-intensive and costly. We use mathematical models to test a new twist on the SMT, using maternally inherited mitochondrial (mtDNA) mutations that affect male, but not female reproductive fitness. 'Trojan females' carrying such mutations, and their female descendants, produce 'sterile-male'-equivalents under natural conditions over multiple generations. We find that the Trojan female technique (TFT) has the potential to be a novel humane approach for pest control. Single large releases and relatively few small repeat releases of Trojan females both provided effective and persistent control within relatively few generations. Although greatest efficacy was predicted for high-turnover species, the additive nature of multiple releases made the TFT applicable to the full range of life histories modelled. The extensive conservation of mtDNA among eukaryotes suggests this approach could have broad utility for pest control.

  19. The Trojan Female Technique: A Novel, Effective and Humane Approach for Pest Population Control

    Energy Technology Data Exchange (ETDEWEB)

    Gemmell, Neil J. [Centre for Reproduction and Genomics and Allan Wilson Centre for Molecular Ecology and Evolution, Department of Anatomy, University of Otago, Dunedin (New Zealand); Jalilzadeh, Aidin [Department of Mathematics and Statistics, University of Otago, Dunedin (New Zealand); Didham, Raphael K. [School of Animal Biology, University of Western Australia (Australia); CSIRO Ecosystem Sciences, Perth, Western Australia (Australia); Soboleva, Tanya [Science and Risk Assessment Directorate, Ministry for Primary Industries, PO Box 2526, Wellington (New Zealand); Tompkins, Daniel M. [Landcare Research, Private Bag 1930, Dunedin (New Zealand); New Zealand Institute for Plant and Food Research Ltd., Christchurch (New Zealand)

    2014-01-15

    Full-text: Humankind's ongoing battle with pest species spans millennia. Pests cause or carry disease, damage or consume food crops and other resources, and drive global environmental change. Conventional approaches to pest management usually involve lethal control, but such approaches are costly, of varying efficiency and often have ethical issues. Thus, pest management via control of reproductive output is increasingly considered an optimal solution. One of the most successful such 'fertility control' strategies developed to date is the sterile male technique (SMT), in which large numbers of sterile males are released into a population each generation. However, this approach is time-consuming, labour- intensive and costly. We use mathematical models to test a new twist on the SMT, using maternally inherited mitochondrial (mtDNA) mutations that affect male, but not female reproductive fitness. 'Trojan females' carrying such mutations, and their female descendants, produce 'sterile-male'-equivalents under natural conditions over multiple generations. We find that the Trojan Female Technique (TFT) has the potential to be a novel humane approach for pest control. Single large releases and relatively few small repeat releases of Trojan females both provided effective and persistent control within relatively few generations. Although greatest efficacy was predicted for high-turnover species, the additive nature of multiple releases made the TFT applicable to the full range of life histories modelled. The extensive conservation of mtDNA among eukaryotes suggests this approach could have broad utility for pest control. (author)

  20. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mtDNA

  1. Mutations of mtDNA polymerase-γ and hyperlactataemia in the HIV ...

    African Journals Online (AJOL)

    Mutations of mtDNA polymerase-γ and hyperlactataemia in the HIV-infected Zulu population of South Africa. ... D B A Ojwach, C Aldous, P Kocheleff, B Sartorius ... of their capacity to impede human mitochondrial DNA polymerase-γ (POLG), ...

  2. The Expansion of mtDNA Haplogroup L3 within and out of Africa

    Czech Academy of Sciences Publication Activity Database

    Soares, P.; Alshamali, F.; Pereira, J. B.; Fernandes, V.; Silva, N. M.; Afonso, C.; Costa, M. D.; Musilová, E.; Macaulay, V.; Richards, M. B.; Černý, Viktor; Pereira, L.

    2012-01-01

    Roč. 29, č. 3 (2012), s. 915-927 ISSN 0737-4038 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA * complete genomes * haplogroup L3 * out of Africa * modern human expansions Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 10.353, year: 2012

  3. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

    Science.gov (United States)

    Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

    2011-01-01

    A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

  4. High Glucose-Induced Oxidative Stress Increases the Copy Number of Mitochondrial DNA in Human Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Ghada Al-Kafaji

    2013-01-01

    Full Text Available Oxidative damage to mitochondrial DNA (mtDNA has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control, as well as in cells cultured in 25 mM glucose in the presence and absence of 200 μM MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

  5. mtDNA sequence diversity of Hazara ethnic group from Pakistan.

    Science.gov (United States)

    Rakha, Allah; Fatima; Peng, Min-Sheng; Adan, Atif; Bi, Rui; Yasmin, Memona; Yao, Yong-Gang

    2017-09-01

    The present study was undertaken to investigate mitochondrial DNA (mtDNA) control region sequences of Hazaras from Pakistan, so as to generate mtDNA reference database for forensic casework in Pakistan and to analyze phylogenetic relationship of this particular ethnic group with geographically proximal populations. Complete mtDNA control region (nt 16024-576) sequences were generated through Sanger Sequencing for 319 Hazara individuals from Quetta, Baluchistan. The population sample set showed a total of 189 distinct haplotypes, belonging mainly to West Eurasian (51.72%), East & Southeast Asian (29.78%) and South Asian (18.50%) haplogroups. Compared with other populations from Pakistan, the Hazara population had a relatively high haplotype diversity (0.9945) and a lower random match probability (0.0085). The dataset has been incorporated into EMPOP database under accession number EMP00680. The data herein comprises the largest, and likely most thoroughly examined, control region mtDNA dataset from Hazaras of Pakistan. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of a sex-ratio distorting endosymbiont on mtDNA variation in a global insect pest

    Directory of Open Access Journals (Sweden)

    Cook James M

    2009-03-01

    Full Text Available Abstract Background Patterns of mtDNA variation within a species reflect long-term population structure, but may also be influenced by maternally inherited endosymbionts, such as Wolbachia. These bacteria often alter host reproductive biology and can drive particular mtDNA haplotypes through populations. We investigated the impacts of Wolbachia infection and geography on mtDNA variation in the diamondback moth, a major global pest whose geographic distribution reflects both natural processes and transport via human agricultural activities. Results The mtDNA phylogeny of 95 individuals sampled from 10 countries on four continents revealed two major clades. One contained only Wolbachia-infected individuals from Malaysia and Kenya, while the other contained only uninfected individuals, from all countries including Malaysia and Kenya. Within the uninfected group was a further clade containing all individuals from Australasia and displaying very limited sequence variation. In contrast, a biparental nuclear gene phylogeny did not have infected and uninfected clades, supporting the notion that maternally-inherited Wolbachia are responsible for the mtDNA pattern. Only about 5% (15/306 of our global sample of individuals was infected with the plutWB1 isolate and even within infected local populations, many insects were uninfected. Comparisons of infected and uninfected isofemale lines revealed that plutWB1 is associated with sex ratio distortion. Uninfected lines have a 1:1 sex ratio, while infected ones show a 2:1 female bias. Conclusion The main correlate of mtDNA variation in P. xylostella is presence or absence of the plutWB1 infection. This is associated with substantial sex ratio distortion and the underlying mechanisms deserve further study. In contrast, geographic origin is a poor predictor of moth mtDNA sequences, reflecting human activity in moving the insects around the globe. The exception is a clade of Australasian individuals, which may

  7. Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

    Directory of Open Access Journals (Sweden)

    Xiaoshan Zhou

    Full Text Available Thymidine kinase 2 (TK2 deficiency in humans causes mitochondrial DNA (mtDNA depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/- that progressively loses its mtDNA. The TK2(-/- mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/- mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/- mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/- mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/- mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

  8. Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

    Science.gov (United States)

    Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

    2013-01-01

    Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/-) mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/-) mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/-) mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

  9. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.D.; Sun, F.; Wallace, D.C. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  10. A Phenotype-Driven Approach to Generate Mouse Models with Pathogenic mtDNA Mutations Causing Mitochondrial Disease

    Directory of Open Access Journals (Sweden)

    Johanna H.K. Kauppila

    2016-09-01

    Full Text Available Mutations of mtDNA are an important cause of human disease, but few animal models exist. Because mammalian mitochondria cannot be transfected, the development of mice with pathogenic mtDNA mutations has been challenging, and the main strategy has therefore been to introduce mutations found in cell lines into mouse embryos. Here, we describe a phenotype-driven strategy that is based on detecting clonal expansion of pathogenic mtDNA mutations in colonic crypts of founder mice derived from heterozygous mtDNA mutator mice. As proof of concept, we report the generation of a mouse line transmitting a heteroplasmic pathogenic mutation in the alanine tRNA gene of mtDNA displaying typical characteristics of classic mitochondrial disease. In summary, we describe a straightforward and technically simple strategy based on mouse breeding and histology to generate animal models of mtDNA-mutation disease, which will be of great importance for studies of disease pathophysiology and preclinical treatment trials.

  11. Patterned control of human locomotion

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

    2012-01-01

    There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost. PMID:22411012

  12. Patterned control of human locomotion.

    Science.gov (United States)

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka

    2012-05-15

    There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost.

  13. Male infertility is significantly associated with multiple deletions in an 8.7-kb segment of sperm mtDNA in Pakistan.

    Science.gov (United States)

    Mughal, Irfan Afzal; Irfan, Asma; Jahan, Sarwat; Hameed, Abdul

    2017-06-12

    This study aimed to find a link between sperm mitochondrial DNA mutations and male infertility in Pakistan. DNA from semen samples was extracted and amplified by PCR using 7.8-kb deletion-specific primers. The PCR products were separated on agarose gel, visualized under UV-illumination, and then photographed. The results were genotyped and the data were analyzed using SPSS. Deletion analysis of the 8.7-kb fragment by long PCR revealed multiple deletions. The frequency of deletion was much higher in infertile groups as compared to the control group. Further, on comparison between different subtypes of infertile groups, the deletions were highest in the oligoasthenoteratozoospermia (OAT) group. The statistical analysis of case and control groups showed a significant association of the 8.7-kb deletion with human male infertile groups (P = 0.031), and particularly a very significant association with the OAT subgroup (P = 0.019). A significant association has been found between human male infertility and mtDNA deletions in an 8.7-kb segment of sperm mtDNA in a Pakistani population.

  14. A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion.

    Science.gov (United States)

    Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D

    2008-07-01

    Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.

  15. Construction and confirmation of the plasmid of human mitochondrial DNA 4977 bp deletion induced by ionizing radiation

    International Nuclear Information System (INIS)

    Chen Xiaosui; Zhou Lijun; Wang Yuxiao; Qu Jia; Feng Jiangbing; Lu Xue; Chen Deqing; Liu Qingjie

    2006-01-01

    Objective: To construct a stable plasmid that spanning deleted human mitochondrial DNA (mtDNA) 4977 bp induced by ionizing radiation and another one for control DNA fragment, in order to use in the human mitochondrial genome study in the future. Methods: The peripheral blood, which had no mtDNA 4977 bp deletion found in previous study, was exposed to 10 Gy 60 Co γ-rays in vitro. The total cell DNA was extracted and PCR was carried out: a nest-PCR of three-round PCR was used for the mtDNA 4977 bp deletion and one- round regular PCR was used for the control ND1 gene. The PCR products were used for transfection by electroporation and the positive clones were obtained after screening. The plasmid DNA was isolated and sequenced after enzymatic digestion and purification. The sequence result was BLASTed with the human mitochondrial genome. Results: The sizes of PCR products for the flanked 4977 bp deletion and the ND1 gene were similar with those predicted according to GeneBank. The sequences for the positive clones were above 99 per cent homologous with the human mitochondrial genome after BLASTed. Conclusion: The plasmids for deleted human mtDNA 4977 bp and control DNA fragment have been constructed successfully, and they could be used in the quality and quantity studies on human mtDNA 4977 bp deletion. (authors)

  16. Intermittent control: a computational theory of human control.

    Science.gov (United States)

    Gawthrop, Peter; Loram, Ian; Lakie, Martin; Gollee, Henrik

    2011-02-01

    The paradigm of continuous control using internal models has advanced understanding of human motor control. However, this paradigm ignores some aspects of human control, including intermittent feedback, serial ballistic control, triggered responses and refractory periods. It is shown that event-driven intermittent control provides a framework to explain the behaviour of the human operator under a wider range of conditions than continuous control. Continuous control is included as a special case, but sampling, system matched hold, an intermittent predictor and an event trigger allow serial open-loop trajectories using intermittent feedback. The implementation here may be described as "continuous observation, intermittent action". Beyond explaining unimodal regulation distributions in common with continuous control, these features naturally explain refractoriness and bimodal stabilisation distributions observed in double stimulus tracking experiments and quiet standing, respectively. Moreover, given that human control systems contain significant time delays, a biological-cybernetic rationale favours intermittent over continuous control: intermittent predictive control is computationally less demanding than continuous predictive control. A standard continuous-time predictive control model of the human operator is used as the underlying design method for an event-driven intermittent controller. It is shown that when event thresholds are small and sampling is regular, the intermittent controller can masquerade as the underlying continuous-time controller and thus, under these conditions, the continuous-time and intermittent controller cannot be distinguished. This explains why the intermittent control hypothesis is consistent with the continuous control hypothesis for certain experimental conditions.

  17. Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution

    Directory of Open Access Journals (Sweden)

    Carlos Y Valenzuela

    2010-01-01

    Full Text Available Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA, the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9 was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

  18. The Control of Behavior: Human and Environmental

    Science.gov (United States)

    Burhoe, Ralph Wendell

    1972-01-01

    Theological perspective on human and environmental behavior, with a view toward man's ultimate concerns or longest range values and the ultimate controls of behavior. Maintains that all human behavior and destiny is ultimately in the hand of a transcendent power which prevails over any human errors.'' (LK)

  19. Human factors challenges for advanced process control

    International Nuclear Information System (INIS)

    Stubler, W.F.; O'Hara, J..M.

    1996-01-01

    New human-system interface technologies provide opportunities for improving operator and plant performance. However, if these technologies are not properly implemented, they may introduce new challenges to performance and safety. This paper reports the results from a survey of human factors considerations that arise in the implementation of advanced human-system interface technologies in process control and other complex systems. General trends were identified for several areas based on a review of technical literature and a combination of interviews and site visits with process control organizations. Human factors considerations are discussed for two of these areas, automation and controls

  20. Human performance interfaces in air traffic control.

    Science.gov (United States)

    Chang, Yu-Hern; Yeh, Chung-Hsing

    2010-01-01

    This paper examines how human performance factors in air traffic control (ATC) affect each other through their mutual interactions. The paper extends the conceptual SHEL model of ergonomics to describe the ATC system as human performance interfaces in which the air traffic controllers interact with other human performance factors including other controllers, software, hardware, environment, and organisation. New research hypotheses about the relationships between human performance interfaces of the system are developed and tested on data collected from air traffic controllers, using structural equation modelling. The research result suggests that organisation influences play a more significant role than individual differences or peer influences on how the controllers interact with the software, hardware, and environment of the ATC system. There are mutual influences between the controller-software, controller-hardware, controller-environment, and controller-organisation interfaces of the ATC system, with the exception of the controller-controller interface. Research findings of this study provide practical insights in managing human performance interfaces of the ATC system in the face of internal or external change, particularly in understanding its possible consequences in relation to the interactions between human performance factors.

  1. Alterations in mtDNA, gastric carcinogenesis and early diagnosis.

    Science.gov (United States)

    Rodrigues-Antunes, S; Borges, B N

    2018-05-26

    Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.

  2. Control system oriented human interface

    International Nuclear Information System (INIS)

    Barale, P.; Jacobson, V.; Kilgore, R.; Rondeau, D.

    1976-11-01

    The on-line control system interface for magnet beam steering and focusing in the Bevalac is described. An Aydin model 5205B display generator was chosen. This display generator will allow the computer to completely rewrite a monitor screen in less than 50 ms and is also capable of controlling a color monitor

  3. SG-ADVISER mtDNA: a web server for mitochondrial DNA annotation with data from 200 samples of a healthy aging cohort.

    Science.gov (United States)

    Rueda, Manuel; Torkamani, Ali

    2017-08-18

    Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians. We have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115-3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002-1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes. SG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdna .

  4. Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals.

    Science.gov (United States)

    Hosseini, Seyed H; Kohler, James J; Haase, Chad P; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

    2007-03-01

    Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-gamma. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity.

  5. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

    Directory of Open Access Journals (Sweden)

    Specht Günther

    2010-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  6. eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

    Science.gov (United States)

    Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2010-03-09

    Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

  7. MtDNA T4216C variation in multiple sclerosis

    DEFF Research Database (Denmark)

    Andalib, Sasan; Emamhadi, Mohammadreza; Yousefzadeh-Chabok, Shahrokh

    2016-01-01

    MtDNA T4216C variation has frequently been investigated in Multiple Sclerosis (MS) patients; nonetheless, controversy has existed about the evidence of association of this variation with susceptibility to MS. The present systematic review and meta-analysis converge the results of the preceding pu...

  8. Biofeedback, voluntary control, and human potential.

    Science.gov (United States)

    Norris, P

    1986-03-01

    This paper examines some of the philosophical and scientific relationships involving self-control, voluntary control, and psychophysiologic self-regulation. The role of biofeedback in mediating conscious and unconscious processes is explored. Demonstrations of superior voluntary control and its relationship to belief, confidence, and expectation are examined. Biofeedback demonstrates the potential of control to oneself, creating confidence in one's ability to establish enhanced and peak performance in athletics, education, and psychophysiologic therapy. Emphasis is placed on the power of images in all human functioning, and in enhancing human potential.

  9. Controlling human oesophagostomiasis in northern Ghana

    NARCIS (Netherlands)

    Ziem, Juventus Benogle

    2006-01-01

    This thesis describes aspects of the epidemiology and attempts to control infection and pathology due to the nematode parasite Oesophagostomum bifurcum . In northern Ghana and Togo O. bifurcum is an important parasite of humans; elsewhere it is predominantly seen as a parasite of non-human primates.

  10. Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.

    Science.gov (United States)

    Badro, Danielle A; Douaihy, Bouchra; Haber, Marc; Youhanna, Sonia C; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F; Wells, R Spencer; Tyler-Smith, Chris; Platt, Daniel E; Zalloua, Pierre A

    2013-01-01

    The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

  11. Human rights and conventionality control in Mexico

    Directory of Open Access Journals (Sweden)

    Azul América Aguiar-Aguilar

    2014-12-01

    Full Text Available The protection of human rights in Mexico has, de jure, suffered an important change in the last years, given a new judicial interpretation delivered by the National Supreme Court of Justice that allows the use of conventionality control, which means, that it allows federal and state judges to verify the conformity of domestic laws with those established in the Inter-American Convention of Human Rights. To what extent domestic actors are protecting human rights using this new legal tool called conventionality control? In this article I explore whom and how is conventionality control being used in Mexico. Using N-Vivo Software I reviewed concluded decisions delivered by intermediate level courts (Collegiate Circuit Courts in three Mexican states. The evidence points that conventionality control is a very useful tool especially to defenders, who appear in sentences claiming compliance with the commitments Mexico has acquired when this country ratified the Convention.

  12. Major Population Expansion of East Asians Began before Neolithic Time: Evidence of mtDNA Genomes

    Science.gov (United States)

    Qin, Zhen-Dong; Wang, Yi; Tan, Jing-Ze; Li, Hui; Jin, Li

    2011-01-01

    It is a major question in archaeology and anthropology whether human populations started to grow primarily after the advent of agriculture, i.e., the Neolithic time, especially in East Asia, which was one of the centers of ancient agricultural civilization. To answer this question requires an accurate estimation of the time of lineage expansion as well as that of population expansion in a population sample without ascertainment bias. In this study, we analyzed all available mtDNA genomes of East Asians ascertained by random sampling, a total of 367 complete mtDNA sequences generated by the 1000 Genome Project, including 249 Chinese (CHB, CHD, and CHS) and 118 Japanese (JPT). We found that major mtDNA lineages underwent expansions, all of which, except for two JPT-specific lineages, including D4, D4b2b, D4a, D4j, D5a2a, A, N9a, F1a1'4, F2, B4, B4a, G2a1 and M7b1'2'4, occurred before 10 kya, i.e., before the Neolithic time (symbolized by Dadiwan Culture at 7.9 kya) in East Asia. Consistent to this observation, the further analysis showed that the population expansion in East Asia started at 13 kya and lasted until 4 kya. The results suggest that the population growth in East Asia constituted a need for the introduction of agriculture and might be one of the driving forces that led to the further development of agriculture. PMID:21998705

  13. Defining mtDNA origins and population stratification in Rio de Janeiro.

    Science.gov (United States)

    Simão, Filipa; Ferreira, Ana Paula; de Carvalho, Elizeu Fagundes; Parson, Walther; Gusmão, Leonor

    2018-05-01

    The genetic composition of the Brazilian population was shaped by interethnic admixture between autochthonous Native Americans, Europeans settlers and African slaves. This structure, characteristic of most American populations, implies the need for large population forensic databases to capture the high diversity that is usually associated with admixed populations. In the present work, we sequenced the control region of mitochondrial DNA from 205 non-related individuals living in the Rio de Janeiro metropolitan region. Overall high haplotype diversity (0.9994 ± 0.0006) was observed, and pairwise comparisons showed a high proportion of haplotype pairs with more than one-point differences. When ignoring homopolymeric tracts, pairwise comparisons showed no differences 0.18% of the time, and differences in a single position were found with a frequency of 0.32%. A high percentage of African mtDNA was found (42%), with lineages showing a major South West origin. For the West Eurasian and Native American haplogroups (representing 32% and 26%, respectively) it was not possible to evaluate a clear geographic or linguistic affiliation. When grouping the mtDNA lineages according to their continental origin (Native American, European and African), differences were observed for the ancestry proportions estimated with autosomal ancestry-informative markers, suggesting some level of genetic substructure. The results from this study are in accordance with historical data where admixture processes are confirmed with a strong maternal contribution of African maternal ancestry and a relevant contribution of Native American maternal ancestry. Moreover, the evidence for some degree of association between mtDNA and autosomal information should be considered when combining these types of markers in forensic analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. mtDNA variation in caste populations of Andhra Pradesh, India.

    Science.gov (United States)

    Bamshad, M; Fraley, A E; Crawford, M H; Cann, R L; Busi, B R; Naidu, J M; Jorde, L B

    1996-02-01

    Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p caste populations of Andhra Pradesh cluster more often with Africans than with Asians or Europeans. This is suggestive of admixture with African populations.

  15. A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.

    Science.gov (United States)

    Diot, Alan; Hinks-Roberts, Alex; Lodge, Tiffany; Liao, Chunyan; Dombi, Eszter; Morten, Karl; Brady, Stefen; Fratter, Carl; Carver, Janet; Muir, Rebecca; Davis, Ryan; Green, Charlotte J; Johnston, Iain; Hilton-Jones, David; Sue, Carolyn; Mortiboys, Heather; Poulton, Joanna

    2015-10-01

    Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments. This process is able to improve mitochondrial DNA (mtDNA) quality in heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA. In disorders where the load of mutant mtDNA determines disease severity it is likely to be an important determinant of disease progression. Measuring mitophagy is technically demanding. We used pharmacological modulators of autophagy to validate two techniques for quantifying mitophagy. First we used the IN Cell 1000 analyzer to quantify mitochondrial co-localisation with LC3-II positive autophagosomes. Unlike conventional fluorescence and electron microscopy, this high-throughput system is sufficiently sensitive to detect transient low frequency autophagosomes. Secondly, because mitophagy preferentially removes pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative metabolism ("energetic stress"). The effects of the pharmacological modulators on these two measures were consistent, confirming that the high throughput imaging output (autophagosomes co-localising with mitochondria) reflects mitochondrial quality control. To further validate these methods, we performed a more detailed study using metformin, the most commonly prescribed antidiabetic drug that is still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This confirmed our initial findings and revealed that metformin inhibits mitophagy at clinically relevant concentrations, suggesting that it may have novel therapeutic uses. Copyright © 2015. Published by Elsevier Ltd.

  16. Evolutionary analyses of entire genomes do not support the association of mtDNA mutations with Ras/MAPK pathway syndromes.

    Directory of Open Access Journals (Sweden)

    Alberto Gómez-Carballa

    Full Text Available BACKGROUND: There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS and related disorders (such as LEOPARD, neurofibromatosis type 1, although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM, which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45, most of them classified as NS patients (n = 42. METHODS/PRINCIPAL FINDINGS: The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg patterns of a typical Iberian dataset (including hgs H, T, J, and U. Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5 are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. CONCLUSIONS/SIGNIFICANCE: As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS.

  17. Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

    Science.gov (United States)

    Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

    2011-01-01

    Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

  18. Detailed mtDNA genotypes permit a reassessment of the settlement and population structure of the Andaman Islands.

    Science.gov (United States)

    Barik, S S; Sahani, R; Prasad, B V R; Endicott, P; Metspalu, M; Sarkar, B N; Bhattacharya, S; Annapoorna, P C H; Sreenath, J; Sun, D; Sanchez, J J; Ho, S Y W; Chandrasekar, A; Rao, V R

    2008-05-01

    The population genetics of the Indian subcontinent is central to understanding early human prehistory due to its strategic location on the proposed corridor of human movement from Africa to Australia during the late Pleistocene. Previous genetic research using mtDNA has emphasized the relative isolation of the late Pleistocene colonizers, and the physically isolated Andaman Island populations of Island South-East Asia remain the source of claims supporting an early split between the populations that formed the patchy settlement pattern along the coast of the Indian Ocean. Using whole-genome sequencing, combined with multiplexed SNP typing, this study investigates the deep structure of mtDNA haplogroups M31 and M32 in India and the Andaman Islands. The identification of a so far unnoticed rare polymorphism shared between these two lineages suggests that they are actually sister groups within a single haplogroup, M31'32. The enhanced resolution of M31 allows for the inference of a more recent colonization of the Andaman Islands than previously suggested, but cannot reject the very early peopling scenario. We further demonstrate a widespread overlap of mtDNA and cultural markers between the two major language groups of the Andaman archipelago. Given the "completeness" of the genealogy based on whole genome sequences, and the multiple scenarios for the peopling of the Andaman Islands sustained by this inferred genealogy, our study hints that further mtDNA based phylogeographic studies are unlikely to unequivocally support any one of these possibilities. (c) 2008 Wiley-Liss, Inc.

  19. Data from complete mtDNA sequencing of Tunisian centenarians: testing haplogroup association and the "golden mean" to longevity.

    Science.gov (United States)

    Costa, Marta D; Cherni, Lotfi; Fernandes, Verónica; Freitas, Fernando; Ammar El Gaaied, Amel Ben; Pereira, Luísa

    2009-04-01

    Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a "golden mean" to longevity.

  20. Human reliability analysis of control room operators

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Isaac J.A.L.; Carvalho, Paulo Victor R.; Grecco, Claudio H.S. [Instituto de Engenharia Nuclear (IEN), Rio de Janeiro, RJ (Brazil)

    2005-07-01

    Human reliability is the probability that a person correctly performs some system required action in a required time period and performs no extraneous action that can degrade the system Human reliability analysis (HRA) is the analysis, prediction and evaluation of work-oriented human performance using some indices as human error likelihood and probability of task accomplishment. Significant progress has been made in the HRA field during the last years, mainly in nuclear area. Some first-generation HRA methods were developed, as THERP (Technique for human error rate prediction). Now, an array of called second-generation methods are emerging as alternatives, for instance ATHEANA (A Technique for human event analysis). The ergonomics approach has as tool the ergonomic work analysis. It focus on the study of operator's activities in physical and mental form, considering at the same time the observed characteristics of operator and the elements of the work environment as they are presented to and perceived by the operators. The aim of this paper is to propose a methodology to analyze the human reliability of the operators of industrial plant control room, using a framework that includes the approach used by ATHEANA, THERP and the work ergonomics analysis. (author)

  1. Anti-replicative recombinant 5S rRNA molecules can modulate the mtDNA heteroplasmy in a glucose-dependent manner.

    Science.gov (United States)

    Loutre, Romuald; Heckel, Anne-Marie; Jeandard, Damien; Tarassov, Ivan; Entelis, Nina

    2018-01-01

    Mutations in mitochondrial DNA are an important source of severe and incurable human diseases. The vast majority of these mutations are heteroplasmic, meaning that mutant and wild-type genomes are present simultaneously in the same cell. Only a very high proportion of mutant mitochondrial DNA (heteroplasmy level) leads to pathological consequences. We previously demonstrated that mitochondrial targeting of small RNAs designed to anneal with mutant mtDNA can decrease the heteroplasmy level by specific inhibition of mutant mtDNA replication, thus representing a potential therapy. We have also shown that 5S ribosomal RNA, partially imported into human mitochondria, can be used as a vector to deliver anti-replicative oligoribonucleotides into human mitochondria. So far, the efficiency of cellular expression of recombinant 5S rRNA molecules bearing therapeutic insertions remained very low. In the present study, we designed new versions of anti-replicative recombinant 5S rRNA targeting a large deletion in mitochondrial DNA which causes the KSS syndrome, analyzed their specific annealing to KSS mitochondrial DNA and demonstrated their import into mitochondria of cultured human cells. To obtain an increased level of the recombinant 5S rRNA stable expression, we created transmitochondrial cybrid cell line bearing a site for Flp-recombinase and used this system for the recombinase-mediated integration of genes coding for the anti-replicative recombinant 5S rRNAs into nuclear genome. We demonstrated that stable expression of anti-replicative 5S rRNA versions in human transmitochondrial cybrid cells can induce a shift in heteroplasmy level of KSS mutation in mtDNA. This shift was directly dependent on the level of the recombinant 5S rRNA expression and the sequence of the anti-replicative insertion. Quantification of mtDNA copy number in transfected cells revealed the absence of a non-specific effect on wild type mtDNA replication, indicating that the decreased proportion

  2. Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia.

    Science.gov (United States)

    Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

    2014-10-01

    It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. © 2014 Wiley Periodicals, Inc.

  3. MtDNA variation in the Altai-Kizhi population of southern Siberia: a synthesis of genetic variation.

    Science.gov (United States)

    Phillips-Krawczak, Christine; Devor, Eric; Zlojutro, Mark; Moffat-Wilson, Kristin; Crawford, Michael H

    2006-08-01

    The native peoples of Gorno Altai in southern Siberia represent a genetically diverse population and have been of great interest to anthropological genetics. In particular, the southern Altaian population is argued to be the best candidate for the New World ancestral population. In this study we sampled Altai-Kizhi from the southern Altaian village of Mendur-Sokkon, analyzed mtDNA RFLP markers and HVS-I sequences, and compared the results to other published mtDNA data from Derenko et al. (2003) and Shields et al. (1993) encompassing the same region. Because each independent study uses different sampling techniques in characterizing gene pools, in this paper we explore the accuracy and reliability of evolutionary studies on human populations. All the major Native American haplogroups (A, B, C, and D) were identified in the Mendur-Sokkon sample, including a single individual belonging to haplogroup X. The most common mtDNA lineages are C (35.7%) and D (13.3%), which is consistent with the haplogroup profiles of neighboring Siberian groups. The Mendur-Sokkon sample exhibits depressed HVS-I diversity values and neutrality test scores, which starkly differs from the Derenko et al. (2003) data set and more closely resembles the results for neighboring south Siberian groups. Furthermore, the multidimensional scaling plot of DA genetic distances does not cluster the Altai samples, showing different genetic affinities with various Asian groups. The findings underscore the importance of sampling strategy in the reconstruction of evolutionary history at the population level.

  4. Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene.

    Science.gov (United States)

    Martín-Hernández, Elena; García-Silva, María Teresa; Quijada-Fraile, Pilar; Rodríguez-García, María Elena; Rivera, Henry; Hernández-Laín, Aurelio; Coca-Robinot, David; Fernández-Toral, Joaquín; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

    2017-01-01

    Whole-exome sequencing was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase, deficiency of mitochondrial complex III and depletion of mtDNA. With whole-exome sequencing data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in thymidine kinase 2 gene ( TK2; NM_004614.4:c.323 C>T, p.T108M). TK2 mutations have been identified mainly in patients with the myopathic form of mtDNA depletion syndromes. This patient presents an atypical TK2-related myopathic form of mtDNA depletion syndromes, because despite having a very low content of mtDNA (TK2 gene in mtDNA depletion syndromes and expanded the phenotypic spectrum.

  5. MtDNA genomes reveal a relaxation of selective constraints in low-BMI individuals in a Uyghur population.

    Science.gov (United States)

    Zheng, Hong-Xiang; Li, Lei; Jiang, Xiao-Yan; Yan, Shi; Qin, Zhendong; Wang, Xiaofeng; Jin, Li

    2017-10-01

    Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence. In this study, we collected and sequenced the mtDNA genomes of 722 Uyghurs, a typical population with a high prevalence of obesity. We identified the variants that occurred in the Uyghur population for each sample and found that the number of nonsynonymous mutations carried by Uyghur individuals declined with elevation of their BMI (P = 0.015). We further calculated the nonsynonymous and synonymous ratio (N/S) of the high-BMI and low-BMI haplogroups, and the results showed that a significantly higher N/S occurred in the whole mtDNA genomes of the low-BMI haplogroups (0.64) than in that of the high-BMI haplogroups (0.35, P = 0.030) and ancestor haplotypes (0.41, P = 0.032); these findings indicated that low-BMI individuals showed a recent relaxation of selective constraints. In addition, we investigated six clinical characteristics and found that fasting plasma glucose might be correlated with the N/S and selective pressures. We hypothesized that a higher proportion of deleterious mutations led to mild mitochondrial dysfunction, which helps to drive glucose consumption and thereby prevents obesity. Our results provide new insights into the relationship between obesity predisposition and mitochondrial genome evolution.

  6. Stressor controllability modulates fear extinction in humans

    Science.gov (United States)

    Hartley, Catherine A.; Gorun, Alyson; Reddan, Marianne C.; Ramirez, Franchesca; Phelps, Elizabeth A.

    2014-01-01

    Traumatic events are proposed to play a role in the development of anxiety disorders, however not all individuals exposed to extreme stress experience a pathological increase in fear. Recent studies in animal models suggest that the degree to which one is able to control an aversive experience is a critical factor determining its behavioral consequences. In this study, we examined whether stressor controllability modulates subsequent conditioned fear expression in humans. Participants were randomly assigned to an escapable stressor condition, a yoked inescapable stressor condition, or a control condition involving no stress exposure. One week later, all participants underwent fear conditioning, fear extinction, and a test of extinction retrieval the following day. Participants exposed to inescapable stress showed impaired fear extinction learning and increased fear expression the following day. In contrast, escapable stress improved fear extinction and prevented the spontaneous recovery of fear. Consistent with the bidirectional controllability effects previously reported in animal models, these results suggest that one's degree of control over aversive experiences may be an important factor influencing the development of psychological resilience or vulnerability in humans. PMID:24333646

  7. Understanding influences of culture and history on mtDNA variation and population structure in three populations from Assam, Northeast India.

    Science.gov (United States)

    Rej, Peter H; Deka, Ranjan; Norton, Heather L

    2017-05-06

    Positioned at the nexus of India, China, and Southeast Asia, Northeast India is presumed to have served as a channel for land-based human migration since the Upper Pleistocene. Assam is the largest state in the Northeast. We characterized the genetic background of three populations and examined the ways in which their population histories and cultural practices have influenced levels of intrasample and intersample variation. We examined sequence data from the mtDNA hypervariable control region and selected diagnostic mutations from the coding region in 128 individuals from three ethnic groups currently living in Assam: two Scheduled tribes (Sonowal Kachari and Rabha), and the non-Scheduled Tai Ahom. The populations of Assam sampled here express mtDNA lineages indicative of South Asian, Southeast Asian, and East Asian ancestry. We discovered two completely novel haplogroups in Assam that accounted for 6.2% of the lineages in our sample. We also identified a new subhaplogroup of M9a that is prevalent in the Sonowal Kachari of Assam (19.1%), but not present in neighboring Arunachal Pradesh, indicating substantial regional population structuring. Employing a large comparative dataset into a series of multidimensional scaling (MDS) analyses, we saw the Rabha cluster with populations sampled from Yunnan Province, indicating that the historical matrilineality of the Rabha has maintained lineages from Southern China. Assam has undergone multiple colonization events in the time since the initial peopling event, with populations from Southern China and Southeast Asia having the greatest influence on maternal lineages in the region. © 2017 Wiley Periodicals, Inc.

  8. Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

    Science.gov (United States)

    Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

    2016-01-01

    Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

  9. Variation and association to diabetes in 2000 full mtDNA sequences mined from an exome study in a Danish population

    DEFF Research Database (Denmark)

    Li, Shengting; Besenbacher, Soren; Li, Yingrui

    2014-01-01

    In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise...

  10. Complete mtDNA genomes of Filipino ethnolinguistic groups: a melting pot of recent and ancient lineages in the Asia-Pacific region

    Science.gov (United States)

    Delfin, Frederick; Min-Shan Ko, Albert; Li, Mingkun; Gunnarsdóttir, Ellen D; Tabbada, Kristina A; Salvador, Jazelyn M; Calacal, Gayvelline C; Sagum, Minerva S; Datar, Francisco A; Padilla, Sabino G; De Ungria, Maria Corazon A; Stoneking, Mark

    2014-01-01

    The Philippines is a strategic point in the Asia-Pacific region for the study of human diversity, history and origins, as it is a cross-road for human migrations and consequently exhibits enormous ethnolinguistic diversity. Following on a previous in-depth study of Y-chromosome variation, here we provide new insights into the maternal genetic history of Filipino ethnolinguistic groups by surveying complete mitochondrial DNA (mtDNA) genomes from a total of 14 groups (11 groups in this study and 3 groups previously published) including previously published mtDNA hypervariable segment (HVS) data from Filipino regional center groups. Comparison of HVS data indicate genetic differences between ethnolinguistic and regional center groups. The complete mtDNA genomes of 14 ethnolinguistic groups reveal genetic aspects consistent with the Y-chromosome, namely: diversity and heterogeneity of groups, no support for a simple dichotomy between Negrito and non-Negrito groups, and different genetic affinities with Asia-Pacific groups that are both ancient and recent. Although some mtDNA haplogroups can be associated with the Austronesian expansion, there are others that associate with South Asia, Near Oceania and Australia that are consistent with a southern migration route for ethnolinguistic group ancestors into the Asia-Pacific, with a timeline that overlaps with the initial colonization of the Asia-Pacific region, the initial colonization of the Philippines and a possible separate post-colonization migration into the Philippine archipelago. PMID:23756438

  11. Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia.

    Directory of Open Access Journals (Sweden)

    Angela L Sremba

    Full Text Available The Antarctic blue whale (Balaenoptera musculus intermedia was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86 have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004, perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST = 0.032, p<0.005 and microsatellite alleles (F(ST = 0.005, p<0.05 among the six Antarctic Areas historically used by the IWC for management of blue whales.

  12. Dysphagia is prevalent in patients with CPEO and single, large-scale deletions in mtDNA

    DEFF Research Database (Denmark)

    Pedersen, Gitte Hedermann; Løkken, Nicoline; Dahlqvist, Julia R.

    2017-01-01

    Background  The aim of this study was to assess the frequency of subjective and objective dysphagia in patients with chronic progressive external ophthalmoplegia (CPEO) due to single, large-scale deletions (LSDs) of mitochondrial DNA (mtDNA). Methods  Sixteen patients with CPEO and single LSDs...... and single LSDs of mtDNA had a prolonged cold-water test, including one with a PEG-tube, who was unable to perform the test, and nine patients reported subjective swallowing problems (56.3%). All mitochondrial myopathy patients in the control group had a normal duration of the cold-water test.  Conclusions......  The study shows that dysphagia is a common problem in patients with CPEO and LSDs of mtDNA. Dysphagia seems to be progressive with age as abnormal swallowing occurred preferentially in persons ≥ 45 years. The study shows that increased awareness of this symptom should be given to address appropriate...

  13. Cells Lacking mtDNA Display Increased dNTP Pools upon DNA Damage

    DEFF Research Database (Denmark)

    Skovgaard, Tine; Rasmussen, Lene Juel; Munch-Petersen, Birgitte

    Imbalanced dNTP pools are highly mutagenic due to a deleterious effect on DNA polymerase fidelity. Mitochondrial DNA defects, including mutations and deletions, are commonly found in a wide variety of different cancer types. In order to further study the interconnection between dNTP pools...... and mitochondrial function we have examined the effect of DNA damage on dNTP pools in cells deficient of mtDNA. We show that DNA damage induced by UV irradiation, in a dose corresponding to LD50, induces an S phase delay in different human osteosarcoma cell lines. The UV pulse also has a destabilizing effect...... shows that normal mitochondrial function is prerequisite for retaining stable dNTP pools upon DNA damage. Therefore it is likely that mitochondrial deficiency defects may cause an increase in DNA mutations by disrupting dNTP pool balance....

  14. Mitochondrial DNA copy number in peripheral blood cell and hypertension risk among mining workers: a case-control study in Chinese coal miners.

    Science.gov (United States)

    Lei, L; Guo, J; Shi, X; Zhang, G; Kang, H; Sun, C; Huang, J; Wang, T

    2017-09-01

    Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant-induced cell damage, has been observed in a wide range of human diseases. However, whether it correlates with hypertension has not been elucidated. We aimed to explore the association between mtDNA copy number and the risk of hypertension in Chinese coal miners. A case-control study was performed with 378 hypertension patients and 325 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staffs with necessary medical knowledge. The mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. No significant differences in mtDNA copy number were observed between hypertension patients and healthy controls. However, in both case and control groups, the mtDNA copy number was statistically significantly lower in the elder population (≥45 years old) compared with the younger subjects (associated with hypertension in coal miners.

  15. Infantile presentation of the mtDNA A3243G tRNA(Leu (UUR)) mutation.

    NARCIS (Netherlands)

    Okhuijsen-Kroes, E.J.; Trijbels, J.M.F.; Sengers, R.C.A.; Mariman, E.C.M.; Heuvel, L.P.W.J. van den; Wendel, U.A.H.; Koch, G.; Smeitink, J.A.M.

    2001-01-01

    Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, ranging from single organ involvement to severe multisystem disease. One of the most frequently observed mtDNA mutations is the A-to-G transition at position 3243 of the tRNA(Leu (UUR)) gene. This mutation is often related to

  16. Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

    Science.gov (United States)

    Furda, Amy M.; Marrangoni, Adele M.; Lokshin, Anna; Van Houten, Bennett

    2013-01-01

    Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60 min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60 min treatment with 2 mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. PMID:22766155

  17. Social Bots: Human-Like by Means of Human Control?

    Science.gov (United States)

    Grimme, Christian; Preuss, Mike; Adam, Lena; Trautmann, Heike

    2017-12-01

    Social bots are currently regarded an influential but also somewhat mysterious factor in public discourse and opinion making. They are considered to be capable of massively distributing propaganda in social and online media, and their application is even suspected to be partly responsible for recent election results. Astonishingly, the term social bot is not well defined and different scientific disciplines use divergent definitions. This work starts with a balanced definition attempt, before providing an overview of how social bots actually work (taking the example of Twitter) and what their current technical limitations are. Despite recent research progress in Deep Learning and Big Data, there are many activities bots cannot handle well. We then discuss how bot capabilities can be extended and controlled by integrating humans into the process and reason that this is currently the most promising way to realize meaningful interactions with other humans. This finally leads to the conclusion that hybridization is a challenge for current detection mechanisms and has to be handled with more sophisticated approaches to identify political propaganda distributed with social bots.

  18. Human Homeostatic Control Matrix in Norm

    Directory of Open Access Journals (Sweden)

    Alexander G. Kruglov

    2016-09-01

    Full Text Available We undertook our research to study and systemize the relationship between hemodynamics and biochemical parameters of arterial and venous blood in healthy people. Hemodynamic and biochemical characteristics were obtained through a probe by using catheterization in various vascular areas (aorta, brain, heart, lungs, and liver. Correlation and factor analyses were conducted to study the relationship between the obtained characteristics of the regional and systemic blood flow. Due to the nature of the correlation analysis, the significant (p<0.05 relation signs (+, 0, - without regard to their power were considered. The obtained results suggested that there are sets of both intra-organ and system regulatory relationships between metabolic and hemodynamic characteristics. The complex of relationships among the studied parameters makes it possible to maintain the homeostatic equilibrium in the body. The psychophysiological control system includes the subsystems we described: 1 the cardiac-hepatic-pulmonary complex having properties of the metabolic and hemodynamic information field providing biological stability of the homeostasis; any significant imbalance of its elements triggers afferent information flows actualizing an afferent synthesis; 2 the mind forming gradient patterns of targeted behavior to eliminate metabolic imbalance, to achieve goals both as coded biological parameters and as the highest forms of behavior, to reach the ultimate goal: parametric, homeostatic equilibrium in the “biosphere” of the human body. By using the results of our research and the complex of dynamic relationships in human homeostasis, we built a homeostatic control matrix (HCM.

  19. mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt).

    Science.gov (United States)

    Kenny, Timothy C; Germain, Doris

    2017-01-01

    While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR mt ) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR mt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR mt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR mt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPR mt in this setting.

