Non-cell autonomous cell death caused by transmission of Huntingtin aggregates in Drosophila.

PubMed

Babcock, Daniel T; Ganetzky, Barry

2015-01-01

Recent evidence indicates that protein aggregates can spread between neurons in several neurodegenerative diseases but much remains unknown regarding the underlying mechanisms responsible for this spreading and its role in disease progression. We recently demonstrated that mutant Huntingtin aggregates spread between cells within the Drosophila brain resulting in non-cell autonomous loss of a pair of large neurons in the posterior protocerebrum. However, the full extent of neuronal loss throughout the brain was not determined. Here we examine the effects of driving expression of mutant Huntingtin in Olfactory Receptor Neurons (ORNs) by using a marker for cleaved caspase activity to monitor neuronal apoptosis as a function of age. We find widespread caspase activity in various brain regions over time, demonstrating that non-cell autonomous damage is widespread. Improved understanding of which neurons are most vulnerable and why should be useful in developing treatment strategies for neurodegenerative diseases that involve transcellular spreading of aggregates.

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

PubMed Central

Anderson, Claire; Williams, Victoria C.; Moyon, Benjamin; Daubas, Philippe; Tajbakhsh, Shahragim; Buckingham, Margaret E.; Shiroishi, Toshihiko; Hughes, Simon M.; Borycki, Anne-Gaëlle

2012-01-01

How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and populated the prospective muscle masses. Here, we show that Sonic hedgehog (Shh) from the zone of polarizing activity (ZPA) drives myogenesis specifically within the ventral muscle mass. Shh directly induces ventral MPCs to initiate Myf5 transcription and myogenesis through essential Gli-binding sites located in the Myf5 limb enhancer. In the absence of Shh signaling, myogenesis is delayed, MPCs fail to migrate distally, and ventral paw muscles fail to form. Thus, Shh production in the limb ZPA is essential for the spatiotemporal control of myogenesis and coordinates muscle and skeletal development by acting directly to regulate the formation of specific ventral muscles. PMID:22987640

Conditional Deletion of Kit in Melanocytes: White Spotting Phenotype Is Cell Autonomous.

PubMed

Aoki, Hitomi; Tomita, Hiroyuki; Hara, Akira; Kunisada, Takahiro

2015-07-01

It is well established that cell-intrinsic signaling through the receptor tyrosine kinase KIT is critical for the development of neural crest-derived melanocytes. Nevertheless, it is not entirely clear whether Kit acts exclusively in a melanocyte-autonomous manner or in addition indirectly through other cell types. To address this question in vivo, we generated a targeted allele of Kit that allowed for CRE recombinase-mediated deletion of the transmembrane domain of KIT. Mice carrying one copy of the targeted allele and expressing CRE under the melanoblast/melanocyte-specific tyrosinase promoter exhibited a white spotting phenotype that was even more extensive compared with that found in mice heterozygous for a Kit-null allele. This phenotype is unlikely the result of sequestration of KIT ligand by neighboring cells or by potentially secreted forms of KIT because the spotting phenotype could not be rescued by overexpression of KITL. Likewise, overexpression of endothelin-3 or hepatocyte growth factor was unable to rescue melanocytes in these mice. Although the severity of the observed phenotype remains to be explained, the findings indicate that melanocyte-selective impairment of Kit is sufficient to interfere with normal melanocyte development.

Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology

PubMed Central

Ballas, Nurit; Lioy, Daniel T.; Grunseich, Christopher; Mandel, Gail

2011-01-01

The neurodevelopmental disorder Rett Syndrome (RTT) is caused by sporadic mutations in the transcriptional factor methyl-CpG binding protein 2 (MeCP2). Although it is thought that the primary cause of RTT is cell autonomous due to lack of functional MeCP2 in neurons, whether non-cell autonomous factors contribute to the disease, is unknown. Here, we show that loss of MeCP2 occurs not only in neurons but also in glial cells of RTT brain. Using an in vitro co-culture system, we find that mutant astrocytes from a RTT mouse model, and their conditioned medium, fail to support normal dendritic morphology of either wild-type or mutant hippocampal neurons. Our studies suggest that in RTT brain, astrocytes carrying MeCP2 mutations have a non-cell autonomous effect on neuronal properties, likely due to aberrant secretion of soluble factor(s). PMID:19234456

JACKDAW controls epidermal patterning in the Arabidopsis root meristem through a non-cell-autonomous mechanism.

PubMed

Hassan, Hala; Scheres, Ben; Blilou, Ikram

2010-05-01

In Arabidopsis, specification of the hair and non-hair epidermal cell types is position dependent, in that hair cells arise over clefts in the underlying cortical cell layer. Epidermal patterning is determined by a network of transcriptional regulators that respond to an as yet unknown cue from underlying tissues. Previously, we showed that JACKDAW (JKD), a zinc finger protein, localizes in the quiescent centre and the ground tissue, and regulates tissue boundaries and asymmetric cell division by delimiting SHORT-ROOT movement. Here, we provide evidence that JKD controls position-dependent signals that regulate epidermal-cell-type patterning. JKD is required for appropriately patterned expression of the epidermal cell fate regulators GLABRA2, CAPRICE and WEREWOLF. Genetic interaction studies indicate that JKD operates upstream of the epidermal patterning network in a SCRAMBLED (SCM)-dependent fashion after embryogenesis, but acts independent of SCM in embryogenesis. Tissue-specific induction experiments indicate non-cell-autonomous action of JKD from the underlying cortex cell layer to specify epidermal cell fate. Our findings are consistent with a model where JKD induces a signal in every cortex cell that is more abundant in the hair cell position owing to the larger surface contact of cells located over a cleft.

Autonomous Agents: The Origins and Co-Evolution of Reproducing Molecular Systems

NASA Technical Reports Server (NTRS)

Kauffman, Stuart

1999-01-01

The central aim of this award concerned an investigation into, and adequate formulation of, the concept of an "autonomous agent." If we consider a bacterium swimming upstream in a glucose gradient, we are willing to say of the bacterium that it is going to get food. That is, we are willing, and do, describe the bacterium as acting on its own behalf in an environment. All free living cells are, in this sense, autonomous agents. But the bacterium is "just" a set of molecules. We define an autonomous agent as a physical system able to act on its own behalf in an environment, then ask, "What must a physical system be to be an autonomous agent?" The tentative definition for a molecular autonomous agent is that it must be self-reproducing and carry out at least one thermodynamic work cycle. The work carried out in this grant involved, among other features, the development of a detailed model of a molecular autonomous agent, and study of the kinetics of this system. In particular, a molecular autonomous agent must, by the above tentative definition, not only reproduce, but must carry out at least one work cycle. I took, as a simple example