  20. The application of human engineering in control room of HFETR

    International Nuclear Information System (INIS)

    Yang Shuchun; Shan Songlin

    2003-01-01

    The human-machine system for improving the working environment in the control room of HFETR is described. The reliability of the equipment, instruments and operation by human engineering is increased. The relations between human engineering and lowering human failure in HFETR are also discussed. It is concluded that the further application of human engineering can increase interaction of the human and machine in the control room and provide assurances for the safe and reliable operation of reactor. (authors)

  1. The application of human engineering in control room of HFETR

    Energy Technology Data Exchange (ETDEWEB)

    Shuchun, Yang; Songlin, Shan [Nuclear Power Inst. of China, Chengdu (China)

    2003-07-01

    The human-machine system for improving the working environment in the control room of HFETR is described. The reliability of the equipment, instruments and operation by human engineering is increased. The relations between human engineering and lowering human failure in HFETR are also discussed. It is concluded that the further application of human engineering can increase interaction of the human and machine in the control room and provide assurances for the safe and reliable operation of reactor. (authors)

  2. No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

    Directory of Open Access Journals (Sweden)

    Hellberg Michael E

    2006-03-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin, by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea. Results The mtDNA surveyed (630 bp of cytochrome oxidase subunit I was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years is similar to that in most plants, but 50–100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. Conclusion Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes.

  3. Changes in the human mitochondrial genome after treatment of malignant disease

    International Nuclear Information System (INIS)

    Wardell, Theresa M.; Ferguson, Elaine; Chinnery, Patrick F.; Borthwick, Gillian M.; Taylor, Robert W.; Jackson, Graham; Craft, Alan; Lightowlers, Robert N.; Howell, Neil; Turnbull, Douglass M.

    2003-01-01

    Mitochondrial DNA (mtDNA) is the only extrachromosomal DNA in human cells. The mitochondrial genome encodes essential information for the synthesis of the mitochondrial respiratory chain. Inherited defects of this genome are an important cause of human disease. In addition, the mitochondrial genome seems to be particularly prone to DNA damage and acquired mutations may have a role in ageing, cancer and neurodegeneration. We wished to determine if radiotherapy and chemotherapy used in the treatment of cancer could induce changes in the mitochondrial genome. Such changes would be an important genetic marker of DNA damage and may explain some of the adverse effects of treatment. We studied samples from patients who had received radiotherapy and chemotherapy for point mutations within the mtDNA control region, and for large-scale deletions. In blood samples from patients, we found a significantly increased number of point mutations compared to the control subjects. In muscle biopsies from 7 of 8 patients whom had received whole body irradiation as well as chemotherapy, the level of a specific mtDNA deletion was significantly greater than in control subjects. Our studies have shown that in patients who have been treated for cancer there is an increased level of mtDNA damage

  4. The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication.

    Science.gov (United States)

    Zhang, Yi; Chen, Yong; Gucek, Marjan; Xu, Hong

    2016-05-17

    Early embryonic development features rapid nuclear DNA replication cycles, but lacks mtDNA replication. To meet the high-energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mtDNA However, the cellular machinery driving massive mtDNA replication in ovaries remains unknown. Here, we describe a Drosophila AKAP protein, MDI that recruits a translation stimulator, La-related protein (Larp), to the mitochondrial outer membrane in ovaries. The MDI-Larp complex promotes the synthesis of a subset of nuclear-encoded mitochondrial proteins by cytosolic ribosomes on the mitochondrial surface. MDI-Larp's targets include mtDNA replication factors, mitochondrial ribosomal proteins, and electron-transport chain subunits. Lack of MDI abolishes mtDNA replication in ovaries, which leads to mtDNA deficiency in mature eggs. Targeting Larp to the mitochondrial outer membrane independently of MDI restores local protein synthesis and rescues the phenotypes of mdi mutant flies. Our work suggests that a selective translational boost by the MDI-Larp complex on the outer mitochondrial membrane might be essential for mtDNA replication and mitochondrial biogenesis during oogenesis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  5. The phylogeny of the four pan-American MtDNA haplogroups: implications for evolutionary and disease studies.

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    Alessandro Achilli

    Full Text Available Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s contributed only six (successful founder haplotypes to these haplogroups. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds.

  6. Reproduction (II): Human Control of Reproductive Processes

    Science.gov (United States)

    Jost, Alfred

    1970-01-01

    Describes methods of intervening in reproduction of animals and humans (artificial insemination, contraception, ovular and blastodisc transplants, pre selection of sex, cloning) and discusses the social implications of their use with humans. (AL)

  7. Mitochondrial DNA (mtDNA haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

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    Juan J. Yunis

    2013-01-01

    Full Text Available The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.

  8. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

    2011-01-01

    Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  9. The amount and integrity of mtDNA in maize decline with development.

    Science.gov (United States)

    Oldenburg, Delene J; Kumar, Rachana A; Bendich, Arnold J

    2013-02-01

    In maize and other grasses there is a developmental gradient from the meristematic cells at the base of the stalk to the differentiated cells at the leaf tip. This gradient presents an opportunity to investigate changes in mitochondrial DNA (mtDNA) that accompany growth under light and dark conditions, as done previously for plastid DNA. Maize mtDNA was analyzed by DAPI-DNA staining of individual mitochondria, gel electrophoresis/blot hybridization, and real-time qPCR. Both the amount and integrity of the mtDNA were found to decline with development. There was a 20-fold decline in mtDNA copy number per cell from the embryo to the light-grown leaf blade. The amount of DNA per mitochondrial particle was greater in dark-grown leaf blade (24 copies, on average) than in the light (2 copies), with some mitochondria lacking any detectable DNA. Three factors that influence the demise of mtDNA during development are considered: (1) the decision to either repair or degrade mtDNA molecules that are damaged by the reactive oxygen species produced as byproducts of respiration; (2) the generation of ATP by photophosphorylation in chloroplasts, reducing the need for respiratory-competent mitochondria; and (3) the shift in mitochondrial function from energy-generating respiration to photorespiration during the transition from non-green to green tissue.

  10. Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors

    International Nuclear Information System (INIS)

    Pereira, Luísa; Soares, Pedro; Máximo, Valdemar; Samuels, David C

    2012-01-01

    The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level. Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO. The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors. Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype

  11. Feather barbs as a good source of mtDNA for bird species identification in forensic wildlife investigations.

    Science.gov (United States)

    Speller, Camilla F; Nicholas, George P; Yang, Dongya Y

    2011-07-28

    The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis. By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl (Glaucidium californicum). The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique. By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis.

  12. Eurasian otters, Lutra lutra, have a dominant mtDNA haplotype from the Iberian Peninsula to Scandinavia.

    Science.gov (United States)

    Ferrando, Ainhoa; Ponsà, Montserrat; Marmi, Josep; Domingo-Roura, Xavier

    2004-01-01

    The Eurasian otter, Lutra lutra, has a Palaearctic distribution and has suffered a severe decline throughout Europe during the last century. Previous studies in this and other mustelids have shown reduced levels of variability in mitochondrial DNA, although otter phylogeographic studies were restricted to central-western Europe. In this work we have sequenced 361 bp of the mtDNA control region in 73 individuals from eight countries and added our results to eight sequences available from GenBank and the literature. The range of distribution has been expanded in relation to previous works north towards Scandinavia, east to Russia and Belarus, and south to the Iberian Peninsula. We found a single dominant haplotype in 91.78% of the samples, and six more haplotypes deviating a maximum of two mutations from the dominant haplotype restricted to a single country. Variability was extremely low in western Europe but higher in eastern countries. This, together with the lack of phylogeographical structuring, supports the postglacial recolonization of Europe from a single refugium. The Eurasian otter mtDNA control region has a 220-bp variable minisatellite in Domain III that we sequenced in 29 otters. We found a total of 19 minisatellite haplotypes, but they showed no phylogenetic information.

  13. Mitochondrial DNA (mtDNA haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Fernandez-Moreno Mercedes

    2011-11-01

    Full Text Available Abstract Background Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2 and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. Methods We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI, age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. Results Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p Conclusions The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase

  14. A 28,000 Years Old Cro-Magnon mtDNA Sequence Differs from All Potentially Contaminating Modern Sequences

    Science.gov (United States)

    Caramelli, David; Milani, Lucio; Vai, Stefania; Modi, Alessandra; Pecchioli, Elena; Girardi, Matteo; Pilli, Elena; Lari, Martina; Lippi, Barbara; Ronchitelli, Annamaria; Mallegni, Francesco; Casoli, Antonella; Bertorelle, Giorgio; Barbujani, Guido

    2008-01-01

    Background DNA sequences from ancient speciments may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal) and early modern (Cro-Magnoid) Europeans. Methodology/Principal Findings We typed the mitochondrial DNA (mtDNA) hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23) and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences. Conclusions/Significance: The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans. PMID:18628960

  15. Targeted Transgenic Overexpression of Mitochondrial Thymidine Kinase (TK2) Alters Mitochondrial DNA (mtDNA) and Mitochondrial Polypeptide Abundance

    Science.gov (United States)

    Hosseini, Seyed H.; Kohler, James J.; Haase, Chad P.; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

    2007-01-01

    Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-γ. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity. PMID:17322372

  16. A 28,000 years old Cro-Magnon mtDNA sequence differs from all potentially contaminating modern sequences.

    Directory of Open Access Journals (Sweden)

    David Caramelli

    Full Text Available BACKGROUND: DNA sequences from ancient specimens may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal and early modern (Cro-Magnoid Europeans. METHODOLOGY/PRINCIPAL FINDINGS: We typed the mitochondrial DNA (mtDNA hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23 and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences. CONCLUSIONS/SIGNIFICANCE: The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans.

  17. Analysis of mtDNA sequence variants in colorectal adenomatous polyps

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    Grizzle William

    2010-10-01

    Full Text Available Abstract Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57% variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17 in tubular and 57% (13/23 in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was

  18. Human factors methods for nuclear control room design. Volume I. Human factors enhancement of existing nuclear control rooms. Final report

    International Nuclear Information System (INIS)

    Seminara, J.L.; Seidenstein, S.; Eckert, S.K.; Smith, D.L.

    1979-11-01

    Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. Human factors approaches were applied in the design of representative nuclear power plant control panels. First, methods for upgrading existing operational control panels were examined. Then, based on detailed human factors analyses of operator information and control requirements, designs of reactor, feedwater, and turbine-generator control panels were developed to improve the operator-control board interface, thereby reducing the potential for operator errors. In addition to examining present-generation concepts, human factors aspects of advanced systems and of hybrid combinations of advanced and conventional designs were investigated. Special attention was given to warning system designs. Also, a survey was conducted among control board designers to (1) develop an overview of design practices in the industry, and (2) establish appropriate measures leading to a more systematic concern for human factors in control board design

  19. HUMAN FACTORS GUIDANCE FOR CONTROL ROOM EVALUATION

    International Nuclear Information System (INIS)

    OHARA, J.; BROWN, W.; STUBLER, W.; HIGGINS, J.; WACHTEL, J.; PERSENSKY, J.J.

    2000-01-01

    The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ''Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1

  20. In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq

    Directory of Open Access Journals (Sweden)

    Olivieri Anna

    2011-10-01

    Full Text Available Abstract Background For millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region. Results To shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates. Conclusions Evidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of

  1. Uniquely Human Self-Control Begins at School Age

    Science.gov (United States)

    Herrmann, Esther; Misch, Antonia; Hernandez-Lloreda, Victoria; Tomasello, Michael

    2015-01-01

    Human beings have remarkable skills of self-control, but the evolutionary origins of these skills are unknown. Here we compare children at 3 and 6 years of age with one of humans' two nearest relatives, chimpanzees, on a battery of reactivity and self-control tasks. Three-year-old children and chimpanzees were very similar in their abilities to…

  2. Phylogeographical analysis of mtDNA data indicates postglacial expansion from multiple glacial refugia in woodland caribou (Rangifer tarandus caribou.

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    Cornelya F C Klütsch

    Full Text Available Glacial refugia considerably shaped the phylogeographical structure of species and may influence intra-specific morphological, genetic, and adaptive differentiation. However, the impact of the Quaternary ice ages on the phylogeographical structure of North American temperate mammalian species is not well-studied. Here, we surveyed ~1600 individuals of the widely distributed woodland caribou (Rangifer tarandus caribou using mtDNA control region sequences to investigate if glacial refugia contributed to the phylogeographical structure in this subspecies. Phylogenetic tree reconstruction, a median-joining network, and mismatch distributions supported postglacial expansions of woodland caribou from three glacial refugia dating back to 13544-22005 years. These three lineages consisted almost exclusively of woodland caribou mtDNA haplotypes, indicating that phylogeographical structure was mainly shaped by postglacial expansions. The putative centres of these lineages are geographically separated; indicating disconnected glacial refugia in the Rocky Mountains, east of the Mississippi, and the Appalachian Mountains. This is in congruence with the fossil record that caribou were distributed in these areas during the Pleistocene. Our results suggest that the last glacial maximum substantially shaped the phylogeographical structure of this large mammalian North American species that will be affected by climatic change. Therefore, the presented results will be essential for future conservation planning in woodland caribou.

  3. MtDNA COI-COII marker and drone congregation area: an efficient method to establish and monitor honeybee (Apis mellifera L.) conservation centres.

    Science.gov (United States)

    Bertrand, Bénédicte; Alburaki, Mohamed; Legout, Hélène; Moulin, Sibyle; Mougel, Florence; Garnery, Lionel

    2015-05-01

    Honeybee subspecies have been affected by human activities in Europe over the past few decades. One such example is the importation of nonlocal subspecies of bees which has had an adverse impact on the geographical repartition and subsequently on the genetic diversity of the black honeybee Apis mellifera mellifera. To restore the original diversity of this local honeybee subspecies, different conservation centres were set up in Europe. In this study, we established a black honeybee conservation centre Conservatoire de l'Abeille Noire d'Ile de France (CANIF) in the region of Ile-de-France, France. CANIF's honeybee colonies were intensively studied over a 3-year period. This study included a drone congregation area (DCA) located in the conservation centre. MtDNA COI-COII marker was used to evaluate the genetic diversity of CANIF's honeybee populations and the drones found and collected from the DCA. The same marker (mtDNA) was used to estimate the interactions and the haplotype frequency between CANIF's honeybee populations and 10 surrounding honeybee apiaries located outside of the CANIF. Our results indicate that the colonies of the conservation centre and the drones of the DCA show similar stable profiles compared to the surrounding populations with lower level of introgression. The mtDNA marker used on both DCA and colonies of the conservation centre seems to be an efficient approach to monitor and maintain the genetic diversity of the protected honeybee populations. © 2014 John Wiley & Sons Ltd.

  4. Human error mode identification for NPP main control room operations using soft controls

    International Nuclear Information System (INIS)

    Lee, Seung Jun; Kim, Jaewhan; Jang, Seung-Cheol

    2011-01-01

    The operation environment of main control rooms (MCRs) in modern nuclear power plants (NPPs) has considerably changed over the years. Advanced MCRs, which have been designed by adapting digital and computer technologies, have simpler interfaces using large display panels, computerized displays, soft controls, computerized procedure systems, and so on. The actions for the NPP operations are performed using soft controls in advanced MCRs. Soft controls have different features from conventional controls. Operators need to navigate the screens to find indicators and controls and manipulate controls using a mouse, touch screens, and so on. Due to these different interfaces, different human errors should be considered in the human reliability analysis (HRA) for advanced MCRs. In this work, human errors that could occur during operation executions using soft controls were analyzed. This work classified the human errors in soft controls into six types, and the reasons that affect the occurrence of the human errors were also analyzed. (author)

  5. Evidence of animal mtDNA recombination between divergent populations of the potato cyst nematode Globodera pallida.

    Science.gov (United States)

    Hoolahan, Angelique H; Blok, Vivian C; Gibson, Tracey; Dowton, Mark

    2012-03-01

    Recombination is typically assumed to be absent in animal mitochondrial genomes (mtDNA). However, the maternal mode of inheritance means that recombinant products are indistinguishable from their progenitor molecules. The majority of studies of mtDNA recombination assess past recombination events, where patterns of recombination are inferred by comparing the mtDNA of different individuals. Few studies assess contemporary mtDNA recombination, where recombinant molecules are observed as direct mosaics of known progenitor molecules. Here we use the potato cyst nematode, Globodera pallida, to investigate past and contemporary recombination. Past recombination was assessed within and between populations of G. pallida, and contemporary recombination was assessed in the progeny of experimental crosses of these populations. Breeding of genetically divergent organisms may cause paternal mtDNA leakage, resulting in heteroplasmy and facilitating the detection of recombination. To assess contemporary recombination we looked for evidence of recombination between the mtDNA of the parental populations within the mtDNA of progeny. Past recombination was detected between a South American population and several UK populations of G. pallida, as well as between two South American populations. This suggests that these populations may have interbred, paternal mtDNA leakage occurred, and the mtDNA of these populations subsequently recombined. This evidence challenges two dogmas of animal mtDNA evolution; no recombination and maternal inheritance. No contemporary recombination between the parental populations was detected in the progeny of the experimental crosses. This supports current arguments that mtDNA recombination events are rare. More sensitive detection methods may be required to adequately assess contemporary mtDNA recombination in animals.

  6. Forensic and phylogeographic characterisation of mtDNA lineages from Somalia.

    Science.gov (United States)

    Mikkelsen, Martin; Fendt, Liane; Röck, Alexander W; Zimmermann, Bettina; Rockenbauer, Eszter; Hansen, Anders J; Parson, Walther; Morling, Niels

    2012-07-01

    The African mitochondrial (mt) phylogeny is coarsely resolved but the majority of population data generated so far is limited to the analysis of the first hypervariable segment (HVS-1) of the control region (CR). Therefore, this study aimed on the investigation of the entire CR of 190 unrelated Somali individuals to enrich the severely underrepresented African mtDNA pool. The majority (60.5 %) of the haplotypes were of sub-Saharan origin with L0a1d, L2a1h and L3f being the most frequently observed haplogroups. This is in sharp contrast to previous data reported from the Y-chromosome, where only about 5 % of the observed haplogroups were of sub-Saharan provenance. We compared the genetic distances based on population pairwise F (st) values between 11 published East, Central and North African as well as western Asian populations and the Somali sequences and displayed them in a multi-dimensional scaling plot. Genetic proximity evidenced by clustering roughly reflected the relative geographic location of the populations. The sequences will be included in the EMPOP database ( www.empop.org ) under accession number EMP00397 upon publication (Parson and Dür Forensic Sci Int Genet 1:88-92, 2007).

  7. Abundant mtDNA diversity and ancestral admixture in Colombian criollo cattle (Bos taurus).

    Science.gov (United States)

    Carvajal-Carmona, Luis G; Bermudez, Nelson; Olivera-Angel, Martha; Estrada, Luzardo; Ossa, Jorge; Bedoya, Gabriel; Ruiz-Linares, Andrés

    2003-11-01

    Various cattle populations in the Americas (known as criollo breeds) have an origin in some of the first livestock introduced to the continent early in the colonial period (16th and 17th centuries). These cattle constitute a potentially important genetic reserve as they are well adapted to local environments and show considerable variation in phenotype. To examine the genetic ancestry and diversity of Colombian criollo we obtained mitochondrial DNA control region sequence information for 110 individuals from seven breeds. Old World haplogroup T3 is the most commonly observed CR lineage in criollo (0.65), in agreement with a mostly European ancestry for these cattle. However, criollo also shows considerable frequencies of haplogroups T2 (0.9) and T1 (0.26), with T1 lineages in criollo being more diverse than those reported for West Africa. The distribution and diversity of Old World lineages suggest some North African ancestry for criollo, probably as a result of the Arab occupation of Iberia prior to the European migration to the New World. The mtDNA diversity of criollo is higher than that reported for European and African cattle and is consistent with a differentiated ancestry for some criollo breeds.

  8. History of Lipizzan horse maternal lines as revealed by mtDNA analysis

    Directory of Open Access Journals (Sweden)

    Dovč Peter

    2002-09-01

    Full Text Available Abstract Sequencing of the mtDNA control region (385 or 695 bp of 212 Lipizzans from eight studs revealed 37 haplotypes. Distribution of haplotypes among studs was biased, including many private haplotypes but only one haplotype was present in all the studs. According to historical data, numerous Lipizzan maternal lines originating from founder mares of different breeds have been established during the breed's history, so the broad genetic base of the Lipizzan maternal lines was expected. A comparison of Lipizzan sequences with 136 sequences of domestic- and wild-horses from GenBank showed a clustering of Lipizzan haplotypes in the majority of haplotype subgroups present in other domestic horses. We assume that haplotypes identical to haplotypes of early domesticated horses can be found in several Lipizzan maternal lines as well as in other breeds. Therefore, domestic horses could arise either from a single large population or from several populations provided there were strong migrations during the early phase after domestication. A comparison of Lipizzan haplotypes with 56 maternal lines (according to the pedigrees showed a disagreement of biological parentage with pedigree data for at least 11% of the Lipizzans. A distribution of haplotype-frequencies was unequal (0.2%–26%, mainly due to pedigree errors and haplotype sharing among founder mares.

  9. Human as the chief controller in the complex system

    International Nuclear Information System (INIS)

    Jung, Yeonsub

    2012-01-01

    Due to accuracy of measurement and improvement of control logic, human beings are freed from time consuming and repeated task. When there are situations where the control logic cannot calculate the next state of system, human beings interrupt the system and steer the system manually. The most scope of human factors is focused on this interruption, and economists are concern how to present information cognitively and reliably. Fukushima nuclear accident has considered the role of human beings again. Human beings are forced to do something without proper knowledge, procedure, and process information. Thus post Fukushima actions should include how for human beings to be trained and how to get real time information. Finally because safety culture can determine behaviors of human beings, the method to cultivate safety culture should be considered

  10. Modeling Human Error Mechanism for Soft Control in Advanced Control Rooms (ACRs)

    International Nuclear Information System (INIS)

    Aljneibi, Hanan Salah Ali; Ha, Jun Su; Kang, Seongkeun; Seong, Poong Hyun

    2015-01-01

    To achieve the switch from conventional analog-based design to digital design in ACRs, a large number of manual operating controls and switches have to be replaced by a few common multi-function devices which is called soft control system. The soft controls in APR-1400 ACRs are classified into safety-grade and non-safety-grade soft controls; each was designed using different and independent input devices in ACRs. The operations using soft controls require operators to perform new tasks which were not necessary in conventional controls such as navigating computerized displays to monitor plant information and control devices. These kinds of computerized displays and soft controls may make operations more convenient but they might cause new types of human error. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or human errors) during NPP operation. The developed model would contribute to a lot of applications to improve human performance (or reduce human errors), HMI designs, and operators' training program in ACRs. The developed model of human error mechanism for the soft control is based on assumptions that a human operator has certain amount of capacity in cognitive resources and if resources required by operating tasks are greater than resources invested by the operator, human error (or poor human performance) is likely to occur (especially in 'slip'); good HMI (Human-machine Interface) design decreases the required resources; operator's skillfulness decreases the required resources; and high vigilance increases the invested resources. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or reduction of human errors) during NPP operation

  11. Modeling Human Error Mechanism for Soft Control in Advanced Control Rooms (ACRs)

    Energy Technology Data Exchange (ETDEWEB)

    Aljneibi, Hanan Salah Ali [Khalifa Univ., Abu Dhabi (United Arab Emirates); Ha, Jun Su; Kang, Seongkeun; Seong, Poong Hyun [KAIST, Daejeon (Korea, Republic of)

    2015-10-15

    To achieve the switch from conventional analog-based design to digital design in ACRs, a large number of manual operating controls and switches have to be replaced by a few common multi-function devices which is called soft control system. The soft controls in APR-1400 ACRs are classified into safety-grade and non-safety-grade soft controls; each was designed using different and independent input devices in ACRs. The operations using soft controls require operators to perform new tasks which were not necessary in conventional controls such as navigating computerized displays to monitor plant information and control devices. These kinds of computerized displays and soft controls may make operations more convenient but they might cause new types of human error. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or human errors) during NPP operation. The developed model would contribute to a lot of applications to improve human performance (or reduce human errors), HMI designs, and operators' training program in ACRs. The developed model of human error mechanism for the soft control is based on assumptions that a human operator has certain amount of capacity in cognitive resources and if resources required by operating tasks are greater than resources invested by the operator, human error (or poor human performance) is likely to occur (especially in 'slip'); good HMI (Human-machine Interface) design decreases the required resources; operator's skillfulness decreases the required resources; and high vigilance increases the invested resources. In this study the human error mechanism during the soft controls is studied and modeled to be used for analysis and enhancement of human performance (or reduction of human errors) during NPP operation.

  12. Human Information Processing and Supervisory Control.

    Science.gov (United States)

    1980-05-01

    errors (that is of the output of the human operator). There is growing evidence (Senders, personal communication; Norman , personal communication...relates to the relative tendency to depend on sensory information or to be more analytic and independent. Norman (personal communication) has referred...decision process model. Ergonomics, 12, 543-557. Senders, J., Elkid, J., Grignetti, M., & Smallwood , R. 1966. An investigation of the visual sampling

  13. Visual servo control for a human-following robot

    CSIR Research Space (South Africa)

    Burke, Michael G

    2011-03-01

    Full Text Available This thesis presents work completed on the design of control and vision components for use in a monocular vision-based human-following robot. The use of vision in a controller feedback loop is referred to as vision-based or visual servo control...

  14. Human factors evaluation of the engineering test reactor control room

    International Nuclear Information System (INIS)

    Banks, W.W.; Boone, M.P.

    1981-03-01

    The Reactor and Process Control Rooms at the Engineering Test Reactor were evaluated by a team of human factors engineers using available human factors design criteria. During the evaluation, ETR, equipment and facilities were compared with MIL-STD-1472-B, Human Engineering design Criteria for Military Systems. The focus of recommendations centered on: (a) displays and controls; placing displays and controls in functional groups; (b) establishing a consistent color coding (in compliance with a standard if possible); (c) systematizing annunciator alarms and reducing their number; (d) organizing equipment in functional groups; and (e) modifying labeling and lines of demarcation

  15. Plant Modeling for Human Supervisory Control

    DEFF Research Database (Denmark)

    Lind, Morten

    1999-01-01

    This paper provides an overview of multilevel flow modelling (MFM) and its application for design of displays for the supervisory control of industrial plant. The problem of designing the inforrrzatian content of sacpervisory displays is discussed and plant representations like MFM using levels...

  16. Land, language, and loci: mtDNA in Native Americans and the genetic history of Peru.

    Science.gov (United States)

    Lewis, Cecil M; Tito, Raúl Y; Lizárraga, Beatriz; Stone, Anne C

    2005-07-01

    Despite a long history of complex societies and despite extensive present-day linguistic and ethnic diversity, relatively few populations in Peru have been sampled for population genetic investigations. In order to address questions about the relationships between South American populations and about the extent of correlation between genetic distance, language, and geography in the region, mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup markers were examined in 33 individuals from the state of Ancash, Peru. These sequences were compared to those from 19 American Indian populations using diversity estimates, AMOVA tests, mismatch distributions, a multidimensional scaling plot, and regressions. The results show correlations between genetics, linguistics, and geographical affinities, with stronger correlations between genetics and language. Additionally, the results suggest a pattern of differential gene flow and drift in western vs. eastern South America, supporting previous mtDNA and Y chromosome investigations. (c) 2004 Wiley-Liss, Inc

  17. DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?

    Directory of Open Access Journals (Sweden)

    Alessandra eMaresca

    2015-03-01

    Full Text Available Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN and Hereditary sensory neuropathy with dementia and hearing loss (HSN1E are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic dominant pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5-methyltransferase 1. DNMT1 is the enzyme responsible for maintaining the nuclear genome methylation patterns during the DNA replication and repair, thus regulating gene expression. The mutations responsible for ADCA-DN and HSN1E affect the replication foci targeting sequence domain, which regulates DNMT1 binding to chromatin. DNMT1 dysfunction is anticipated to lead to a global alteration of the DNA methylation pattern with predictable downstream consequences on gene expression. Interestingly, ADCA-DN and HSN1E phenotypes share some clinical features typical of mitochondrial diseases, such as optic atrophy, peripheral neuropathy and deafness, and some biochemical evidence of mitochondrial dysfunction. The recent discovery of a mitochondrial isoform of DNMT1 and its proposed role in methylating mitochondrial DNA (mtDNA suggests that DNMT1 mutations may directly affect mtDNA and mitochondrial physiology. On the basis of this latter finding the link between DNMT1 abnormal activity and mitochondrial dysfunction in ADCA-DN and HSN1E appears intuitive, however mtDNA methylation remains highly debated. In the last years several groups demonstrated the presence of 5-methylcytosine in mtDNA by different approaches, but, on the other end, the opposite evidence that mtDNA is not methylated has also been published. Since over 1500 mitochondrial proteins are encoded by the nuclear genome, the altered methylation of these genes may well have a critical role in leading to the mitochondrial impairment observed in ADCA-DN and HSN1E. Thus, many open questions still remain unanswered, such as why mtDNA should be methylated, and how this process is

  18. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

    International Nuclear Information System (INIS)

    Wang Chengye; Kong Qingpeng; Yao Yonggang; Zhang Yaping

    2006-01-01

    Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL

  19. Human Papilloma Virus Vaccination for Control of Cervical Cancer ...

    African Journals Online (AJOL)

    Human Papilloma Virus Vaccination for Control of Cervical Cancer: A ... Primary HPV prevention may be the key to reducing incidence and burden of cervical cancer ... Other resources included locally-published articles and additional internet ...

  20. Taking account of human factors in control-room design

    International Nuclear Information System (INIS)

    Dien, Y.; Montmayeul, R.

    1995-07-01

    Since the Three Mile Island accident two ways for improving the Human-Machine Interface have mainly been followed: the development of computerized operator aids in existing control-rooms and the design of advanced control-rooms. Insufficient attention paid to human factors in the design of operator aids has generally led to these aids being neglected or unused by their potential users. While for the design of advanced control-rooms efforts have been made for dealing with human factors in more extensive way. Based upon this experience, a general method for taking account of human factors in a control-room design has been devised and is described in this paper. (author)

  1. Mechanics of human voice production and control.

    Science.gov (United States)

    Zhang, Zhaoyan

    2016-10-01

    As the primary means of communication, voice plays an important role in daily life. Voice also conveys personal information such as social status, personal traits, and the emotional state of the speaker. Mechanically, voice production involves complex fluid-structure interaction within the glottis and its control by laryngeal muscle activation. An important goal of voice research is to establish a causal theory linking voice physiology and biomechanics to how speakers use and control voice to communicate meaning and personal information. Establishing such a causal theory has important implications for clinical voice management, voice training, and many speech technology applications. This paper provides a review of voice physiology and biomechanics, the physics of vocal fold vibration and sound production, and laryngeal muscular control of the fundamental frequency of voice, vocal intensity, and voice quality. Current efforts to develop mechanical and computational models of voice production are also critically reviewed. Finally, issues and future challenges in developing a causal theory of voice production and perception are discussed.

  2. Human factors methods for nuclear control room design. Volume 2. Human factors survey of control room design practices

    International Nuclear Information System (INIS)

    Seminara, J.L.; Parsons, S.O.

    1979-11-01

    An earlier review of the control rooms of operating nuclear power plants identified many design problems having potential for degrading operator performance. As a result, the formal application of human factors principles was found to be needed. This report demonstrates the use of human factors in the design of power plant control rooms. The approaches shown in the report can be applied to operating power plants, as well as to those in the design stage. This study documents human factors techniques required to provide a sustained concern for the man-machine interface from control room concept definition to system implementation

  3. Safety Metrics for Human-Computer Controlled Systems

    Science.gov (United States)

    Leveson, Nancy G; Hatanaka, Iwao

    2000-01-01

    The rapid growth of computer technology and innovation has played a significant role in the rise of computer automation of human tasks in modem production systems across all industries. Although the rationale for automation has been to eliminate "human error" or to relieve humans from manual repetitive tasks, various computer-related hazards and accidents have emerged as a direct result of increased system complexity attributed to computer automation. The risk assessment techniques utilized for electromechanical systems are not suitable for today's software-intensive systems or complex human-computer controlled systems.This thesis will propose a new systemic model-based framework for analyzing risk in safety-critical systems where both computers and humans are controlling safety-critical functions. A new systems accident model will be developed based upon modem systems theory and human cognitive processes to better characterize system accidents, the role of human operators, and the influence of software in its direct control of significant system functions Better risk assessments will then be achievable through the application of this new framework to complex human-computer controlled systems.

  4. Modular control of limb movements during human locomotion

    NARCIS (Netherlands)

    Ivanenko, Yuri P; Cappellini, Germana; Dominici, Nadia; Poppele, Richard E; Lacquaniti, Francesco

    2007-01-01

    The idea that the CNS may control complex interactions by modular decomposition has received considerable attention. We explored this idea for human locomotion by examining limb kinematics. The coordination of limb segments during human locomotion has been shown to follow a planar law for walking at

  5. Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

    Science.gov (United States)

    Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

    2017-06-26

    Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

  6. Statistical physics of human beings in games: Controlled experiments

    International Nuclear Information System (INIS)

    Liang Yuan; Huang Ji-Ping

    2014-01-01

    It is important to know whether the laws or phenomena in statistical physics for natural systems with non-adaptive agents still hold for social human systems with adaptive agents, because this implies whether it is possible to study or understand social human systems by using statistical physics originating from natural systems. For this purpose, we review the role of human adaptability in four kinds of specific human behaviors, namely, normal behavior, herd behavior, contrarian behavior, and hedge behavior. The approach is based on controlled experiments in the framework of market-directed resource-allocation games. The role of the controlled experiments could be at least two-fold: adopting the real human decision-making process so that the system under consideration could reflect the performance of genuine human beings; making it possible to obtain macroscopic physical properties of a human system by tuning a particular factor of the system, thus directly revealing cause and effect. As a result, both computer simulations and theoretical analyses help to show a few counterparts of some laws or phenomena in statistical physics for social human systems: two-phase phenomena or phase transitions, entropy-related phenomena, and a non-equilibrium steady state. This review highlights the role of human adaptability in these counterparts, and makes it possible to study or understand some particular social human systems by means of statistical physics coming from natural systems. (topical review - statistical physics and complex systems)

  7. Statistical physics of human beings in games: Controlled experiments

    Science.gov (United States)

    Liang, Yuan; Huang, Ji-Ping

    2014-07-01

    It is important to know whether the laws or phenomena in statistical physics for natural systems with non-adaptive agents still hold for social human systems with adaptive agents, because this implies whether it is possible to study or understand social human systems by using statistical physics originating from natural systems. For this purpose, we review the role of human adaptability in four kinds of specific human behaviors, namely, normal behavior, herd behavior, contrarian behavior, and hedge behavior. The approach is based on controlled experiments in the framework of market-directed resource-allocation games. The role of the controlled experiments could be at least two-fold: adopting the real human decision-making process so that the system under consideration could reflect the performance of genuine human beings; making it possible to obtain macroscopic physical properties of a human system by tuning a particular factor of the system, thus directly revealing cause and effect. As a result, both computer simulations and theoretical analyses help to show a few counterparts of some laws or phenomena in statistical physics for social human systems: two-phase phenomena or phase transitions, entropy-related phenomena, and a non-equilibrium steady state. This review highlights the role of human adaptability in these counterparts, and makes it possible to study or understand some particular social human systems by means of statistical physics coming from natural systems.

  8. Phylogeography of mtDNA haplogroup R7 in the Indian peninsula

    Directory of Open Access Journals (Sweden)

    Shukla Parul

    2008-08-01

    Full Text Available Abstract Background Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic speaking populations originated in India or derive from a relatively recent migration from further East. Results Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1, is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between

  9. Analysis of mtDNT 4977bp deletion induced by ionizing radiation in human peripheral blood nucleated cells using real-time PCR

    International Nuclear Information System (INIS)

    Fan Tianli; Wang Ping; Han Lin; Liu Yulong; Liu Yumin

    2010-01-01

    To detect mitochondrial DNA(mtDNA) 4977bp deletion(triangle open mtDNA 4977 ) in human peripheral blood nucleated cells exposed to ionizing radiation in vitro by using real-time PCR, and explore possibility of the index as biodosimetry for estimating biological dose in radiation accident,six healthy individuals' peripheral blood was collected,and the blood samples were irradiated with 0,1,2,3,4 and 5 Gy 60 Co gamma-ray. The triangle open mtDNA 4977 and total mtDNA copy number(mtDNA total ) in the mtDNA samples were detected, and then the deletion rates were calculated. The results showed that the mtDNA total and triangle open mtDNA 4977 copy number, and the deletion rates of mtDNA 4977bp in the mtDNA samples from 6 healthy individuals' blood exposed to 1-5 Gy radiation were higher than that with the samples exposed to 0 Gy radiation(p 0.05). The results indicated that ionizing radiation can induce accumulation of the triangle open mtDNA 4977 and increase of mtDNA total copy number in human peripheral blood nucleated cells,but both the mtDNA 4977bp deletion and exposure dose(0-5 Gy) were not obviously correlated. (authors)

  10. Buried waste integrated demonstration human engineered control station. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-09-01

    This document describes the Human Engineered Control Station (HECS) project activities including the conceptual designs. The purpose of the HECS is to enhance the effectiveness and efficiency of remote retrieval by providing an integrated remote control station. The HECS integrates human capabilities, limitations, and expectations into the design to reduce the potential for human error, provides an easy system to learn and operate, provides an increased productivity, and reduces the ultimate investment in training. The overall HECS consists of the technology interface stations, supporting engineering aids, platform (trailer), communications network (broadband system), and collision avoidance system.

  11. Buried waste integrated demonstration human engineered control station. Final report

    International Nuclear Information System (INIS)

    1994-09-01

    This document describes the Human Engineered Control Station (HECS) project activities including the conceptual designs. The purpose of the HECS is to enhance the effectiveness and efficiency of remote retrieval by providing an integrated remote control station. The HECS integrates human capabilities, limitations, and expectations into the design to reduce the potential for human error, provides an easy system to learn and operate, provides an increased productivity, and reduces the ultimate investment in training. The overall HECS consists of the technology interface stations, supporting engineering aids, platform (trailer), communications network (broadband system), and collision avoidance system

  12. Mechanisms of mtDNA segregation and mitochondrial signalling in cells with the pathogenic A3243G mutation

    NARCIS (Netherlands)

    Jahangir Tafrechi, Roshan Sakineh

    2008-01-01

    Using newly developed single cell A3243G mutation load assays a novel mechanism of mtDNA segregation was identified in which the multi-copy mtDNA nucleoid takes a central position. Furthermore, likely due to low level changes in gene expression, no genes or gene sets could be identified with gene

  13. Human factors survey of advanced instrumentation and controls

    International Nuclear Information System (INIS)

    Carter, R.J.

    1989-01-01

    A survey oriented towards identifying the human factors issues in regard to the use of advanced instrumentation and controls (I ampersand C) in the nuclear industry was conducted. A number of United States (US) and Canadian nuclear vendors and utilities were participants in the survey. Human factors items, subsumed under the categories of computer-generated displays (CGD), controls, organizational support, training, and related topics, were discussed. The survey found the industry to be concerned about the human factors issues related to the implementation of advanced I ampersand C. Fifteen potential human factors problems were identified. They include: the need for an advanced I ampersand C guideline equivalent to NUREG-0700; a role change in the control room from operator to supervisor; information overload; adequacy of existing training technology for advanced I ampersand C; and operator acceptance and trust. 11 refs., 1 tab

  14. Human machine interface for research reactor instrumentation and control system

    International Nuclear Information System (INIS)

    Mohd Sabri Minhat; Mohd Idris Taib; Izhar Abu Hussin; Zareen Khan Abdul Jalil Khan; Nurfarhana Ayuni Joha

    2010-01-01

    Most present design of Human Machine Interface for Research Reactor Instrumentation and Control System is modular-based, comprise of several cabinets such as Reactor Protection System, Control Console, Information Console as well as Communication Console. The safety, engineering and human factor will be concerned for the design. Redundancy and separation of signal and power supply are the main factor for safety consideration. The design of Operator Interface absolutely takes consideration of human and environmental factors. Physical parameters, experiences, trainability and long-established habit patterns are very important for user interface, instead of the Aesthetic and Operator-Interface Geometry. Physical design for New Instrumentation and Control System of RTP are proposed base on the state-of- the-art Human Machine Interface design. (author)

  15. Control room design and human engineering in power plants

    International Nuclear Information System (INIS)

    Herbst, L.; Hinz, W.

    1982-01-01

    The concept for modern plant control rooms is primary influenced by: The automation of protection, binary control and closed loop control functions; organization employing functional areas; computer based information processing; human engineered design. Automation reduces the human work load. Employment of functional areas permits optimization of operational sequences. Computer based information processing makes it possible to output information in accordance with operating requirements. Design based on human engineering principles assures the quality of the interaction between the operator and the equipment. The degree to which these conceptional features play a role in design of power plant control rooms depends on the unit rating, the mode of operation and on the requirements respecting safety and availability of the plant. (orig.)

  16. Allozyme and mtDNA variation of white seabream Diplodus sargus ...

    African Journals Online (AJOL)

    These results can be explained by the chaotic genetic patchiness hypothesis. In contrast, the mtDNA data indicated genetic homogeneity among localities showing the absence of structure in white seabream populations across the Siculo-Tunisian Strait. Historical demography of this species suggests that it has undergone ...

  17. Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

    Science.gov (United States)

    Peñaloza-Espinosa, Rosenda I; Arenas-Aranda, Diego; Cerda-Flores, Ricardo M; Buentello-Malo, Leonor; González-Valencia, Gerardo; Torres, Javier; Alvarez, Berenice; Mendoza, Irma; Flores, Mario; Sandoval, Lucila; Loeza, Francisco; Ramos, Irma; Muñoz, Leopoldo; Salamanca, Fabio

    2007-06-01

    In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.

  18. Comprehensive view of the population history of Arabia as inferred by mtDNA variation

    Czech Academy of Sciences Publication Activity Database

    Černý, Viktor; Čížková, M.; Poloni, E. S.; Al-Meeri, A.; Mulligan, C. J.

    2016-01-01

    Roč. 159, č. 4 (2016), s. 607-616 ISSN 0002-9483 R&D Projects: GA ČR GA13-37998S Institutional support: RVO:67985912 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.552, year: 2016

  19. Human performance: An essential element in materials control and accountability

    International Nuclear Information System (INIS)

    Haber, S.B.; Allentuck, J.

    1996-01-01

    The importance of the role of human performance in the successful and effective operation of many activities throughout many industries has been well documented. Most closely related to the materials control and accountability area is the work in human factors that has been ongoing in the U.S. nuclear industry since the Three Mile Island Nuclear Power Plant accident in 1979. Research related to the role of human reliability, human-system interface, and organization and management influences has been and is still being conducted to identify ways to enhance the safe and effective operation of nuclear facilities. This paper will discuss these human performance areas and how they relate to the materials control and accountability area. Particular attention will be focussed on the notion of open-quotes safety cultureclose quotes and how it can be defined and measured for understanding the values and attitudes held by individuals working in the materials control area. It is widely believed that the culture of an organization, which reflects the expectations and values of the management of an organization, is a key element to the operation of that organization. The human performance element is one which has not received a great deal of consideration in the materials control and accountability area and yet it will be demonstrated that it is an essential component to ensure the success of safeguards activities

  20. Control room human engineering influences on operator performance

    International Nuclear Information System (INIS)

    Finlayson, F.C.

    1977-01-01

    Three general groups of factors influence operator performance in fulfilling their responsibilities in the control room: (1) control room and control system design, informational data displays (operator inputs) as well as control board design (for operator output); (2) operator characteristics, including those skills, mental, physical, and emotional qualities which are functions of operator selection, training, and motivation; (3) job performance guides, the prescribed operating procedures for normal and emergency operations. This paper presents some of the major results of an evaluation of the effect of human engineering on operator performance in the control room. Primary attention is given to discussion of control room and control system design influence on the operator. Brief observations on the influences of operator characteristics and job performance guides (operating procedures) on performance in the control room are also given. Under the objectives of the study, special emphasis was placed on the evaluation of the control room-operator relationships for severe emergency conditions in the power plant. Consequently, this presentation is restricted largely to material related to emergency conditions in the control room, though it is recognized that human engineering of control systems is of equal (or greater) importance for many other aspects of plant operation

  1. Human Factors Engineering Aspects of Modifications in Control Room Modernization

    Energy Technology Data Exchange (ETDEWEB)

    Hugo, Jacques [Idaho National Lab. (INL), Idaho Falls, ID (United States); Clefton, Gordon [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-01

    This report describes the basic aspects of control room modernization projects in the U.S. nuclear industry and the need for supplementary guidance on the integration of human factors considerations into the licensing and regulatory aspects of digital upgrades. The report pays specific attention to the integration of principles described in NUREG-0711 (Human Factors Engineering Program Review Model) and how supplementary guidance can help to raise general awareness in the industry regarding the complexities of control room modernization projects created by many interdependent regulations, standards and guidelines. The report also describes how human factors engineering principles and methods provided by various resources and international standards can help in navigating through the process of licensing digital upgrades. In particular, the integration of human factors engineering guidance and requirements into the process of licensing digital upgrades can help reduce uncertainty related to development of technical bases for digital upgrades that will avoid the introduction of new failure modes.

  2. Human Engineering of Space Vehicle Displays and Controls

    Science.gov (United States)

    Whitmore, Mihriban; Holden, Kritina L.; Boyer, Jennifer; Stephens, John-Paul; Ezer, Neta; Sandor, Aniko

    2010-01-01

    Proper attention to the integration of the human needs in the vehicle displays and controls design process creates a safe and productive environment for crew. Although this integration is critical for all phases of flight, for crew interfaces that are used during dynamic phases (e.g., ascent and entry), the integration is particularly important because of demanding environmental conditions. This panel addresses the process of how human engineering involvement ensures that human-system integration occurs early in the design and development process and continues throughout the lifecycle of a vehicle. This process includes the development of requirements and quantitative metrics to measure design success, research on fundamental design questions, human-in-the-loop evaluations, and iterative design. Processes and results from research on displays and controls; the creation and validation of usability, workload, and consistency metrics; and the design and evaluation of crew interfaces for NASA's Crew Exploration Vehicle are used as case studies.

  3. Everyday robotic action: Lessons from human action control

    Directory of Open Access Journals (Sweden)

    Roy eDe Kleijn

    2014-03-01

    Full Text Available Robots are increasingly capable of performing everyday human activities such as cooking, cleaning, and doing the laundry. This requires the real-time planning and execution of complex, temporally-extended sequential actions under high degrees of uncertainty, which provides many challenges to traditional approaches to robot action control. We argue that important lessons in this respect can be learned from research on human action control. We provide a brief overview of available psychological insights into this issue and focus on four principles that we think could be particularly beneficial for robot control: the integration of symbolic and subsymbolic planning of action sequences, the integration of feedforward and feedback control, the clustering of complex actions into subcomponents, and the contextualization of action-control structures through goal representations.

  4. Updating phylogeny of mitochondrial DNA macrohaplogroup m in India: dispersal of modern human in South Asian corridor.

    Directory of Open Access Journals (Sweden)

    Adimoolam Chandrasekar

    2009-10-01

    Full Text Available To construct maternal phylogeny and prehistoric dispersals of modern human being in the Indian sub continent, a diverse subset of 641 complete mitochondrial DNA (mtDNA genomes belonging to macrohaplogroup M was chosen from a total collection of 2,783 control-region sequences, sampled from 26 selected tribal populations of India. On the basis of complete mtDNA sequencing, we identified 12 new haplogroups--M53 to M64; redefined/ascertained and characterized haplogroups M2, M3, M4, M5, M6, M8'C'Z, M9, M10, M11, M12-G, D, M18, M30, M33, M35, M37, M38, M39, M40, M41, M43, M45 and M49, which were previously described by control and/or coding-region polymorphisms. Our results indicate that the mtDNA lineages reported in the present study (except East Asian lineages M8'C'Z, M9, M10, M11, M12-G, D are restricted to Indian region.The deep rooted lineages of macrohaplogroup 'M' suggest in-situ origin of these haplogroups in India. Most of these deep rooting lineages are represented by multiple ethnic/linguist groups of India. Hierarchical analysis of molecular variation (AMOVA shows substantial subdivisions among the tribes of India (Fst = 0.16164. The current Indian mtDNA gene pool was shaped by the initial settlers and was galvanized by minor events of gene flow from the east and west to the restricted zones. Northeast Indian mtDNA pool harbors region specific lineages, other Indian lineages and East Asian lineages. We also suggest the establishment of an East Asian gene in North East India through admixture rather than replacement.

  5. Optogenetic control of human neurons in organotypic brain cultures

    DEFF Research Database (Denmark)

    Andersson, My; Avaliani, Natalia; Svensson, Andreas

    2016-01-01

    Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

  6. Sensing human hand motions for controlling dexterous robots

    Science.gov (United States)

    Marcus, Beth A.; Churchill, Philip J.; Little, Arthur D.

    1988-01-01

    The Dexterous Hand Master (DHM) system is designed to control dexterous robot hands such as the UTAH/MIT and Stanford/JPL hands. It is the first commercially available device which makes it possible to accurately and confortably track the complex motion of the human finger joints. The DHM is adaptable to a wide variety of human hand sizes and shapes, throughout their full range of motion.

  7. INTEGRATED ROBOT-HUMAN CONTROL IN MINING OPERATIONS

    Energy Technology Data Exchange (ETDEWEB)

    George Danko

    2005-04-01

    This report contains a detailed description of the work conducted in the first year of the project on Integrated Robot-Human Control in Mining Operations at University of Nevada, Reno. This project combines human operator control with robotic control concepts to create a hybrid control architecture, in which the strengths of each control method are combined to increase machine efficiency and reduce operator fatigue. The kinematics reconfiguration type differential control of the excavator implemented with a variety of ''software machine kinematics'' is the key feature of the project. This software re-configured excavator is more desirable to execute a given digging task. The human operator retains the master control of the main motion parameters, while the computer coordinates the repetitive movement patterns of the machine links. These repetitive movements may be selected from a pre-defined family of trajectories with different transformations. The operator can make adjustments to this pattern in real time, as needed, to accommodate rapidly-changing environmental conditions. A Bobcat{reg_sign} 435 excavator was retrofitted with electro-hydraulic control valve elements. The modular electronic control was tested and the basic valve characteristics were measured for each valve at the Robotics Laboratory at UNR. Position sensors were added to the individual joint control actuators, and the sensors were calibrated. An electronic central control system consisting of a portable computer, converters and electronic driver components was interfaced to the electro-hydraulic valves and position sensors. The machine is operational with or without the computer control system depending on whether the computer interface is on or off. In preparation for emulated mining tasks tests, typical, repetitive tool trajectories during surface mining operations were recorded at the Newmont Mining Corporation's ''Lone Tree'' mine in Nevada.

  8. Ascaris phylogeny based on multiple whole mtDNA genomes

    DEFF Research Database (Denmark)

    Nejsum, Peter; Hawash, Mohamed B F; Betson, Martha

    2016-01-01

    and C) of human and pig Ascaris based on partial cox1 sequences. In the present study, we selected major haplotypes from these different clusters to characterize their whole mitochondrial genomes for phylogenetic analysis. We also undertook coalescent simulations to investigate the evolutionary history...

  9. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    Directory of Open Access Journals (Sweden)

    Keeney Paula M

    2009-09-01

    Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age

  10. INTEGRATED ROBOT-HUMAN CONTROL IN MINING OPERATIONS

    Energy Technology Data Exchange (ETDEWEB)

    George Danko

    2006-04-01

    This report describes the results of the 2nd year of a research project on the implementation of a novel human-robot control system for hydraulic machinery. Sensor and valve re-calibration experiments were conducted to improve open loop machine control. A Cartesian control example was tested both in simulation and on the machine; the results are discussed in detail. The machine tests included open-loop as well as closed-loop motion control. Both methods worked reasonably well, due to the high-quality electro-hydraulic valves used on the experimental machine. Experiments on 3-D analysis of the bucket trajectory using marker tracking software are also presented with the results obtained. Open-loop control is robustly stable and free of short-term dynamic problems, but it allows for drifting away from the desired motion kinematics of the machine. A novel, closed-loop control adjustment provides a remedy, while retaining much of the advantages of the open-loop control based on kinematics transformation. Additional analysis of previously recorded, three-dimensional working trajectories of the bucket of large mine shovels was completed. The motion patterns, when transformed into a family of curves, serve as the basis for software-controlled machine kinematics transformation in the new human-robot control system.

  11. Local control stations: Human engineering issues and insights

    International Nuclear Information System (INIS)

    Brown, W.S.; Higgins, J.C.; O'Hara, J.M.

    1994-09-01

    The objective of this research project was to evaluate current human engineering at local control stations (LCSs) in nuclear power plants, and to identify good human engineering practices relevant to the design of these operator interfaces. General literature and reports of operating experience were reviewed to determine the extent and type of human engineering deficiencies at LCSs in nuclear power plants. In-plant assessments were made of human engineering at single-function as well as multifunction LCSs. Besides confirming the existence of human engineering deficiencies at LCSs, the in-plant assessments provided information about the human engineering upgrades that have been made at nuclear power plants. Upgrades were typically the result of any of three influences regulatory activity, broad industry initiatives such as INPO, and specific in-plant programs (e.g. activities related to training). It is concluded that the quality of LCSs is quite variable and might be improved if there were greater awareness of good practices and existing human engineering guidance relevant to these operator interfaces, which is available from a variety of sources. To make such human engineering guidance more readily accessible, guidelines were compiled from such sources and included in the report as an appendix

  12. Randomized controlled trials for influenza drugs and vaccines: a review of controlled human infection studies

    Directory of Open Access Journals (Sweden)

    Shobana Balasingam

    2016-08-01

    Conclusions: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.

  13. Intelligent (Autonomous) Power Controller Development for Human Deep Space Exploration

    Science.gov (United States)

    Soeder, James; Raitano, Paul; McNelis, Anne

    2016-01-01

    As NASAs Evolvable Mars Campaign and other exploration initiatives continue to mature they have identified the need for more autonomous operations of the power system. For current human space operations such as the International Space Station, the paradigm is to perform the planning, operation and fault diagnosis from the ground. However, the dual problems of communication lag as well as limited communication bandwidth beyond GEO synchronous orbit, underscore the need to change the operation methodology for human operation in deep space. To address this need, for the past several years the Glenn Research Center has had an effort to develop an autonomous power controller for human deep space vehicles. This presentation discusses the present roadmap for deep space exploration along with a description of conceptual power system architecture for exploration modules. It then contrasts the present ground centric control and management architecture with limited autonomy on-board the spacecraft with an advanced autonomous power control system that features ground based monitoring with a spacecraft mission manager with autonomous control of all core systems, including power. It then presents a functional breakdown of the autonomous power control system and examines its operation in both normal and fault modes. Finally, it discusses progress made in the development of a real-time power system model and how it is being used to evaluate the performance of the controller and well as using it for verification of the overall operation.

  14. Cooperative research for human factors review of advanced control rooms

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Park, Jae Chang; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul

    2000-12-01

    This project has been performed as cooperative research between KAERI and USNRC. Human factors issues related to soft controls, which is one of key features of advanced HSI, are identified in this project. The issues are analyzed for the evaluation approaches in either experimental or analytical ways. Also, issues requiring additional researches for the evaluation of advanced HSI are identified in the areas of advanced information systems design, computer-based procedure systems, soft controls, human systems interface and plant modernization process, and maintainability of digital systems. The issues are analyzed to discriminate the urgency of researches on it to high, medium, and low levels in consideration of advanced HSI development status in Korea, and some of the issues that can be handled by experimental researches are identified. Additionally, an experimental study is performed to compare operator's performance on human error detection in advanced control rooms vs. in conventional control rooms. It is found that advanced control rooms have several design characteristics hindering operator's error detection performance compared to conventional control rooms.

  15. Cooperative research for human factors review of advanced control rooms

    International Nuclear Information System (INIS)

    Lee, Jung Woon; Park, Jae Chang; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul

    2000-12-01

    This project has been performed as cooperative research between KAERI and USNRC. Human factors issues related to soft controls, which is one of key features of advanced HSI, are identified in this project. The issues are analyzed for the evaluation approaches in either experimental or analytical ways. Also, issues requiring additional researches for the evaluation of advanced HSI are identified in the areas of advanced information systems design, computer-based procedure systems, soft controls, human systems interface and plant modernization process, and maintainability of digital systems. The issues are analyzed to discriminate the urgency of researches on it to high, medium, and low levels in consideration of advanced HSI development status in Korea, and some of the issues that can be handled by experimental researches are identified. Additionally, an experimental study is performed to compare operator's performance on human error detection in advanced control rooms vs. in conventional control rooms. It is found that advanced control rooms have several design characteristics hindering operator's error detection performance compared to conventional control rooms

  16. Demography or selection on linked cultural traits or genes? Investigating the driver of low mtDNA diversity in the sperm whale using complementary mitochondrial and nuclear genome analyses.

    Science.gov (United States)

    Morin, Phillip A; Foote, Andrew D; Baker, C Scott; Hancock-Hanser, Brittany L; Kaschner, Kristin; Mate, Bruce R; Mesnick, Sarah L; Pease, Victoria L; Rosel, Patricia E; Alexander, Alana

    2018-04-19

    Mitochondrial DNA has been heavily utilized in phylogeography studies for several decades. However, underlying patterns of demography and phylogeography may be misrepresented due to coalescence stochasticity, selection, variation in mutation rates, and cultural hitchhiking (linkage of genetic variation to culturally transmitted traits affecting fitness). Cultural hitchhiking has been suggested as an explanation for low genetic diversity in species with strong social structures, counteracting even high mobility, abundance and limited barriers to dispersal. One such species is the sperm whale, which shows very limited phylogeographic structure and low mtDNA diversity despite a worldwide distribution and large population. Here, we use analyses of 175 globally distributed mitogenomes and three nuclear genomes to evaluate hypotheses of a population bottleneck/expansion versus a selective sweep due to cultural-hitchhiking or selection on mtDNA as the mechanism contributing to low worldwide mitochondrial diversity in sperm whales. In contrast to mtDNA control region (CR) data, mitogenome haplotypes are largely ocean-specific, with only one of 80 shared between the Atlantic and Pacific. Demographic analyses of nuclear genomes suggest low mtDNA diversity is consistent with a global reduction in population size that ended approximately 125,000 years ago, correlated with the Eemian interglacial. Phylogeographic analysis suggests that extant sperm whales descend from maternal lineages endemic to the Pacific during the period of reduced abundance, and have subsequently colonized the Atlantic several times. Results highlight the apparent impact of past climate change, and suggest selection and hitchhiking are not the sole processes responsible for low mtDNA diversity in this highly social species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

    Science.gov (United States)

    Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

    2012-03-01

    Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

  18. Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

    Directory of Open Access Journals (Sweden)

    Scalais Emmanuel

    2009-06-01

    Full Text Available Abstract Background In muscle cytochrome oxidase (COX negative fibers (mitochondrial mosaics have often been visualized. Methods COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis. Results Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Conclusion Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent

  19. Meaningful Human Control over Autonomous Systems: A Philosophical Account

    Directory of Open Access Journals (Sweden)

    Filippo Santoni de Sio

    2018-02-01

    Full Text Available Debates on lethal autonomous weapon systems have proliferated in the past 5 years. Ethical concerns have been voiced about a possible raise in the number of wrongs and crimes in military operations and about the creation of a “responsibility gap” for harms caused by these systems. To address these concerns, the principle of “meaningful human control” has been introduced in the legal–political debate; according to this principle, humans not computers and their algorithms should ultimately remain in control of, and thus morally responsible for, relevant decisions about (lethal military operations. However, policy-makers and technical designers lack a detailed theory of what “meaningful human control” exactly means. In this paper, we lay the foundation of a philosophical account of meaningful human control, based on the concept of “guidance control” as elaborated in the philosophical debate on free will and moral responsibility. Following the ideals of “Responsible Innovation” and “Value-sensitive Design,” our account of meaningful human control is cast in the form of design requirements. We identify two general necessary conditions to be satisfied for an autonomous system to remain under meaningful human control: first, a “tracking” condition, according to which the system should be able to respond to both the relevant moral reasons of the humans designing and deploying the system and the relevant facts in the environment in which the system operates; second, a “tracing” condition, according to which the system should be designed in such a way as to grant the possibility to always trace back the outcome of its operations to at least one human along the chain of design and operation. As we think that meaningful human control can be one of the central notions in ethics of robotics and AI, in the last part of the paper, we start exploring the implications of our account for the design and use of non

  20. mtDNA copy number in oocytes of different sizes from individual pre- and post-pubertal pigs

    DEFF Research Database (Denmark)

    Pedersen, Hanne Skovsgaard; Løvendahl, Peter; Larsen, Knud Erik

    2014-01-01

    from ovaries of 10 pre- and 10 post-pubertal pigs. Cumulus cells were removed and the oocytes were measured (inside-ZP-diameter). Oocytes were transferred to DNAase-free tubes, snap-frozen, and stored at –80°C. The genes ND1 and COX1 were used to determine the mtDNA copy number. Plasmid preparations...... Reproduction 131, 233–245). However, the correlation between size and mtDNA copy number in single oocytes has not been determined. This study describes the relation between oocytes of defined diameters from individual pre- and postpubertal pigs and mtDNA copy number. Cumulus-oocyte complexes were aspirated...

  1. Prosthetic Leg Control in the Nullspace of Human Interaction.

    Science.gov (United States)

    Gregg, Robert D; Martin, Anne E

    2016-07-01

    Recent work has extended the control method of virtual constraints, originally developed for autonomous walking robots, to powered prosthetic legs for lower-limb amputees. Virtual constraints define desired joint patterns as functions of a mechanical phasing variable, which are typically enforced by torque control laws that linearize the output dynamics associated with the virtual constraints. However, the output dynamics of a powered prosthetic leg generally depend on the human interaction forces, which must be measured and canceled by the feedback linearizing control law. This feedback requires expensive multi-axis load cells, and actively canceling the interaction forces may minimize the human's influence over the prosthesis. To address these limitations, this paper proposes a method for projecting virtual constraints into the nullspace of the human interaction terms in the output dynamics. The projected virtual constraints naturally render the output dynamics invariant with respect to the human interaction forces, which instead enter into the internal dynamics of the partially linearized prosthetic system. This method is illustrated with simulations of a transfemoral amputee model walking with a powered knee-ankle prosthesis that is controlled via virtual constraints with and without the proposed projection.

  2. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures.

    Science.gov (United States)

    Stray, Kirsten M; Park, Yeojin; Babusis, Darius; Callebaut, Christian; Cihlar, Tomas; Ray, Adrian S; Perron, Michel

    2017-04-01

    HIV-infected patients treated with certain nucleoside reverse transcriptase inhibitors (NRTIs) have experienced adverse effects due to drug-related mitochondrial toxicity. Tenofovir alafenamide (TAF) is a novel prodrug of the NRTI tenofovir (TFV) with an improved safety profile compared to tenofovir disoproxil fumarate (TDF). Prior in vitro studies have demonstrated that the parent nucleotide TFV has no significant effects on mtDNA synthesis. This study investigated whether clinically relevant TAF and TDF exposures affect mtDNA content in human lymphocytes. First, activated or resting peripheral blood mononuclear cells (PBMCs), as well as MT-2 and Jurkat T-cell lines, were continuously treated with ddC for 10 days to establish their susceptibility to mtDNA depletion. PBMCs had low sensitivity to NRTI-mediated mtDNA depletion in vitro. In contrast, ddC treatment of rapidly dividing MT-2 and Jurkat cells resulted in a dose-dependent decrease in mtDNA. Therefore, these two T-cell lines were selected for evaluating TAF and TDF treatment effects. MT-2 and Jurkat cells were pulse-treated with TAF or TDF every 24 h for 10 days to mimic pharmacologically relevant drug exposures. Pulse treatment of cells with 3.3 μM TAF or 1.1 μM TDF for 10 days resulted in 2- to 7-fold greater steady-state intracellular TFV-diphosphate (TFV-DP) levels than those observed clinically in TAF- or TDF-treated patients. At these concentrations, no significant TAF- (106.7% and 84.1% of control; p = 0.77 and 0.12 for MT-2 and Jurkat, respectively) or TDF- (100.6% and 91.0% of control; p = 0.91 and 0.37, respectively) associated reduction in mtDNA content was observed compared with untreated control cells. This study demonstrates that, despite delivering higher intracellular levels of TFV-DP than TDF, TAF does not inhibit mtDNA synthesis in vitro at concentrations exceeding the clinically relevant intracellular drug exposures. Thus, TAF has a low potential for mitochondrial toxicity in

  3. Determinants of human resource investment in internal controls

    Directory of Open Access Journals (Sweden)

    Jong-Hag Choi

    2013-09-01

    Full Text Available Using the unique reporting environment in Korea, this study investigates the determinants of human resource investment in internal controls for 1352 listed firms disclosing the number of personnel who are in charge of internal control-related tasks (IC personnel from 2005 to 2008. We find that the number of IC personnel within a firm and several key departments increase with firm size, number of employees, complexity and for Chaebols, and decrease in rapidly growing firms. Additional analysis reveals that the factors influencing internal control systems have an accentuated effect on firms with relatively larger firm size.

  4. Human-Machine Systems concepts applied to Control Engineering Education

    OpenAIRE

    Marangé , Pascale; Gellot , François; Riera , Bernard

    2008-01-01

    International audience; In this paper, we interest us to Human-Machine Systems (HMS) concepts applied to Education. It is shown how the HMS framework enables to propose original solution in matter of education in the field of control engineering. We focus on practical courses on control of manufacturing systems. The proposed solution is based on an original use of real and large-scale systems instead of simulation. The main idea is to enable the student, whatever his/her level to control the ...

  5. When soft controls get slippery: User interfaces and human error

    International Nuclear Information System (INIS)

    Stubler, W.F.; O'Hara, J.M.

    1998-01-01

    Many types of products and systems that have traditionally featured physical control devices are now being designed with soft controls--input formats appearing on computer-based display devices and operated by a variety of input devices. A review of complex human-machine systems found that soft controls are particularly prone to some types of errors and may affect overall system performance and safety. This paper discusses the application of design approaches for reducing the likelihood of these errors and for enhancing usability, user satisfaction, and system performance and safety

  6. Effect of intermittent feedback control on robustness of human-like postural control system

    Science.gov (United States)

    Tanabe, Hiroko; Fujii, Keisuke; Suzuki, Yasuyuki; Kouzaki, Motoki

    2016-03-01

    Humans have to acquire postural robustness to maintain stability against internal and external perturbations. Human standing has been recently modelled using an intermittent feedback control. However, the causality inside of the closed-loop postural control system associated with the neural control strategy is still unknown. Here, we examined the effect of intermittent feedback control on postural robustness and of changes in active/passive components on joint coordinative structure. We implemented computer simulation of a quadruple inverted pendulum that is mechanically close to human tiptoe standing. We simulated three pairs of joint viscoelasticity and three choices of neural control strategies for each joint: intermittent, continuous, or passive control. We examined postural robustness for each parameter set by analysing the region of active feedback gain. We found intermittent control at the hip joint was necessary for model stabilisation and model parameters affected the robustness of the pendulum. Joint sways of the pendulum model were partially smaller than or similar to those of experimental data. In conclusion, intermittent feedback control was necessary for the stabilisation of the quadruple inverted pendulum. Also, postural robustness of human-like multi-link standing would be achieved by both passive joint viscoelasticity and neural joint control strategies.

  7. The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

    Science.gov (United States)

    Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji

    2018-01-01

    Background Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. Methodology We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. Conclusions We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity. PMID:29304129

  8. The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

    Science.gov (United States)

    Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji; Mannen, Hideyuki

    2018-01-01

    Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity.

  9. mtDNA of Fulani Nomads and Their Genetic Relationships to Neighboring Sedentary Populations

    Czech Academy of Sciences Publication Activity Database

    Černý, Viktor; Hájek, Martin; Bromová, Markéta; Čmejla, R.; Diallo, I.; Brdička, R.

    2006-01-01

    Roč. 78, č. 1 (2006), s. 9-27 ISSN 0018-7143 R&D Projects: GA ČR(CZ) GA404/03/0318 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * HVS-I * Fulani nomads * sub-Saharan populations * Chad * Cameroon * Burkina Faso Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 1.132, year: 2006

  10. Control room design and human engineering in power plants

    International Nuclear Information System (INIS)

    Herbst, L.; Hinz, W.

    1981-01-01

    Automation reduces the human work load. Employment of functional areas permits optimization of operational sequences. Computer based information processing makes it possible to output information in accordance with operating requirements. Design based on human engineering principles assures the quality of the interaction between the operator and the equipment. The degree to which these conceptional features play a role in design of power plant control rooms depends on the unit rating, the mode of operation and on the requirements respecting safety and availability of the plant. (orig./RW)

  11. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

  12. Integrated Robot-Human Control in Mining Operations

    Energy Technology Data Exchange (ETDEWEB)

    George Danko

    2007-09-30

    This report contains a detailed description of the work conducted for the project on Integrated Robot-Human Control in Mining Operations at University of Nevada, Reno. This project combines human operator control with robotic control concepts to create a hybrid control architecture, in which the strengths of each control method are combined to increase machine efficiency and reduce operator fatigue. The kinematics reconfiguration type differential control of the excavator implemented with a variety of 'software machine kinematics' is the key feature of the project. This software re-configured excavator is more desirable to execute a given digging task. The human operator retains the master control of the main motion parameters, while the computer coordinates the repetitive movement patterns of the machine links. These repetitive movements may be selected from a pre-defined family of trajectories with different transformations. The operator can make adjustments to this pattern in real time, as needed, to accommodate rapidly-changing environmental conditions. A working prototype has been developed using a Bobcat 435 excavator. The machine is operational with or without the computer control system depending on whether the computer interface is on or off. In preparation for emulated mining tasks tests, typical, repetitive tool trajectories during surface mining operations were recorded at the Newmont Mining Corporation's 'Lone Tree' mine in Nevada. Analysis of these working trajectories has been completed. The motion patterns, when transformed into a family of curves, may serve as the basis for software-controlled machine kinematics transformation in the new human-robot control system. A Cartesian control example has been developed and tested both in simulation and on the experimental excavator. Open-loop control is robustly stable and free of short-term dynamic problems, but it allows for drifting away from the desired motion kinematics of the

  13. Genetic diversity of mtDNA D-loop sequences in four native Chinese chicken breeds.

    Science.gov (United States)

    Guo, H W; Li, C; Wang, X N; Li, Z J; Sun, G R; Li, G X; Liu, X J; Kang, X T; Han, R L

    2017-10-01

    1. To explore the genetic diversity of Chinese indigenous chicken breeds, a 585 bp fragment of the mitochondrial DNA (mtDNA) region was sequenced in 102 birds from the Xichuan black-bone chicken, Yunyang black-bone chicken and Lushi chicken. In addition, 30 mtDNA D-loop sequences of Silkie fowls were downloaded from NCBI. The mtDNA D-loop sequence polymorphism and maternal origin of 4 chicken breeds were analysed in this study. 2. The results showed that a total of 33 mutation sites and 28 haplotypes were detected in the 4 chicken breeds. The haplotype diversity and nucleotide diversity of these 4 native breeds were 0.916 ± 0.014 and 0.012 ± 0.002, respectively. Three clusters were formed in 4 Chinese native chickens and 12 reference breeds. Both the Xichuan black-bone chicken and Yunyang black-bone chicken were grouped into one cluster. Four haplogroups (A, B, C and E) emerged in the median-joining network in these breeds. 3. It was concluded that these 4 Chinese chicken breeds had high genetic diversity. The phylogenetic tree and median network profiles showed that Chinese native chickens and its neighbouring countries had at least two maternal origins, one from Yunnan, China and another from Southeast Asia or its surrounding area.

  14. mtDNA variation in the Yanomami: evidence for additional New World founding lineages.

    Science.gov (United States)

    Easton, R D; Merriwether, D A; Crews, D E; Ferrell, R E

    1996-07-01

    Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types.

  15. Reflex control of robotic gait using human walking data.

    Directory of Open Access Journals (Sweden)

    Catherine A Macleod

    Full Text Available Control of human walking is not thoroughly understood, which has implications in developing suitable strategies for the retraining of a functional gait following neurological injuries such as spinal cord injury (SCI. Bipedal robots allow us to investigate simple elements of the complex nervous system to quantify their contribution to motor control. RunBot is a bipedal robot which operates through reflexes without using central pattern generators or trajectory planning algorithms. Ground contact information from the feet is used to activate motors in the legs, generating a gait cycle visually similar to that of humans. Rather than developing a more complicated biologically realistic neural system to control the robot's stepping, we have instead further simplified our model by measuring the correlation between heel contact and leg muscle activity (EMG in human subjects during walking and from this data created filter functions transferring the sensory data into motor actions. Adaptive filtering was used to identify the unknown transfer functions which translate the contact information into muscle activation signals. Our results show a causal relationship between ground contact information from the heel and EMG, which allows us to create a minimal, linear, analogue control system for controlling walking. The derived transfer functions were applied to RunBot II as a proof of concept. The gait cycle produced was stable and controlled, which is a positive indication that the transfer functions have potential for use in the control of assistive devices for the retraining of an efficient and effective gait with potential applications in SCI rehabilitation.

  16. Comparison between Mt-DNA D-Loop and Cyt B primers for porcine DNA detection in meat products

    Science.gov (United States)

    Hamzah, Azhana; Mutalib, Sahilah Abd.; Babji, Abdul Salam

    2013-11-01

    This study was conducted to detect the presence of porcine DNA in meat products in the market using conventional polymerase chain reaction (PCR) and commercial PCR-southern hybridization analysis. Porcine DNA detection in meat products was tested due to some issues associated with the adulteration of food products in Malaysia. This is an important issue especially for Halal authentication which is required for some religious practices such as in Islam and Hinduisms. Many techniques have been developed for determining the Halal status of food products. In this paper, mt-DNA D-loop primer and cytochrome (cyt) b were used to detect the presence of porcine DNA in meat products. Positive and negative controls were always present for each batch of extraction. DNA of raw pork meat was used as a positive control while nucleus free water is used as negative control. A pair of oligonucleotide primer was used namely Pork1 and Pork2 which produced amplicon of 531 base pair (bp) in size. While, PCR-southern hybridization was conducted using primers readily supplied by commercial PCR-Southern hybridization and produced amplicon with 276 bp in size. In the present study, demonstrated that none of the samples were contaminated with porcine residuals but selected samples with pork meat were positive. The species-specific PCR amplification yielded excellent results for identification of pork derivatives in food products and it is a potentially reliable and suitable technique in routine food analysis for Halal certification.

  17. Human factors in remote control engineering development activities

    International Nuclear Information System (INIS)

    Clarke, M.M.; Hamel, W.R.; Draper, J.V.

    1983-01-01

    Human factors engineering, which is an integral part of the advanced remote control development activities at the Oak Ridge National Laboratory, is described. First, work at the Remote Systems Development Facility (RSDF) has shown that operators can perform a wide variety of tasks, some of which were not specifically designed for remote systems, with a dextrous electronic force-reflecting servomanipulator and good television remote viewing capabilities. Second, the data collected during mock-up remote maintenance experiments at the RSDF have been analyzed to provide guidelines for the design of human interfaces with an integrated advanced remote maintenance system currently under development. Guidelines have been provided for task allocation between operators, remote viewing systems, and operator controls. 6 references, 5 figures, 2 tables

  18. Wood smoke in a controlled exposure experiment with human volunteers

    DEFF Research Database (Denmark)

    Riddervold, Ingunn Skogstad; Bønløkke, Jakob Hjort; Mølhave, Lars

    2011-01-01

    Exposure to wood smoke in the general population is increasing and concurrently, also our awareness. This article describes a wood-smoke generating system for studying human exposure to wood smoke and symptoms related to this exposure. Twenty nonsmoking atopic human participants with normal lung...... function and normal bronchial reactivity were randomly exposed for 3h at three different exposure conditions; clean filtered air (control exposure) and wood smoke with a characteristic particulate matter (PM) concentration of 200 µg/m3 (low) and 400 µg/m3 (high) under controlled environmental conditions.......0007), “irritative body perceptions” (p = 0.0127), “psychological/neurological effects” (p = 0.0075) and “weak inflammatory responses” (p = 0.0003). Furthermore, significant effects (p = 0.0192) on self-reported general mucosa irritation were found. In conclusion, exposure to wood smoke affected symptom rating...

  19. MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

    Directory of Open Access Journals (Sweden)

    Santa-Rita Pedro

    2005-06-01

    Full Text Available Abstract Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143 of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a breeds tend to display haplotypes belonging to different haplogroups; (b haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the

  20. Identification of the unstable human postural control system

    Directory of Open Access Journals (Sweden)

    Sungjae eHwang

    2016-03-01

    Full Text Available Maintaining upright bipedal posture requires a control system that continually adapts to changing environmental conditions, such as different support surfaces. Behavioral changes associated with different support surfaces, such as the predominance of an ankle or hip strategy, is considered to reflect a change in the control strategy. However, tracing such behavioral changes to a specific component in a closed loop control system is challenging. Here we used the joint input-output (JIO method of closed-loop system identification to identify the musculoskeletal and neural feedback components of the human postural control loop. The goal was to establish changes in the control loop corresponding to behavioral changes observed on different support surfaces. Subjects were simultaneously perturbed by two independent mechanical and two independent sensory perturbations while standing on a normal or short support surface. The results show a dramatic phase reversal between visual input and body kinematics due to the change in surface condition from trunk leads legs to legs lead trunk with increasing frequency of the visual perturbation. Through decomposition of the control loop, we found that behavioral change is not necessarily due to a change in control strategy, but in the case of different support surfaces, is linked to changes in properties of the plant. The JIO method is an important tool to identify the contribution of specific components within a closed loop control system to overall postural behavior and may be useful to devise better treatment of balance disorders.

  1. Human factors in aviation: Terminal control area boundary conflicts

    Science.gov (United States)

    Monan, William P.

    1989-01-01

    Air-to-air conflicts in the vicinity of Terminal Control Area (TCA) boundaries were studied to obtain a better understanding of the causal dynamics of these events with particular focus on human factor issues. The study dataset consisted of 381 Instrument Flight Rules/Visual Flight Rules (IFR/VFR) traffic conflicts in airspace layers above TCA ceiling and below TCA floors; 213 reports of incursions in TCA terminal airspace by VFR aircraft, of which 123 resulted in conflicts; and an additional set of reports describing problems with Air Traffic Control (ATC) services in and around TCAs. Results and conclusions are detailed.

  2. Determination of PBDEs in human milk. Analysis and quality control

    Energy Technology Data Exchange (ETDEWEB)

    Paepke, O.; Herrmann, T. [Ergo Research, Hamburg (Germany); Vieth, B.; Ostermann, B. [Federal Institute for Risk Assessment, Berlin (Germany)

    2004-09-15

    Polybrominated diphenylethers (PBDEs) are widely used as flame retardants in polymer materials, textiles, electronic boards and various other materials. Technical PBDE preparations are produced as mixtures of mainly penta-, octa- or decabromobiphenyl ethers. PBDEs are structurally similar to other environmental pollutants, such as dioxins and PCBs. They are lipophilic and persistent compounds and widespread in the environment. For certain congeners, bioaccumulation has been observed. Recent findings of increasing levels in humans showed that more detailed investigations of human milk (or other suitable matrices) will be required in order to evaluate the general human exposure to this group of environmental contaminants. Only a few data on PBDE levels in breast milk from Germany had been published. To fill the data gaps, in 2001 a controlled study was started to characterize the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. 103 samples were analyzed in this study so far including 10 hidden pool samples provided by Federal Institute for Risk Assessment to ERGO laboratory (total number of samples finally will be 157 (including 14 hidden pool samples)). This paper describes the analytical procedure applied and emphasizes on the quality control procedure.

  3. Studies in the Human Use of Controlled English

    Science.gov (United States)

    2015-12-01

    Controlled English (CE) is intended to aid human problem solving processes when analysing data and generating high-value conclusions in collaboration...state of affairs. The second approach is to guide a user face-to-face to formulate free English sentences into CE to solve a logic problem. The paper describes both approaches and provides an informal analysis of the results to date.

  4. Engineering human factors into the Westinghouse advanced control room

    International Nuclear Information System (INIS)

    Easter, J.R.

    1987-01-01

    By coupling the work of the Riso Laboratory in Denmark on human behaviour with new digital computation and display technology, Westinghouse has developed a totally new control room design. This design features a separate, co-ordinated work station to support the systems management role in decision making, as well as robust alarm and display systems. This coupling of the functional and physical data presentation is now being implemented in test facilities. (author)

  5. An Inverse Optimal Control Approach to Explain Human Arm Reaching Control Based on Multiple Internal Models.

    Science.gov (United States)

    Oguz, Ozgur S; Zhou, Zhehua; Glasauer, Stefan; Wollherr, Dirk

    2018-04-03

    Human motor control is highly efficient in generating accurate and appropriate motor behavior for a multitude of tasks. This paper examines how kinematic and dynamic properties of the musculoskeletal system are controlled to achieve such efficiency. Even though recent studies have shown that the human motor control relies on multiple models, how the central nervous system (CNS) controls this combination is not fully addressed. In this study, we utilize an Inverse Optimal Control (IOC) framework in order to find the combination of those internal models and how this combination changes for different reaching tasks. We conducted an experiment where participants executed a comprehensive set of free-space reaching motions. The results show that there is a trade-off between kinematics and dynamics based controllers depending on the reaching task. In addition, this trade-off depends on the initial and final arm configurations, which in turn affect the musculoskeletal load to be controlled. Given this insight, we further provide a discomfort metric to demonstrate its influence on the contribution of different inverse internal models. This formulation together with our analysis not only support the multiple internal models (MIMs) hypothesis but also suggest a hierarchical framework for the control of human reaching motions by the CNS.

  6. Control of the exercise hyperpnoea in humans: a modeling perspective.

    Science.gov (United States)

    Ward, S A

    2000-09-01

    Models of the exercise hyperpnoea have classically incorporated elements of proportional feedback (carotid and medullary chemosensory) and feedforward (central and/or peripheral neurogenic) control. However, the precise details of the control process remain unresolved, reflecting in part both technical and interpretational limitations inherent in isolating putative control mechanisms in the intact human, and also the challenges to linear control theory presented by multiple-input integration, especially with regard to the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic acidosis. While some combination of neurogenic, chemoreflex and circulatory-coupled processes are likely to contribute to the control, the system appears to evidence considerable redundancy. This, coupled with the lack of appreciable error signals in the mean levels of arterial blood gas tensions and pH over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e. memory). The challenge is to discriminate between robust competing control models that: (a) integrate such processes within plausible physiological equivalents; and (b) account for both the dynamic and steady-state system response over a range of exercise intensities. Such models are not yet available.

  7. The human factors specialist in nuclear control centre design

    International Nuclear Information System (INIS)

    Wilson, R.B.; Beattie, J.D.

    The main focus at Ontario Hydro for man-machine interface design is in the design of control centres. Because the control of a nuclear generating unit is highly centralized there is an increasing need for effective information display and control layout. Control panel design innovations such as the use of CRT displays and the extended use of computerized control in the Darlington station have made it possible for Ontario Hydro to continue to have one first operator for each generating unit. The human factors specialist involved in control panel design must deal with people who know much more about the specific systems being controlled, and must become a generalist in all these systems as well. Designers have to use conceptual techniques such as task analysis, systems design, panel mock-ups, anthropometric data, and personal judgement based on experience as they design panels. They must find a balance between becoming locked into existing technology and methods, slavishly following the latest technological trends, and forgetting that real people will be using what they design

  8. Human regulatory B cells control the TFH cell response.

    Science.gov (United States)

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe

    2017-07-01

    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. Reconstructing the origin of the Lapita Cultural Complex: mtDNA analyses of East Sepik Province, PNG.

    Science.gov (United States)

    Vilar, Miguel G; Kaneko, Akira; Hombhanje, Francis W; Tsukahara, Takahiro; Hwaihwanje, Ilomo; Lum, J Koji

    2008-01-01

    The colonization of Oceania occurred in two waves. By 32,000 BP, humans had reached New Guinea and settled all intervisible islands east to the Solomon Islands. Around 3,500 BP, a distinct intrusive group from Southeast Asia reached coastal New Guinea, integrated their components with indigenous resources, and gave rise to the Lapita Cultural Complex. Within 2,500 years, Lapita and its descendant cultures colonized the Pacific. To uncover the origin of the Lapita Cultural Complex, we analyzed the hypervariable region I of the mitochondrial deoxyribonucleic acid (mtDNA) in 219 individuals from eight East Sepik Province villages: two villages in each of four environmental zones. Same-zone villages spoke different languages: one Austronesian and three Papuan (Arapesh, Abelam, and Boiken). Our analysis examined whether language or geography better predicted gene flow. In general, language better predicted genetic affinities. Boiken villages across all four zones showed no significant genetic difference (F(ST) P value > 0.05). In contrast, the Austronesian village was significantly different to most other villages (P 0.05). We interpret the data to reflect limited gene flow inland by Austronesians overshadowed by a regional displacement by inland Boiken speakers migrating seaward. These results are consistent with oral histories and ethnographic accounts.

  10. Characterizing the human postural control system using detrended fluctuation analysis

    Science.gov (United States)

    Teresa Blázquez, M.; Anguiano, Marta; de Saavedra, Fernando Arias; Lallena, Antonio M.; Carpena, Pedro

    2010-01-01

    Detrended fluctuation analysis is used to study the behaviour of the time series of the position of the center of pressure, output from the activity of a human postural control system. The results suggest that these trajectories present a crossover in their scaling properties from persistent (for high frequencies, short-range time scale) to anti-persistent (for low frequencies, long-range time scale) behaviours. The values of the scaling exponent found for the persistent parts of the trajectories are very similar for all the cases analysed. The similarity of the results obtained for the measurements done with both eyes open and both eyes closed indicate either that the visual system may be disregarded by the postural control system, while maintaining quiet standing, or that the control mechanisms associated with each type of information (visual, vestibular and somatosensory) cannot be disentangled with this technique.

  11. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  12. Endangered species: mitochondrial DNA loss as a mechanism of human disease.

    Science.gov (United States)

    Herrera, Alan; Garcia, Iraselia; Gaytan, Norma; Jones, Edith; Maldonado, Alicia; Gilkerson, Robert

    2015-06-01

    Human mitochondrial DNA (mtDNA) is a small maternally inherited DNA, typically present in hundreds of copies in a single human cell. Thus, despite its small size, the mitochondrial genome plays a crucial role in the metabolic homeostasis of the cell. Our understanding of mtDNA genotype-phenotype relationships is derived largely from studies of the classical mitochondrial neuromuscular diseases, in which mutations of mtDNA lead to compromised mitochondrial bioenergetic function, with devastating pathological consequences. Emerging research suggests that loss, rather than mutation, of mtDNA plays a major role across a range of prevalent human diseases, including diabetes mellitus, cardiovascular disease, and aging. Here, we examine the 'rules' of mitochondrial genetics and function, the clinical settings in which loss of mtDNA is an emerging pathogenic mechanism, and explore mtDNA damage and its consequences for the organellar network and cell at large. As extranuclear genetic material arrayed throughout the cell to support metabolism, mtDNA is increasingly implicated in a host of disease conditions, opening a range of exciting questions regarding mtDNA and its role in cellular homeostasis.

  13. Hibernation Control Mechanism and Possible Applications to Humans

    Science.gov (United States)

    Kondo, N.

    Mammalian hibernation, characterized by the ability to survive temporarily at low body temperatures close to 0oC, has been reported to increase resistance to various lethal events such as low body temperature, severe ischemia, bacterial infection and irradiation, and to prolong the life span. The application of this physiological phenomenon to space life has been dreamed of. However, realization of this dream has been prevented by a poor understanding of the control mechanisms of hibernation. Recent findings of a novel and unique protein complex (HP) in the blood of chipmunks, a rodent hibernator, which is controlled by the endogenous circannual rhythm of hibernation, allowed new developments in understanding the molecular mechanism of hibernation and its physiological significance. From these studies, two hormones regulated by the brain were identified as promising candidate molecules controlling HP production in the liver, assuming that hibernation is controlled via the neuroendocrine system and regulated by the endogenous circannual rhythm in the brain. A circannual HP rhythm was observed in chipmunks maintaining euthermia under conditions of constant warmth, suggesting that the physiological control of hibernation progresses without a lowering of body temperature. Furthermore, the study of HP rhythm on longevity revealed that a circannual rhythm plays an essential role in the much longer life span of hibernators. The present progress in hibernation research may open a new pathway for manipulating a circannual rhythm controlling hibernation in humans. In the future, this will make it feasible to take advantage of hibernation in space life.

  14. Aspects of computer control from the human engineering standpoint

    International Nuclear Information System (INIS)

    Huang, T.V.

    1979-03-01

    A Computer Control System includes data acquisition, information display and output control signals. In order to design such a system effectively we must first determine the required operational mode: automatic control (closed loop), computer assisted (open loop), or hybrid control. The choice of operating mode will depend on the nature of the plant, the complexity of the operation, the funds available, and the technical expertise of the operating staff, among many other factors. Once the mode has been selected, consideration must be given to the method (man/machine interface) by which the operator interacts with this system. The human engineering factors are of prime importance to achieving high operating efficiency and very careful attention must be given to this aspect of the work, if full operator acceptance is to be achieved. This paper will discuss these topics and will draw on experience gained in setting up the computer control system in Main Control Center for Stanford University's Accelerator Center (a high energy physics research facility)

  15. Are Children with Autism More Responsive to Animated Characters? A Study of Interactions with Humans and Human-Controlled Avatars

    Science.gov (United States)

    Carter, Elizabeth J.; Williams, Diane L.; Hodgins, Jessica K.; Lehman, Jill F.

    2014-01-01

    Few direct comparisons have been made between the responsiveness of children with autism to computer-generated or animated characters and their responsiveness to humans. Twelve 4-to 8-year-old children with autism interacted with a human therapist; a human-controlled, interactive avatar in a theme park; a human actor speaking like the avatar; and…

  16. Human reliability analysis for advanced control room of KNGR

    International Nuclear Information System (INIS)

    Kim, Myung-Ro; Park, Seong-Kyu

    2000-01-01

    There are two purposes in Human Reliability Analysis (HRA) which was performed during Korean Next Generation Reactor (KNGR) Phase 2 research project. One is to present the human error probability quantification results for Probabilistic Safety Assessment (PSA) and the other is to provide a list of the critical operator actions for Human Factor Engineering (HFE). Critical operator actions were identified from the KNGR HRA/RSA based on selection criteria and incorporated in the MMI Task Analysis, where they receive additional treatment. The use of HRA/PSA results in design, procedure development, and training was ensured by their incorporation in the MMI task analysis and MCR design such as fixed position alarms, displays and controls. Any dominant PSA sequence that takes credit for human performance to achieve acceptable results was incorporated in MMIS validation activities through the PSA-based critical operator actions. The integration of KNGR HRA into MMI design was sufficiently addressed all applicable review criteria of NUREG-0800, Chapter 18, Section 2 F and NUREG-0711. (S.Y.)

  17. Controlled human infection models for vaccine development: Zika virus debate.

    Science.gov (United States)

    Gopichandran, Vijayaprasad

    2018-01-01

    An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

  18. Control of human parasitic diseases: Context and overview.

    Science.gov (United States)

    Molyneux, David H

    2006-01-01

    The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and

  19. Optimizing the human engineering design of control panels in nuclear power plant control rooms

    International Nuclear Information System (INIS)

    Behrendt, V.; Krehbiehl, T.; Hartfiel, H.D.; Mannhaupt, H.R.

    1986-12-01

    The study contains two parts. In the first part an analytical procedure is developed to logically and reproducibly subdivide the control room personnel tasks resulting in a list of the elements (operations) and the structure (operations scheme) of a task. The second part lists together all knowledge of and influences on human engineering which are known at this time and which should be taken into account in designing control rooms. The content of this catalogue can best be used and presented by using a personal computer. Two fundamental different ways are possible to use the catalogue. Designing new control rooms or new parts of control rooms the results of the task analysis which should be done first, should guide the search in the catalogue to find the right human engineering factors. For assessing existing control room panels the performance shaping factors which are establishing the table of content, permit a quick access to the catalogue. Both the specific procedure of the task analysis and the different ways of access to the catalogue of human engineering knowledge for designing nuclear power plant control rooms have been proven by experienced system engineers and safety experts. The results are presented. They have been considered in this version of the study. (orig.) [de

  20. Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity.

    Science.gov (United States)

    Pokrzywinski, Kaytee L; Biel, Thomas G; Kryndushkin, Dmitry; Rao, V Ashutosh

    2016-01-01

    Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis.

  1. The using of the control room automation against human errors

    International Nuclear Information System (INIS)

    Kautto, A.

    1993-01-01

    The control room automation has developed very strongly during the 80's in IVO (Imatran Voima Oy). The former work expanded strongly with building of the full scope training simulator to the Loviisa plant. The important milestones has been, for example the testing of the Critical Function Monitoring System, a concept developed by Combustion Eng. Inc., in Loviisa training simulator 1982, the replacing of the process and simulator computers in Loviisa 1989, and 1990 and the presenting the use of the computer based procedures in training of operators 1993. With developing of automation and procedures it is possible to minimize the probability of human error. However, it is not possible totally eliminate the risks caused by human errors. (orig.)

  2. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  3. Stability and Control of Human Trunk Movement During Walking.

    Science.gov (United States)

    Wu, Q.; Sepehri, N.; Thornton-Trump, A. B.; Alexander, M.

    1998-01-01

    A mathematical model has been developed to study the control mechanisms of human trunk movement during walking. The trunk is modeled as a base-excited inverted pendulum with two-degrees of rotational freedom. The base point, corresponding to the bony landmark of the sacrum, can move in three-dimensional space in a general way. Since the stability of upright posture is essential for human walking, a controller has been designed such that the stability of the pendulum about the upright position is guaranteed. The control laws are developed based on Lyapunov's stability theory and include feedforward and linear feedback components. It is found that the feedforward component plays a critical role in keeping postural stability, and the linear feedback component, (resulting from viscoelastic function of the musculoskeletal system) can effectively duplicate the pattern of trunk movement. The mathematical model is validated by comparing the simulation results with those based on gait measurements performed in the Biomechanics Laboratory at the University of Manitoba.

  4. Human movement data for malaria control and elimination strategic planning.

    Science.gov (United States)

    Pindolia, Deepa K; Garcia, Andres J; Wesolowski, Amy; Smith, David L; Buckee, Caroline O; Noor, Abdisalan M; Snow, Robert W; Tatem, Andrew J

    2012-06-18

    Recent increases in funding for malaria control have led to the reduction in transmission in many malaria endemic countries, prompting the national control programmes of 36 malaria endemic countries to set elimination targets. Accounting for human population movement (HPM) in planning for control, elimination and post-elimination surveillance is important, as evidenced by previous elimination attempts that were undermined by the reintroduction of malaria through HPM. Strategic control and elimination planning, therefore, requires quantitative information on HPM patterns and the translation of these into parasite dispersion. HPM patterns and the risk of malaria vary substantially across spatial and temporal scales, demographic and socioeconomic sub-groups, and motivation for travel, so multiple data sets are likely required for quantification of movement. While existing studies based on mobile phone call record data combined with malaria transmission maps have begun to address within-country HPM patterns, other aspects remain poorly quantified despite their importance in accurately gauging malaria movement patterns and building control and detection strategies, such as cross-border HPM, demographic and socioeconomic stratification of HPM patterns, forms of transport, personal malaria protection and other factors that modify malaria risk. A wealth of data exist to aid filling these gaps, which, when combined with spatial data on transport infrastructure, traffic and malaria transmission, can answer relevant questions to guide strategic planning. This review aims to (i) discuss relevant types of HPM across spatial and temporal scales, (ii) document where datasets exist to quantify HPM, (iii) highlight where data gaps remain and (iv) briefly put forward methods for integrating these datasets in a Geographic Information System (GIS) framework for analysing and modelling human population and Plasmodium falciparum malaria infection movements.

  5. Human movement data for malaria control and elimination strategic planning

    Directory of Open Access Journals (Sweden)

    Pindolia Deepa K

    2012-06-01

    Full Text Available Abstract Recent increases in funding for malaria control have led to the reduction in transmission in many malaria endemic countries, prompting the national control programmes of 36 malaria endemic countries to set elimination targets. Accounting for human population movement (HPM in planning for control, elimination and post-elimination surveillance is important, as evidenced by previous elimination attempts that were undermined by the reintroduction of malaria through HPM. Strategic control and elimination planning, therefore, requires quantitative information on HPM patterns and the translation of these into parasite dispersion. HPM patterns and the risk of malaria vary substantially across spatial and temporal scales, demographic and socioeconomic sub-groups, and motivation for travel, so multiple data sets are likely required for quantification of movement. While existing studies based on mobile phone call record data combined with malaria transmission maps have begun to address within-country HPM patterns, other aspects remain poorly quantified despite their importance in accurately gauging malaria movement patterns and building control and detection strategies, such as cross-border HPM, demographic and socioeconomic stratification of HPM patterns, forms of transport, personal malaria protection and other factors that modify malaria risk. A wealth of data exist to aid filling these gaps, which, when combined with spatial data on transport infrastructure, traffic and malaria transmission, can answer relevant questions to guide strategic planning. This review aims to (i discuss relevant types of HPM across spatial and temporal scales, (ii document where datasets exist to quantify HPM, (iii highlight where data gaps remain and (iv briefly put forward methods for integrating these datasets in a Geographic Information System (GIS framework for analysing and modelling human population and Plasmodium falciparum malaria infection movements.

  6. Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model.

    Science.gov (United States)

    Despa, Sanda; Sharma, Savita; Harris, Todd R; Dong, Hua; Li, Ning; Chiamvimonvat, Nipavan; Taegtmeyer, Heinrich; Margulies, Kenneth B; Hammock, Bruce D; Despa, Florin

    2014-08-21

    Chronic hypersecretion of the pancreatic hormone amylin is common in humans with obesity or prediabetic insulin resistance and induces amylin aggregation and proteotoxicity in the pancreas. We recently showed that hyperamylinemia also affects the cardiovascular system. Here, we investigated whether amylin aggregates interact directly with cardiac myocytes and whether controlling hyperamylinemia protects the heart. By Western blot, we found abundant amylin aggregates in lysates of cardiac myocytes from obese patients, but not in controls. Aggregated amylin was elevated in failing hearts, suggesting a role in myocyte injury. Using rats overexpressing human amylin in the pancreas (HIP rats) and control myocytes incubated with human amylin, we show that amylin aggregation at the sarcolemma induces oxidative stress and Ca(2+) dysregulation. In time, HIP rats developed cardiac hypertrophy and left-ventricular dilation. We then tested whether metabolites with antiaggregation properties, such as eicosanoid acids, limit myocardial amylin deposition. Rats were treated with an inhibitor of soluble epoxide hydrolase, the enzyme that degrades endogenous eicosanoids. Treatment doubled the blood concentration of eicosanoids, which drastically reduced incorporation of aggregated amylin in cardiac myocytes and blood cells, without affecting pancreatic amylin secretion. Animals in the treated group showed reduced cardiac hypertrophy and left-ventricular dilation. The cardioprotective mechanisms included the mitigation of amylin-induced cardiac oxidative stress and Ca(2+) dysregulation. The results suggest blood amylin as a novel therapeutic target in diabetic heart disease and elevating blood levels of antiaggregation metabolites as a pharmacological strategy to reduce amylin aggregation and amylin-mediated cardiotoxicity. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. A thermal manikin with human thermoregulatory control: implementation and validation.

    Science.gov (United States)

    Foda, Ehab; Sirén, Kai

    2012-09-01

    Tens of different sorts of thermal manikins are employed worldwide, mainly in the evaluation of clothing thermal insulation and thermal environments. They are regulated thermally using simplified control modes. This paper reports on the implementation and validation of a new thermoregulatory control mode for thermal manikins. The new control mode is based on a multi-segmental Pierce (MSP) model. In this study, the MSP control mode was implemented, using the LabVIEW platform, onto the control system of the thermal manikin 'Therminator'. The MSP mode was then used to estimate the segmental equivalent temperature (t(eq)) along with constant surface temperature (CST) mode under two asymmetric thermal conditions. Furthermore, subjective tests under the same two conditions were carried out using 17 human subjects. The estimated segmental t(eq) from the experiments with the two modes and from the subjective assessment were compared in order to validate the use of the MSP mode for the estimation of t(eq). The results showed that the t(eq) values estimated by the MSP mode were closer to the subjective mean votes under the two test conditions for most body segments and compared favourably with values estimated by the CST mode.

  8. Heterogeneous periodicity of drosophila mtDNA: new refutations of neutral and nearly neutral evolution

    Directory of Open Access Journals (Sweden)

    Carlos Y Valenzuela

    2011-01-01

    Full Text Available We found a consistent 3-site periodicity of the X²9 values for the heterogeneity of the distribution of the second base in relation to the first base of dinucleotides separated by 0 (contiguous, 1, 2, 3 ... 17 (K nucleotide sites in Drosophila mtDNA. Triplets of X²9 values were found where the first was over 300 and the second and third ranged between 37 and 114 (previous studies. In this study, the periodicity was significant until separation of 2011K, and a structure of deviations from randomness among dinucleotides was found. The most deviant dinucleotides were G-G, G-C and C-G for the first, second and third element of the triplet, respectively. In these three cases there were more dinucleotides observed than expected. This inter-bases correlation and periodicity may be related to the tertiary structure of circular DNA, like that of prokaryotes and mitochondria, to protect and preserve it. The mtDNA with 19.517 bp was divided into four equal segments of 4.879 bp. The fourth sub-segment presented a very low proportion of G and C, the internucleotide interaction was weaker in this sub-segment and no periodicity was found. The maintenance of this mtDNA structure and organization for millions of generations, in spite of a high recurrent mutation rate, does not support the notion of neutralism or near neutralism. The high level of internucleotide interaction and periodicity indicate that every nucleotide is co-adapted with the residual genome.

  9. A HUMAN FACTORS ENGINEERING PROCESS TO SUPPORT HUMAN-SYSTEM INTERFACE DESIGN IN CONTROL ROOM MODERNIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Kovesdi, C.; Joe, J.; Boring, R.

    2017-05-01

    The primary objective of the United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program is to sustain operation of the existing commercial nuclear power plants (NPPs) through a multi-pathway approach in conducting research and development (R&D). The Advanced Instrumentation, Information, and Control (II&C) System Technologies pathway conducts targeted R&D to address aging and reliability concerns with legacy instrumentation and control (I&C) and other information systems in existing U.S. NPPs. Control room modernization is an important part following this pathway, and human factors experts at Idaho National Laboratory (INL) have been involved in conducting R&D to support migration of new digital main control room (MCR) technologies from legacy analog and legacy digital I&C. This paper describes a human factors engineering (HFE) process that supports human-system interface (HSI) design in MCR modernization activities, particularly with migration of old digital to new digital I&C. The process described in this work is an expansion from the LWRS Report INL/EXT-16-38576, and is a requirements-driven approach that aligns with NUREG-0711 requirements. The work described builds upon the existing literature by adding more detail around key tasks and decisions to make when transitioning from HSI Design into Verification and Validation (V&V). The overall objective of this process is to inform HSI design and elicit specific, measurable, and achievable human factors criteria for new digital technologies. Upon following this process, utilities should have greater confidence with transitioning from HSI design into V&V.

  10. Three reciprocally monophyletic mtDNA lineages elucidate the taxonomic status of Grant's gazelles

    DEFF Research Database (Denmark)

    Lorenzen, Eline Deidre; Arctander, Peter; Siegismund, Hans Redlef

    2008-01-01

    are discussed in reference to the four currently recognised subspecies. We suggest Grant's gazelles be raised to the superspecies Nanger (granti) comprising three taxonomic units corresponding to the three mtDNA lineages. There was no evidence of gene flow between the notata and granti lineages, despite...... their geographic proximity, suggesting reproductive isolation. These constitute evolutionary significant units within the adaptive evolutionary framework. Due to its restricted geographic distribution and genetic and morphological distinctiveness, we suggest the petersii lineage be raised to the species Nanger...

  11. The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities.

    Science.gov (United States)

    Hertweck, Kate L; Dasgupta, Santanu

    2017-01-01

    Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

  12. Forensic and phylogeographic characterisation of mtDNA lineages from Somalia

    DEFF Research Database (Denmark)

    Mikkelsen, Martin; Fendt, Liane; Röck, Alexander W.

    2012-01-01

    Somali individuals to enrich the severely underrepresented African mtDNA pool. The majority (60.5 %) of the haplotypes were of sub-Saharan origin with L0a1d, L2a1h and L3f being the most frequently observed haplogroups. This is in sharp contrast to previous data reported from the Y-chromosome, where only...... about 5 % of the observed haplogroups were of sub-Saharan provenance. We compared the genetic distances based on population pairwise F (st) values between 11 published East, Central and North African as well as western Asian populations and the Somali sequences and displayed them in a multi...

  13. Contextual control of attentional allocation in human discrimination learning.

    Science.gov (United States)

    Uengoer, Metin; Lachnit, Harald; Lotz, Anja; Koenig, Stephan; Pearce, John M

    2013-01-01

    In 3 human predictive learning experiments, we investigated whether the allocation of attention can come under the control of contextual stimuli. In each experiment, participants initially received a conditional discrimination for which one set of cues was trained as relevant in Context 1 and irrelevant in Context 2, and another set was relevant in Context 2 and irrelevant in Context 1. For Experiments 1 and 2, we observed that a second discrimination based on cues that had previously been trained as relevant in Context 1 during the conditional discrimination was acquired more rapidly in Context 1 than in Context 2. Experiment 3 revealed a similar outcome when new stimuli from the original dimensions were used in the test stage. Our results support the view that the associability of a stimulus can be controlled by the stimuli that accompany it.

  14. Remote controlled capsules in human drug absorption (HDA) studies.

    Science.gov (United States)

    Wilding, Ian R; Prior, David V

    2003-01-01

    The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery.

  15. Effects of External Loads on Human Head Movement Control Systems

    Science.gov (United States)

    Nam, M. H.; Choi, O. M.

    1984-01-01

    The central and reflexive control strategies underlying movements were elucidated by studying the effects of external loads on human head movement control systems. Some experimental results are presented on dynamic changes weigh the addition of aviation helmet (SPH4) and lead weights (6 kg). Intended time-optimal movements, their dynamics and electromyographic activity of neck muscles in normal movements, and also in movements made with external weights applied to the head were measured. It was observed that, when the external loads were added, the subject went through complex adapting processes and the head movement trajectory and its derivatives reached steady conditions only after transient adapting period. The steady adapted state was reached after 15 to 20 seconds (i.e., 5 to 6 movements).

  16. Design of intelligent comfort control system with human learning and minimum power control strategies

    International Nuclear Information System (INIS)

    Liang, J.; Du, R.

    2008-01-01

    This paper presents the design of an intelligent comfort control system by combining the human learning and minimum power control strategies for the heating, ventilating and air conditioning (HVAC) system. In the system, the predicted mean vote (PMV) is adopted as the control objective to improve indoor comfort level by considering six comfort related variables, whilst a direct neural network controller is designed to overcome the nonlinear feature of the PMV calculation for better performance. To achieve the highest comfort level for the specific user, a human learning strategy is designed to tune the user's comfort zone, and then, a VAV and minimum power control strategy is proposed to minimize the energy consumption further. In order to validate the system design, a series of computer simulations are performed based on a derived HVAC and thermal space model. The simulation results confirm the design of the intelligent comfort control system. In comparison to the conventional temperature controller, this system can provide a higher comfort level and better system performance, so it has great potential for HVAC applications in the future

  17. Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction

    Directory of Open Access Journals (Sweden)

    Shishkin S. L.

    2017-09-01

    Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

  18. Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

    Energy Technology Data Exchange (ETDEWEB)

    Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček, Tomáš; Pajuelo Reguera, David; Jabůrek, Martin; Ježek, Petr

    2016-07-01

    Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM

  19. Effects of Probiotics on Human Obesity Control: An Unproven Hypothesis

    Directory of Open Access Journals (Sweden)

    Amparo Arias

    2014-01-01

    Full Text Available The objective of the present study is to review the different publications associated with probiotics and obesity, as well as to get some new insights regarding the role of the microbiome in diseases such as obesity. An extensive search for scientific publications (studies in animal models, cells, clinical trials and reviews was performed in the following specialist computer databases (PubMed central (PMC-NCBI, Elsevier Journal, Scielo Spain, Scirus, Science Direct to establish the current status of the potential effect of probiotics in the control of obesity in humans, as well as the relationship between intestinal microbiota and obesity. The intestinal microbiota and oral probiotics have a positive effect on human health, as they can regulate the immune functions and protect from infections and chronic inflammatory processes. Although divergent results have recently been reported, it has been shown but not confirmed that intestinal microbiota might play a role as a new factor associated with the regulation of body weight and obesity-related diseases. The international MetaHIT project has shown that human microbiome populations can be grouped into three different enterotypes. Two of these enterotypes (Bacteroides and Ruminococcus seem to encode functions related to obesity. Although the relationship between intestinal microbiota and obesity are not yet well established, the attempt to manipulate intestinal microbiota through diet is suggested as a new plausible approach to prevent, or modify the risk of, obesity and its related diseases.

  20. Identification of West Eurasian mitochondrial haplogroups by mtDNA SNP screening: results of the 2006-2007 EDNAP collaborative exercise

    DEFF Research Database (Denmark)

    Parson, Walther; Fendt, Liane; Ballard, David

    2008-01-01

    no previous experience with the technology and/or mtDNA analysis. The results of this collaborative exercise stimulate the expansion of screening methods in forensic laboratories to increase efficiency and performance of mtDNA typing, and thus demonstrates that mtDNA SNP typing is a powerful tool for forensic......The European DNA Profiling (EDNAP) Group performed a collaborative exercise on a mitochondrial (mt) DNA screening assay that targeted 16 nucleotide positions in the coding region and allowed for the discrimination of major west Eurasian mtDNA haplogroups. The purpose of the exercise was to evaluate...

  1. Structure, function, and control of the human musculoskeletal network.

    Directory of Open Access Journals (Sweden)

    Andrew C Murphy

    2018-01-01

    Full Text Available The human body is a complex organism, the gross mechanical properties of which are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we address this gap in knowledge by utilizing medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We constructed a highly simplified whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrated that, using this simplified model, a muscle's role in this network could offer a theoretical prediction of the susceptibility of surrounding components to secondary injury. Finally, we illustrated that sets of muscles cluster into network communities that mimic the organization of control modules in primary motor cortex. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments.

  2. mtDNA analysis of human remains from an early Danish Christian cemetery

    DEFF Research Database (Denmark)

    Rudbeck, Lars; Gilbert, M Thomas P; Willerslev, Eske

    2005-01-01

    One of Denmark's earliest Christian cemeteries is Kongemarken, dating to around AD 1000-1250. A feature of early Scandinavian Christian cemeteries is sex segregation, with females buried on the northern sides and males on the southern sides. However, such separation was never complete; in the few...

  3. MtDNA barcode identification of fish larvae in the southern Great Barrier Reef – Australia

    Directory of Open Access Journals (Sweden)

    Graham G. Pegg

    2006-10-01

    Full Text Available Planktonic larvae were captured above a shallow coral reef study site on the Great Barrier Reef (GBR around spring-summer new moon periods (October-February using light trap or net capture devices. Larvae were identified to the genus or species level by comparison with a phylogenetic tree of tropical marine fish species using mtDNA HVR1 sequence data. Further analysis showed that within-species HVR1 sequence variation was typically 1-3%, whereas between-species variation for the same genus ranged up to 50%, supporting the suitability of HVR1 for species identification. Given the current worldwide interest in DNA barcoding and species identification using an alternative mtDNA gene marker (cox1, we also explored the efficacy of different primer sets for amplification of cox1 in reef fish, and its suitability for species identification. Of those tested, the Fish-F1 and -R1 primer set recently reported by Ward et al. (2005 gave the best results.

  4. Phenotypic and mtDNA variation in Philippine Kappaphycus cottonii (Gigartinales, Rhodophyta).

    Science.gov (United States)

    Dumilag, Richard V; Gallardo, William George M; Garcia, Christian Philip C; You, YeaEun; Chaves, Alyssa Keren G; Agahan, Lance

    2017-11-09

    Members of the carrageenan-producing seaweeds of the genus Kappapphycus have a complicated taxonomic history particularly with regard to species identification. Many taxonomic challenges in this group have been currently addressed with the use of mtDNA sequences. The phylogenetic status and genetic diversity of one of the lesser known species, Kappaphycus cottonii, have repeatedly come into question. This study explored the genetic variation in Philippine K. cottonii using the mtDNA COI-5P gene and cox2-3 spacer sequences. The six phenotypic forms in K. cottonii did not correspond to the observed genetic variability; hinting at the greater involvement of environmental factors in determining changes to the morphology of this alga. Our results revealed that the Philippine K. cottonii has the richest number of haplotypes that have been detected, so far, for any Kappaphycus species. Our inferred phylogenetic trees suggested two lineages: a lineage, which exclusively includes K. cottonii and another lineage comprising the four known Kappaphycus species: K. alvarezii, K. inermis, K. malesianus, and K. striatus. The dichotomy supports the apparent synamorphy for each of these lineages (the strictly terete thalli, lack of protuberances, and the presence of a hyphal central core in the latter group, while the opposite of these morphologies in K. cottonii). These findings shed new light on understanding the evolutionary history of the genus. Assessing the breadth of the phenotypic and genetic variation in K. cottonii has implications for the conservation and management of the overall Kappaphycus genetic resources, especially in the Philippines.

  5. Molecular Characterization of Sudanese and Southern Sudanese Chicken Breeds Using mtDNA D-Loop

    Directory of Open Access Journals (Sweden)

    Charles E. Wani

    2014-01-01

    Full Text Available The objective of this study was to assess the genetic relationships and diversity and to estimate the amount of gene flow among the five chicken populations from Sudan and South Sudan and commercial strain of egg line White Leghorn chickens. The chicken populations were genotyped using mtDNA D-loop as a molecular marker. PCR product of the mtDNA D-loop segment was 600 bp and 14 haplotypes were identified. The neighbor-joining phylogenetic tree indicated that the indigenous Sudanese chickens can be grouped into two clades, IV and IIIa only. Median joining networks analysis showed that haplotype LBB49 has the highest frequency. The hierarchal analysis of molecular variance (AMOVA showed that genetic variation within the population was 88.6% and the differentiation among the population was 11.4%. When the populations was redefined into two geographical zones, rich and poor Savanna, the results were fractioned into three genetic variations: between individuals within population 95.5%, between populations within the group 0.75%, and genetic variation between groups 3.75%. The pair wise Fst showed high genetic difference between Betwil populations and the rest with Fst ranging from 0.1492 to 0.2447. We found that there is large number of gene exchanges within the Sudanese indigenous chicken (Nm=4.622.

  6. A new view on dam lines in Polish Arabian horses based on mtDNA analysis

    Directory of Open Access Journals (Sweden)

    Sell Jerzy

    2007-09-01

    Full Text Available Abstract Polish Arabian horses are one of the oldest and the most important Arab populations in the world. The Polish Arabian Stud Book and the Genealogical Charts by Skorkowski are the main sources of information on the ancestors of Polish Arabs. Both publications were viewed as credible sources of information until the 1990s when the data regarding one of the dam lines was questioned. The aim of the current study was to check the accuracy of the pedigree data of Polish dam lines using mtDNA analysis. The analyses of a 458 bp mtDNA D-loop fragment from representatives of 15 Polish Arabian dam lines revealed 14 distinct haplotypes. The results were inconsistent with pedigree data in the case of two lines. A detailed analysis of the historical sources was performed to explain these discrepancies. Our study revealed that representatives of different lines shared the same haplotypes. We also noted a genetic identity between some lines founded by Polish mares of unknown origin and lines established by desert-bred mares.

  7. 76 FR 35130 - Pipeline Safety: Control Room Management/Human Factors

    Science.gov (United States)

    2011-06-16

    ...: Control Room Management/Human Factors AGENCY: Pipeline and Hazardous Materials Safety Administration... the Control Room Management/Human Factors regulations in order to realize the safety benefits sooner... FR 5536). By this amendment to the Control Room Management/Human Factors (CRM) rule, an operator must...

  8. Comparative mtDNA analyses of three sympatric macropodids from a conservation area on the Huon Peninsula, Papua New Guinea.

    Science.gov (United States)

    McGreevy, Thomas J; Dabek, Lisa; Husband, Thomas P

    2016-07-01

    Matschie's tree kangaroo (Dendrolagus matschiei), New Guinea pademelon (Thylogale browni), and small dorcopsis (Dorcopsulus vanheurni) are sympatric macropodid taxa, of conservation concern, that inhabit the Yopno-Urawa-Som (YUS) Conservation Area on the Huon Peninsula, Papua New Guinea. We sequenced three partial mitochondrial DNA (mtDNA) genes from the three taxa to (i) investigate network structure; and (ii) identify conservation units within the YUS Conservation Area. All three taxa displayed a similar pattern in the spatial distribution of their mtDNA haplotypes and the Urawa and Som rivers on the Huon may have acted as a barrier to maternal gene flow. Matschie's tree kangaroo and New Guinea pademelon within the YUS Conservation Area should be managed as single conservation units because mtDNA nucleotides were not fixed for a given geographic area. However, two distinct conservation units were identified for small dorcopsis from the two different mountain ranges within the YUS Conservation Area.

  9. Movement augmentation to evaluate human control of locomotor stability.

    Science.gov (United States)

    Brown, Geoffrey; Wu, Mengnan Mary; Huang, Felix C; Gordon, Keith E

    2017-07-01

    Controlling center of mass (COM) position and velocity within a dynamic base of support is essential for gait stability. This skill is often compromised following neurologic injury, creating a need to develop effective interventions to enhance gait stability. A movement augmentation paradigm applied to walking could potentially be used to improve control of COM dynamics. We have developed a cable robot system, the Agility Trainer, to apply continuous frontal-plane forces to the pelvis during treadmill walking. This cable robot system uses a set of series elastic actuators powered by linear motors to create bilateral forces. Here we use the Agility Trainer to create a negative viscosity force field proportional to the subject's lateral velocity. Two healthy young subjects performed two 10-minute walking trials, Baseline and Negative Viscosity. During the first minute of walking in the Negative Viscosity field, participants' lateral COM motion became less controlled when compared to the rhythmic sinusoidal motion observed during Baseline walking. By the 10th minute of walking in the Negative Viscosity field the participants had adapted their gait patterns, decreasing their variation in peak lateral COM speed each stride. These results demonstrate that it is feasible to use the Agility Trainer to apply a movement augmentation paradigm to human walking.

  10. MELAS and Kearns–Sayre overlap syndrome due to the mtDNA m. A3243G mutation and large-scale mtDNA deletions

    Directory of Open Access Journals (Sweden)

    Nian Yu

    2016-09-01

    Full Text Available This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome and Kearns–Sayre syndrome (KSS. He was admitted to our hospital with the chief complaint of “acute fever, headache and slow reaction for 21 days”. He was initially misdiagnosed as “viral encephalitis”. This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff–Parkinson–White syndrome. By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.

  11. Host control of human papillomavirus infection and disease.

    Science.gov (United States)

    Doorbar, John

    2018-02-01

    Most human papillomaviruses cause inapparent infections, subtly affecting epithelial homeostasis, to ensure genome persistence in the epithelial basal layer. As with conspicuous papillomas, these self-limiting lesions shed viral particles to ensure population level maintenance and depend on a balance between viral gene expression, immune cell stimulation and immune surveillance for persistence. The complex immune evasion strategies, characteristic of high-risk HPV types, also allow the deregulated viral gene expression that underlies neoplasia. Neoplasia occurs at particular epithelial sites where vulnerable cells such as the reserve or cuboidal cells of the cervical transformation zone are found. Beta papillomavirus infection can also predispose an individual with immune deficiencies to the development of cancers. The host control of HPV infections thus involves local interactions between keratinocytes and the adaptive immune response. Effective immune detection and surveillance limits overt disease, leading to HPV persistence as productive microlesions or in a true latent state. Copyright © 2017. Published by Elsevier Ltd.

  12. mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

    Science.gov (United States)

    Saada, Ann; Shaag, Avraham; Elpeleg, Orly

    2003-05-01

    Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.

  13. Collaborative human-machine analysis using a controlled natural language

    Science.gov (United States)

    Mott, David H.; Shemanski, Donald R.; Giammanco, Cheryl; Braines, Dave

    2015-05-01

    A key aspect of an analyst's task in providing relevant information from data is the reasoning about the implications of that data, in order to build a picture of the real world situation. This requires human cognition, based upon domain knowledge about individuals, events and environmental conditions. For a computer system to collaborate with an analyst, it must be capable of following a similar reasoning process to that of the analyst. We describe ITA Controlled English (CE), a subset of English to represent analyst's domain knowledge and reasoning, in a form that it is understandable by both analyst and machine. CE can be used to express domain rules, background data, assumptions and inferred conclusions, thus supporting human-machine interaction. A CE reasoning and modeling system can perform inferences from the data and provide the user with conclusions together with their rationale. We present a logical problem called the "Analysis Game", used for training analysts, which presents "analytic pitfalls" inherent in many problems. We explore an iterative approach to its representation in CE, where a person can develop an understanding of the problem solution by incremental construction of relevant concepts and rules. We discuss how such interactions might occur, and propose that such techniques could lead to better collaborative tools to assist the analyst and avoid the "pitfalls".

  14. Human error recovery failure probability when using soft controls in computerized control rooms

    International Nuclear Information System (INIS)

    Jang, Inseok; Kim, Ar Ryum; Seong, Poong Hyun; Jung, Wondea

    2014-01-01

    Many literatures categorized recovery process into three phases; detection of problem situation, explanation of problem causes or countermeasures against problem, and end of recovery. Although the focus of recovery promotion has been on categorizing recovery phases and modeling recovery process, research related to human recovery failure probabilities has not been perform actively. On the other hand, a few study regarding recovery failure probabilities were implemented empirically. Summarizing, researches that have performed so far have several problems in terms of use in human reliability analysis (HRA). By adopting new human-system interfaces that are based on computer-based technologies, the operation environment of MCRs in NPPs has changed from conventional MCRs to advanced MCRs. Because of the different interfaces between conventional and advanced MCRs, different recovery failure probabilities should be considered in the HRA for advanced MCRs. Therefore, this study carries out an empirical analysis of human error recovery probabilities under an advanced MCR mockup called compact nuclear simulator (CNS). The aim of this work is not only to compile a recovery failure probability database using the simulator for advanced MCRs but also to collect recovery failure probability according to defined human error modes to compare that which human error mode has highest recovery failure probability. The results show that recovery failure probability regarding wrong screen selection was lowest among human error modes, which means that most of human error related to wrong screen selection can be recovered. On the other hand, recovery failure probabilities of operation selection omission and delayed operation were 1.0. These results imply that once subject omitted one task in the procedure, they have difficulties finding and recovering their errors without supervisor's assistance. Also, wrong screen selection had an effect on delayed operation. That is, wrong screen

  15. Human strongyloidiasis: identifying knowledge gaps, with emphasis on environmental control

    Directory of Open Access Journals (Sweden)

    Taylor MJ

    2014-08-01

    Full Text Available Michael J Taylor, Tara A Garrard, Francis J O'Donahoo, Kirstin E Ross Health and Environment, School of the Environment, Flinders University, Adelaide, SA, Australia Abstract: Strongyloides is a human parasitic nematode that is poorly understood outside a clinical context. This article identifies gaps within the literature, with particular emphasis on gaps that are hindering environmental control of Strongyloides. The prevalence and distribution of Strongyloides is unclear. An estimate of 100–370 million people infected worldwide has been proposed; however, inaccuracy of diagnosis, unreliability of prevalence mapping, and the fact that strongyloidiasis remains a neglected disease suggest that the higher figure of more than 300 million cases is likely to be a more accurate estimate. The complexity of Strongyloides life cycle means that laboratory cultures cannot be maintained outside of a host. This currently limits the range of laboratory-based research, which is vital to controlling Strongyloides through environmental alteration or treatment. Successful clinical treatment with antihelminthic drugs has meant that controlling Strongyloides through environmental control, rather than clinical intervention, has been largely overlooked. These control measures may encompass alteration of the soil environment through physical means, such as desiccation or removal of nutrients, or through chemical or biological agents. Repeated antihelminthic treatment of individuals with recurrent strongyloidiasis has not been observed to result in the selection of resistant strains; however, this has not been explicitly demonstrated, and relying on such assumptions in the long-term may prove to be shortsighted. It is ultimately naive to assume that continued administration of antihelminthics will be without any negative long-term effects. In Australia, strongyloidiasis primarily affects Indigenous communities, including communities from arid central Australia. This

  16. The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

    Directory of Open Access Journals (Sweden)

    Kotal M

    2008-08-01

    Full Text Available Abstract Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP. However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is

  17. Recent introgressive hybridization revealed by exclusive mtDNA transfer from Oreochromis leucostictus (Trewavas, 1933) to Oreochromis niloticus (Linnaeus, 1758) in Lake Baringo, Kenya

    OpenAIRE

    Nyingi, Dorothy W.; Agnèse, Jean-François

    2007-01-01

    Nuclear DNA and mtDNA polymorphisms were surveyed in various species of East African Oreochromis. In Lake Baringo, where only Oreochromis niloticus baringoensis is present, alien mtDNA haplotypes were observed, apparently the result of introgressive hybridization with Oreochromis leucostictus. This introgression is not accompanied by any substantial or recorded transfer of nuclear genes into O. n. baringoensis.

  18. Thalamic control of human attention driven by memory and learning.

    Science.gov (United States)

    de Bourbon-Teles, José; Bentley, Paul; Koshino, Saori; Shah, Kushal; Dutta, Agneish; Malhotra, Paresh; Egner, Tobias; Husain, Masud; Soto, David

    2014-05-05

    The role of the thalamus in high-level cognition-attention, working memory (WM), rule-based learning, and decision making-remains poorly understood, especially in comparison to that of cortical frontoparietal networks [1-3]. Studies of visual thalamus have revealed important roles for pulvinar and lateral geniculate nucleus in visuospatial perception and attention [4-10] and for mediodorsal thalamus in oculomotor control [11]. Ventrolateral thalamus contains subdivisions devoted to action control as part of a circuit involving the basal ganglia [12, 13] and motor, premotor, and prefrontal cortices [14], whereas anterior thalamus forms a memory network in connection with the hippocampus [15]. This connectivity profile suggests that ventrolateral and anterior thalamus may represent a nexus between mnemonic and control functions, such as action or attentional selection. Here, we characterize the role of thalamus in the interplay between memory and visual attention. We show that ventrolateral lesions impair the influence of WM representations on attentional deployment. A subsequent fMRI study in healthy volunteers demonstrates involvement of ventrolateral and, notably, anterior thalamus in biasing attention through WM contents. To further characterize the memory types used by the thalamus to bias attention, we performed a second fMRI study that involved learning of stimulus-stimulus associations and their retrieval from long-term memory to optimize attention in search. Responses in ventrolateral and anterior thalamic nuclei tracked learning of the predictiveness of these abstract associations and their use in directing attention. These findings demonstrate a key role for human thalamus in higher-level cognition, notably, in mnemonic biasing of attention. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Feedforward neural control of toe walking in humans.

    Science.gov (United States)

    Lorentzen, Jakob; Willerslev-Olsen, Maria; Hüche Larsen, Helle; Svane, Christian; Forman, Christian; Frisk, Rasmus; Farmer, Simon Francis; Kersting, Uwe; Nielsen, Jens Bo

    2018-03-23

    Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped. Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking. We argue that toe walking is supported by feedforward control at ground contact. Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h -1 ). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H-reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle-tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon-muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large-diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor-evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of

  20. Controlled Human Malaria Infection: Applications, Advances, and Challenges.

    Science.gov (United States)

    Stanisic, Danielle I; McCarthy, James S; Good, Michael F

    2018-01-01

    Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration. Copyright © 2017 American Society for Microbiology.

  1. A collaborative EDNAP exercise on SNaPshot™-based mtDNA control region typing

    DEFF Research Database (Denmark)

    Weiler, NEC; Baca, K; Ballard, D

    2017-01-01

    A collaborative European DNA Profiling (EDNAP) Group exercise was undertaken to assess the performance of an earlier described SNaPshot™-based screening assay (denoted mini-mtSNaPshot) (Weiler et al., 2016) [1] that targets 18 single nucleotide polymorphism (SNP) positions in the mitochondrial (m...... and derived from a subset of the participants, indicating a need for training and guidelines regarding mini-mtSNaPshot data interpretation....

  2. Genetic diversity in the mtDNA control region and population ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-17

    Dec 17, 2008 ... have played important roles in creating isolated populations by cutting ... marginal seas separate Asia from the Pacific, straddling the world's largest ... from the Pacific. Ocean by the NE–SW-extending Ryukyu Islands Arc. The.

  3. Tandemly repeated sequence in 5'end of mtDNA control region of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-17

    Dec 17, 2008 ... chain reaction (PCR). Japanese Spanish ... mainly covered general ecology and fishery biology. No study concerning the ... Conserved sequence blocks and the repeat units are indicated by boxes. performed using the exact ...

  4. The monitoring and control of task sequences in human and non-human primates

    Directory of Open Access Journals (Sweden)

    Theresa M Desrochers

    2016-01-01

    Full Text Available Our ability to plan and execute a series of tasks leading to a desired goal requires remarkable coordination between sensory, motor, and decision-related systems. Prefrontal cortex is thought to play a central role in this coordination, especially when actions must be assembled extemporaneously and cannot be programmed as a rote series of movements. A central component of this flexible behavior is the moment-by-moment allocation of working memory and attention. The ubiquity of sequence planning in our everyday lives belies the neural complexity that supports this capacity, and little is known about how frontal cortical regions orchestrate the monitoring and control of sequential behaviors. For example, it remains unclear if and how sensory cortical areas, which provide essential driving inputs for behavior, are modulated by the frontal cortex during these tasks. Here we review what is known about moment-to-moment monitoring as it relates to visually guided, rule-driven behaviors that change over time. We highlight recent human work that shows how the rostrolateral prefrontal cortex (RLPFC participates in monitoring during task sequences. Neurophysiological data from monkeys suggests that monitoring may be accomplished by neurons that respond to items within the sequence and may in turn influence the tuning properties of neurons in posterior sensory areas. Understanding the interplay between proceduralized or habitual acts and supervised control of sequences is key to our understanding of sequential task execution. A crucial bridge will be the use of experimental protocols that allow for the examination of the functional homology between monkeys and humans. We illustrate how task sequences may be parceled into components and examined experimentally, thereby opening future avenues of investigation into the neural basis of sequential monitoring and control.

  5. Human-level control through deep reinforcement learning

    Science.gov (United States)

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A.; Veness, Joel; Bellemare, Marc G.; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K.; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-01

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  6. Human-level control through deep reinforcement learning.

    Science.gov (United States)

    Mnih, Volodymyr; Kavukcuoglu, Koray; Silver, David; Rusu, Andrei A; Veness, Joel; Bellemare, Marc G; Graves, Alex; Riedmiller, Martin; Fidjeland, Andreas K; Ostrovski, Georg; Petersen, Stig; Beattie, Charles; Sadik, Amir; Antonoglou, Ioannis; King, Helen; Kumaran, Dharshan; Wierstra, Daan; Legg, Shane; Hassabis, Demis

    2015-02-26

    The theory of reinforcement learning provides a normative account, deeply rooted in psychological and neuroscientific perspectives on animal behaviour, of how agents may optimize their control of an environment. To use reinforcement learning successfully in situations approaching real-world complexity, however, agents are confronted with a difficult task: they must derive efficient representations of the environment from high-dimensional sensory inputs, and use these to generalize past experience to new situations. Remarkably, humans and other animals seem to solve this problem through a harmonious combination of reinforcement learning and hierarchical sensory processing systems, the former evidenced by a wealth of neural data revealing notable parallels between the phasic signals emitted by dopaminergic neurons and temporal difference reinforcement learning algorithms. While reinforcement learning agents have achieved some successes in a variety of domains, their applicability has previously been limited to domains in which useful features can be handcrafted, or to domains with fully observed, low-dimensional state spaces. Here we use recent advances in training deep neural networks to develop a novel artificial agent, termed a deep Q-network, that can learn successful policies directly from high-dimensional sensory inputs using end-to-end reinforcement learning. We tested this agent on the challenging domain of classic Atari 2600 games. We demonstrate that the deep Q-network agent, receiving only the pixels and the game score as inputs, was able to surpass the performance of all previous algorithms and achieve a level comparable to that of a professional human games tester across a set of 49 games, using the same algorithm, network architecture and hyperparameters. This work bridges the divide between high-dimensional sensory inputs and actions, resulting in the first artificial agent that is capable of learning to excel at a diverse array of challenging tasks.

  7. Rare mtDNA haplogroups and genetic differences in rich and poor Danish Iron-Age villages

    DEFF Research Database (Denmark)

    Melchior, L; Gilbert, M T P; Kivisild, T

    2008-01-01

    The Roman Iron-Age (0-400 AD) in Southern Scandinavia was a formative period, where the society changed from archaic chiefdoms to a true state formation, and the population composition has likely changed in this period due to immigrants from Middle Scandinavia. We have analyzed mtDNA from 22 indi...

  8. An economical mtDNA SNP assay detecting different mitochondrial haplogroups in identical HVR 1 samples of Caucasian ancestry.

    Science.gov (United States)

    Köhnemann, Stephan; Hohoff, Carsten; Pfeiffer, Heidi

    2009-09-01

    We had sequenced 329 Caucasian samples in Hypervariable Region 1 (HVR 1) and found that they belong to eleven different mitochondrial DNA (mtDNA) haplotypes. The sample set was further analysed by an mtDNA assay examining 32 single nucleotide polymorphisms (SNPs) for haplogroup discrimination. In a validation study on 160 samples of different origin it was shown that these SNPs were able to discriminate between the evolved superhaplogroups worldwide (L, M and N) and between the nine most common Caucasian haplogroups (H, I, J, K, T, U, V, W and X). The 32 mtDNA SNPs comprised 42 different SNP haplotypes instead of only eleven haplotypes after HVR 1 sequencing. The assay provided stable results in a range of 5ng genomic DNA down to virtually no genomic DNA per reaction. It was possible to detect samples of African, Asian and Eurasian ancestry, respectively. The 32 mtDNA SNP assay is a helpful adjunct to further distinguish between identical HVR 1 sequences of Caucasian origin. Our results suggest that haplogroup prediction using HVR 1 sequencing provides instable results. The use of coding region SNPs for haplogroup assignment is more suited than using HVR 1 haplotypes.

  9. Y-chromosome and mtDNA variation confirms independent domestications and directional hybridization in South American camelids.

    Science.gov (United States)

    Marín, J C; Romero, K; Rivera, R; Johnson, W E; González, B A

    2017-10-01

    Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally-inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex-specific markers (male specific Y-chromosome and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns. Three male-specific Y-chromosome markers and control region sequences of mitochondrial DNA are studied here. Although no sequence variation was found in SRY and ZFY, there were seven variable sites in DBY generating five haplotypes on the Y-chromosome. The haplotype network showed clear separation between haplogroups of guanaco-llama and vicuña-alpaca, indicating two genetically distinct patrilineages with near absence of shared haplotypes between guanacos and vicuñas. Although we document some examples of directional hybridization, the patterns strongly support the hypothesis that llama (Lama glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos) from vicuña (Vicugna vicugna). Within male guanacos we identified a haplogroup formed by three haplotypes with different geographical distributions, the northernmost of which (Peru and northern Chile) was also observed in llamas, supporting the commonly held hypothesis that llamas were domesticated from the northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared the other two haplotypes. A second haplogroup, consisting of two haplotypes, was mostly present in vicuñas and alpacas. However, Y-chromosome variation did not distinguish the two subspecies of vicuñas. © 2017 Stichting International Foundation for Animal Genetics.

  10. An empirical study on the basic human error probabilities for NPP advanced main control room operation using soft control

    International Nuclear Information System (INIS)

    Jang, Inseok; Kim, Ar Ryum; Harbi, Mohamed Ali Salem Al; Lee, Seung Jun; Kang, Hyun Gook; Seong, Poong Hyun

    2013-01-01

    Highlights: ► The operation environment of MCRs in NPPs has changed by adopting new HSIs. ► The operation action in NPP Advanced MCRs is performed by soft control. ► Different basic human error probabilities (BHEPs) should be considered. ► BHEPs in a soft control operation environment are investigated empirically. ► This work will be helpful to verify if soft control has positive or negative effects. -- Abstract: By adopting new human–system interfaces that are based on computer-based technologies, the operation environment of main control rooms (MCRs) in nuclear power plants (NPPs) has changed. The MCRs that include these digital and computer technologies, such as large display panels, computerized procedures, soft controls, and so on, are called Advanced MCRs. Among the many features in Advanced MCRs, soft controls are an important feature because the operation action in NPP Advanced MCRs is performed by soft control. Using soft controls such as mouse control, touch screens, and so on, operators can select a specific screen, then choose the controller, and finally manipulate the devices. However, because of the different interfaces between soft control and hardwired conventional type control, different basic human error probabilities (BHEPs) should be considered in the Human Reliability Analysis (HRA) for advanced MCRs. Although there are many HRA methods to assess human reliabilities, such as Technique for Human Error Rate Prediction (THERP), Accident Sequence Evaluation Program (ASEP), Human Error Assessment and Reduction Technique (HEART), Human Event Repository and Analysis (HERA), Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR), Cognitive Reliability and Error Analysis Method (CREAM), and so on, these methods have been applied to conventional MCRs, and they do not consider the new features of advance MCRs such as soft controls. As a result, there is an insufficient database for assessing human reliabilities in advanced

  11. Is function-based control room design human-centered?

    International Nuclear Information System (INIS)

    Norros, L.; Savioja, P.

    2006-01-01

    Function-based approaches to system interface design appears an appealing possibility in helping designers and operators to cope with the vast amount of information needed to control complex processes. In this paper we provide evidence of operator performance analyses showing that outcome-centered performance measures may not be sufficiently informative for design. We need analyses indicating habitual patterns of using information, operator practices. We argue that practices that portray functional orienting to the task support mastery of the process. They also create potential to make use of function-based information presentation. We see that functional design is not an absolute value. Instead, such design should support communication of the functional significance of the process information to the operators in variable situations. Hence, it should facilitate development of practices that focus to interpreting this message. Successful function-based design facilitates putting operations into their contexts and is human-centered in an extended sense: It aids making sense in the complex, dynamic and uncertain environment. (authors)

  12. MitoLSDB: a comprehensive resource to study genotype to phenotype correlations in human mitochondrial DNA variations.

    Directory of Open Access Journals (Sweden)

    Shamnamole K

    Full Text Available Human mitochondrial DNA (mtDNA encodes a set of 37 genes which are essential structural and functional components of the electron transport chain. Variations in these genes have been implicated in a broad spectrum of diseases and are extensively reported in literature and various databases. In this study, we describe MitoLSDB, an integrated platform to catalogue disease association studies on mtDNA (http://mitolsdb.igib.res.in. The main goal of MitoLSDB is to provide a central platform for direct submissions of novel variants that can be curated by the Mitochondrial Research Community. MitoLSDB provides access to standardized and annotated data from literature and databases encompassing information from 5231 individuals, 675 populations and 27 phenotypes. This platform is developed using the Leiden Open (source Variation Database (LOVD software. MitoLSDB houses information on all 37 genes in each population amounting to 132397 variants, 5147 unique variants. For each variant its genomic location as per the Revised Cambridge Reference Sequence, codon and amino acid change for variations in protein-coding regions, frequency, disease/phenotype, population, reference and remarks are also listed. MitoLSDB curators have also reported errors documented in literature which includes 94 phantom mutations, 10 NUMTs, six documentation errors and one artefactual recombination. MitoLSDB is the largest repository of mtDNA variants systematically standardized and presented using the LOVD platform. We believe that this is a good starting resource to curate mtDNA variants and will facilitate direct submissions enhancing data coverage, annotation in context of pathogenesis and quality control by ensuring non-redundancy in reporting novel disease associated variants.

  13. Chapter 2. Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.

    Science.gov (United States)

    Mas-Coma, Santiago; Valero, María Adela; Bargues, María Dolores

    2009-01-01

    Fascioliasis, caused by liver fluke species of the genus Fasciola, has always been well recognized because of its high veterinary impact but it has been among the most neglected diseases for decades with regard to human infection. However, the increasing importance of human fascioliasis worldwide has re-launched interest in fascioliasis. From the 1990s, many new concepts have been developed regarding human fascioliasis and these have furnished a new baseline for the human disease that is very different to a simple extrapolation from fascioliasis in livestock. Studies have shown that human fascioliasis presents marked heterogeneity, including different epidemiological situations and transmission patterns in different endemic areas. This heterogeneity, added to the present emergence/re-emergence of the disease both in humans and animals in many regions, confirms a worrying global scenario. The huge negative impact of fascioliasis on human communities demands rapid action. When analyzing how better to define control measures for endemic areas differing at such a level, it would be useful to have genetic markers that could distinguish each type of transmission pattern and epidemiological situation. Accordingly, this chapter covers aspects of aetiology, geographical distribution, epidemiology, transmission and control in order to obtain a solid baseline for the interpretation of future results. The origins and geographical spread of F. hepatica and F. gigantica in both the ruminant pre-domestication times and the livestock post-domestication period are analyzed. Paleontological, archaeological and historical records, as well as genetic data on recent dispersal of livestock species, are taken into account to establish an evolutionary framework for the two fasciolids across all continents. Emphasis is given to the distributional overlap of both species and the roles of transportation, transhumance and trade in the different overlap situations. Areas with only one Fasciola

  14. Human factors considerations in the design and evaluation of flight deck displays and controls

    Science.gov (United States)

    2013-11-01

    The objective of this effort is to have a single source document for human factors regulatory and guidance material for flight deck displays and controls, in the interest of improving aviation safety. This document identifies guidance on human factor...

  15. Human Reliability Analysis in Support of Risk Assessment for Positive Train Control

    Science.gov (United States)

    2003-06-01

    This report describes an approach to evaluating the reliability of human actions that are modeled in a probabilistic risk assessment : (PRA) of train control operations. This approach to human reliability analysis (HRA) has been applied in the case o...

  16. Objective evaluation of human manual control adaptation boundaries using a cybernetic approach

    NARCIS (Netherlands)

    Lu, T.

    2018-01-01

    Manual control tasks can be found everywhere in our daily activities, and the human ability to adapt in controlling many different vehicles such as cars and airplanes make it possible for us to travel farther, faster and higher. The human adaptation ability to changes in the controlled element

  17. 75 FR 69912 - Pipeline Safety: Control Room Management/Human Factors

    Science.gov (United States)

    2010-11-16

    ... 192 and 195 [Docket ID PHMSA-2007-27954] RIN 2137-AE64 Pipeline Safety: Control Room Management/Human... Control Room Management/Human Factors rule at 49 CFR 192.631 and 195.446. The NPRM proposes to expedite... rule and to engage in open discussions with the agency at PHMSA's Control Room Management...

  18. Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China

    Science.gov (United States)

    2013-01-01

    Background Anopheles sinensis is a principal vector for Plasmodium vivax malaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China. Methods The present study investigated the genetic structure of An. sinensis populations using a 729 bp fragment of mtDNA ND5 among 10 populations collected from seven provinces in China. Results ND5 was polymorphic by single mutations within three groups of An. sinensis that were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation of An. sinensis varied from low to moderate across China and with a FST range of 0.00065 – 0.341. Genealogy analysis clustered the populations of An. sinensis into three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in the An. sinensis populations from China. Three clusters of An. sinensis populations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations of An. sinensis (R2 = 0.058; P = 0.301). Conclusions The results indicate that the ND5 gene of mtDNA is highly polymorphic in An. sinensis and has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion in An. sinensis populations. PMID:24192424

  19. Objective Model Selection for Identifying the Human Feedforward Response in Manual Control

    OpenAIRE

    Drop, F.M.; Pool, D.M.; van Paassen, M.M.; Mulder, M.; Bülthoff, Heinrich H.

    2017-01-01

    Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification proce...

  20. Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

    Science.gov (United States)

    Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-10-01

    1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

  1. An Integrated Gait and Balance Analysis System to Define Human Locomotor Control

    Science.gov (United States)

    2016-04-29

    test hypotheses they developed about how people walk. An Integrated Gait and Balance Analysis System to define Human Locomotor Control W911NF-14-R-0009...An Integrated Gait and Balance Analysis System to Define Human Locomotor Control Walking is a complicated task that requires the motor coordination...Gait and Balance Analysis System to Define Human Locomotor Control Report Title Walking is a complicated task that requires the motor coordination across

  2. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  3. Human factors measurement for future air traffic control systems.

    Science.gov (United States)

    Langan-Fox, Janice; Sankey, Michael J; Canty, James M

    2009-10-01

    This article provides a critical review of research pertaining to the measurement of human factors (HF) issues in current and future air traffic control (ATC). Growing worldwide air traffic demands call for a radical departure from current ATC systems. Future systems will have a fundamental impact on the roles and responsibilities of ATC officers (ATCOs). Valid and reliable methods of assessing HF issues associated with these changes, such as a potential increase (or decrease) in workload, are of utmost importance for advancing theory and for designing systems, procedures, and training. We outline major aviation changes and how these relate to five key HF issues in ATC. Measures are outlined, compared, and evaluated and are followed by guidelines for assessing these issues in the ATC domain. Recommendations for future research are presented. A review of the literature suggests that situational awareness and workload have been widely researched and assessed using a variety of measures, but researchers have neglected the areas of trust, stress, and boredom. We make recommendations for use of particular measures and the construction of new measures. It is predicted that, given the changing role of ATCOs and profound future airspace requirements and configurations, issues of stress, trust, and boredom will become more significant. Researchers should develop and/or refine existing measures of all five key HF issues to assess their impact on ATCO performance. Furthermore, these issues should be considered in a holistic manner. The current article provides an evaluation of research and measures used in HF research on ATC that will aid research and ATC measurement.

  4. Telomerase levels control the lifespan of human T lymphocytes

    NARCIS (Netherlands)

    Roth, Alexander; Yssel, Hans; Pene, Jerome; Chavez, Elizabeth A.; Schertzer, Mike; Lansdorp, Peter M.; Spits, Hergen; Luiten, Rosalie M.

    2003-01-01

    The loss of telomeric DNA with each cell division contributes to the limited replicative lifespan of human T lymphocytes. Although telomerase is transiently expressed in T lymphocytes upon activation, it is insufficient to confer immortality. We have previously shown that immortalization of human

  5. Control of a Robot Dancer for Enhancing Haptic Human-Robot Interaction in Waltz.

    Science.gov (United States)

    Hongbo Wang; Kosuge, K

    2012-01-01

    Haptic interaction between a human leader and a robot follower in waltz is studied in this paper. An inverted pendulum model is used to approximate the human's body dynamics. With the feedbacks from the force sensor and laser range finders, the robot is able to estimate the human leader's state by using an extended Kalman filter (EKF). To reduce interaction force, two robot controllers, namely, admittance with virtual force controller, and inverted pendulum controller, are proposed and evaluated in experiments. The former controller failed the experiment; reasons for the failure are explained. At the same time, the use of the latter controller is validated by experiment results.

  6. Human-FES cooperative control for wrist movement: a preliminary study

    Directory of Open Access Journals (Sweden)

    Kai Gui

    2016-07-01

    Full Text Available Functional electrical stimulation (FES sometimes applies to patients with partial paralysis, so human voluntary control and FES control both exist. Our study aims to build a cooperative controller to achieve human-FES cooperation. This cooperative controller is formed by a classical FES controller and an impedance controller. The FES controller consists of a back propagation (BP neural network-based feedforward controller and a PID-based feedback controller. The function of impedance controller is to convert volitional force/torque, which is estimated from a three-stage filter based on EMG, into additional angle. The additional angle can reduce the FES intensity in our cooperative controller, comparing to that in classical FES controller. Some assessment experiments are designed to test the performance of the cooperative controller.

  7. Talking with a Virtual Human : Controlling the Human Experience and Behavior in a Virtual Conversation

    NARCIS (Netherlands)

    Qu, C.

    2014-01-01

    Virtual humans are often designed to replace real humans in virtual reality applications for e.g., psychotherapy, education and entertainment. In general, applications with virtual humans are created for modifying a person's knowledge, beliefs, attitudes, emotions or behaviors. Reaching these

  8. Effects of controlled element dynamics on human feedforward behavior in ramp-tracking tasks.

    Science.gov (United States)

    Laurense, Vincent A; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus René M; Mulder, Max

    2015-02-01

    In real-life manual control tasks, human controllers are often required to follow a visible and predictable reference signal, enabling them to use feedforward control actions in conjunction with feedback actions that compensate for errors. Little is known about human control behavior in these situations. This paper investigates how humans adapt their feedforward control dynamics to the controlled element dynamics in a combined ramp-tracking and disturbance-rejection task. A human-in-the-loop experiment is performed with a pursuit display and vehicle-like controlled elements, ranging from a single integrator through second-order systems with a break frequency at either 3, 2, or 1 rad/s, to a double integrator. Because the potential benefits of feedforward control increase with steeper ramp segments in the target signal, three steepness levels are tested to investigate their possible effect on feedforward control with the various controlled elements. Analyses with four novel models of the operator, fitted to time-domain data, reveal feedforward control for all tested controlled elements and both (nonzero) tested levels of ramp steepness. For the range of controlled element dynamics investigated, it is found that humans adapt to these dynamics in their feedforward response, with a close to perfect inversion of the controlled element dynamics. No significant effects of ramp steepness on the feedforward model parameters are found.

  9. Human-Inspired Eigenmovement Concept Provides Coupling-Free Sensorimotor Control in Humanoid Robot.

    Science.gov (United States)

    Alexandrov, Alexei V; Lippi, Vittorio; Mergner, Thomas; Frolov, Alexander A; Hettich, Georg; Husek, Dusan

    2017-01-01

    Control of a multi-body system in both robots and humans may face the problem of destabilizing dynamic coupling effects arising between linked body segments. The state of the art solutions in robotics are full state feedback controllers. For human hip-ankle coordination, a more parsimonious and theoretically stable alternative to the robotics solution has been suggested in terms of the Eigenmovement (EM) control. Eigenmovements are kinematic synergies designed to describe the multi DoF system, and its control, with a set of independent, and hence coupling-free , scalar equations. This paper investigates whether the EM alternative shows "real-world robustness" against noisy and inaccurate sensors, mechanical non-linearities such as dead zones, and human-like feedback time delays when controlling hip-ankle movements of a balancing humanoid robot. The EM concept and the EM controller are introduced, the robot's dynamics are identified using a biomechanical approach, and robot tests are performed in a human posture control laboratory. The tests show that the EM controller provides stable control of the robot with proactive ("voluntary") movements and reactive balancing of stance during support surface tilts and translations. Although a preliminary robot-human comparison reveals similarities and differences, we conclude (i) the Eigenmovement concept is a valid candidate when different concepts of human sensorimotor control are considered, and (ii) that human-inspired robot experiments may help to decide in future the choice among the candidates and to improve the design of humanoid robots and robotic rehabilitation devices.

  10. Oxidative damage of mitochondrial and nuclear DNA induced by ionizing radiation in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Morales, Albert; Miranda, Merce; Sanchez-Reyes, Alberto; Biete, Alberto; Fernandez-Checa, Jose C.

    1998-01-01

    Purpose: Since reactive oxygen species (ROS) act as mediators of radiation-induced cellular damage, the aim of our studies was to determine the effects of ionizing radiation on the regulation of hepatocellular reduced glutathione (GSH), survival and integrity of nuclear and mitochondrial DNA (mtDNA) in human hepatoblastoma cells (Hep G2) depleted of GSH prior to radiation. Methods and Materials: GSH, oxidized glutathione (GSSG), and generation of ROS were determined in irradiated (50-500 cGy) Hep G2 cells. Clonogenic survival, nuclear DNA fragmentation, and integrity of mtDNA were assessed in cells depleted of GSH prior to radiation. Results: Radiation of Hep G2 cells (50-400 cGy) resulted in a dose-dependent generation of ROS, an effect accompanied by a decrease of reduced GSH, ranging from a 15% decrease for 50 cGy to a 25% decrease for 400 cGy and decreased GSH/GSSG from a ratio of 17 to a ratio of 7 for controls and from 16 to 6 for diethyl maleate (DEM)-treated cells. Depletion of GSH prior to radiation accentuated the increase of ROS by 40-50%. The depletion of GSH by radiation was apparent in different subcellular sites, being particularly significant in mitochondria. Furthermore, depletion of nuclear GSH to 50-60% of initial values prior to irradiation (400 cGy) resulted in DNA fragmentation and apoptosis. Consequently, the survival of Hep G2 to radiation was reduced from 25% of cells not depleted of GSH to 10% of GSH-depleted cells. Fitting the survival rate of cells as a function of GSH using a theoretical model confirmed cellular GSH as a key factor in determining intrinsic sensitivity of Hep G2 cells to radiation. mtDNA displayed an increased susceptibility to the radiation-induced loss of integrity compared to nuclear DNA, an effect that was potentiated by GSH depletion in mitochondria (10-15% intact mtDNA in GSH-depleted cells vs. 25-30% of repleted cells). Conclusion: GSH plays a critical protective role in maintaining nuclear and mtDNA functional

  11. Use of the Human Centered Design concept when designing ergonomic NPP control rooms

    International Nuclear Information System (INIS)

    Skrehot, Petr A.; Houser, Frantisek; Riha, Radek; Tuma, Zdenek

    2015-01-01

    Human-Centered Design is a concept aimed at reconciling human needs on the one hand and limitations posed by the design disposition of the room being designed on the other hand. This paper describes the main aspects of application of the Human-Centered Design concept to the design of nuclear power plant control rooms. (orig.)

  12. Discussion on verification criterion and method of human factors engineering for nuclear power plant controller

    International Nuclear Information System (INIS)

    Yang Hualong; Liu Yanzi; Jia Ming; Huang Weijun

    2014-01-01

    In order to prevent or reduce human error and ensure the safe operation of nuclear power plants, control device should be verified from the perspective of human factors engineering (HFE). The domestic and international human factors engineering guidelines about nuclear power plant controller were considered, the verification criterion and method of human factors engineering for nuclear power plant controller were discussed and the application examples were provided for reference in this paper. The results show that the appropriate verification criterion and method should be selected to ensure the objectivity and accuracy of the conclusion. (authors)

  13. The Role of Inhibitory Control in the Development of Human Figure Drawing in Young Children

    Science.gov (United States)

    Riggs, Kevin J.; Jolley, Richard P.; Simpson, Andrew

    2013-01-01

    We investigated the role of inhibitory control in young children's human figure drawing. We used the Bear-Dragon task as a measure of inhibitory control and used the classification system devised by Cox and Parkin to measure the development of human figure drawing. We tested 50 children aged between 40 and 64 months. Regression analysis showed…

  14. Human Factors Analysis of Pipeline Monitoring and Control Operations: Final Technical Report

    Science.gov (United States)

    2008-11-26

    The purpose of the Human Factors Analysis of Pipeline Monitoring and Control Operations project was to develop procedures that could be used by liquid pipeline operators to assess and manage the human factors risks in their control rooms that may adv...

  15. MtDNA diversity and genetic lineages of four cattle breeds in Malaysia

    Directory of Open Access Journals (Sweden)

    Somarny, W.W.M.Z.

    2015-06-01

    Full Text Available There is lack of comprehensive studies on the genetic diversity or phylogenetic analysis of beef cattle breeds in Malaysia. In this study, the partial sequence of mitochondrial DNA cytochrome b gene (cyt b was analysed from blood samples obtained from 25 Chinese Yellow Cattle (CY, 33 Kedah-Kelantan (KK, 32 Brakmas (BM and 30 Bali cattle (BC. Based on these 120 individuals, 19 mtDNA haplotypes (GenBank Accession No. GU67340 - GU67358 were identified by polymorphisms at 31 sites. Hap19 was predominant in BM (78%, KK (82% and CY (100% indicating similar origin or gene flow between breeds whilst Hap11 was exclusively for BC. However, there were only two nucleotide differences between these two major haplotypes. These results can be interpreted that these representative cattle in these haplotypes are admixtures of B. indicus or B. javanicus through maternal ancestry. Conversely, the CY cattle investigated are highly inbred where no variation could be observed in the short segment investigated.

  16. Regional Variation in mtDNA of the Lesser Prairie-Chicken

    Science.gov (United States)

    Hagen, Christian A.; Pitman, James C.; Sandercock, Brett K.; Wolfe, Don H.; Robel, Robel J.; Applegate, Roger D.; Oyler-McCance, Sara J.

    2010-01-01

    Cumulative loss of habitat and long-term decline in the populations of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) have led to concerns for the species' viability throughout its range in the southern Great Plains. For more efficient conservation past and present distributions of genetic variation need to be understood. We examined the distribution of mitochondrial DNA (mtDNA) variation in the Lesser Prairie-Chicken across Kansas, Colorado, Oklahoma, and New Mexico. Throughout the range we found little genetic differentiation except for the population in New Mexico, which was significantly different from most other publications. We did, however, find significant isolation by distance at the rangewide scale (r=0.698). We found no relationship between haplotype phylogeny and geography, and our analyses provide evidence for a post-glacial population expansion within the species that is consistent with the idea that speciation within Tympanuchus is recent. Conservation actions that increase the likelihood of genetically viable populations in the future should be evaluated for implementation.

  17. Species phylogeny and diversification process of Northeast Asian Pungitius revealed by AFLP and mtDNA markers

    DEFF Research Database (Denmark)

    Takahashi, Hiroshi; Møller, Peter Rask; Shedko, Sergei V.

    2016-01-01

    Pungitius is a highly diversified genus of sticklebacks (Gasterosteidae) occurring widely in northern parts of the Northern Hemisphere. Several ecologically and genetically divergent types that are largely isolated reproductively but occasionally hybridize in sympatry have been discovered...... of hybridization and mtDNA introgression among distinct species. Our results highlight that the marginal seas of Northeast Asia played a key role as barriers to or facilitators of gene flow in the evolution of species diversity of Pungitius concentrated in this region...

  18. The GMOC Model : Supporting Development of Systems for Human Control

    OpenAIRE

    Tschirner, Simon

    2015-01-01

    Train traffic control is a complex task in a dynamic environment. Different actors have to cooperate to meet strong requirements regarding safety, punctuality, capacity utilization, energy consumption, and more. The GMOC model has been developed and utilized in a number of studies in several different areas. This thesis describes GMOC and uses train traffic control as the application area for evaluating its utility. The GMOC model has its origin in control theory and relates to concepts of dy...

  19. SCHEME (Soft Control Human error Evaluation MEthod) for advanced MCR HRA

    International Nuclear Information System (INIS)

    Jang, Inseok; Jung, Wondea; Seong, Poong Hyun

    2015-01-01

    The Technique for Human Error Rate Prediction (THERP), Korean Human Reliability Analysis (K-HRA), Human Error Assessment and Reduction Technique (HEART), A Technique for Human Event Analysis (ATHEANA), Cognitive Reliability and Error Analysis Method (CREAM), and Simplified Plant Analysis Risk Human Reliability Assessment (SPAR-H) in relation to NPP maintenance and operation. Most of these methods were developed considering the conventional type of Main Control Rooms (MCRs). They are still used for HRA in advanced MCRs even though the operating environment of advanced MCRs in NPPs has been considerably changed by the adoption of new human-system interfaces such as computer-based soft controls. Among the many features in advanced MCRs, soft controls are an important feature because the operation action in NPP advanced MCRs is performed by soft controls. Consequently, those conventional methods may not sufficiently consider the features of soft control execution human errors. To this end, a new framework of a HRA method for evaluating soft control execution human error is suggested by performing the soft control task analysis and the literature reviews regarding widely accepted human error taxonomies. In this study, the framework of a HRA method for evaluating soft control execution human error in advanced MCRs is developed. First, the factors which HRA method in advanced MCRs should encompass are derived based on the literature review, and soft control task analysis. Based on the derived factors, execution HRA framework in advanced MCRs is developed mainly focusing on the features of soft control. Moreover, since most current HRA database deal with operation in conventional type of MCRs and are not explicitly designed to deal with digital HSI, HRA database are developed under lab scale simulation

  20. Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

    Science.gov (United States)

    Kullar, Peter J; Gomez-Duran, Aurora; Gammage, Payam A; Garone, Caterina; Minczuk, Michal; Golder, Zoe; Wilson, Janet; Montoya, Julio; Häkli, Sanna; Kärppä, Mikko; Horvath, Rita; Majamaa, Kari; Chinnery, Patrick F

    2018-01-01

    The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  1. An Analysis and Quantification Method of Human Errors of Soft Controls in Advanced MCRs

    International Nuclear Information System (INIS)

    Lee, Seung Jun; Kim, Jae Whan; Jang, Seung Cheol

    2011-01-01

    In this work, a method was proposed for quantifying human errors that may occur during operation executions using soft control. Soft controls of advanced main control rooms (MCRs) have totally different features from conventional controls, and thus they may have different human error modes and occurrence probabilities. It is important to define the human error modes and to quantify the error probability for evaluating the reliability of the system and preventing errors. This work suggests a modified K-HRA method for quantifying error probability

  2. Design for the human-machine interface of a digitalized reactor control-room

    International Nuclear Information System (INIS)

    Qu Ronghong; Zhang Liangju; Li Duo; Yu Hui

    2005-01-01

    Digitalized technology is implemented in the instrumentation and control system of an in-construction research reactor, which advances information display in both contents and styles in a nuclear reactor control-room, and greatly improves human-machine interface. In the design for a digitalized nuclear reactor control-room there are a series of new problems and technologies should be considered seriously. This paper mainly introduces the design for the digitalized control-room of the research nuclear reactor and covered topics include design principle of human-machine interface, organization and classification of interface graphics, technologies and principles based on human factors engineering and implemented in the graphics design. (authors)

  3. The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

    KAUST Repository

    Blomme, Jonas

    2017-04-19

    In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gainand loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development.

  4. Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and physiological traits in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Wen C Aw

    Full Text Available Here we determine the sex-specific influence of mtDNA type (mitotype and diet on mitochondrial functions and physiology in two Drosophila melanogaster lines. In many species, males and females differ in aspects of their energy production. These sex-specific influences may be caused by differences in evolutionary history and physiological functions. We predicted the influence of mtDNA mutations should be stronger in males than females as a result of the organelle's maternal mode of inheritance in the majority of metazoans. In contrast, we predicted the influence of diet would be greater in females due to higher metabolic flexibility. We included four diets that differed in their protein: carbohydrate (P:C ratios as they are the two-major energy-yielding macronutrients in the fly diet. We assayed four mitochondrial function traits (Complex I oxidative phosphorylation, reactive oxygen species production, superoxide dismutase activity, and mtDNA copy number and four physiological traits (fecundity, longevity, lipid content, and starvation resistance. Traits were assayed at 11 d and 25 d of age. Consistent with predictions we observe that the mitotype influenced males more than females supporting the hypothesis of a sex-specific selective sieve in the mitochondrial genome caused by the maternal inheritance of mitochondria. Also, consistent with predictions, we found that the diet influenced females more than males.

  5. [Sequence polymorphism of mtDNA HVR Iand HVR II of Oroqen ethnic group in Inner Mongolia].

    Science.gov (United States)

    Yan, Chun-Xia; Chen, Feng; Dang, Yong-Hui; Li, Tao; Zheng, Hai-Bo; Chen, Teng; Li, Sheng-Bin

    2008-04-01

    Venous blood samples from 50 unrelated Oroqen individuals living in Inner Mongolia were collected and their mtDNA HVR I and HVR II sequences were detected by using ABI PRISM377 sequencers. The number of polymorphic loci, haplotype, haplotype frequence, average nucleotide variability and other polymorphic parameters were calculated. Based on Oroqen mtDNA sequence data obtained in our experiments and published data, genetic distance between Oroqen ethnic group and other populations were computered by Nei's measure. Phylogenetic tree was constructed by Neighbor Joining method. Comparing with Anderson sequence, 52 polymorphic loci in HVR I and 24 loci in HVR II were found in Oroqen mtDNA sequence, 38 and 27 haplotypes were defined herewith. Haplotype diversity and average nucleotide variability were 0.964+/-0.018 and 7.379 in HVR I, 0.929+/-0.019 and 2.408 in HVR II respectively. Fst and dA genetic distance between 12 populations were calculated based on HVR I sequence, and their relative coefficients were 0.993(P HVR I and HVR II in Oroqen ethnic group has some specificities compared with that of other populations. These data provide a useful tool in forensic identification, population genetic study and other research fields.

  6. Human Systems Integration Assessment of Network Centric Command and Control

    National Research Council Canada - National Science Library

    Quashnock, Dee; Kelly, Richard T; Dunaway, John; Smillie, Robert J

    2004-01-01

    .... FORCEnet is the operational construct and architectural framework for Naval Network Centric Warfare in the information age that integrates warriors, sensors, networks, command and control, platforms...

  7. Associative learning and the control of human dietary behavior.

    Science.gov (United States)

    Brunstrom, Jeffrey M

    2007-07-01

    Most of our food likes and disliked are learned. Relevant forms of associative learning have been identified in animals. However, observations of the same associative processes are relatively scarce in humans. The first section of this paper outlines reasons why this might be the case. Emphasis is placed on recent research exploring individual differences and the importance or otherwise of hunger and contingency awareness. The second section briefly considers the effect of learning on meal size, and the author revisits the question of how learned associations might come to influence energy intake in humans.

  8. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Ramasharma, K.; Li, C.H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  9. Analysis on nuclear power plant control room system design and improvement based on human factor engineering

    International Nuclear Information System (INIS)

    Gao Feng; Liu Yanzi; Sun Yongbin

    2014-01-01

    The design of nuclear power plant control room system is a process of improvement with the implementation of human factor engineering theory and guidance. The method of implementation human factor engineering principles into the nuclear power plant control room system design and improvement was discussed in this paper. It is recommended that comprehensive address should be done from control room system function, human machine interface, digital procedure, control room layout and environment design based on the human factor engineering theory and experience. The main issues which should be paid more attention during the control room system design and improvement also were addressed in this paper, and then advices and notices for the design and improvement of the nuclear power plant control room system were afforded. (authors)

  10. Sensory feedback in artificial control of human mobility

    NARCIS (Netherlands)

    Veltink, Petrus H.

    1999-01-01

    Artificial motor control systems may reduce the handicap of motor impaired individuals. Sensors are essential components in feedback control of these systems and in the information exchange with the user. The objective of this paper is to give an overview of the applications of sensors in the

  11. Control of the risk of human toxoplasmosis transmitted by meat

    NARCIS (Netherlands)

    Kijlstra, A.; Jongert, E.

    2008-01-01

    One-third of the human world population is infected with the protozoan parasite Toxoplasma gondii. Recent calculations of the disease burden of toxoplasmosis rank this foodborne disease at the same level as salmonellosis or campylobacteriosis. The high disease burden in combination with

  12. Controlling simulations of human-artifact interaction with scenario bundles

    NARCIS (Netherlands)

    Van der Vegte, W.F.; Rusák, Z.

    2008-01-01

    We introduce a methodology for modeling and simulating fully virtual human-artifact systems, aiming to resolve two issues in virtual prototyping: (i) integration of distinct modeling and simulation approaches, and (ii) extending the deployability of simulations towards conceptual design. We are

  13. Integrated Human and Animal Disease Control for Tanzanian ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The research focuses on two agro-ecological zones of the cattle corridor in Tanzania - Ngorongoro and Kibaha/Kilosa districts - and will be led by a regional scientific network, the ... They will look at interactions between human and animal health, environmental change, gender, and other socio-economic conditions.

  14. Relating Eye Activity Measures to Human Controller Remnant Characteristics

    NARCIS (Netherlands)

    Popovici, A; Zaal, P.M.T.; Pool, D.M.; Mulder, M.; Sawaragi, T

    2016-01-01

    This study attempts to partially explain the characteristics of the human perceptual remnant, following Levison’s representation of the remnant as an equivalent observation noise. Eye activity parameters are recorded using an eye tracker in two compensatory tracking tasks in which the visual

  15. Human-Centered Command and Control of Future Autonomous Systems

    Science.gov (United States)

    2013-06-01

    introduce challenges with situation awareness, automation reliance, and accountability (Bainbridge, 1983). If not carefully designed and integrated...into users’ tasks, automation’s costs can quickly outweigh its benefits. A tempting solution to compensate for inherent human cognitive limitations is... Drury & Scott, 2008; Nehme, Scott, Cummings, & Furusho, 2006; Scott & Cummings, 2006). However, there have not been detailed prescriptive task

  16. Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Bai, Xiyuan; Oberley-Deegan, Rebecca E; Bai, An; Ovrutsky, Alida R; Kinney, William H; Weaver, Michael; Zhang, Gong; Honda, Jennifer R; Chan, Edward D

    2016-07-01

    With the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosis-an effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). An in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. We found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFκB) activation. Curcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. © 2016 Asian Pacific Society of Respirology.

  17. In vivo human corneal hydration control dynamics: A new model

    NARCIS (Netherlands)

    Odenthal, M.T.P.; Nieuwendaal, C.P.; Venema, H.W.; Oosting, J.; Kok, J.H.C.; Kijlstra, A.

    1999-01-01

    PURPOSE. To introduce a new model describing human in vivo corneal deswelling after hypoxic contact lens wear, based on a damped harmonic oscillator, which can describe an overshoot in corneal deswelling, to compare this new model with the currently used exponential model, and also to test whether a

  18. In vivo human corneal hydration control dynamics: a new model

    NARCIS (Netherlands)

    Odenthal, M. T.; Nieuwendaal, C. P.; Venema, H. W.; Oosting, J.; Kok, J. H. C.; Kijlstra, A.

    1999-01-01

    PURPOSE: To introduce a new model describing human in vivo corneal deswelling after hypoxic contact lens wear, based on a damped harmonic oscillator, which can describe an overshoot in corneal deswelling, to compare this new model with the currently used exponential model, and also to test whether a

  19. Human factors design review guidelines for advanced nuclear control room technologies

    International Nuclear Information System (INIS)

    O'Hara, J.; Brown, W.; Granda, T.; Baker, C.

    1991-01-01

    Advanced control rooms (ACRs) for future nuclear power plants are being designed utilizing computer-based technologies. The US Nuclear Regulatory Commission reviews the human engineering aspects of such control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported in order to protect public health and safety. This paper describes the rationale, general approach, and initial development of an NRC Advanced Control Room Design Review Guideline. 20 refs., 1 fig

  20. Global mtDNA genetic structure and hypothesized invasion history of a major pest of citrus, Diaphorina citri (Hemiptera: Liviidae).

    Science.gov (United States)

    Luo, Yufa; Agnarsson, Ingi

    2018-01-01

    The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the global mtDNA population genetic structure, and possible dispersal history of the pest, we investigated genetic variation at the COI gene collating newly collected samples with all previously published data. Our dataset consists of 356 colonies from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 ± 0.017), low nucleotide diversity (π-mean = 0.003), and significant positive selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were identified, clustered into two matrilines: Both occur in southeastern and southern Asia, North and South America, and Africa; lineages A and B also occur in eastern and western Asia, respectively. The most abundant haplotypes were Hap4 in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network identified them as the ancestral haplotypes within their respective lineages. Analysis of molecular variance showed significant genetic structure ( F ST  = 0.62, p  analysis suggests geographic structuring. We hypothesize a southern and/or southeastern Asia origin, three dispersal routes, and parallel expansions of two lineages. The hypothesized first route involved the expansion of lineage B from southern Asia into North America via West Asia. The second, the expansion of some lineage A individuals from Southeast Asia into East Asia, and the third involved both lineages from Southeast Asia spreading westward into Africa and subsequently into South America. To test these hypotheses and gain a deeper understanding of the global history of D. citri , more data-rich approaches will be necessary from the ample toolkit of next-generation sequencing (NGS). However, this study may serve to guide such sampling and in the development of biological control programs against the global pest D. citri .

  1. Flight to the future : human factors in air traffic control

    Science.gov (United States)

    1997-01-01

    The nation's air traffic control system is responsible for managing a complex : mixture of air traffic from commercial, general, corporate, and military : aviation. Despite a strong safety record, the system does suffer occasional : serious disruptio...

  2. Sympathetic reflex control of blood flow in human peripheral tissues

    DEFF Research Database (Denmark)

    Henriksen, O

    1991-01-01

    Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

  3. An innovative strategy to clone positive modifier genes of defects caused by mtDNA mutations: MRPS18C as suppressor gene of m.3946G>A mutation in MT-ND1 gene.

    Science.gov (United States)

    Rodríguez-García, María Elena; Cotrina-Vinagre, Francisco Javier; Carnicero-Rodríguez, Patricia; Martínez-Azorín, Francisco

    2017-07-01

    We have developed a new functional complementation approach to clone modifier genes which overexpression is able to suppress the biochemical defects caused by mtDNA mutations (suppressor genes). This strategy consists in transferring human genes into respiratory chain-deficient fibroblasts, followed by a metabolic selection in a highly selective medium. We used a normalized expression cDNA library in an episomal vector (pREP4) to transfect the fibroblasts, and a medium with glutamine and devoid of any carbohydrate source to select metabolically. Growing the patient's fibroblasts in this selective medium, the deficient cells rapidly disappear unless they are rescued by the cDNA of a suppressor gene. The use of an episomal vector allows us to carry out several rounds of transfection/selection (cyclical phenotypic rescue) to enrich the rescue with true clones of suppressor genes. Using fibroblasts from a patient with epileptic encephalopathy with the m.3946G>A (p.E214K) mutation in the MT-ND1 gene, several candidate genes were identified and one of them was characterized functionally. Thus, overexpression of MRPS18C gene (that encode for bS18m protein) suppressed the molecular defects produced by this mtDNA mutation, recovering the complex I activity and reducing the ROS produced by this complex to normal levels. We suggest that modulation of bS18m expression may be an effective therapeutic strategy for the patients with this mutation.

  4. Human Resource Management in COSO Internal Control: Integrated Framework

    OpenAIRE

    Uysal, Gürhan

    2010-01-01

    COSO perceives human resource management (HRM) as an organizational governance technic. Because COSO aims to increase efficency and effectiveness of business operations, reliability of financial reporting, and compliance with applicable laws and regulations. Therefore, for example, in COSO HRM policy and practices should enable organizations to achieve organizational goals and objectives. Moreover, HRM is to find out best-ability and capable employees for managerial positions. In addition, or...

  5. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

    Science.gov (United States)

    Bertola, Laura D.; Tensen, Laura; van Hooft, Pim; White, Paula A.; Driscoll, Carlos A.; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A.; Tumenta, Pricelia N.; Jirmo, Tuqa H.; de Snoo, Geert R.

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. PMID:26466139

  6. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

    Science.gov (United States)

    Bertola, Laura D; Tensen, Laura; van Hooft, Pim; White, Paula A; Driscoll, Carlos A; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A; Tumenta, Pricelia N; Jirmo, Tuqa H; de Snoo, Geert R; de Iongh, Hans H; Vrieling, Klaas

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

  7. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

    Directory of Open Access Journals (Sweden)

    Laura D Bertola

    Full Text Available The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1 West/Central Africa, 2 East Africa, 3 Southern Africa and 4 India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

  8. MtDNA genetic diversity and structure of Eurasian Collared Dove (Streptopelia decaocto).

    Science.gov (United States)

    Bagi, Zoltán; Dimopoulos, Evangelos Antonis; Loukovitis, Dimitrios; Eraud, Cyril; Kusza, Szilvia

    2018-01-01

    The Eurasian Collared Dove (Streptopelia decaocto) is one of the most successful biological invaders among terrestrial vertebrates. However, little information is available on the genetic diversity of the species. A total of 134 Eurasian Collared Doves from Europe, Asia and the Caribbean (n = 20) were studied by sequencing a 658-bp length of mitochondrial DNA (mtDNA) cytochrome oxidase I (COI). Fifty-two different haplotypes and relatively high haplotype and nucleotide diversities (Hd±SD = 0.843±0.037 and π±SD = 0.026±0.013) were detected. Haplotype Ht1 was particularly dominant: it included 44.03% of the studied individuals, and contained sequences from 75% of the studied countries. Various analyses (FST, AMOVA, STRUCTURE) distinguished 2 groups on the genetic level, designated 'A' and 'B'. Two groups were also separated in the median-joining network and the maximum likelihood tree. The results of the neutrality tests were negative (Fu FS = -25.914; Tajima D = -2.606) and significantly different from zero (P≤0.001) for group A, whereas both values for group B were positive (Fu FS = 1.811; Tajima D = 0.674) and not significant (P>0.05). Statistically significant positive autocorrelation was revealed among individuals located up to 2000 km apart (r = 0.124; P = 0.001). The present results provide the first information on the genetic diversity and structure of the Eurasian Collared Dove, and can thereby serve as a factual and comparative basis for similar studies in the future.

  9. Proceedings of the eighth European annual conference on human decision making and manual control

    International Nuclear Information System (INIS)

    Lind, M.; Hollnagel, E.

    1989-01-01

    The papers contributed at the eighth European annual conference on human decision making and manual control cover the subject areas of vehicle control, robotics, modeling, operator support and cognitive engineering, artificial intelligence and neural network. Some of the papers are relevant to power plant control and in this respect to nuclear safety. (AB)

  10. Human manual control performance in hyper-gravity.

    Science.gov (United States)

    Clark, Torin K; Newman, Michael C; Merfeld, Daniel M; Oman, Charles M; Young, Laurence R

    2015-05-01

    Hyper-gravity provides a unique environment to study how misperceptions impact control of orientation relative to gravity. Previous studies have found that static and dynamic roll tilts are perceptually overestimated in hyper-gravity. The current investigation quantifies how this influences control of orientation. We utilized a long-radius centrifuge to study manual control performance in hyper-gravity. In the dark, subjects were tasked with nulling out a pseudo-random roll disturbance on the cab of the centrifuge using a rotational hand controller to command their roll rate in order to remain perceptually upright. The task was performed in 1, 1.5, and 2 G's of net gravito-inertial acceleration. Initial performance, in terms of root-mean-square deviation from upright, degraded in hyper-gravity relative to 1 G performance levels. In 1.5 G, initial performance degraded by 26 % and in 2 G, by 45 %. With practice, however, performance in hyper-gravity improved to near the 1 G performance level over several minutes. Finally, pre-exposure to one hyper-gravity level reduced initial performance decrements in a different, novel, hyper-gravity level. Perceptual overestimation of roll tilts in hyper-gravity leads to manual control performance errors, which are reduced both with practice and with pre-exposure to alternate hyper-gravity stimuli.

  11. Human-telerobot interactions - Information, control, and mental models

    Science.gov (United States)

    Smith, Randy L.; Gillan, Douglas J.

    1987-01-01

    A part of the NASA's Space Station will be a teleoperated robot (telerobot) with arms for grasping and manipulation, feet for holding onto objects, and television cameras for visual feedback. The objective of the work described in this paper is to develop the requirements and specifications for the user-telerobot interface and to determine through research and testing that the interface results in efficient system operation. The focus of the development of the user-telerobot interface is on the information required by the user, the user inputs, and the design of the control workstation. Closely related to both the information required by the user and the user's control of the telerobot is the user's mental model of the relationship between the control inputs and the telerobot's actions.

  12. Verification and validation of human factors issues in control room design and upgrades

    Energy Technology Data Exchange (ETDEWEB)

    Green, M.; Collier, S. [Inst. for Energiteknikk, Halden (Norway). OECD Halden Reactor Project

    1999-12-01

    Systems, facilities and equipment are periodically updated during a power plant's lifetime. This has human factors implications, especially if the central control room is involved. Human factors work may therefore be required. There is an extensive literature on human factors itself, but not so much on how it is verified and validated. Therefore, HRP and the Swedish Nuclear Power Inspectorate commissioned a study. The objective was to review the literature and establish a knowledge base on verification and validation (V and V) of human factors issues. The report first discusses verification and validation as applied to human factors work. It describes a design process and the typical human factors topics involved. It then presents a generic method for V and V of human factors. This is built on a review of standards, guidelines and other references given in an annotated bibliography. The method is illustrated by application to some human factors topics.

  13. Verification and validation of human factors issues in control room design and upgrades

    International Nuclear Information System (INIS)

    Green, M.; Collier, S.

    1999-12-01

    Systems, facilities and equipment are periodically updated during a power plant's lifetime. This has human factors implications, especially if the central control room is involved. Human factors work may therefore be required. There is an extensive literature on human factors itself, but not so much on how it is verified and validated. Therefore, HRP and the Swedish Nuclear Power Inspectorate commissioned a study. The objective was to review the literature and establish a knowledge base on verification and validation (V and V) of human factors issues. The report first discusses verification and validation as applied to human factors work. It describes a design process and the typical human factors topics involved. It then presents a generic method for V and V of human factors. This is built on a review of standards, guidelines and other references given in an annotated bibliography. The method is illustrated by application to some human factors topics

  14. Contraceptive vaccines for the humane control of community cat populations

    Science.gov (United States)

    Levy, Julie K.

    2011-01-01

    Problem Free-roaming unowned stray and feral cats exist throughout the world, creating concerns regarding their welfare as well as their impact on the environment on public health. Millions of healthy cats are culled each year in an attempt to control their numbers. Surgical sterilization followed by return to the environment is an effective nonlethal population control method but is limited in scope due to expense and logistical impediments. Immunocontraception has the potential to be a more practical and cost-effective method of control. Method of study This is a review of current research in immunocontraception in domestic cats. Functional characteristics of an ideal immunocontraceptive for community cats would include a wide margin of safety for target animals and the environment, rapid onset and long duration of activity following a single treatment in males and females of all ages, and sex hormone inhibition. In addition, product characteristics should include stability and ease of use under field conditions, efficient manufacturing process, and low cost to the user. Two reproductive antigens, zona pellucida and GnRH, have been identified as possible targets for fertility control in cats. Results Zona pellucida, which is used successfully in multiple wildlife species, has achieved little success in cats. In contrast, immunization against GnRH has resulted in long-term contraception in both male and female cats following a single dose. GnRH is an ideal contraceptive target because it regulates pituitary and gonadal hormone responses in both males and females, thus suppressing nuisance behaviors associated with sex hormones in addition to preventing pregnancy. Conclusion The responsiveness of cats to fertility control via GnRH suppression should encourage researchers and cat control stakeholders to continue efforts to optimize vaccines that induce multi-year contraception following a single dose in a high proportion of treated cats. PMID:21501281

  15. Condition-based Human Reliability Assessment for digitalized control room

    International Nuclear Information System (INIS)

    Kang, H. G.; Jang, S. C.; Eom, H. S.; Ha, J. J.

    2005-04-01

    In safety-critical systems, the generation failure of an actuation signal is caused by the concurrent failures of the automated systems and an operator action. These two sources of safety signals are complicatedly correlated. The failures of sensors or automated systems will cause a lack of necessary information for a human operator and result in error-forcing contexts such as the loss of corresponding alarms and indications. In the conventional analysis, the Human Error Probabilities (HEP) are estimated based on the assumption of 'normal condition of indications and alarms'. In order to construct a more realistic signal-generation failure model, we have to consider more complicated conditions in a more realistic manner. In this study, we performed two kinds of investigation for addressing this issue. We performed the analytic calculations for estimating the effect of sensors failures on the system unavailability and plant risk. For the single-parameter safety signals, the analysis result reveals that the quantification of the HEP should be performed by focusing on the 'no alarm from the automatic system and corresponding indications unavailable' situation. This study also proposes a Condition-Based Human Reliability Assessment (CBHRA) method in order to address these complicated conditions in a practical way. We apply the CBHRA method to the manual actuation of the safety features such as a reactor trip and auxiliary feedwater actuation in Korean Standard Nuclear Power Plants. In the case of conventional single HEP method, it is very hard to consider the multiple HE conditions. The merit of CBHRA is clearly shown in the application to the AFAS generation where no dominating HE condition exits. In this case, even if the HE conditions are carefully investigated, the single HEP method cannot accommodate the multiple conditions in a fault tree. On the other hand, the application result of the reactor trip in SLOCA shows that if there is a dominating condition, the use

  16. Homeostasis lighting control based on relationship between lighting environment and human behavior

    Science.gov (United States)

    Ueda, Risa; Mita, Akira

    2015-03-01

    Although each person has own preferences, living spaces which can respond to various preferences and needs have not become reality. Focusing on the lighting environments which influence on the impression of living spaces, this research aims to offer comfortable lighting environments for each resident by a flexible control. This research examines the relationship between lighting environments and human behaviors considering colored lights. In accord with the relationship, this research proposes an illuminance-color control system which flexibly changes spatial environments responding to human conditions. Firstly, the psychological evaluation was conducted in order to build human models for various environments. As a result, preferred lighting environments for each examinee were determined for particular behaviors. Moreover, satisfaction levels of lighting environments were calculated by using seven types of impression of the environments as parameters. The results were summarized as human models. Secondly, this research proposed "Homeostasis Lighting Control System", which employs the human models. Homeostasis lighting control system embodies the algorithm of homeostasis, which is one of the functions of the physiological adaptation. Human discomfort feelings are obtained automatically by the sensor agent robot. The system can offer comfortable lighting environments without controlling environments by residents autonomously based on the information from the robot. This research takes into accounts both illuminance and color. The robot communicates with the server which contains human models, then the system corresponds to individuals. Combining these three systems, the proposed system can effectively control the lighting environment. At last, the feasibility of the proposed system was verified by simulation experiments.

  17. Applying human factors to the design of control centre and workstation of a nuclear reactor

    International Nuclear Information System (INIS)

    Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Goncalves, Gabriel de L.; Souza, Tamara D.M.F.; Falcao, Mariana A.

    2013-01-01

    Human factors is a body of scientific factors about human characteristics, covering biomedical, psychological and psychosocial considerations, including principles and applications in the personnel selection areas, training, job performance aid tools and human performance evaluation. Control Centre is a combination of control rooms, control suites and local control stations which are functionally related and all on the same site. Digital control room includes an arrangement of systems, equipment such as computers and communication terminals and workstations at which control and monitoring functions are conducted by operators. Inadequate integration between control room and operators reduces safety, increases the operation complexity, complicates operator training and increases the likelihood of human errors occurrence. The objective of this paper is to present a specific approach for the conceptual and basic design of the control centre and workstation of a nuclear reactor used to produce radioisotope. The approach is based on human factors standards, guidelines and the participation of a multidisciplinary team in the conceptual and basic phases of the design. Using the information gathered from standards and from the multidisciplinary team, an initial sketch 3D of the control centre and workstation are being developed. (author)

  18. Applying human factors to the design of control centre and workstation of a nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Goncalves, Gabriel de L., E-mail: luquetti@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Souza, Tamara D.M.F.; Falcao, Mariana A. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Dept. de Desenho Industrial

    2013-07-01

    Human factors is a body of scientific factors about human characteristics, covering biomedical, psychological and psychosocial considerations, including principles and applications in the personnel selection areas, training, job performance aid tools and human performance evaluation. Control Centre is a combination of control rooms, control suites and local control stations which are functionally related and all on the same site. Digital control room includes an arrangement of systems, equipment such as computers and communication terminals and workstations at which control and monitoring functions are conducted by operators. Inadequate integration between control room and operators reduces safety, increases the operation complexity, complicates operator training and increases the likelihood of human errors occurrence. The objective of this paper is to present a specific approach for the conceptual and basic design of the control centre and workstation of a nuclear reactor used to produce radioisotope. The approach is based on human factors standards, guidelines and the participation of a multidisciplinary team in the conceptual and basic phases of the design. Using the information gathered from standards and from the multidisciplinary team, an initial sketch 3D of the control centre and workstation are being developed. (author)

  19. Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples.

    Science.gov (United States)

    Szulzewsky, Frank; Arora, Sonali; de Witte, Lot; Ulas, Thomas; Markovic, Darko; Schultze, Joachim L; Holland, Eric C; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

    2016-08-01

    Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs. In comparison to human control microglia hGAMs upregulated genes associated with mitotic cell cycle, cell migration, cell adhesion, and extracellular matrix organization. We validated the expression of several genes associated with extracellular matrix organization in samples of human control microglia, hGAMs, and the hGAMs-depleted fraction via qPCR. The comparison to murine GAMs (mGAMs) showed that both cell populations share a significant fraction of upregulated transcripts compared with their respective controls. These genes were mostly related to mitotic cell cycle. However, in contrast to murine cells, human GAMs did not upregulate genes associated to immune activation. Comparison of human and murine GAMs expression data to several data sets of in vitro-activated human macrophages and murine microglia showed that, in contrast to mGAMs, hGAMs share a smaller overlap to these data sets in general and in particular to cells activated by proinflammatory stimulation with LPS + INFγ or TNFα. Our findings provide new insights into the biology of human glioblastoma-associated microglia/monocytes and give detailed information about the validity of murine experimental models. GLIA 2016 GLIA 2016;64:1416-1436. © 2016 Wiley Periodicals, Inc.

  20. Predictive Models of Procedural Human Supervisory Control Behavior

    Science.gov (United States)

    2011-01-01

    821708, Brest , France. Page 139 of 150 Boussemart, Y. and M. L. Cummings (2010). "Predicting Supervisory Control Behavior with Hidden Markov Models...Strategies for Strike Planning. COGIS 2006 - Cognitive Systems with Interactive Sensors, Paris . Burges, C. (1998). "A Tutorial on Support Vector Machines

  1. Human African Trypanosomiasis and challenges to its control in ...

    African Journals Online (AJOL)

    There was poor capacity for most of the health facilities in the diagnosis, treatment and control of HAT. In both districts, communities were knowledgeable of the tsetse identity (82.4%) and had experienced tsetse bites (94%). The majority (91.4%) of the community members knew that they were at risk of acquiring HAT.

  2. A PET study on brain control of micturition in humans

    NARCIS (Netherlands)

    Blok, BFM; Willemsen, ATM; Holstege, G

    Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important because their dysfunction is thought to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem

  3. Quantitative estimation of the human error probability during soft control operations

    International Nuclear Information System (INIS)

    Lee, Seung Jun; Kim, Jaewhan; Jung, Wondea

    2013-01-01

    Highlights: ► An HRA method to evaluate execution HEP for soft control operations was proposed. ► The soft control tasks were analyzed and design-related influencing factors were identified. ► An application to evaluate the effects of soft controls was performed. - Abstract: In this work, a method was proposed for quantifying human errors that can occur during operation executions using soft controls. Soft controls of advanced main control rooms have totally different features from conventional controls, and thus they may have different human error modes and occurrence probabilities. It is important to identify the human error modes and quantify the error probability for evaluating the reliability of the system and preventing errors. This work suggests an evaluation framework for quantifying the execution error probability using soft controls. In the application result, it was observed that the human error probabilities of soft controls showed both positive and negative results compared to the conventional controls according to the design quality of advanced main control rooms

  4. Information Flow Analysis for Human-System Interaction in the SG Level Control

    International Nuclear Information System (INIS)

    Kim, Jong Hyun; Shin, Yeong Cheol

    2008-01-01

    Interaction between automatic control and operators is one of main issues in the application of automation technology. Inappropriate information from automatic control systems causes unexpected problems in human-automation collaboration. Poor information becomes critical, especially when the operator takes over the control from an automation system. Operators cannot properly handle the situation transferred from the automatic mode because of inadequate situation awareness, if the operator is out-of-the loop and the automatic control system fails. Some cases of unplanned reactor trips during the transition between the manual mode and the automatic mode are reported in nuclear power plants (NPPs). Among unplanned reactor trips since 2002, two cases were partially caused by automation-related failures of steam generator (SG) level control. This paper conducts information flow analysis to identify information and control requirement for human-system interaction of SG level control. At first, this paper identifies the level of automation in SG level control systems and then function allocation between system control and human operators. Then information flow analysis for monitoring and transition of automation is performed by adapting job process chart. Information and control requirements will be useful as an input for the human-system interface (HSI) design of SG level control

  5. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    DEFF Research Database (Denmark)

    Hoof, Ilka; Kesmir, Can; Lund, Ole

    2008-01-01

    and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors. Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

  6. Integrated application of human factors to a power plant control room information system

    International Nuclear Information System (INIS)

    Fish, H.C. Jr.; Gutierrez, R.

    1988-01-01

    The human factors plan was developed as a methodology to apply human factors from the conceptual design of the EPIC system to the functional verification conducted at the plant. An integral part of the Human Factors Plan was the Functional Verification Plan. Developed in parallel, this second plan and its resultant programs verified functional appropriateness of the SPDS display, NSSS displays, EOP displays, man-machine interfaces (MMI), and workstation designs. The functional verification process was performed at the hardware/software developer's factory and at the JAFNPP, following installation of the EPIC system. Because the EPIC system replaces existing control room equipment, it is important that human factors be applied in a systematic manner consistent with other control room displays and controls. To ensure that this goal was met, a human factors plan was developed

  7. On the evidence for human use and control of fire at Schöningen.

    Science.gov (United States)

    Stahlschmidt, Mareike C; Miller, Christopher E; Ligouis, Bertrand; Hambach, Ulrich; Goldberg, Paul; Berna, Francesco; Richter, Daniel; Urban, Brigitte; Serangeli, Jordi; Conard, Nicholas J

    2015-12-01

    When and how humans began to control fire has been a central debate in Paleolithic archaeology for decades. Fire plays an important role in technology, social organization, subsistence, and manipulation of the environment and is widely seen as a necessary adaptation for the colonization of northern latitudes. Many researchers view purported hearths, burnt wooden implements, and heated flints from Schöningen as providing the best evidence for the control of fire in the Lower Paleolithic of Northern Europe. Here we present results of a multianalytical study of the purported hearths along with a critical examination of other possible evidence of human use or control of fire at Schöningen. We conclude that the analyzed features and artifacts present no convincing evidence for human use or control of fire. Our study also shows that a multianalytical, micro-contextual approach is the best methodology for evaluating claims of early evidence of human-controlled fire. We advise caution with macroscopic, qualitative identification of combustion features, burnt flint, and burnt wood without the application of such techniques as micromorphology, Fourier transform infrared (FTIR) spectroscopy, organic petrology, luminescence, and analysis of mineral magnetic parameters. The lack of evidence for the human control of fire at Schöningen raises the possibility that fire control was not a necessary adaptation for the human settlement of northern latitudes in the Lower Paleolithic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A mathematical model for incorporating biofeedback into human postural control

    Directory of Open Access Journals (Sweden)

    Ersal Tulga

    2013-02-01

    Full Text Available Abstract Background Biofeedback of body motion can serve as a balance aid and rehabilitation tool. To date, mathematical models considering the integration of biofeedback into postural control have represented this integration as a sensory addition and limited their application to a single degree-of-freedom representation of the body. This study has two objectives: 1 to develop a scalable method for incorporating biofeedback into postural control that is independent of the model’s degrees of freedom, how it handles sensory integration, and the modeling of its postural controller; and 2 to validate this new model using multidirectional perturbation experimental results. Methods Biofeedback was modeled as an additional torque to the postural controller torque. For validation, this biofeedback modeling approach was applied to a vibrotactile biofeedback device and incorporated into a two-link multibody model with full-state-feedback control that represents the dynamics of bipedal stance. Average response trajectories of body sway and center of pressure (COP to multidirectional surface perturbations of subjects with vestibular deficits were used for model parameterization and validation in multiple perturbation directions and for multiple display resolutions. The quality of fit was quantified using average error and cross-correlation values. Results The mean of the average errors across all tactor configurations and perturbations was 0.24° for body sway and 0.39 cm for COP. The mean of the cross-correlation value was 0.97 for both body sway and COP. Conclusions The biofeedback model developed in this study is capable of capturing experimental response trajectory shapes with low average errors and high cross-correlation values in both the anterior-posterior and medial-lateral directions for all perturbation directions and spatial resolution display configurations considered. The results validate that biofeedback can be modeled as an additional

  9. A mathematical model for incorporating biofeedback into human postural control

    Science.gov (United States)

    2013-01-01

    Background Biofeedback of body motion can serve as a balance aid and rehabilitation tool. To date, mathematical models considering the integration of biofeedback into postural control have represented this integration as a sensory addition and limited their application to a single degree-of-freedom representation of the body. This study has two objectives: 1) to develop a scalable method for incorporating biofeedback into postural control that is independent of the model’s degrees of freedom, how it handles sensory integration, and the modeling of its postural controller; and 2) to validate this new model using multidirectional perturbation experimental results. Methods Biofeedback was modeled as an additional torque to the postural controller torque. For validation, this biofeedback modeling approach was applied to a vibrotactile biofeedback device and incorporated into a two-link multibody model with full-state-feedback control that represents the dynamics of bipedal stance. Average response trajectories of body sway and center of pressure (COP) to multidirectional surface perturbations of subjects with vestibular deficits were used for model parameterization and validation in multiple perturbation directions and for multiple display resolutions. The quality of fit was quantified using average error and cross-correlation values. Results The mean of the average errors across all tactor configurations and perturbations was 0.24° for body sway and 0.39 cm for COP. The mean of the cross-correlation value was 0.97 for both body sway and COP. Conclusions The biofeedback model developed in this study is capable of capturing experimental response trajectory shapes with low average errors and high cross-correlation values in both the anterior-posterior and medial-lateral directions for all perturbation directions and spatial resolution display configurations considered. The results validate that biofeedback can be modeled as an additional torque to the postural

  10. Control volume based hydrocephalus research; analysis of human data

    Science.gov (United States)

    Cohen, Benjamin; Wei, Timothy; Voorhees, Abram; Madsen, Joseph; Anor, Tomer

    2010-11-01

    Hydrocephalus is a neuropathophysiological disorder primarily diagnosed by increased cerebrospinal fluid volume and pressure within the brain. To date, utilization of clinical measurements have been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Pressure volume models and electric circuit analogs enforce volume conservation principles in terms of pressure. Control volume analysis, through the integral mass and momentum conservation equations, ensures that pressure and volume are accounted for using first principles fluid physics. This approach is able to directly incorporate the diverse measurements obtained by clinicians into a simple, direct and robust mechanics based framework. Clinical data obtained for analysis are discussed along with data processing techniques used to extract terms in the conservation equation. Control volume analysis provides a non-invasive, physics-based approach to extracting pressure information from magnetic resonance velocity data that cannot be measured directly by pressure instrumentation.

  11. Human-Inspired Eigenmovement Concept Provides Coupling-Free Sensorimotor Control in Humanoid Robot

    Directory of Open Access Journals (Sweden)

    Thomas Mergner

    2017-04-01

    Full Text Available Control of a multi-body system in both robots and humans may face the problem of destabilizing dynamic coupling effects arising between linked body segments. The state of the art solutions in robotics are full state feedback controllers. For human hip-ankle coordination, a more parsimonious and theoretically stable alternative to the robotics solution has been suggested in terms of the Eigenmovement (EM control. Eigenmovements are kinematic synergies designed to describe the multi DoF system, and its control, with a set of independent, and hence coupling-free, scalar equations. This paper investigates whether the EM alternative shows “real-world robustness” against noisy and inaccurate sensors, mechanical non-linearities such as dead zones, and human-like feedback time delays when controlling hip-ankle movements of a balancing humanoid robot. The EM concept and the EM controller are introduced, the robot's dynamics are identified using a biomechanical approach, and robot tests are performed in a human posture control laboratory. The tests show that the EM controller provides stable control of the robot with proactive (“voluntary” movements and reactive balancing of stance during support surface tilts and translations. Although a preliminary robot-human comparison reveals similarities and differences, we conclude (i the Eigenmovement concept is a valid candidate when different concepts of human sensorimotor control are considered, and (ii that human-inspired robot experiments may help to decide in future the choice among the candidates and to improve the design of humanoid robots and robotic rehabilitation devices.

  12. Thalamic Control of Human Attention Driven by Memory and Learning

    OpenAIRE

    de Bourbon-Teles, José; Bentley, Paul; Koshino, Saori; Shah, Kushal; Dutta, Agneish; Malhotra, Paresh; Egner, Tobias; Husain, Masud; Soto, David

    2014-01-01

    Summary The role of the thalamus in high-level cognition—attention, working memory (WM), rule-based learning, and decision making—remains poorly understood, especially in comparison to that of cortical frontoparietal networks [1–3]. Studies of visual thalamus have revealed important roles for pulvinar and lateral geniculate nucleus in visuospatial perception and attention [4–10] and for mediodorsal thalamus in oculomotor control [11]. Ventrolateral thalamus contains subdivisions devoted to ac...

  13. Review of Methods Related to Assessing Human Performance in Nuclear Power Plant Control Room Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Katya L Le Blanc; Ronald L Boring; David I Gertman

    2001-11-01

    With the increased use of digital systems in Nuclear Power Plant (NPP) control rooms comes a need to thoroughly understand the human performance issues associated with digital systems. A common way to evaluate human performance is to test operators and crews in NPP control room simulators. However, it is often challenging to characterize human performance in meaningful ways when measuring performance in NPP control room simulations. A review of the literature in NPP simulator studies reveals a variety of ways to measure human performance in NPP control room simulations including direct observation, automated computer logging, recordings from physiological equipment, self-report techniques, protocol analysis and structured debriefs, and application of model-based evaluation. These methods and the particular measures used are summarized and evaluated.

  14. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Science.gov (United States)

    2010-02-03

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration 49 CFR Parts...: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... following correcting amendments: PART 192--TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE: MINIMUM...

  15. Human-factors engineering-control-room design review: Shoreham Nuclear Power Station. Draft audit report

    International Nuclear Information System (INIS)

    Peterson, L.R.; Preston-Smith, J.; Savage, J.W.; Rousseau, W.F.

    1981-01-01

    A human factors engineering preliminary design review of the Shoreham control room was performed at the site on March 30 through April 3, 1981. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. This report was prepared on the basis of the HFEB's review of the applicant's Preliminary Design Assessment and the human factors engineering design review/audit performed at the site. The presented sections are numbered to conform to the guidelines of the draft version of NUREG-0700. They summarize the teams's observations of the control room design and layout, and of the control room operators' interface with the control room environment

  16. Grape seed extract for control of human enteric viruses.

    Science.gov (United States)

    Su, Xiaowei; D'Souza, Doris H

    2011-06-01

    Grape seed extract (GSE) is reported to have many pharmacological benefits, including antioxidant, anti-inflammatory, anticarcinogenic, and antimicrobial properties. However, the effect of this inexpensive rich source of natural phenolic compounds on human enteric viruses has not been well documented. In the present study, the effect of commercial GSE, Gravinol-S, on the infectivity of human enteric virus surrogates (feline calicivirus, FCV-F9; murine norovirus, MNV-1; and bacteriophage MS2) and hepatitis A virus (HAV; strain HM175) was evaluated. GSE at concentrations of 0.5, 1, and 2 mg/ml was individually mixed with equal volumes of each virus at titers of ∼7 log(10) PFU/ml or ∼5 log(10) PFU/ml and incubated for 2 h at room temperature or 37°C. The infectivity of the recovered viruses after triplicate treatments was evaluated by standardized plaque assays. At high titers (∼7 log(10) PFU/ml), FCV-F9 was significantly reduced by 3.64, 4.10, and 4.61 log(10) PFU/ml; MNV-1 by 0.82, 1.35, and 1.73 log(10) PFU/ml; MS2 by 1.13, 1.43, and 1.60 log(10) PFU/ml; and HAV by 1.81, 2.66, and 3.20 log(10) PFU/ml after treatment at 37°C with 0.25, 0.50, and 1 mg/ml GSE, respectively (P PFU/ml) at 37°C also showed viral reductions. Room-temperature treatments with GSE caused significant reduction of the four viruses, with higher reduction for low-titer FCV-F9, MNV-1, and HAV compared to high titers. Our results indicate that GSE shows promise for application in the food industry as an inexpensive novel natural alternative to reduce viral contamination and enhance food safety.

  17. Humans, 'things' and space: costing hospital infection control interventions.

    Science.gov (United States)

    Page, K; Graves, N; Halton, K; Barnett, A G

    2013-07-01

    Previous attempts at costing infection control programmes have tended to focus on accounting costs rather than economic costs. For studies using economic costs, estimates tend to be quite crude and probably underestimate the true cost. One of the largest costs of any intervention is staff time, but this cost is difficult to quantify and has been largely ignored in previous attempts. To design and evaluate the costs of hospital-based infection control interventions or programmes. This article also discusses several issues to consider when costing interventions, and suggests strategies for overcoming these issues. Previous literature and techniques in both health economics and psychology are reviewed and synthesized. This article provides a set of generic, transferable costing guidelines. Key principles such as definition of study scope and focus on large costs, as well as pitfalls (e.g. overconfidence and uncertainty), are discussed. These new guidelines can be used by hospital staff and other researchers to cost their infection control programmes and interventions more accurately. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  18. Advanced control rooms and crew performance issues: Implications for human reliability

    International Nuclear Information System (INIS)

    O'Hara, J.M.; Hall, R.E.

    1991-01-01

    Recent trends in advanced control room (ACR) design are considered with respect to their impact on human performance. It is concluded that potentially negative influences exist, however, a variety of factors make it difficult to model, analyze, and quantify these effects for human reliability analyses (HRAs)

  19. Controlled delivery of antiangiogenic drug to human eye tissue using a MEMS device

    KAUST Repository

    Pirmoradi, Fatemeh Nazly; Ou, Kevin; Jackson, John K.; Letchford, Kevin; Cui, Jing; Wolf, Ki Tae; Graber, Florian; Zhao, Tom; Matsubara, Joanne A.; Burt, Helen; Chiao, Mu; Lin, Liwei

    2013-01-01

    We demonstrate an implantable MEMS drug delivery device to conduct controlled and on-demand, ex vivo drug transport to human eye tissue. Remotely operated drug delivery to human post-mortem eyes was performed via a MEMS device. The developed curved

  20. A Model-based Framework for Risk Assessment in Human-Computer Controlled Systems

    Science.gov (United States)

    Hatanaka, Iwao

    2000-01-01

    The rapid growth of computer technology and innovation has played a significant role in the rise of computer automation of human tasks in modem production systems across all industries. Although the rationale for automation has been to eliminate "human error" or to relieve humans from manual repetitive tasks, various computer-related hazards and accidents have emerged as a direct result of increased system complexity attributed to computer automation. The risk assessment techniques utilized for electromechanical systems are not suitable for today's software-intensive systems or complex human-computer controlled systems. This thesis will propose a new systemic model-based framework for analyzing risk in safety-critical systems where both computers and humans are controlling safety-critical functions. A new systems accident model will be developed based upon modem systems theory and human cognitive processes to better characterize system accidents, the role of human operators, and the influence of software in its direct control of significant system functions. Better risk assessments will then be achievable through the application of this new framework to complex human-computer controlled systems.

  1. The place of human-factors in the work of the Atomic Energy Control Board

    International Nuclear Information System (INIS)

    Barkow, B.

    1982-01-01

    The AECB do not effectively regulate human factors in nuclear power plants since they have no staff trained to do so. Two new positions are recommended and their activities are outlined. Special problems are identified in the certification of personnel, management information control, and in accommodating human factors to AECB style

  2. Robust control of dielectric elastomer diaphragm actuator for human pulse signal tracking

    Science.gov (United States)

    Ye, Zhihang; Chen, Zheng; Asmatulu, Ramazan; Chan, Hoyin

    2017-08-01

    Human pulse signal tracking is an emerging technology that is needed in traditional Chinese medicine. However, soft actuation with multi-frequency tracking capability is needed for tracking human pulse signal. Dielectric elastomer (DE) is one type of soft actuating that has great potential in human pulse signal tracking. In this paper, a DE diaphragm actuator was designed and fabricated to track human pulse pressure signal. A physics-based and control-oriented model has been developed to capture the dynamic behavior of DE diaphragm actuator. Using the physical model, an H-infinity robust control was designed for the actuator to reject high-frequency sensing noises and disturbances. The robust control was then implemented in real-time to track a multi-frequency signal, which verified the tracking capability and robustness of the control system. In the human pulse signal tracking test, a human pulse signal was measured at the City University of Hong Kong and then was tracked using DE actuator at Wichita State University in the US. Experimental results have verified that the DE actuator with its robust control is capable of tracking human pulse signal.

  3. Application of oligonucleotide array CGH to the simultaneous detection of a deletion in the nuclear TK2 gene and mtDNA depletion.

    Science.gov (United States)

    Zhang, Shulin; Li, Fang-Yuan; Bass, Harold N; Pursley, Amber; Schmitt, Eric S; Brown, Blaire L; Brundage, Ellen K; Mardach, Rebecca; Wong, Lee-Jun

    2010-01-01

    Thymidine kinase 2 (TK2), encoded by the TK2 gene on chromosome 16q22, is one of the deoxyribonucleoside kinases responsible for the maintenance of mitochondrial deoxyribonucleotide pools. Defects in TK2 mainly cause a myopathic form of the mitochondrial DNA depletion syndrome (MDDS). Currently, only point mutations and small insertions and deletions have been reported in TK2 gene; gross rearrangements of TK2 gene and possible hepatic involvement in patients with TK2 mutations have not been described. We report a non-consanguineous Jordanian family with three deceased siblings due to mtDNA depletion. Sequence analysis of the father detected a heterozygous c.761T>A (p.I254N) mutation in his TK2 gene; however, point mutations in the mother were not detected. Subsequent gene dosage analysis using oligonucleotide array CGH identified an intragenic approximately 5.8-kb deletion encompassing the 5'UTR to intron 2 of her TK2 gene. Sequence analysis confirmed that the deletion spans c.1-495 to c.283-2899 of the TK2 gene (nucleotide 65,136,256-65,142,086 of chromosome 16). Analysis of liver and muscle specimens from one of the deceased infants in this family revealed compound heterozygosity for the paternal point mutation and maternal intragenic deletion. In addition, a significant reduction of the mtDNA content in liver and muscle was detected (10% and 20% of age- and tissue-matched controls, respectively). Prenatal diagnosis was performed in the third pregnancy. The fetus was found to carry both the point mutation and the deletion. This child died 6months after birth due to myopathy. A serum specimen demonstrated elevated liver transaminases in two of the infants from whom results were available. This report expands the mutation spectrum associated with TK2 deficiency. While the myopathic form of MDDS appears to be the main phenotype of TK2 mutations, liver dysfunction may also be a part of the mitochondrial depletion syndrome caused by TK2 gene defects.

  4. Intelligent Systems Approach for Automated Identification of Individual Control Behavior of a Human Operator

    Science.gov (United States)

    Zaychik, Kirill B.; Cardullo, Frank M.

    2012-01-01

    Results have been obtained using conventional techniques to model the generic human operator?s control behavior, however little research has been done to identify an individual based on control behavior. The hypothesis investigated is that different operators exhibit different control behavior when performing a given control task. Two enhancements to existing human operator models, which allow personalization of the modeled control behavior, are presented. One enhancement accounts for the testing control signals, which are introduced by an operator for more accurate control of the system and/or to adjust the control strategy. This uses the Artificial Neural Network which can be fine-tuned to model the testing control. Another enhancement takes the form of an equiripple filter which conditions the control system power spectrum. A novel automated parameter identification technique was developed to facilitate the identification process of the parameters of the selected models. This utilizes a Genetic Algorithm based optimization engine called the Bit-Climbing Algorithm. Enhancements were validated using experimental data obtained from three different sources: the Manual Control Laboratory software experiments, Unmanned Aerial Vehicle simulation, and NASA Langley Research Center Visual Motion Simulator studies. This manuscript also addresses applying human operator models to evaluate the effectiveness of motion feedback when simulating actual pilot control behavior in a flight simulator.

  5. Cardiovascular and fluid volume control in humans in space

    DEFF Research Database (Denmark)

    Norsk, Peter

    2005-01-01

    on this complex interaction, because it is the only way to completely abolish the effects of gravity over longer periods. Results from space have been unexpected, because astronauts exhibit a fluid and sodium retaining state with activation of the sympathetic nervous system, which subjects during simulations...... by head-down bed rest do not. Therefore, the concept as to how weightlessness affects the cardiovascular system and modulates regulation of body fluids should be revised and new simulation models developed. Knowledge as to how gravity and weightlessness modulate integrated fluid volume control...

  6. Association of genetic variations in the mitochondrial DNA control region with presbycusis.

    Science.gov (United States)

    Falah, Masoumeh; Farhadi, Mohammad; Kamrava, Seyed Kamran; Mahmoudian, Saeid; Daneshi, Ahmad; Balali, Maryam; Asghari, Alimohamad; Houshmand, Massoud

    2017-01-01

    The prominent role of mitochondria in the generation of reactive oxygen species, cell death, and energy production contributes to the importance of this organelle in the intracellular mechanism underlying the progression of the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial DNA (mtDNA) gene expression and coding region variation have frequently been reported as being associated with the development of presbycusis. The mtDNA control region regulates gene expression and replication of the genome of this organelle. To comprehensively understand of the role of mitochondria in the progression of presbycusis, we compared variations in the mtDNA control region between subjects with presbycusis and controls. A total of 58 presbycusis patients and 220 control subjects were enrolled in the study after examination by the otolaryngologist and audiology tests. Variations in the mtDNA control region were investigated by polymerase chain reaction and Sanger sequencing. A total of 113 sequence variants were observed in mtDNA, and variants were detected in 100% of patients, with 84% located in hypervariable regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and 15,954 A>C, were significantly different between presbycusis and control subjects. The statistically significant difference in the frequencies of four nucleotide variants in the mtDNA control region of presbycusis patients and controls is in agreement with previous experimental evidence and supports the role of mitochondria in the intracellular mechanism underlying presbycusis development. Moreover, these variants have potential as diagnostic markers for individuals at a high risk of developing presbycusis. The data also suggest the possible presence of changes in the mtDNA control region in presbycusis, which could alter regulatory factor binding sites and influence mtDNA gene expression and copy number.

  7. The Human Eye Position Control System in a Rehabilitation Setting

    Directory of Open Access Journals (Sweden)

    Yvonne Nolan

    2005-01-01

    Full Text Available Our work at Ireland’s National Rehabilitation Hospital involves designing communication systems for people suffering from profound physical disabilities. One such system uses the electro-oculogram, which is an (x,y system of voltages picked up by pairs of electrodes placed, respectively, above and below and on either side of the eyes. The eyeball has a dc polarisation between cornea and back, arising from the photoreceptor rods and cones in the retina. As the eye rotates, the varying voltages projected onto the electrodes drive a cursor over a mimic keyboard on a computer screen. Symbols are selected with a switching action derived, for example, from a blink. Experience in using this mode of communication has given us limited facilities to study the eye position control system. We present here a resulting new feedback model for rotation in either the vertical or the horizontal plane, which involves the eyeball controlled by an agonist-antagonist muscle pair, modelled by a single equivalent bidirectional muscle with torque falling off linearly with angular velocity. We have incorporated muscle spindles and have tuned them by pole assignment associated with an optimum stability criterion.

  8. The Control of Human Immunosystem by Using Paeony Root Drug

    Directory of Open Access Journals (Sweden)

    Hideo Tsuboi

    2010-10-01

    Full Text Available Paeoniflorin (PF, isolated from paeony root, has been used as a herbal medicine for more than 1200 years in China, Korea and Japan for its anti-allergic, anti-inflamatory and immunoregulatory effects. In this study, we found that PF induces apoptosis in both murine T-lineage cells and human T-cell leukemia Jurkat cells. This apoptosis was mediated through the reduction of mitochondrial membrane potential, activation of caspase and fragmentation of DNA. Interestingly, PF induced generation of reactive oxygen species (ROS and a reducing agent, dithiothreitol (DTT, and a ROS scavenger, N-acetyl cysteine (NAC, successfully attenuated the PF-induced apoptosis. Additionally, PF induced the phosphorylation of three mitogen-activated protein (MAP family kinases, extracellular signal-regulated kinase, c-Jun amino-terminal kinase (JNK and p38 MAP kinase. Curcumin, an anti-oxidant and JNK inhibitor, inhibited PF-induced apoptosis, suggesting the possible involvement of curcumin-sensitive JNK or other redox-sensitive elements in PF-induced apoptosis. These results partially explain the action mechanism of PF-containing paeony root as a herbal medicine.

  9. Human rhinovirus capsid dynamics is controlled by canyon flexibility

    International Nuclear Information System (INIS)

    Reisdorph, Nichole; Thomas, John J.; Katpally, Umesh; Chase, Elaine; Harris, Ken; Siuzdak, Gary; Smith, Thomas J.

    2003-01-01

    Quantitative enzyme accessibility experiments using nano liquid chromatography electrospray mass spectrometry combined with limited proteolysis and isotope-labeling was used to examine the dynamic nature of the human rhinovirus (HRV) capsid in the presence of three antiviral compounds, a neutralizing Fab, and drug binding cavity mutations. Using these methods, it was found that the antivirals WIN 52084 and picovir (pleconaril) stabilized the capsid, while dansylaziridine caused destabilization. Site-directed mutations in the drug-binding cavity were found to stabilize the HRV14 capsid against proteolytic digestion in a manner similar to WIN 52084 and pleconaril. Antibodies that bind to the NIm-IA antigenic site and penetrate the canyon were also observed to protect the virion against proteolytic cleavage. These results demonstrate that quantifying the effects of antiviral ligands on protein 'breathing' can be used to compare their mode of action and efficacy. In this case, it is apparent that hydrophobic antiviral agents, antibodies, or mutations in the canyon region block viral breathing. Therefore, these studies demonstrate that mobility in the canyon region is a major determinant in capsid breathing

  10. Human-system interfaces for the ABWR control room

    International Nuclear Information System (INIS)

    Gutierrez, R.; O'Neil, T.J.

    1993-01-01

    The 1300-MW(electric) advanced boiling water reactor (ABWR) design has been developed by General Electric Co. (G.E.) and its technical associates, Hitachi Ltd. and Toshiba Corporation, under the sponsorship of the Tokyo Electric Power Company. Key features of the ABWR include simplification, improved safety and reliability, reduced occupational exposure and radwaste, improved maneuverability, and reduced construction, fuel, and operating costs. The ABWR incorporates the best proven features from BWR designs in Japan, Europe, and the United States, combined with the broad-scope application of leading-edge technology. The first application of the ABWR design will be at TEP-CO's Kashiwazaki-Kariwa nuclear power station units 6 and 7, which are scheduled to begin commercial operation in 1996 and 1997, respectively. The ABWR is also the lead plant in the U.S. standard plant design certification program. It is scheduled to receive final approval from the U.S. Nuclear Regulatory Commission in early 1994. The development of the human system interaces (HSI) for the ABWR is an extension of the operating experience of existing man-machine interfaces currently being used at GE-designed plants

  11. Preparation and quality control of MAA human serum albumin kit

    International Nuclear Information System (INIS)

    Yassin, T.; Dadokh, M.; Almalki, R.

    2005-05-01

    MAA Macro aggregate Kit for pulmonary perfusion after labeling with 99m Tc was prepared according to an optimum conditions, where each vial contains 0.8 mg of HSA and 0.17 mg of stannous chloride dehydrate (SnCl 2 2H 2 O),The prepared kit showed high quality satisfying the requirements of international pharmacopoeias from the points of physical, chemical, radiochemical and biological purities, and its validity for human injection. And the labeling yield exceeded 99 % with average value of about 99.74 ± 0.27 % for 2mCi/2ml radioactivity, The bio distribution study in rats showed that an average of 93.87 ± 3.97% of injected dose was located in the lungs after 10 minutes where only about 0.99 ± 0.41 % of it was located in the liver and about 0.41 ± 0.14% in the kidneys and blood clearance 1.235 ± 0.78 %. This study also showed that each vial content can be labeled with maximum activity of 99m Tc of about 50 mCi. (Authors)

  12. Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses.

    Science.gov (United States)

    Lin, Xiang; Zheng, Hong-Xiang; Davie, Allan; Zhou, Shi; Wen, Li; Meng, Jun; Zhang, Yong; Aladaer, Qimude; Liu, Bin; Liu, Wu-Jun; Yao, Xin-Kui

    2018-03-01

    Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (p = .0003) and its sub-haplogroup L3b1a (p = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (p > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.

  13. HuRECA: Human Reliability Evaluator for Computer-based Control Room Actions

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Lee, Seung Jun; Jang, Seung Cheol

    2011-01-01

    As computer-based design features such as computer-based procedures (CBP), soft controls (SCs), and integrated information systems are being adopted in main control rooms (MCR) of nuclear power plants, a human reliability analysis (HRA) method capable of dealing with the effects of these design features on human reliability is needed. From the observations of human factors engineering verification and validation experiments, we have drawn some major important characteristics on operator behaviors and design-related influencing factors (DIFs) from the perspective of human reliability. Firstly, there are new DIFs that should be considered in developing an HRA method for computer-based control rooms including especially CBP and SCs. In the case of the computer-based procedure rather than the paper-based procedure, the structural and managerial elements should be considered as important PSFs in addition to the procedural contents. In the case of the soft controllers, the so-called interface management tasks (or secondary tasks) should be reflected in the assessment of human error probability. Secondly, computer-based control rooms can provide more effective error recovery features than conventional control rooms. Major error recovery features for computer-based control rooms include the automatic logic checking function of the computer-based procedure and the information sharing feature of the general computer-based designs

  14. Targeted Transgenic Overexpression of Mitochondrial Thymidine Kinase (TK2) Alters Mitochondrial DNA (mtDNA) and Mitochondrial Polypeptide Abundance : Transgenic TK2, mtDNA, and Antiretrovirals

    OpenAIRE

    Hosseini, Seyed H.; Kohler, James J.; Haase, Chad P.; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

    2007-01-01

    Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-γ. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK...

  15. Fuzzy variable impedance control based on stiffness identification for human-robot cooperation

    Science.gov (United States)

    Mao, Dachao; Yang, Wenlong; Du, Zhijiang

    2017-06-01

    This paper presents a dynamic fuzzy variable impedance control algorithm for human-robot cooperation. In order to estimate the intention of human for co-manipulation, a fuzzy inference system is set up to adjust the impedance parameter. Aiming at regulating the output fuzzy universe based on the human arm’s stiffness, an online stiffness identification method is developed. A drag interaction task is conducted on a 5-DOF robot with variable impedance control. Experimental results demonstrate that the proposed algorithm is superior.

  16. On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola

    Directory of Open Access Journals (Sweden)

    Beleza Sandra

    2009-04-01

    Full Text Available Abstract Background Current information about the expansion of Bantu-speaking peoples is hampered by the scarcity of genetic data from well identified populations from southern Africa. Here, we fill an important gap in the analysis of the western edge of the Bantu migrations by studying for the first time the patterns of Y-chromosome, mtDNA and lactase persistence genetic variation in four representative groups living around the Namib Desert in southwestern Angola (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale. We assessed the differentiation between these populations and their levels of admixture with Khoe-San groups, and examined their relationship with other sub-Saharan populations. We further combined our dataset with previously published data on Y-chromosome and mtDNA variation to explore a general isolation with migration model and infer the demographic parameters underlying current genetic diversity in Bantu populations. Results Correspondence analysis, lineage sharing patterns and admixture estimates indicate that the gene pool from southwestern Angola is predominantly derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people were additionally characterized by relatively high frequencies of Y-chromosome (12% and mtDNA (22% Khoe-San lineages, as well as by the presence of the -14010C lactase persistence mutation (6%, which likely originated in non-Bantu pastoralists from East Africa. Inferred demographic parameters show that both male and female populations underwent significant size growth after the split between the western and eastern branches of Bantu expansions occurring 4000 years ago. However, males had lower population sizes and migration rates than females throughout the Bantu dispersals. Conclusion Genetic variation in southwestern Angola essentially results from the encounter of an offshoot of West-Central Africa with autochthonous Khoisan-speaking peoples from the south. Interactions between the Bantus

  17. Screening of respiration deficiency mutants of yeasts (Saccharomyces cerevisiae) induced by ion irradiation and the mtDNA restriction analysis

    International Nuclear Information System (INIS)

    Mao Shuhong; Chinese Academy of Sciences, Beijing; Jin Genming; Wei Zengquan; Xie Hongmei; Ma Qiufeng; Gu Ying

    2005-01-01

    Screening of the respiration deficiency mutants of Saccharomyces cerevisiae induced by 5.19 MeV/u 22 Ne 5+ ion irradiation is reported in this paper. Some respiration deficiency mutants of white colony phenotype, in a condition of selective culture of TTC medium, were obtained. A new and simplified method based on mtDNA restriction analysis is described. The authors found that there are many obvious differences in mtDNAs between wild yeasts and the respiration deficiency mutants. The mechanism of obtaining the respiration deficiency mutants induced by heavy ion irradiation is briefly discussed. (authors)

  18. The Great Diversion: Danube Delta under Human Control (Invited)

    Science.gov (United States)

    Giosan, L.

    2009-12-01

    Many deltas around the world are suffering from sediment deficits that render them unstable to current and predicted rates of sea level rise. One solution proposed to alleviate the complete or partial drowning of such deltas is the use of river diversions to increase the quantity of sediment supplied to the delta plain to support marsh accretion. We examine the results of a half century old program of diversion in the Danube delta that led to the creation of an extensive diversion channel network akin in scope and size to a natural deltaic network. Danube’s importance as a shipping route increased after the Crimean War in the 1850s; the European Danube Commission was charged with maintaining the Sulina distributary as a shipping channel until 1940s. In the same period, several canals were dug to aid fishing in lakes and bring freshwater to brackish lagoons. After World War II, Communist authorities dramatically increased the number of canals for fishing, fish-farming and reed harvesting. New data on sedimentation rates and estimates of sediment fluxes suggest that the intensive canalization in the second half of the 20th Century led to increased sediment deposition that compensated the decreasing sediment discharge linked to damming within the internal fluvial part of the delta; however, the external marine delta has become increasingly sediment starved during the same interval. We emphasize the similarities and contrasts between the “human-controlled” and natural deltaic channel networks of the Danube delta and discuss the sustainability of the delta as a sediment budget problem within a sea level rise context.

  19. Genetic characterisation of populations of the critically endangered Goliath grouper ( Epinephelus itajara, Serranidae from the Northern Brazilian coast through analyses of mtDNA

    Directory of Open Access Journals (Sweden)

    Gláucia C. Silva-Oliveira

    2008-01-01

    Full Text Available The Goliath grouper ( Epinephelus itajara is one of the most endangered species of fish of the subfamily Epinephelinae. Slow to develop and mature, and dependent on mangrove habitats for breeding, the species also suffers intense harvesting, which has reduced drastically in numbers in many areas. To contribute to the understanding of the characteristics of E. itajara populations, we conducted a molecular genetics study of the species, focusing on populations from the Northern Brazilian coast. The mtDNA control region (D-loop of 116 individuals from five localities (Bragança, Ajuruteua, Parnaíba, Fortaleza and Natal was analysed, and a sequence of 499 base pairs identified. Analyses of the sequences indicated that genetic variability was generally lower in E. itajara than in other endangered species of the genus. AMOVA found no significant grouping structure among the populations. Nested Clade Analysis revealed a significant association between genetic variability and geographic distribution among only three populations (Ajuruteua, Parnaíba and Natal. Genetic diversity was higher in populations from the Amazon region, which may be related to the better conservation of mangrove habitats in this area. Therefore, the present study could be used for the implementation of conservation and management measures in order to protect and consolidate these populations.

  20. Restricted gene flow at the micro- and macro-geographical scale in marble trout based on mtDNA and microsatellite polymorphism

    Directory of Open Access Journals (Sweden)

    Patarnello Tomaso

    2011-04-01

    Full Text Available Abstract Background The genetic structure of the marble trout Salmo trutta marmoratus, an endemic salmonid of northern Italy and the Balkan peninsula, was explored at the macro- and micro-scale level using a combination of mitochondrial DNA (mtDNA and microsatellite data. Results Sequence variation in the mitochondrial control region showed the presence of nonindigenous haplotypes indicative of introgression from brown trout into marble trout. This was confirmed using microsatellite markers, which showed a higher introgression at nuclear level. Microsatellite loci revealed a strong genetic differentiation across the geographical range of marble trout, which suggests restricted gene flow both at the micro-geographic (within rivers and macro-geographic (among river systems scale. A pattern of Isolation-by-Distance was found, in which genetic samples were correlated with hydrographic distances. A general West-to-East partition of the microsatellite polymorphism was observed, which was supported by the geographic distribution of mitochondrial haplotypes. Conclusion While introgression at both mitochondrial and nuclear level is unlikely to result from natural migration and might be the consequence of current restocking practices, the pattern of genetic substructuring found at microsatellites has been likely shaped by historical colonization patterns determined by the geological evolution of the hydrographic networks.

  1. Human factors inspection of current control room panel in Jose Cabrera NPP

    International Nuclear Information System (INIS)

    Almeida, P.; O'Hara, J.; Higgins, J.

    2002-01-01

    Within the process of renewal of Exploitation Permit of Jose Cabrera Nuclear Power Plant, UNION FENOSA GENERACIO, S. A. (UFG) has carried out an analysis and evaluation project regarding human factors implications of current control room panel arrangement. The project has been developed in two phases. In the first phase, leaded by EPRI and carried out by experts from SAIC, an independent review from a double viewpoint of human reliability and human factors was developed. In the second phase, a multidisciplinary team (composed by human factors, risk analysis, operation, engineering, training and instrumentation and controls experts) has developed a study on human factors implications of current panel arrangement, following the methodology pointed out in NUREG-0711. The project has been developed under the direction of Brookhaven National Laboratory (BNL), organisation that has authored the aforementioned methodology, with the participation of UFG and SOLUZIONA Ingenieria. For the development of the second study the following steps were taken: Firstly, the potential effects of panel arrangement on crew performance were identified its real evidence was analysed and the goals for the improvement of control room operation were established; following NUREG-0711. After this, several design alternatives that addressed these goals were identified and were analysed along three dimensions: human factors, risk analysis and economic costs. Finally the results of these evaluations were combined using a multi-attribute decision method to arrive at a recommended alternative as he best proposal to incorporate human factors criteria and good practices in the design of control room panels. (Author)

  2. Human factors review of nuclear power plant control room design. Final report

    International Nuclear Information System (INIS)

    Seminara, J.L.; Gonzalez, W.R.; Parsons, S.O.

    1976-11-01

    The human factors aspects of five representative nuclear power plant control rooms were evaluated using such methods as a checklist guided observation system, structured interviews with operators and trainers, direct observations of operator behavior, task analyses and procedure evaluation, and historical error analyses. The human factors aspects of design practices are illustrated, and many improvements in current practices are suggested. The study recommends that a detailed set of applicable human factors standards be developed to stimulate a uniform and systematic concern for human factors in design considerations

  3. Analysis of Human Error Types and Performance Shaping Factors in the Next Generation Main Control Room

    International Nuclear Information System (INIS)

    Sin, Y. C.; Jung, Y. S.; Kim, K. H.; Kim, J. H.

    2008-04-01

    Main control room of nuclear power plants has been computerized and digitalized in new and modernized plants, as information and digital technologies make great progresses and become mature. Survey on human factors engineering issues in advanced MCRs: Model-based approach, Literature survey-based approach. Analysis of human error types and performance shaping factors is analysis of three human errors. The results of project can be used for task analysis, evaluation of human error probabilities, and analysis of performance shaping factors in the HRA analysis

  4. Development and Control of Compliant Hybrid Joints for Human-Symbiotic Mobile Manipulators

    Directory of Open Access Journals (Sweden)

    Zhijun Li

    2007-03-01

    Full Text Available In this paper, we develop a robot with the ability to secure human safety in human-robot collisions arising in our living and working environments. The human-symbiotic service robot using compliant hybrid joints realizes human safety, absorbs impact force, and fulfills task. In unexpected or expected collisions with human, the arising impulse force is attenuated effectively by the proposed physical model. Owing to the displacement of the links, several recovery controls have been developed for the end-effector to maintain its desired task position after the collision. The force attenuation property has been verified through collision simulations and experiments in that the capability of the proposed passive arm in overcoming the limitations of active compliance control has been demonstrated.

  5. Human Factors and Data Fusion as Part of Control Systems Resilience

    Energy Technology Data Exchange (ETDEWEB)

    David I. Gertman

    2009-05-01

    Human performance and human decision making is counted upon as a crucial aspect of overall system resilience. Advanced control systems have the potential to provide operators and asset owners a wide range of data, deployed at different levels that can be used to support operator situation awareness. However, the sheer amount of data available can make it challenging for operators to assimilate information and respond appropriately. This paper reviews some of the challenges and issues associated with providing operators with actionable state awareness and argues for the over arching importance of integrating human factors as part of intelligent control systems design and implementation. It is argued that system resilience is improved by implementing human factors in operations and maintenance. This paper also introduces issues associated with resilience and data fusion and highlights areas in which human factors including field studies hold promise.

  6. MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    Science.gov (United States)

    Stumpf, Jeffrey D; Copeland, William C

    2014-10-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  7. Human kinematics and event control: On-line movement registration as a means for experimental manipulation

    NARCIS (Netherlands)

    Oudejans, R.R.D.; Coolen, H.

    2003-01-01

    In human movement and sports science, manipulations of perception and action are common and often comprise the control of events, such as opening or closing liquid crystal goggles. Most of these events are externally controlled, independent of the actions of the participants. Less common, although

  8. Human-Inspired Eigenmovement Concept Provides Coupling-Free Sensorimotor Control in Humanoid Robot

    Czech Academy of Sciences Publication Activity Database

    Alexandrov, A.V.; Lippi, V.; Mergner, T.; Frolov, A. A.; Hettich, G.; Húsek, Dušan

    2017-01-01

    Roč. 11, 25 April (2017), č. článku 22. ISSN 1662-5188 Institutional support: RVO:67985807 Keywords : human sensorimotor system * neuromechanics * biorobotics * motor control * eigenmovements Subject RIV: JD - Computer Applications, Robotics OBOR OECD: Robotics and automatic control Impact factor: 1.821, year: 2016

  9. Bilateral human-robot control for semi-autonomous UAV navigation

    NARCIS (Netherlands)

    Wopereis, Han Willem; Fumagalli, Matteo; Stramigioli, Stefano; Carloni, Raffaella

    2015-01-01

    This paper proposes a semi-autonomous bilateral control architecture for unmanned aerial vehicles. During autonomous navigation, a human operator is allowed to assist the autonomous controller of the vehicle by actively changing its navigation parameters to assist it in critical situations, such as

  10. Optimal control predicts human performance on objects with internal degrees of freedom.

    Directory of Open Access Journals (Sweden)

    Arne J Nagengast

    2009-06-01

    Full Text Available On a daily basis, humans interact with a vast range of objects and tools. A class of tasks, which can pose a serious challenge to our motor skills, are those that involve manipulating objects with internal degrees of freedom, such as when folding laundry or using a lasso. Here, we use the framework of optimal feedback control to make predictions of how humans should interact with such objects. We confirm the predictions experimentally in a two-dimensional object manipulation task, in which subjects learned to control six different objects with complex dynamics. We show that the non-intuitive behavior observed when controlling objects with internal degrees of freedom can be accounted for by a simple cost function representing a trade-off between effort and accuracy. In addition to using a simple linear, point-mass optimal control model, we also used an optimal control model, which considers the non-linear dynamics of the human arm. We find that the more realistic optimal control model captures aspects of the data that cannot be accounted for by the linear model or other previous theories of motor control. The results suggest that our everyday interactions with objects can be understood by optimality principles and advocate the use of more realistic optimal control models for the study of human motor neuroscience.

  11. The design and operation of the THORP central control room: a human factors perspective

    International Nuclear Information System (INIS)

    Reed, Julie.

    1996-01-01

    The new Thermal Oxide Reprocessing Plant (THORP) at British Nuclear Fuels (BNFL) Sellafield Site is now operational. This paper describes the Central Control Room (CCR), focusing on the control system components. Throughout the design, commissioning and operation of THORP, human factors played an important part. (author)

  12. Human factors engineering control-room-design review/audit report: Palo Verde Nuclear Generating Station, Arizona Public Service Company

    International Nuclear Information System (INIS)

    Savage, J.W.; Lappa, D.A.

    1981-01-01

    A human factors engineering design review of the Palo Verde control room simulator was performed at the site on September 15 through September 17, 1981. Observed human factors design discrepancies were given priority ratings. This report summarizes the team's observations of the control room design and layout and of the control room operators' interface with the control room environment. A list of the human factors strengths observed in the Palo Verde control room simulator is given

  13. Survey of control-room design practices with respect to human factors engineering

    International Nuclear Information System (INIS)

    Seminara, J.L.; Parsons, S.O.

    1980-01-01

    Human factors engineering is an interdisciplinary speciality concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. This emphasis has been applied to most military and space systems in the past 30 y. A review of five nuclear power-plant control rooms, reported in the November-December 1977 issue of Nuclear Safety, revealed that human factors principles of design have generally not been incorporated in present-generation control rooms. This article summarizes the findings of a survey of 20 control-board designers from a mix of nuclear steam-supply system and architect-engineering firms. The interviews with these designers probed design methods currently used in developing control rooms. From these data it was concluded that there is currently no consistent, formal, uniform concern for the human factors aspects of control-room design on the part of the design organizations, the utilities, or the Nuclear Regulatory Commission. Although all the parties involved are concerned with human factors issues, this responsibility is not focused, and human factors yardsticks, or design standards, specific to power plants have not been evolved and applied in the development and verification of control-room designs from the standpoint of the man-machine interface

  14. Measuring Human Performance in Simulated Nuclear Power Plant Control Rooms Using Eye Tracking

    Energy Technology Data Exchange (ETDEWEB)

    Kovesdi, Casey Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rice, Brandon Charles [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bower, Gordon Ross [Idaho National Lab. (INL), Idaho Falls, ID (United States); Spielman, Zachary Alexander [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hill, Rachael Ann [Idaho National Lab. (INL), Idaho Falls, ID (United States); LeBlanc, Katya Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-11-01

    Control room modernization will be an important part of life extension for the existing light water reactor fleet. As part of modernization efforts, personnel will need to gain a full understanding of how control room technologies affect performance of human operators. Recent advances in technology enables the use of eye tracking technology to continuously measure an operator’s eye movement, which correlates with a variety of human performance constructs such as situation awareness and workload. This report describes eye tracking metrics in the context of how they will be used in nuclear power plant control room simulator studies.

  15. Measuring Human Performance in Simulated Nuclear Power Plant Control Rooms Using Eye Tracking

    International Nuclear Information System (INIS)

    Kovesdi, Casey Robert; Rice, Brandon Charles; Bower, Gordon Ross; Spielman, Zachary Alexander; Hill, Rachael Ann; LeBlanc, Katya Lee

    2015-01-01

    Control room modernization will be an important part of life extension for the existing light water reactor fleet. As part of modernization efforts, personnel will need to gain a full understanding of how control room technologies affect performance of human operators. Recent advances in technology enables the use of eye tracking technology to continuously measure an operator's eye movement, which correlates with a variety of human performance constructs such as situation awareness and workload. This report describes eye tracking metrics in the context of how they will be used in nuclear power plant control room simulator studies.

  16. Functional MRI in human motor control studies and clinical applications

    International Nuclear Information System (INIS)

    Toma, Keiichiro

    2002-01-01

    Functional magnetic resonance imaging (fMRI) has been a useful tool for the noninvasive mapping of brain function associated with various motor and cognitive tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD) effect, it does not directly record neural activity. With the fMRI technique, distinguishing BOLD signals creased by cortical projection neurons from those created by intracortical neurons appears to be difficult. Two major experimental designs are used in fMRI studies: block designs and event-related designs. Block-designed fMRI presupposes the steady state of regional cerebral blood flow and has been applied to examinations of brain activation caused by tasks requiring sustained or repetitive movements. By contrast, the more recently developed event-related fMRI with time resolution of a few seconds allows the mapping of brain activation associated with a single movement according to the transient aspects of the hemodynamic response. Increasing evidence suggests that multiple motor areas are engaged in a networked manner to execute various motor acts. In order to understand functional brain maps, it is important that one understands sequential and parallel organizations of anatomical connections between multiple motor areas. In fMRI studies of complex motor tasks, elementary parameters such as movement length, force, velocity, acceleration and frequency should be controlled, because inconsistency in those parameters may alter the extent and intensity of motor cortical activation, confounding interpretation of the findings obtained. In addition to initiation of movements, termination of movements plays an important role in the successful achievement of complex movements. Brain areas exclusively related to the termination of movements have been, for the first time, uncovered with an event-related fMRI technique. We propose the application of fMRI to the elucidation of the pathophysiology of movement disorders, particularly dystonia

  17. Functional MRI in human motor control studies and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Toma, Keiichiro [Kyoto Univ. (Japan). Graduate School of Medicine; Nakai, Toshiharu [Inst. of Biomedical Research and Innovation, Kobe (Japan)

    2002-07-01

    Functional magnetic resonance imaging (fMRI) has been a useful tool for the noninvasive mapping of brain function associated with various motor and cognitive tasks. Because fMRI is based on the blood oxygenation level dependent (BOLD) effect, it does not directly record neural activity. With the fMRI technique, distinguishing BOLD signals creased by cortical projection neurons from those created by intracortical neurons appears to be difficult. Two major experimental designs are used in fMRI studies: block designs and event-related designs. Block-designed fMRI presupposes the steady state of regional cerebral blood flow and has been applied to examinations of brain activation caused by tasks requiring sustained or repetitive movements. By contrast, the more recently developed event-related fMRI with time resolution of a few seconds allows the mapping of brain activation associated with a single movement according to the transient aspects of the hemodynamic response. Increasing evidence suggests that multiple motor areas are engaged in a networked manner to execute various motor acts. In order to understand functional brain maps, it is important that one understands sequential and parallel organizations of anatomical connections between multiple motor areas. In fMRI studies of complex motor tasks, elementary parameters such as movement length, force, velocity, acceleration and frequency should be controlled, because inconsistency in those parameters may alter the extent and intensity of motor cortical activation, confounding interpretation of the findings obtained. In addition to initiation of movements, termination of movements plays an important role in the successful achievement of complex movements. Brain areas exclusively related to the termination of movements have been, for the first time, uncovered with an event-related fMRI technique. We propose the application of fMRI to the elucidation of the pathophysiology of movement disorders, particularly dystonia

  18. International Guidelines on Human Rights and Drug Control: A Tool for Securing Women's Rights in Drug Control Policy.

    Science.gov (United States)

    Schleifer, Rebecca; Pol, Luciana

    2017-06-01

    Discrimination and inequality shape women's experiences of drug use and in the drug trade and the impact of drug control efforts on them, with disproportionate burdens faced by poor and otherwise marginalized women. In recent years, UN member states and UN drug control and human rights entities have recognized this issue and made commitments to integrate a 'gender perspective' into drug control policies, with 'gender' limited to those conventionally deemed women. But the concept of gender in international law is broader, rooted in socially constructed and culturally determined norms and expectations around gender roles, sex, and sexuality. Also, drug control policies often fail to meaningfully address the specific needs and circumstances of women (inclusively defined), leaving them at risk of recurrent violations of their rights in the context of drugs. This article explores what it means to 'mainstream' this narrower version of gender into drug control efforts, using as examples various women's experiences as people who use drugs, in the drug trade, and in the criminal justice system. It points to international guidelines on human rights and drug control as an important tool to ensure attention to women's rights in drug control policy design and implementation.

  19. The Roles of Feedback and Feedforward as Humans Learn to Control Unknown Dynamic Systems.

    Science.gov (United States)

    Zhang, Xingye; Wang, Shaoqian; Hoagg, Jesse B; Seigler, T Michael

    2018-02-01

    We present results from an experiment in which human subjects interact with an unknown dynamic system 40 times during a two-week period. During each interaction, subjects are asked to perform a command-following (i.e., pursuit tracking) task. Each subject's performance at that task improves from the first trial to the last trial. For each trial, we use subsystem identification to estimate each subject's feedforward (or anticipatory) control, feedback (or reactive) control, and feedback time delay. Over the 40 trials, the magnitudes of the identified feedback controllers and the identified feedback time delays do not change significantly. In contrast, the identified feedforward controllers do change significantly. By the last trial, the average identified feedforward controller approximates the inverse of the dynamic system. This observation provides evidence that a fundamental component of human learning is updating the anticipatory control until it models the inverse dynamics.

  20. To reduce the global burden of human schistosomiasis, use ‘old fashioned’ snail control

    Science.gov (United States)

    Sokolow, Susanne H.; Wood, Chelsea L.; Jones, Isabel J.; Lafferty, Kevin D.; Kuris, Armand; Hsieh, Michael H.; De Leo, Giulio A.

    2018-01-01

    Control strategies to reduce human schistosomiasis have evolved from ‘snail picking’ campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and ‘outside the box’ strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly’s stated goal to eliminate schistosomiasis, it is time to give snail control another look.

  1. Autotuning of PID controller by means of human machine interface device

    Directory of Open Access Journals (Sweden)

    Michał Awtoniuk

    2017-06-01

    Full Text Available More and more control systems are based on industry microprocessors like PLC controllers (Programmable Logic Controller. The most commonly used control algorithm is PID (Proportional-Integral-Derivative algorithm. Autotuning procedure is not available in every PLC. These controllers are typically used in cooperation with HMI (Human Machine Interface devices. In the study two procedures of autotuning of the PID controller were implemented in the HMI device: step method and relay method. Six tuning rules for step methods and one for relay method were chosen. The autotuning procedures on simulated controlled object and PLC controller without build-in autotuning were tested. The object of control was first order system plus time delay.

  2. Objective Model Selection for Identifying the Human Feedforward Response in Manual Control.

    Science.gov (United States)

    Drop, Frank M; Pool, Daan M; van Paassen, Marinus Rene M; Mulder, Max; Bulthoff, Heinrich H

    2018-01-01

    Realistic manual control tasks typically involve predictable target signals and random disturbances. The human controller (HC) is hypothesized to use a feedforward control strategy for target-following, in addition to feedback control for disturbance-rejection. Little is known about human feedforward control, partly because common system identification methods have difficulty in identifying whether, and (if so) how, the HC applies a feedforward strategy. In this paper, an identification procedure is presented that aims at an objective model selection for identifying the human feedforward response, using linear time-invariant autoregressive with exogenous input models. A new model selection criterion is proposed to decide on the model order (number of parameters) and the presence of feedforward in addition to feedback. For a range of typical control tasks, it is shown by means of Monte Carlo computer simulations that the classical Bayesian information criterion (BIC) leads to selecting models that contain a feedforward path from data generated by a pure feedback model: "false-positive" feedforward detection. To eliminate these false-positives, the modified BIC includes an additional penalty on model complexity. The appropriate weighting is found through computer simulations with a hypothesized HC model prior to performing a tracking experiment. Experimental human-in-the-loop data will be considered in future work. With appropriate weighting, the method correctly identifies the HC dynamics in a wide range of control tasks, without false-positive results.

  3. Human factors engineering applied to Control Centre Design of a research nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R., E-mail: larissapfarias@ymail.com [Instituto de Engenharia Nuclear (DENN/SEESC/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab, de Usabilidade e Confiabilidade Humana; Monteiro, Beany G. [Universidade Federal do Rio Janeiro (UFRJ), Rio Janeiro, RJ (Brazil). Departamento de Desenho Industrial

    2017-07-01

    The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

  4. Availability verification of information for human system interface in automatic SG level control using activity diagram

    Energy Technology Data Exchange (ETDEWEB)

    Nuraslinda, Anuar; Kim, Dong Young; Kim, Jong Hyun [KEPCO International Nuclear Graduate School, Uljugun (Korea, Republic of)

    2012-10-15

    Steam Generator (SG) level control system in OPR 1000 is one of representative automatic systems that falls under the Supervisory Control level in Endsley's taxonomy. Supervisory control of automated systems is classified as a form of out of the loop (OOTL) performance due to passive involvement in the systems operation, which could lead to loss of situation awareness (SA). There was a reported event, which was caused by inadequate human automation communication that contributed to an unexpected reactor trip in July 2005. A high SG level trip occurred in Yeonggwang (YGN) Unit 6 Nuclear Power Plant (NPP) due to human operator failure to recognize the need to change the control mode of the economizer valve controller (EVC) to manual mode during swap over (the transition from low power mode to high power mode) after the loss of offsite power (LOOP) event was recovered. This paper models the human system interaction in NPP SG level control system using Unified Modeling Language (UML) Activity Diagram. Then, it identifies the missing information for operators in the OPR1000 Main Control Room (MCR) and suggests some means of improving the human system interaction.

  5. Availability verification of information for human system interface in automatic SG level control using activity diagram

    International Nuclear Information System (INIS)

    Nuraslinda, Anuar; Kim, Dong Young; Kim, Jong Hyun

    2012-01-01

    Steam Generator (SG) level control system in OPR 1000 is one of representative automatic systems that falls under the Supervisory Control level in Endsley's taxonomy. Supervisory control of automated systems is classified as a form of out of the loop (OOTL) performance due to passive involvement in the systems operation, which could lead to loss of situation awareness (SA). There was a reported event, which was caused by inadequate human automation communication that contributed to an unexpected reactor trip in July 2005. A high SG level trip occurred in Yeonggwang (YGN) Unit 6 Nuclear Power Plant (NPP) due to human operator failure to recognize the need to change the control mode of the economizer valve controller (EVC) to manual mode during swap over (the transition from low power mode to high power mode) after the loss of offsite power (LOOP) event was recovered. This paper models the human system interaction in NPP SG level control system using Unified Modeling Language (UML) Activity Diagram. Then, it identifies the missing information for operators in the OPR1000 Main Control Room (MCR) and suggests some means of improving the human system interaction

  6. Human factors engineering applied to Control Centre Design of a research nuclear reactor

    International Nuclear Information System (INIS)

    Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Monteiro, Beany G.

    2017-01-01

    The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

  7. Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

    Directory of Open Access Journals (Sweden)

    AMIEN RAMADHAN ISHAK

    2014-12-01

    Full Text Available Mitochondrial gene mutation plays a role in the development of type two diabetes mellitus (T2DM. A point mutation in the mitochondrial gene Nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND1 gene mainly reported as the most common mutation related to T2DM. However, several studies have identified another SNP (single-nucleotide polymorphisms in the RNA region of mtDNA from patients from specific ethnic populations in Indonesia. Building on those findings, this study aimed to use PCR and DNA sequencing technology to identify nucleotides in RNA and ND1 fragment from 20 Gorontalonese and 20 Javanese T2DM patients, that may trigger T2DM expression. The results showed successful amplification of RNA along 294 bp for all samples. From these samples, we found two types of point mutation in Javanese patients in the G3316A and T3200C points of the rRNA and ND1 gene. In samples taken from Gorontalonese patients, no mutation were found in the RNA or ND1 region. We conclude that T2DM was triggered differently in our two populations. While genetic mutation is implicated for the 20 Javanese patients, T2DM pathogenesis in the Gorontalonese patients must be traced to other genetic, environmental, or behavioral factors.

  8. A review of human thermal comfort experiments in controlled and semi-controlled environments

    NARCIS (Netherlands)

    Craenendonck, Van Stijn; Lauriks, Leen; Vuye, Cedric; Kampen, Jarl

    2018-01-01

    There are three main methods to improve thermal comfort in existing buildings: modeling, experiments and measurements. Regarding experiments, no standardized procedure exists. This article provides an answer to the question: “What is the most common practice for human thermal comfort experiments in

  9. The effect of chronic alcohol consumption on mitochondrial DNA mutagenesis in human blood

    Energy Technology Data Exchange (ETDEWEB)

    Wurmb-Schwark, N. von [Institute of Legal Medicine, Christian Albrecht University of Kiel, Arnold-Heller-Str. 12, 24105 Kiel (Germany)], E-mail: nvonwurmb@rechtsmedizin.uni-kiel.de; Ringleb, A.; Schwark, T. [Institute of Legal Medicine, Christian Albrecht University of Kiel, Arnold-Heller-Str. 12, 24105 Kiel (Germany); Broese, T.; Weirich, S.; Schlaefke, D. [Clinic of Psychiatry and Psychotherapy, University of Rostock, Gehlsheimer Str. 20, Rostock (Germany); Wegener, R. [Institute of Legal Medicine, St-Georg-Str. 108, University of Rostock, 18055 Rostock (Germany); Oehmichen, M. [Institute of Legal Medicine, Christian Albrecht University of Kiel, Arnold-Heller-Str. 12, 24105 Kiel (Germany)

    2008-01-01

    The 4977 bp deletion of mitochondrial DNA (mtDNA) is known to accumulate with increasing age in post mitotic tissues. Recently, studies came out detecting this specific alteration also in fast replicating cells, e.g. in blood or skin tissue, often in correlation to specific diseases or - specifically in skin - external stressors such as UV radiation. In this study, we investigated mitochondrial mutagenesis in 69 patients with a chronic alcoholic disease and 46 age matched controls with a moderate drinking behavior. Two different fragments, specific for total and for deleted mtDNA (dmtDNA) were amplified in a duplex-PCR. A subsequent fragment analysis was performed and for relative quantification, the quotient of the peak areas of amplification products specific for deleted and total mtDNA was determined. Additionally, a real time PCR was performed to quantify mtDNA copy number. The relative amount of 4977 bp deleted mtDNA in alcoholics was significantly increased compared to controls. On the other hand, no difference regarding the mtDNA/nuclear DNA ratio in both investigated groups was detected. Additionally, no age dependence could be found nor in alcoholics, neither in the control group. These findings indicate that mtDNA mutagenesis in blood can be influenced by stressors such as alcohol. Ethanol seems to be a significant factor to alter mitochondrial DNA in blood and might be an additional contributor for the cellular aging process.

  10. The effect of chronic alcohol consumption on mitochondrial DNA mutagenesis in human blood

    International Nuclear Information System (INIS)

    Wurmb-Schwark, N. von; Ringleb, A.; Schwark, T.; Broese, T.; Weirich, S.; Schlaefke, D.; Wegener, R.; Oehmichen, M.

    2008-01-01

    The 4977 bp deletion of mitochondrial DNA (mtDNA) is known to accumulate with increasing age in post mitotic tissues. Recently, studies came out detecting this specific alteration also in fast replicating cells, e.g. in blood or skin tissue, often in correlation to specific diseases or - specifically in skin - external stressors such as UV radiation. In this study, we investigated mitochondrial mutagenesis in 69 patients with a chronic alcoholic disease and 46 age matched controls with a moderate drinking behavior. Two different fragments, specific for total and for deleted mtDNA (dmtDNA) were amplified in a duplex-PCR. A subsequent fragment analysis was performed and for relative quantification, the quotient of the peak areas of amplification products specific for deleted and total mtDNA was determined. Additionally, a real time PCR was performed to quantify mtDNA copy number. The relative amount of 4977 bp deleted mtDNA in alcoholics was significantly increased compared to controls. On the other hand, no difference regarding the mtDNA/nuclear DNA ratio in both investigated groups was detected. Additionally, no age dependence could be found nor in alcoholics, neither in the control group. These findings indicate that mtDNA mutagenesis in blood can be influenced by stressors such as alcohol. Ethanol seems to be a significant factor to alter mitochondrial DNA in blood and might be an additional contributor for the cellular aging process

  11. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  12. IMPROVING CONTROL ROOM DESIGN AND OPERATIONS BASED ON HUMAN FACTORS ANALYSES OR HOW MUCH HUMAN FACTORS UPGRADE IS ENOUGH ?

    Energy Technology Data Exchange (ETDEWEB)

    HIGGINS,J.C.; OHARA,J.M.; ALMEIDA,P.

    2002-09-19

    THE JOSE CABRERA NUCLEAR POWER PLANT IS A ONE LOOP WESTINGHOUSE PRESSURIZED WATER REACTOR. IN THE CONTROL ROOM, THE DISPLAYS AND CONTROLS USED BY OPERATORS FOR THE EMERGENCY OPERATING PROCEDURES ARE DISTRIBUTED ON FRONT AND BACK PANELS. THIS CONFIGURATION CONTRIBUTED TO RISK IN THE PROBABILISTIC SAFETY ASSESSMENT WHERE IMPORTANT OPERATOR ACTIONS ARE REQUIRED. THIS STUDY WAS UNDERTAKEN TO EVALUATE THE IMPACT OF THE DESIGN ON CREW PERFORMANCE AND PLANT SAFETY AND TO DEVELOP DESIGN IMPROVEMENTS.FIVE POTENTIAL EFFECTS WERE IDENTIFIED. THEN NUREG-0711 [1], PROGRAMMATIC, HUMAN FACTORS, ANALYSES WERE CONDUCTED TO SYSTEMATICALLY EVALUATE THE CR-LA YOUT TO DETERMINE IF THERE WAS EVIDENCE OF THE POTENTIAL EFFECTS. THESE ANALYSES INCLUDED OPERATING EXPERIENCE REVIEW, PSA REVIEW, TASK ANALYSES, AND WALKTHROUGH SIMULATIONS. BASED ON THE RESULTS OF THESE ANALYSES, A VARIETY OF CONTROL ROOM MODIFICATIONS WERE IDENTIFIED. FROM THE ALTERNATIVES, A SELECTION WAS MADE THAT PROVIDED A REASONABLEBALANCE BE TWEEN PERFORMANCE, RISK AND ECONOMICS, AND MODIFICATIONS WERE MADE TO THE PLANT.

  13. Human Factors Guidance for Control Room and Digital Human-System Interface Design and Modification, Guidelines for Planning, Specification, Design, Licensing, Implementation, Training, Operation and Maintenance

    Energy Technology Data Exchange (ETDEWEB)

    R. Fink, D. Hill, J. O' Hara

    2004-11-30

    Nuclear plant operators face a significant challenge designing and modifying control rooms. This report provides guidance on planning, designing, implementing and operating modernized control rooms and digital human-system interfaces.

  14. Human Factors Guidance for Control Room and Digital Human-System Interface Design and Modification. Guidelines for Planning, Specification, Design, Licensing, Implementation, Training, Operation and Maintenance

    International Nuclear Information System (INIS)

    Fink, R.; Hill, D.; O'Hara, J.

    2004-01-01

    Nuclear plant operators face a significant challenge designing and modifying control rooms. This report provides guidance on planning, designing, implementing and operating modernized control rooms and digital human-system interfaces

  15. Trends in control and decision-making for human-robot collaboration systems

    CERN Document Server

    Zhang, Fumin

    2017-01-01

    This book provides an overview of recent research developments in the automation and control of robotic systems that collaborate with humans. A measure of human collaboration being necessary for the optimal operation of any robotic system, the contributors exploit a broad selection of such systems to demonstrate the importance of the subject, particularly where the environment is prone to uncertainty or complexity. They show how such human strengths as high-level decision-making, flexibility, and dexterity can be combined with robotic precision, and ability to perform task repetitively or in a dangerous environment. The book focuses on quantitative methods and control design for guaranteed robot performance and balanced human experience. Its contributions develop and expand upon material presented at various international conferences. They are organized into three parts covering: one-human–one-robot collaboration; one-human–multiple-robot collaboration; and human–swarm collaboration. Individual topic ar...

  16. Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity

    DEFF Research Database (Denmark)

    van der Spoel, Evie; Jansen, Steffy W; Akintola, Abimbola A

    2016-01-01

    Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long......-living families from the Leiden Longevity Study together with 18 of their partners as controls. Circulating GH concentrations were measured every 10 min and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) every 4 h. Using deconvolution analysis, we found that 24-h.......39-0.53)] compared with controls [0.66 (0.56-0.77)], indicating tighter control of GH secretion. No significant differences were observed in circulating levels of IGF-1 and IGFBP3 between offspring and controls. In conclusion, GH secretion in human familial longevity is characterized by diminished secretion rate...

  17. Adaptive control of human action: The role of outcome representations and reward signals

    Directory of Open Access Journals (Sweden)

    Hans eMarien

    2013-09-01

    Full Text Available The present paper aims to advance the understanding of the control of human behavior by integrating two lines of literature that so far have led separate lives. First, one line of literature is concerned with the ideomotor principle of human behavior, according to which actions are represented in terms of their outcomes. The second line of literature mainly considers the role of reward signals in adaptive control. Here, we offer a combined perspective on how outcome representations and reward signals work together to modulate adaptive control processes. We propose that reward signals signify the value of outcome representations and facilitate the recruitment of control resources in situations where behavior needs to be maintained or adapted to attain the represented outcome. We discuss recent research demonstrating how adaptive control of goal-directed behavior may emerge when outcome representations are co-activated with positive reward signals.

  18. Template model inspired leg force feedback based control can assist human walking.

    Science.gov (United States)

    Zhao, Guoping; Sharbafi, Maziar; Vlutters, Mark; van Asseldonk, Edwin; Seyfarth, Andre

    2017-07-01

    We present a novel control approach for assistive lower-extremity exoskeletons. In particular, we implement a virtual pivot point (VPP) template model inspired leg force feedback based controller on a lower-extremity powered exoskeleton (LOPES II) and demonstrate that it can effectively assist humans during walking. It has been shown that the VPP template model is capable of stabilizing the trunk and reproduce a human-like hip torque during the stance phase of walking. With leg force and joint angle feedback inspired by the VPP template model, our controller provides hip and knee torque assistance during the stance phase. A pilot experiment was conducted with four healthy subjects. Joint kinematics, leg muscle electromyography (EMG), and metabolic cost were measured during walking with and without assistance. Results show that, for 0.6 m/s walking, our controller can reduce leg muscle activations, especially for the medial gastrocnemius (about 16.0%), while hip and knee joint kinematics remain similar to the condition without the controller. Besides, the controller also reduces 10% of the net metabolic cost during walking. This paper demonstrates walking assistance benefits of the VPP template model for the first time. The support of human walking is achieved by a force feedback of leg force applied to the control of hip and knee joints. It can help us to provide a framework for investigating walking assistance control in the future.

  19. Intelligent systems approach for automated identification of individual control behavior of a human operator

    Science.gov (United States)

    Zaychik, Kirill B.

    Acceptable results have been obtained using conventional techniques to model the generic human operator's control behavior. However, little research has been done in an attempt to identify an individual based on his/her control behavior. The main hypothesis investigated in this dissertation is that different operators exhibit different control behavior when performing a given control task. Furthermore, inter-person differences are manifested in the amplitude and frequency content of the non-linear component of the control behavior. Two enhancements to the existing models of the human operator, which allow personalization of the modeled control behavior, are presented in this dissertation. One of the proposed enhancements accounts for the "testing" control signals, which are introduced by an operator for more accurate control of the system and/or to adjust his/her control strategy. Such enhancement uses the Artificial Neural Network (ANN), which can be fine-tuned to model the "testing" control behavior of a given individual. The other model enhancement took the form of an equiripple filter (EF), which conditions the power spectrum of the control signal before it is passed through the plant dynamics block. The filter design technique uses Parks-McClellan algorithm, which allows parameterization of the desired levels of power at certain frequencies. A novel automated parameter identification technique (APID) was developed to facilitate the identification process of the parameters of the selected models of the human operator. APID utilizes a Genetic Algorithm (GA) based optimization engine called the Bit-climbing Algorithm (BCA). Proposed model enhancements were validated using the experimental data obtained at three different sources: the Manual Control Laboratory software experiments, Unmanned Aerial Vehicle simulation, and NASA Langley Research Center Visual Motion Simulator studies. Validation analysis involves comparison of the actual and simulated control

  20. Application of human engineering to design of central control room and evaluation

    International Nuclear Information System (INIS)

    Tani, Mamoru

    1986-01-01

    The central control room of a nuclear power station is the center of the operation control, monitoring and management of the plant, therefore, the design by the application of human engineering has been performed on the basis of the experience and achievement in thermal power stations and other industries. In this report, the application of human engineering to the development of the new control boards for PWRs and the evaluation are described. In a nuclear power station, the number of the machinery and equipment composing it is large, and the interrelation among them is complex, accordingly, in the information processing system for operation monitoring and control, the man-machine interface works with high density. The concept of multiple protection design requires to show numerous plant parameters on a central control board, and this also complicates the man-machine interface. The introduction of human engineering was seriously studied after the TMI accident. In order to increase the safety and reliability of a plant, the new central control and monitoring system aims at facilitating operation and monitoring, and lightening burden and preventing mistakes in handling and judgement. The operational sequence diagram and mock-up varification, the application of human engineering and the evaluation, the synthetic real-time verification at the time of abnormality and accident, and the evaluation of the reliability improvement of men are reported. (Kako, I.)

  1. Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language

    Science.gov (United States)

    2016-09-06

    conversational agent with information exchange disabled until the end of the experiment run. The meaning of the indicator in the top- right of the agent... Human Computer Collaboration at the Edge: Enhancing Collective Situation Understanding with Controlled Natural Language Alun Preece∗, William...email: PreeceAD@cardiff.ac.uk †Emerging Technology Services, IBM United Kingdom Ltd, Hursley Park, Winchester, UK ‡US Army Research Laboratory, Human

  2. Application of fuzzy synthetic assessment to assess human factors design level on reactor control panel

    International Nuclear Information System (INIS)

    Peng Xuecheng

    1999-01-01

    Reactor control panel design level on human factors must be considered by designer. The author evaluated the human factor design level of arrangement and combinations including the switch buttons, meter dials and indication lamps on Minjiang Reactor and High-Flux Engineer Test Reactor (HFETR) critical device by application of fuzzy synthetic assessment method in mathematics. From the assessment results, the advantages and shortcomings are fount, and some modification suggestions have also been proposed

  3. An Overview of the Application of Human Factors Guidance to Control Room Design

    International Nuclear Information System (INIS)

    Yondola, Paul R.; Karlewicz, George T.

    2002-01-01

    A new power plant design has the goal of making major improvements in cost and ease of operation over previous designs. Improvements in the way information is organized and presented to control room operators based on established Human Factors Engineering (HFE) criteria is key to achieving these goals. An overview of the process and methods being employed in an ongoing design effort will be discussed, including the ways in which current Human Factors guidance is being applied in a unique operating environment

  4. Novel 12S mtDNA findings in sloths (Pilosa, Folivora) and anteaters (Pilosa, Vermilingua) suggest a true case of long branch attraction

    OpenAIRE

    Barros, Maria Claudene; Sampaio, Iracilda; Schneider, Horacio

    2008-01-01

    We sequenced 12S RNA mtDNA for the majority of the extant species of sloths and anteaters and compared our results with previous data obtained by our group using 16S RNA mtDNA in the same specimens and to GenBank sequences of the extinct giant sloth Mylodon. Our results suggest that pigmy-anteaters may be a case of the long-branch attraction phenomenon and also show the large genetic difference between the Amazonian and Atlantic forest three-toed sloths, contrasting with the small differences...

  5. Human factors review of nuclear power plant control room design. Summary report

    International Nuclear Information System (INIS)

    Seminara, J.L.; Gonzalez, W.R.; Parsons, S.O.

    1976-11-01

    Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. The human factors aspects of five representative nuclear power plant control rooms were evaluated using such methods as a checklist-guided observation system, structured interviews with operators and trainers, direct observations of operator behavior, task analyses and procedure evaluation, and historical error analyses. The human factors aspects of design practices are illustrated, and many improvements in current practices are suggested. The study recommends that a detailed set of applicable human factors standards be developed to stimulate a uniform and systematic concern for human factors in design considerations

  6. Human-Robot Control Strategies for the NASA/DARPA Robonaut

    Science.gov (United States)

    Diftler, M. A.; Culbert, Chris J.; Ambrose, Robert O.; Huber, E.; Bluethmann, W. J.

    2003-01-01

    The Robotic Systems Technology Branch at the NASA Johnson Space Center (JSC) is currently developing robot systems to reduce the Extra-Vehicular Activity (EVA) and planetary exploration burden on astronauts. One such system, Robonaut, is capable of interfacing with external Space Station systems that currently have only human interfaces. Robonaut is human scale, anthropomorphic, and designed to approach the dexterity of a space-suited astronaut. Robonaut can perform numerous human rated tasks, including actuating tether hooks, manipulating flexible materials, soldering wires, grasping handrails to move along space station mockups, and mating connectors. More recently, developments in autonomous control and perception for Robonaut have enabled dexterous, real-time man-machine interaction. Robonaut is now capable of acting as a practical autonomous assistant to the human, providing and accepting tools by reacting to body language. A versatile, vision-based algorithm for matching range silhouettes is used for monitoring human activity as well as estimating tool pose.

  7. Herpes viruses and human papilloma virus in nasal polyposis and controls

    Directory of Open Access Journals (Sweden)

    Dimitrios Ioannidis

    2015-12-01

    Full Text Available ABSTRACT INTRODUCTION: Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. OBJECTIVE: To compare the prevalence of human herpes viruses (1-6 and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. METHODS: Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. RESULTS: Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4% versus controls (4/38; 10.5%, but the difference did not reach significance (p = 0.06. Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29% versus controls (10/38; 26.32%,p = 0.13. In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%, and another was cytomegalovirus-positive (1/91; 1.1%, versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and low-risk-human papilloma viruses (6, 11. CONCLUSION: Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis.

  8. Herpes viruses and human papilloma virus in nasal polyposis and controls.

    Science.gov (United States)

    Ioannidis, Dimitrios; Lachanas, Vasileios A; Florou, Zoe; Bizakis, John G; Petinaki, Efthymia; Skoulakis, Charalampos E

    2015-01-01

    Chronic rhinosinusitis with nasal polyps is a multifactorial disease entity with an unclear pathogenesis. Contradictory data exist in the literature on the potential implication of viral elements in adult patients with chronic rhinosinusitis. To compare the prevalence of human herpes viruses (1-6) and Human Papilloma Virus in adult patients with chronic rhinosinusitis with nasal polyps and healthy controls. Viral DNA presence was evaluated by real-time polymerase chain reaction application to nasal polyps specimens from 91 chronic rhinosinusitis with nasal polyps patients and nasal turbinate mucosa from 38 healthy controls. Epstein-Barr virus positivity was higher in nasal polyps (24/91; 26.4%) versus controls (4/38; 10.5%), but the difference did not reach significance (p=0.06). Human herpes virus-6 positivity was lower in nasal polyps (13/91; 14.29%) versus controls (10/38; 26.32%, p=0.13). In chronic rhinosinusitis with nasal polyps group, 1 sample was herpes simplex virus-1-positive (1/91; 1.1%), and another was cytomegalovirus-positive (1/91; 1.1%), versus none in controls. No sample was positive for herpes simplex virus-2, varicella-zoster virus, high-risk-human papilloma viruses (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59) and low-risk-human papilloma viruses (6, 11). Differences in Epstein-Barr virus and human herpes virus-6 positivity among patients with chronic rhinosinusitis with nasal polyps and healthy controls are not statistically significant, weakening the likelihood of their implication in chronic rhinosinusitis with nasal polyps pathogenesis. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  9. The effects of human relations training on reported teacher stress, pupil control ideology and locus of control.

    Science.gov (United States)

    Hall, E; Hall, C; Abaci, R

    1997-12-01

    This study presents the reported outcomes of a two-year, part-time Masters' programme in human relations using an experiential learning methodology based mainly on humanistic psychological theory. The following hypotheses were examined. That as a result of the two-year programme: the experience of reported stress would be reduced; reported attitudes to student classroom control would shift from custodial to humanistic; there would be an increase in reports from participants of a sense of control over their lives; changes of behaviour in work, social settings and at home related to these three variables would be reported. Involved in the study were 42 experienced teachers. These included 32 women and 10 men, with an average age of 35, who worked in a wide range of educational institutions. Their learning style preferences were also considered as independent variables. A control group of 42 was established with similar demographic characteristics. Prior to the course, the experimental group and the control group were given the Maslach Burnout Inventory and the Pupil Control Ideology Form. In the early stages of the course, the experimental group completed the Kolb Learning Style Inventory and an informal measure of locus of control which was repeated at the end of the first year of the course. A sample of 32 from the experimental group were given semi-structured interviews relating to changes in their professional and personal lives. The results indicated that, following the training, there was a reduction in reported stress, indications of a more humanistic orientation towards pupil control and an increase in a sense of an internal locus of control. The quantitative data were confirmed by qualitative data generated from semi-structured interviews, which involved substantial reports of applications of the training in their professional and personal lives. These results provide support for including experiential human relations training as part of both the in

  10. Human chorionic gonadotropin, angiogenic factors, and preeclampsia risk: a nested case-control study.

    Science.gov (United States)

    Asvold, Bjørn O; Eskild, Anne; Vatten, Lars J

    2014-05-01

    To study whether human chorionic gonadotropin concentrations during pregnancy or combinations of human chorionic gonadotropin and other angiogenic factors, soluble fms-like tyrosine kinase 1 and placental growth factor (PlGF), are associated with preeclampsia risk. Nested case-control study. Population cohort of pregnant women. A total of 121 cases of preterm (cases of term preeclampsia (≥37 weeks of gestation) and 356 women without preeclampsia (controls). Women with preeclampsia were identified by linkage to the Medical Birth Registry of Norway. Concentrations of human chorionic gonadotropin, soluble fms-like tyrosine kinase 1 and PlGF were measured in maternal serum samples collected in each trimester of pregnancy. Odds ratios of preterm and term preeclampsia. High human chorionic gonadotropin concentrations (highest quartile) in the first trimester were associated with reduced risk for preterm preeclampsia (OR 0.3, 95% CI 0.1-0.9), compared with low human chorionic gonadotropin (lowest quartile), whereas high human chorionic gonadotropin concentrations in the second trimester were associated with increased risk for preterm preeclampsia (OR 4.0, 95% CI 1.8-8.9). High human chorionic gonadotropin concentrations in the third trimester were associated with increased risk for term preeclampsia (OR 4.8, 95% CI 1.8-13.3). Concentrations of human chorionic gonadotropin above the median value combined with PlGF below the median in the second trimester were associated with very high risk for preterm preeclampsia (OR 36.9, 95% CI 8.2-165.8). The results suggest an important role of human chorionic gonadotropin in the pathophysiological processes that lead to preeclampsia. The combined association of human chorionic gonadotropin and PlGF indicates a possible synergism between underlying biological pathways. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  11. Control objectives design for the human and resources module of SAP

    OpenAIRE

    Collado Antón, Jesús

    2010-01-01

    Català: En aquest projecte trobem la definició d'objectius de control i d'activitats de control per al módul de recursos humans de SAP, donant especial importància a l'adecuada segregació de funcions dins el módul. Castellano: En este proyecto de encuentra la definición de objetivos de control i actividades de control para el módulo de recursos humanos de SAP, dando especial importancia a la adecuada segregación de funciones dentro de éste módulo. English: In this project we can find th...

  12. Safety review for human factors engineering and control rooms of nuclear power plants

    International Nuclear Information System (INIS)

    Yang Mengzhuo

    1998-01-01

    Safety review for human factors engineering and control rooms of nuclear power plants (NPP) is in a forward position of science and technology, which began at American TMI severe accident and had been implemented in China. The importance and the significance of the safety review are expounded, the requirements of its scope and profundity are explained in detail. In addition, the situation of the technical document system for nuclear safety regulation on human factors engineering and control rooms of NPP in China is introduced briefly, on which the safety review is based

  13. An overview of neural function and feedback control in human communication.

    Science.gov (United States)

    Hood, L J

    1998-01-01

    The speech and hearing mechanisms depend on accurate sensory information and intact feedback mechanisms to facilitate communication. This article provides a brief overview of some components of the nervous system important for human communication and some electrophysiological methods used to measure cortical function in humans. An overview of automatic control and feedback mechanisms in general and as they pertain to the speech motor system and control of the hearing periphery is also presented, along with a discussion of how the speech and auditory systems interact.

  14. Modulation of Mitochondrial DNA Copy Number to Induce Hepatocytic Differentiation of Human Amniotic Epithelial Cells.

    Science.gov (United States)

    Vaghjiani, Vijesh; Cain, Jason E; Lee, William; Vaithilingam, Vijayaganapathy; Tuch, Bernard E; St John, Justin C

    2017-10-15

    Mitochondrial deoxyribonucleic acid (mtDNA) copy number is tightly regulated during pluripotency and differentiation. There is increased demand of cellular adenosine triphosphate (ATP) during differentiation for energy-intensive cell types such as hepatocytes and neurons to meet the cell's functional requirements. During hepatocyte differentiation, mtDNA copy number should be synchronously increased to generate sufficient ATP through oxidative phosphorylation. Unlike bone marrow mesenchymal cells, mtDNA copy number failed to increase by 28 days of differentiation of human amniotic epithelial cells (hAEC) into hepatocyte-like cells (HLC) despite their expression of some end-stage hepatic markers. This was due to higher levels of DNA methylation at exon 2 of POLGA, the mtDNA-specific replication factor. Treatment with a DNA demethylation agent, 5-azacytidine, resulted in increased mtDNA copy number, reduced DNA methylation at exon 2 of POLGA, and reduced hepatic gene expression. Depletion of mtDNA followed by subsequent differentiation did not increase mtDNA copy number, but reduced DNA methylation at exon 2 of POLGA and increased expression of hepatic and pluripotency genes. We encapsulated hAEC in barium alginate microcapsules and subsequently differentiated them into HLC. Encapsulation resulted in no net increase of mtDNA copy number but a significant reduction in DNA methylation of POLGA. RNAseq analysis showed that differentiated HLC express hepatocyte-specific genes but also increased expression of inflammatory interferon genes. Differentiation in encapsulated cells showed suppression of inflammatory genes as well as increased expression of genes associated with hepatocyte function pathways and networks. This study demonstrates that an increase in classical hepatic gene expression can be achieved in HLC through encapsulation, although they fail to effectively regulate mtDNA copy number.

  15. Self-organized critical noise amplification in human closed loop control

    Directory of Open Access Journals (Sweden)

    Felix Patzelt

    2007-11-01

    Full Text Available When humans perform closed loop control tasks like in upright standing or while balancing a stick, their behavior exhibits non-Gaussian fluctuations with long-tailed distributions. The origin of these fluctuations is not known. Here, we investigate if they are caused by selforganized critical noise amplification which emerges in control systems when an unstable dynamics becomes stabilized by an adaptive controller that has finite memory. Starting from this theory, we formulate a realistic model of adaptive closed loop control by including constraints on memory and delays. To test this model, we performed psychophysical experiments where humans balanced an unstable target on a screen. It turned out that the model reproduces the long tails of the distributions together with other characteristic features of the human control dynamics. Fine-tuning the model to match the experimental dynamics identifies parameters characterizing a subject’s control system which can be independently tested. Our results suggest that the nervous system involved in closed loop motor control nearly optimally estimates system parameters on-line from very short epochs of past observations.

  16. Methodology for allocating nuclear power plant control functions to human or automatic control

    International Nuclear Information System (INIS)

    Pulliam, R.; Price, H.E.; Bongarra, J.; Sawyer, C.R.; Kisner, R.A.

    1983-08-01

    This report describes a general method for allocating control functions to man or machine during nuclear power plant (NPP) design, or for evaluating their allocation in an existing design. The research examined some important characeristics of the systems design process, and the results make it clear that allocation of control functions is an intractable problem, one which increases complexity of systems. The method is reported in terms of specific steps which should be taken during early stages of a new system design, and which will lead to an optimal allocation at the functional design level of detail

  17. Balancing the roles of humans and machines in power plant control

    International Nuclear Information System (INIS)

    Lipsett, J.J.

    1989-05-01

    A number of factors are leading to a re-examination of the balance between the roles of the operators and the machine in controlling nuclear power plants. Some of these factors are: the advent of new and advanced computer technologies; increased plant complexity, placing heavy workloads and stress on the control room operator; and increasing concerns about the role of human reliability in industrial mishaps. In light of the changing control aspects, we examine the meaning of automation, we discuss a proposed model of the control process, the concept of control within a few defined reactor states, a decision-making sequence; and we identify some possible problem areas in implementing new control technologies. Significant benefits should come from the new control methods and these opportunities should be exploited as soon as prudence allows, taking great care that the safety of the plants is improved

  18. Human Rights and Drug Control : Access to Controlled Essential Medicines in Resource-Constrained Countries

    NARCIS (Netherlands)

    Gispen, M.E.C.

    2017-01-01

    Millions of people worldwide suffer a range of health and socio-economic related problems because of inadequate availability and use of controlled essential medicines like morphine and codeine for pain treatment. As a result, millions of people, often living in lesser-advanced conditions, suffer in

  19. Genetic diversity and phylogeography of highly zoonotic Echinococcus granulosus genotype G1 in the Americas (Argentina, Brazil, Chile and Mexico) based on 8279bp of mtDNA.

    Science.gov (United States)

    Laurimäe, Teivi; Kinkar, Liina; Andresiuk, Vanessa; Haag, Karen Luisa; Ponce-Gordo, Francisco; Acosta-Jamett, Gerardo; Garate, Teresa; Gonzàlez, Luis Miguel; Saarma, Urmas

    2016-11-01

    Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian patients with non-syndromic hearing loss

    International Nuclear Information System (INIS)

    Mkaouar-Rebai, Emna; Tlili, Abdelaziz; Masmoudi, Saber; Charfeddine, Ilhem; Fakhfakh, Faiza

    2008-01-01

    The 12S rRNA gene was shown to be a hot spot for aminoglycoside-induced and non-syndromic hearing loss since several deafness-associated mtDNA mutations were identified in this gene. Among them, we distinguished the A1555G, the C1494T and the T1095C mutations and C-insertion or deletion at position 961. One hundred Tunisian patients with non-syndromic hearing loss and 100 hearing individuals were analysed in this study. A PCR-RFLP analysis with HaeIII restriction enzyme showed the presence of the A1555G mutation in the 12S rRNA gene in only one out of the 100 patients. In addition, PCR-RFLP and radioactive PCR revealed the presence of a new HaeIII polymorphic restriction site in the same gene of 12S rRNA site in 4 patients with non-syndromic hearing loss. UVIDOC-008-XD analyses showed the presence of this new polymorphic restriction site with a variable heteroplasmic rates at position +1517 of the human mitochondrial genome. On the other hand, direct sequencing of the entire mitochondrial 12S rRNA gene in the 100 patients and in 100 hearing individuals revealed the presence of the A750G and A1438G polymorphisms and the absence of the C1494T, T1095C and 961insC mutations in all the tested individuals. Sequencing of the whole mitochondrial genome in the 4 patients showing the new HaeIII polymorphic restriction site revealed only the presence of the A8860G transition in the MT-ATP6 gene and the A4769G polymorphism in the ND2 gene

  1. The 3D Human Motion Control Through Refined Video Gesture Annotation

    Science.gov (United States)

    Jin, Yohan; Suk, Myunghoon; Prabhakaran, B.

    In the beginning of computer and video game industry, simple game controllers consisting of buttons and joysticks were employed, but recently game consoles are replacing joystick buttons with novel interfaces such as the remote controllers with motion sensing technology on the Nintendo Wii [1] Especially video-based human computer interaction (HCI) technique has been applied to games, and the representative game is 'Eyetoy' on the Sony PlayStation 2. Video-based HCI technique has great benefit to release players from the intractable game controller. Moreover, in order to communicate between humans and computers, video-based HCI is very crucial since it is intuitive, easy to get, and inexpensive. On the one hand, extracting semantic low-level features from video human motion data is still a major challenge. The level of accuracy is really dependent on each subject's characteristic and environmental noises. Of late, people have been using 3D motion-capture data for visualizing real human motions in 3D space (e.g, 'Tiger Woods' in EA Sports, 'Angelina Jolie' in Bear-Wolf movie) and analyzing motions for specific performance (e.g, 'golf swing' and 'walking'). 3D motion-capture system ('VICON') generates a matrix for each motion clip. Here, a column is corresponding to a human's sub-body part and row represents time frames of data capture. Thus, we can extract sub-body part's motion only by selecting specific columns. Different from low-level feature values of video human motion, 3D human motion-capture data matrix are not pixel values, but is closer to human level of semantics.

  2. Controllability modulates the anticipatory response in the human ventromedial prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Deborah Lucille Kerr

    2012-12-01

    Full Text Available Research has consistently shown that control is critical to psychological functioning, with perceived lack of control considered to play a crucial role in the manifestation of symptoms in psychiatric disorders. In a model of behavioral control based on nonhuman animal work, Maier and colleagues posited that the presence of control activates areas of the ventromedial prefrontal cortex (vmPFC, which in turn inhibit the normative stress response in the dorsal raphe nucleus and amygdala. To test Maier’s model in humans, we investigated the effects of control over potent aversive stimuli by presenting video clips of snakes to 21 snake phobics who were otherwise healthy with no comorbid psychopathologies. Based on prior research documenting that disrupted neural processing during the anticipation of adverse events can be influenced by different forms of cognitive processing such as perceptions of control, analyses focused on the anticipatory activity preceding the videos. We found that phobics exhibited greater vmPFC activity during the anticipation of snake videos when they had control over whether the videos were presented as compared to when they had no control over the presentation of the videos. In addition, observed functional connectivity between the vmPFC and the amygdala is consistent with previous work documenting vmPFC inhibition of the amygdala. Our results provide evidence to support the extension of Maier’s model of behavioral control to include anticipatory function in humans.

  3. Human factors engineering evaluation of the Advanced Test Reactor Control Room

    International Nuclear Information System (INIS)

    Boone, M.P.; Banks, W.W.

    1980-12-01

    The information presented here represents preliminary findings related to an ongoing human engineering evaluation of the Advanced Test Reactor (ATR) Control Room. Although many of the problems examined in this report have been previously noted by ATR operations personnel, the systematic approach used in this investigation produced many new insights. While many violations of Human Engineering military standards (MIL-STD) are noted, and numerous recommendations made, the recommendations should be examined cautiously. The reason for our suggested caution lies in the fact that many ATR operators have well over 10-years experience in operating the controls, meters, etc. Hence, it is assumed adaptation to the existing system is quite developed and the introduction of hardware/control changes, even though the changes enhance the system, may cause short-term (or long-term, depending upon the amount of operator experience and training) adjustment problems for operators adapting to the new controls/meters and physical layout

  4. The Effects of Control of Resources on Magnitudes of Sex Differences in Human Mate Preferences

    Directory of Open Access Journals (Sweden)

    Fhionna Moore

    2010-10-01

    Full Text Available We tested the hypothesis that magnitudes of sex differences in human mate preferences would be inversely related to control of resources. Specifically, we predicted that the ideal partner age, maximum and minimum partner ages tolerated and preferences for “physical attractiveness” over “good financial prospects” of female participants would approach parity with that of men with increasing control of resources. In a sample of 3770 participants recruited via an online survey, the magnitudes of sex differences in age preferences increased with resource control whereas the sex difference in preferences for “physical attractiveness” over “good financial prospects” disappeared when resource control was high. Results are inconsistent, and are discussed in the context of adaptive tradeoff and biosocial models of sex differences in human mate preferences.

  5. Mitochondrial DNA maintenance is regulated in human hepatoma cells by glycogen synthase kinase 3β and p53 in response to tumor necrosis factor α.

    Science.gov (United States)

    Vadrot, Nathalie; Ghanem, Sarita; Braut, Françoise; Gavrilescu, Laura; Pilard, Nathalie; Mansouri, Abdellah; Moreau, Richard; Reyl-Desmars, Florence

    2012-01-01

    During chronic liver inflammation, up-regulated Tumor Necrosis Factor alpha (TNF-α) targets hepatocytes and induces abnormal reactive oxygen species (ROS) production responsible for mitochondrial DNA (mtDNA) alterations. The serine/threonine Glycogen Synthase Kinase 3 beta (GSK3β) plays a pivotal role during inflammation but its involvement in the maintenance of mtDNA remains unknown. The aim of this study was to investigate its involvement in TNF-α induced mtDNA depletion and its interrelationship with p53 a protein known to maintain mtDNA copy numbers. Using quantitative polymerase chain reaction (qPCR) we found that at 30 min in human hepatoma HepG2 cells TNF-α induced 0.55±0.10 mtDNA lesions per 10 Kb and a 52.4±2.8% decrease in mtDNA content dependent on TNF-R1 receptor and ROS production. Both lesions and depletion returned to baseline from 1 to 6 h after TNF-α exposure. Luminol-amplified chemiluminescence (LAC) was used to measure the rapid (10 min) and transient TNF-α induced increase in ROS production (168±15%). A transient 8-oxo-dG level of 1.4±0.3 ng/mg DNA and repair of abasic sites were also measured by ELISA assays. Translocation of p53 to mitochondria was observed by Western Blot and co-immunoprecipitations showed that TNF-α induced p53 binding to GSK3β and mitochondrial transcription factor A (TFAM). In addition, mitochondrial D-loop immunoprecipitation (mtDIP) revealed that TNF-α induced p53 binding to the regulatory D-loop region of mtDNA. The knockdown of p53 by siRNAs, inhibition by the phosphoSer(15)p53 antibody or transfection of human mutant active GSK3βS9A pcDNA3 plasmid inhibited recovery of mtDNA content while blockade of GSK3β activity by SB216763 inhibitor or knockdown by siRNAs suppressed mtDNA depletion. This study is the first to report the involvement of GSK3β in TNF-α induced mtDNA depletion. We suggest that p53 binding to GSK3β, TFAM and D-loop could induce recovery of mtDNA content through mtDNA repair.

  6. Mitochondrial DNA maintenance is regulated in human hepatoma cells by glycogen synthase kinase 3β and p53 in response to tumor necrosis factor α.

    Directory of Open Access Journals (Sweden)

    Nathalie Vadrot

    Full Text Available During chronic liver inflammation, up-regulated Tumor Necrosis Factor alpha (TNF-α targets hepatocytes and induces abnormal reactive oxygen species (ROS production responsible for mitochondrial DNA (mtDNA alterations. The serine/threonine Glycogen Synthase Kinase 3 beta (GSK3β plays a pivotal role during inflammation but its involvement in the maintenance of mtDNA remains unknown. The aim of this study was to investigate its involvement in TNF-α induced mtDNA depletion and its interrelationship with p53 a protein known to maintain mtDNA copy numbers. Using quantitative polymerase chain reaction (qPCR we found that at 30 min in human hepatoma HepG2 cells TNF-α induced 0.55±0.10 mtDNA lesions per 10 Kb and a 52.4±2.8% decrease in mtDNA content dependent on TNF-R1 receptor and ROS production. Both lesions and depletion returned to baseline from 1 to 6 h after TNF-α exposure. Luminol-amplified chemiluminescence (LAC was used to measure the rapid (10 min and transient TNF-α induced increase in ROS production (168±15%. A transient 8-oxo-dG level of 1.4±0.3 ng/mg DNA and repair of abasic sites were also measured by ELISA assays. Translocation of p53 to mitochondria was observed by Western Blot and co-immunoprecipitations showed that TNF-α induced p53 binding to GSK3β and mitochondrial transcription factor A (TFAM. In addition, mitochondrial D-loop immunoprecipitation (mtDIP revealed that TNF-α induced p53 binding to the regulatory D-loop region of mtDNA. The knockdown of p53 by siRNAs, inhibition by the phosphoSer(15p53 antibody or transfection of human mutant active GSK3βS9A pcDNA3 plasmid inhibited recovery of mtDNA content while blockade of GSK3β activity by SB216763 inhibitor or knockdown by siRNAs suppressed mtDNA depletion. This study is the first to report the involvement of GSK3β in TNF-α induced mtDNA depletion. We suggest that p53 binding to GSK3β, TFAM and D-loop could induce recovery of mtDNA content through mtDNA repair.

  7. Formal Process Modeling to Improve Human Decision-Making in Test and Evaluation Acoustic Range Control

    Science.gov (United States)

    2017-09-01

    MODELING TO IMPROVE HUMAN DECISION-MAKING DURING TEST AND EVALUATION RANGE CONTROL by William Carlson September 2017 Thesis Advisor...the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington, DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT...MAKING DURING TEST AND EVALUATION RANGE CONTROL 5. FUNDING NUMBERS 6. AUTHOR(S) William Carlson 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES

  8. Direct microcomputer controlled determination of zinc in human serum by flow injection atomic absorption spectrometry

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Nielsen, Bent; Jensen, Arne

    1986-01-01

    A procedure is described for the direct determination of zinc in human serum by fully automated, microcomputer controlled flow injection atomic absorption spectrometry (Fl-AAS). The Fl system is pumpless, using the negative pressure created by the nebuliser. It only consists of a three-way valve......, programmable from the microcomputer, to control the sample volume. No pre-treatment of the samples is necessary. The limit of detection is 0.14 mg l–1, and only small amounts of serum (

  9. Public health measures to control tuberculosis in low-income countries: ethics and human rights considerations.

    Science.gov (United States)

    Kraemer, J D; Cabrera, O A; Singh, J A; Depp, T B; Gostin, L O

    2011-06-01

    In low-income countries, tuberculosis (TB) control measures should be guided by ethical concerns and human rights obligations. Control programs should consider the principles of necessity, reasonableness and effectiveness of means, proportionality, distributive justice, and transparency. Certain measures-detention, infection control, and treatment to prevent transmission-raise particular concerns. While isolation is appropriate under certain circumstances, quarantine is never an acceptable control measure for TB, and any detention must be limited by necessity and conducted humanely. States have a duty to implement hospital infection control to the extent of their available resources and to provide treatment to health care workers (HCWs) infected on the job. HCWs, in turn, have an obligation to provide care unless conditions are unreasonably and unforeseeably unsafe. Finally, states have an obligation to provide adequate access to treatment, as a means of preventing transmission, as broadly as possible and in a non-discriminatory fashion. Along with treatment, states should provide support to increase treatment adherence and retention with respect for patient privacy and autonomy. Compulsory treatment is almost never acceptable. Governments should take care to respect human rights and ethical obligations as they execute TB control programs.

  10. Complexity and dynamics of switched human balance control during quiet standing.

    Science.gov (United States)

    Nema, Salam; Kowalczyk, Piotr; Loram, Ian

    2015-10-01

    In this paper, we use a combination of numerical simulations, time series analysis, and complexity measures to investigate the dynamics of switched systems with noise, which are often used as models of human balance control during quiet standing. We link the results with complexity measures found in experimental data of human sway motion during quiet standing. The control model ensuring balance, which we use, is based on an act-and-wait control concept, that is, a human controller is switched on when a certain sway angle is reached. Otherwise, there is no active control present. Given a time series data, we determine how does it look a typical pattern of control strategy in our model system. We detect the switched nonlinearity in the system using a frequency analysis method in the absence of noise. We also analyse the effect of time delay on the existence of limit cycles in the system in the absence of noise. We perform the entropy and detrended fluctuation analyses in view of linking the switchings (and the dead zone) with the occurrences of complexity in the model system in the presence of noise. Finally, we perform the entropy and detrended fluctuation analyses on experimental data and link the results with numerical findings in our model example.

  11. Dual Extended Kalman Filter for the Identification of Time-Varying Human Manual Control Behavior

    Science.gov (United States)

    Popovici, Alexandru; Zaal, Peter M. T.; Pool, Daan M.

    2017-01-01

    A Dual Extended Kalman Filter was implemented for the identification of time-varying human manual control behavior. Two filters that run concurrently were used, a state filter that estimates the equalization dynamics, and a parameter filter that estimates the neuromuscular parameters and time delay. Time-varying parameters were modeled as a random walk. The filter successfully estimated time-varying human control behavior in both simulated and experimental data. Simple guidelines are proposed for the tuning of the process and measurement covariance matrices and the initial parameter estimates. The tuning was performed on simulation data, and when applied on experimental data, only an increase in measurement process noise power was required in order for the filter to converge and estimate all parameters. A sensitivity analysis to initial parameter estimates showed that the filter is more sensitive to poor initial choices of neuromuscular parameters than equalization parameters, and bad choices for initial parameters can result in divergence, slow convergence, or parameter estimates that do not have a real physical interpretation. The promising results when applied to experimental data, together with its simple tuning and low dimension of the state-space, make the use of the Dual Extended Kalman Filter a viable option for identifying time-varying human control parameters in manual tracking tasks, which could be used in real-time human state monitoring and adaptive human-vehicle haptic interfaces.

  12. Compliance control based on PSO algorithm to improve the feeling during physical human-robot interaction.

    Science.gov (United States)

    Jiang, Zhongliang; Sun, Yu; Gao, Peng; Hu, Ying; Zhang, Jianwei

    2016-01-01

    Robots play more important roles in daily life and bring us a lot of convenience. But when people work with robots, there remain some significant differences in human-human interactions and human-robot interaction. It is our goal to make robots look even more human-like. We design a controller which can sense the force acting on any point of a robot and ensure the robot can move according to the force. First, a spring-mass-dashpot system was used to describe the physical model, and the second-order system is the kernel of the controller. Then, we can establish the state space equations of the system. In addition, the particle swarm optimization algorithm had been used to obtain the system parameters. In order to test the stability of system, the root-locus diagram had been shown in the paper. Ultimately, some experiments had been carried out on the robotic spinal surgery system, which is developed by our team, and the result shows that the new controller performs better during human-robot interaction.

  13. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    Science.gov (United States)

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  14. Basic human error probabilities in advanced MCRs when using soft control

    International Nuclear Information System (INIS)

    Jang, In Seok; Seong, Poong Hyun; Kang, Hyun Gook; Lee, Seung Jun

    2012-01-01

    In a report on one of the renowned HRA methods, Technique for Human Error Rate Prediction (THERP), it is pointed out that 'The paucity of actual data on human performance continues to be a major problem for estimating HEPs and performance times in nuclear power plant (NPP) task'. However, another critical difficulty is that most current HRA databases deal with operation in conventional type of MCRs. With the adoption of new human system interfaces that are based on computer based technologies, the operation environment of MCRs in NPPs has changed. The MCRs including these digital and computer technologies, such as large display panels, computerized procedures, soft controls, and so on, are called advanced MCRs. Because of the different interfaces, different Basic Human Error Probabilities (BHEPs) should be considered in human reliability analyses (HRAs) for advanced MCRs. This study carries out an empirical analysis of human error considering soft controls. The aim of this work is not only to compile a database using the simulator for advanced MCRs but also to compare BHEPs with those of a conventional MCR database

  15. Dissociation of Survival, Proliferation, and State Control in Human Hematopoietic Stem Cells.

    Science.gov (United States)

    Knapp, David J H F; Hammond, Colin A; Miller, Paul H; Rabu, Gabrielle M; Beer, Philip A; Ricicova, Marketa; Lecault, Véronique; Da Costa, Daniel; VanInsberghe, Michael; Cheung, Alice M; Pellacani, Davide; Piret, James; Hansen, Carl; Eaves, Connie J

    2017-01-10

    The role of growth factors (GFs) in controlling the biology of human hematopoietic stem cells (HSCs) remains limited by a lack of information concerning the individual and combined effects of GFs directly on the survival, Mitogenesis, and regenerative activity of highly purified human HSCs. We show that the initial input HSC activity of such a purified starting population of human cord blood cells can be fully maintained over a 21-day period in serum-free medium containing five GFs alone. HSC survival was partially supported by any one of these GFs, but none were essential, and different combinations of GFs variably stimulated HSC proliferation. However, serial transplantability was not detectably compromised by many conditions that reduced human HSC proliferation and/or survival. These results demonstrate the dissociated control of these three human HSC bio-responses, and set the stage for future improvements in strategies to modify and expand human HSCs ex vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. GUIDANCE FOR NUCLEAR POWER PLANT CONTROL ROOM AND HUMAN-SYSTEM INTERFACE MODERNIZATION

    International Nuclear Information System (INIS)

    Naser, J.; Morris, G.

    2004-01-01

    Several nuclear power plants in the United States are starting instrumentation and control (I and C) modernization programs using digital equipment to address obsolescence issues and the need to improve plant performance while maintaining high levels of safety. As an integral part of the I and C modernization program at a nuclear power plant, the control room and other human-system interfaces (HSIs) are also being modernized. To support safe and effective operation, it is critical to plan, design, implement, train for, operate, and maintain the control room and HSI changes to take advantage of human cognitive processing abilities. A project, jointly funded by the Electric Power Research Institute (EPRI) and the United States Department of Energy (DOE) under the Nuclear Energy Plant Optimization (NEPO) Program, is developing guidance for specifying and designing control rooms, remote shut-down panels, HSIs etc. The guidance is intended for application by utilities and suppliers of control room and HSI modernization. The guidance will facilitate specification, design, implementation, operations, maintenance, training, and licensing activities. This guidance will be used to reduce the likelihood of human errors and licensing risk, to gain maximum benefit of implemented technology, and to increase performance. The guidance is of five types. The first is planning guidance to help a utility develop its plant-specific control room operating concepts, its plant-specific endpoint vision for the control room, its migration path to achieve that endpoint vision, and its regulatory, licensing, and human factors program plans. The second is process guidance for general HSI design and integration, human factors engineering analyses, verification and validation, in-service monitoring processes, etc. The third is detailed human factors engineering guidance for control room and HSI technical areas. The fourth is guidance for licensing. The fifth is guidance for special topics

  17. Robust Control of a Cable-Driven Soft Exoskeleton Joint for Intrinsic Human-Robot Interaction.

    Science.gov (United States)

    Jarrett, C; McDaid, A J

    2017-07-01

    A novel, cable-driven soft joint is presented for use in robotic rehabilitation exoskeletons to provide intrinsic, comfortable human-robot interaction. The torque-displacement characteristics of the soft elastomeric core contained within the joint are modeled. This knowledge is used in conjunction with a dynamic system model to derive a sliding mode controller (SMC) to implement low-level torque control of the joint. The SMC controller is experimentally compared with a baseline feedback-linearised proportional-derivative controller across a range of conditions and shown to be robust to un-modeled disturbances. The torque controller is then tested with six healthy subjects while they perform a selection of activities of daily living, which has validated its range of performance. Finally, a case study with a participant with spastic cerebral palsy is presented to illustrate the potential of both the joint and controller to be used in a physiotherapy setting to assist clinical populations.

  18. [Current situation of human resources of parasitic disease control and prevention organizations in Henan Province].

    Science.gov (United States)

    Ya-Lan, Zhang; Yan-Kun, Zhu; Wei-Qi, Chen; Yan, Deng; Peng, Li

    2018-01-10

    To understand the current status of human resources of parasitic disease control and prevention organizations in Henan Province, so as to provide the reference for promoting the integrative ability of the prevention and control of parasitic diseases in Henan Province. The questionnaires were designed and the method of census was adopted. The information, such as the amounts, majors, education background, technical titles, working years, and turnover in each parasitic disease control and prevention organization was collected by the centers for disease control and prevention (CDCs) at all levels. The data were descriptively analyzed. Totally 179 CDCs were investigated, in which only 19.0% (34/179) had the independent parasitic diseases control institution (department) . There were only 258 full-time staffs working on parasitic disease control and prevention in the whole province, in which only 61.9% (159/258) were health professionals. Those with junior college degree or below in the health professionals accounted for 60.3% (96/159) . Most of them (42.1%) had over 20 years of experience, but 57.9% (92/159) of their technical post titles were at primary level or below. The proportion of the health professionals is low in the parasitic disease control and prevention organizations in Henan Province. The human resource construction for parasitic disease control and prevention at all levels should be strengthened.

  19. Towards Human-Friendly Efficient Control of Multi-Robot Teams

    Science.gov (United States)

    Stoica, Adrian; Theodoridis, Theodoros; Barrero, David F.; Hu, Huosheng; McDonald-Maiers, Klaus

    2013-01-01

    This paper explores means to increase efficiency in performing tasks with multi-robot teams, in the context of natural Human-Multi-Robot Interfaces (HMRI) for command and control. The motivating scenario is an emergency evacuation by a transport convoy of unmanned ground vehicles (UGVs) that have to traverse, in shortest time, an unknown terrain. In the experiments the operator commands, in minimal time, a group of rovers through a maze. The efficiency of performing such tasks depends on both, the levels of robots' autonomy, and the ability of the operator to command and control the team. The paper extends the classic framework of levels of autonomy (LOA), to levels/hierarchy of autonomy characteristic of Groups (G-LOA), and uses it to determine new strategies for control. An UGVoriented command language (UGVL) is defined, and a mapping is performed from the human-friendly gesture-based HMRI into the UGVL. The UGVL is used to control a team of 3 robots, exploring the efficiency of different G-LOA; specifically, by (a) controlling each robot individually through the maze, (b) controlling a leader and cloning its controls to followers, and (c) controlling the entire group. Not surprisingly, commands at increased G-LOA lead to a faster traverse, yet a number of aspects are worth discussing in this context.

  20. The Application of Human Rights Law to Everyday Life under Rebel Control

    NARCIS (Netherlands)

    Fortin, K.M.A.

    2016-01-01

    This article draws upon social science literature to offer a new assessment of the normative value of human rights law vis-à-vis international humanitarian law in territory under armed groups’ control. In particular, the article considers how the two bodies of law can be applied in a complementary

  1. Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

    NARCIS (Netherlands)

    Shekalaghe, S.; Rutaihwa, M.; Billingsley, P.F.; Chemba, M.; Daubenberger, C.A.; James, E.R.; Mpina, M.; Juma, O. Ali; Schindler, T.; Huber, E.; Gunasekera, A.; Manoj, A.; Simon, B.; Saverino, E.; Church, L.W.; Hermsen, C.C.; Sauerwein, R.W.; Plowe, C.; Venkatesan, M.; Sasi, P.; Lweno, O.; Mutani, P.; Hamad, A.; Mohammed, A.; Urassa, A.; Mzee, T.; Padilla, D.; Ruben, A.; Sim, B.K.; Tanner, M.; Abdulla, S.; Hoffman, S.L.

    2014-01-01

    Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic,

  2. Series elasticity of the human triceps surae muscle : Measurement by controlled-release vs. resonance methods.

    NARCIS (Netherlands)

    Hof, AL; Boom, H; Robinson, C; Rutten, W; Neuman, M; Wijkstra, H

    1997-01-01

    With a newly developed Controlled-Release Ergometer the complete characteristic of the series elastic component can be measured in human muscles. Previous estimates were based on the resonance method: muscle elasticity was assessed from the resonance frequency of the muscle elasticity connected to a

  3. THE DEVELOPMENT OF DETAILED HUMAN FACTORS ENGINEERING GUIDELINES FOR DIGITAL CONTROL ROOM UPGRADES

    International Nuclear Information System (INIS)

    BROWN, W.; O'HARA, J.M.

    2004-01-01

    As part of the Department of Energy and Electric Power Research Institute's hybrid control room project, detailed human factors engineering guidance was developed for designing human-system interfaces that may be affected by introduction of additional digital technology during modernization of nuclear power plants. The guidance addresses several aspects of human-system interaction: information display, interface management, soft controls, alarms, computer-based procedures, computerized operator support systems, communications, and workstation/workplace design. In this paper, the ways in which digital upgrades might affect users' interaction with systems in each of these contexts are briefly described, and the contents of the guidance developed for each of the topics is also described

  4. Development and Control of Compliant Hybrid Joints for Human-Symbiotic Mobile Manipulators

    Directory of Open Access Journals (Sweden)

    Zhijun Li

    2008-11-01

    Full Text Available In this paper, we develop a robot with the ability to secure human safety in humanrobot collisions arising in our living and working environments. The humansymbiotic service robot using compliant hybrid joints realizes human safety, absorbs impact force, and fulfills task. In unexpected or expected collisions with human, the arising impulse force is attenuated effectively by the proposed physical model. Owing to the displacement of the links, several recovery controls have been developed for the endeffector to maintain its desired task position after the collision. The force attenuation property has been verified through collision simulations and experiments in that the capability of the proposed passive arm in overcoming the limitations of active compliance control has been demonstrated.

  5. Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups.

    Science.gov (United States)

    Chen, Feng; Dang, Yong-hui; Yan, Chun-xia; Liu, Yan-ling; Deng, Ya-jun; Fulton, David J R; Chen, Teng

    2009-10-01

    The purpose of this study was to investigate mitochondrial DNA (mtDNA) hypervariable segment-I (HVS-I) C-stretch variations and explore the significance of these variations in forensic and population genetics studies. The C-stretch sequence variation was studied in 919 unrelated individuals from 8 Chinese ethnic groups using both direct and clone sequencing approaches. Thirty eight C-stretch haplotypes were identified, and some novel and population specific haplotypes were also detected. The C-stretch genetic diversity (GD) values were relatively high, and probability (P) values were low. Additionally, C-stretch length heteroplasmy was observed in approximately 9% of individuals studied. There was a significant correlation (r=-0.961, Ppopulations. The results from the Fst and dA genetic distance matrix, neighbor-joining tree, and principal component map also suggest that C-stretch could be used as a reliable genetic marker in population genetics.

  6. Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

    Directory of Open Access Journals (Sweden)

    Arthur Gusman

    2016-12-01

    Full Text Available There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA in the animal kingdom: a system named doubly uniparental inheritance (DUI, which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841and the veneroid Scrobicularia plana(Da Costa,1778, increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented.

  7. Molecular phylogeny of grey mullets (Teleostei: Mugilidae) in Greece: evidence from sequence analysis of mtDNA segments.

    Science.gov (United States)

    Papasotiropoulos, Vasilis; Klossa-Kilia, Elena; Alahiotis, Stamatis N; Kilias, George

    2007-08-01

    Mitochondrial DNA sequence analysis has been used to explore genetic differentiation and phylogenetic relationships among five species of the Mugilidae family, Mugil cephalus, Chelon labrosus, Liza aurata, Liza ramada, and Liza saliens. DNA was isolated from samples originating from the Messolongi Lagoon in Greece. Three mtDNA segments (12s rRNA, 16s rRNA, and CO I) were PCR amplified and sequenced. Sequencing analysis revealed that the greatest genetic differentiation was observed between M. cephalus and all the other species studied, while C. labrosus and L. aurata were the closest taxa. Dendrograms obtained by the neighbor-joining method and Bayesian inference analysis exhibited the same topology. According to this topology, M. cephalus is the most distinct species and the remaining taxa are clustered together, with C. labrosus and L. aurata forming a single group. The latter result brings into question the monophyletic origin of the genus Liza.

  8. A molecular phylogeny of the Cephinae (Hymenoptera, Cephidae based on mtDNA COI gene: a test of traditional classification

    Directory of Open Access Journals (Sweden)

    Mahir Budak

    2011-09-01

    Full Text Available Cephinae is traditionally divided into three tribes and about 24 genera based on morphology and host utilization. There has been no study testing the monophyly of taxa under a strict phylogenetic criterion. A molecular phylogeny of Cephinae based on a total of 68 sequences of mtDNA COI gene, representing seven genera of Cephinae, is reconstructed to test the traditional limits and relationships of taxa. Monophyly of the traditional tribes is not supported. Monophyly of the genera are largely supported except for Pachycephus. A few host shift events are suggested based on phylogenetic relationships among taxa. These results indicate that a more robust phylogeny is required for a more plausible conclusion. We also report two species of Cephus for the first time from Turkey.

  9. Prevalence and control of H7 avian influenza viruses in birds and humans.

    Science.gov (United States)

    Abdelwhab, E M; Veits, J; Mettenleiter, T C

    2014-05-01

    The H7 subtype HA gene has been found in combination with all nine NA subtype genes. Most exhibit low pathogenicity and only rarely high pathogenicity in poultry (and humans). During the past few years infections of poultry and humans with H7 subtypes have increased markedly. This review summarizes the emergence of avian influenza virus H7 subtypes in birds and humans, and the possibilities of its control in poultry. All H7Nx combinations were reported from wild birds, the natural reservoir of the virus. Geographically, the most prevalent subtype is H7N7, which is endemic in wild birds in Europe and was frequently reported in domestic poultry, whereas subtype H7N3 is mostly isolated from the Americas. In humans, mild to fatal infections were caused by subtypes H7N2, H7N3, H7N7 and H7N9. While infections of humans have been associated mostly with exposure to domestic poultry, infections of poultry have been linked to wild birds or live-bird markets. Generally, depopulation of infected poultry was the main control tool; however, inactivated vaccines were also used. In contrast to recent cases caused by subtype H7N9, human infections were usually self-limiting and rarely required antiviral medication. Close genetic and antigenic relatedness of H7 viruses of different origins may be helpful in development of universal vaccines and diagnostics for both animals and humans. Due to the wide spread of H7 viruses and their zoonotic importance more research is required to better understand the epidemiology, pathobiology and virulence determinants of these viruses and to develop improved control tools.

  10. Applications of MALDI-TOF MS to large-scale human mtDNA population-based studies

    Czech Academy of Sciences Publication Activity Database

    Cerezo, M.; Černý, Viktor; Carracedo, Á.; Salas, A.

    2009-01-01

    Roč. 30, č. 21 (2009), s. 3665-3673 ISSN 0173-0835 R&D Projects: GA ČR GA206/08/1587 Institutional research plan: CEZ:AV0Z80020508 Keywords : Haplogroup * High-throughput SNP genotyping * MALDI-TOF MS * Mitochondrial DNA * Multiplex assay Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 3.077, year: 2009 http://www3.interscience.wiley.com/journal/122665008/abstract?CRETRY=1&SRETRY=0

  11. Applications of human factors engineering to LNG release prevention and control

    Energy Technology Data Exchange (ETDEWEB)

    Shikiar, R.; Rankin, W.L.; Rideout, T.B.

    1982-06-01

    The results of an investigation of human factors engineering and human reliability applications to LNG release prevention and control are reported. The report includes a discussion of possible human error contributions to previous LNG accidents and incidents, and a discussion of generic HF considerations for peakshaving plants. More specific recommendations for improving HF practices at peakshaving plants are offered based on visits to six facilities. The HF aspects of the recently promulgated DOT regulations are reviewed, and recommendations are made concerning how these regulations can be implemented utilizing standard HF practices. Finally, the integration of HF considerations into overall system safety is illustrated by a presentation of human error probabilities applicable to LNG operations and by an expanded fault tree analysis which explicitly recognizes man-machine interfaces.

  12. Using human factors engineering to improve the effectiveness of infection prevention and control.

    Science.gov (United States)

    Anderson, Judith; Gosbee, Laura Lin; Bessesen, Mary; Williams, Linda

    2010-08-01

    Human factors engineering is a discipline that studies the capabilities and limitations of humans and the design of devices and systems for improved performance. The principles of human factors engineering can be applied to infection prevention and control to study the interaction between the healthcare worker and the system that he or she is working with, including the use of devices, the built environment, and the demands and complexities of patient care. Some key challenges in infection prevention, such as delayed feedback to healthcare workers, high cognitive workload, and poor ergonomic design, are explained, as is how human factors engineering can be used for improvement and increased compliance with practices to prevent hospital-acquired infections.

  13. Human factors issues in the use of artificial intelligence in air traffic control. October 1990 Workshop

    Science.gov (United States)

    Hockaday, Stephen; Kuhlenschmidt, Sharon (Editor)

    1991-01-01

    The objective of the workshop was to explore the role of human factors in facilitating the introduction of artificial intelligence (AI) to advanced air traffic control (ATC) automation concepts. AI is an umbrella term which is continually expanding to cover a variety of techniques where machines are performing actions taken based upon dynamic, external stimuli. AI methods can be implemented using more traditional programming languages such as LISP or PROLOG, or they can be implemented using state-of-the-art techniques such as object-oriented programming, neural nets (hardware or software), and knowledge based expert systems. As this technology advances and as increasingly powerful computing platforms become available, the use of AI to enhance ATC systems can be realized. Substantial efforts along these lines are already being undertaken at the FAA Technical Center, NASA Ames Research Center, academic institutions, industry, and elsewhere. Although it is clear that the technology is ripe for bringing computer automation to ATC systems, the proper scope and role of automation are not at all apparent. The major concern is how to combine human controllers with computer technology. A wide spectrum of options exists, ranging from using automation only to provide extra tools to augment decision making by human controllers to turning over moment-by-moment control to automated systems and using humans as supervisors and system managers. Across this spectrum, it is now obvious that the difficulties that occur when tying human and automated systems together must be resolved so that automation can be introduced safely and effectively. The focus of the workshop was to further explore the role of injecting AI into ATC systems and to identify the human factors that need to be considered for successful application of the technology to present and future ATC systems.

  14. Deciphering the link between doubly uniparental inheritance of mtDNA and sex determination in bivalves: Clues from comparative transcriptomics

    Science.gov (United States)

    Capt, Charlotte; Renaut, Sébastien; Ghiselli, Fabrizio; Milani, Liliana; Johnson, Nathan A.; Sietman, Bernard E.; Stewart, Donald; Breton, Sophie

    2018-01-01

    Bivalves exhibit an astonishing diversity of sexual systems and sex-determining mechanisms. They can be gonochoric, hermaphroditic or androgenetic, with both genetic and environmental factors known to determine or influence sex. One unique sex-determining system involving the mitochondrial genome has also been hypothesized to exist in bivalves with doubly uniparental inheritance (DUI) of mtDNA. However, the link between DUI and sex determination remains obscure. In this study, we performed a comparative gonad transcriptomics analysis for two DUI-possessing freshwater mussel species to better understand the mechanisms underlying sex determination and DUI in these bivalves. We used a BLAST reciprocal analysis to identify orthologs between Venustaconcha ellipsiformis and Utterbackia peninsularis and compared our results with previously published sex-specific bivalve transcriptomes to identify conserved sex-determining genes. We also compared our data with other DUI species to identify candidate genes possibly involved in the regulation of DUI. A total of ∼12,000 orthologous relationships were found, with 2,583 genes differentially expressed in both species. Among these genes, key sex-determining factors previously reported in vertebrates and in bivalves (e.g., Sry, Dmrt1, Foxl2) were identified, suggesting that some steps of the sex-determination pathway may be deeply conserved in metazoans. Our results also support the hypothesis that a modified ubiquitina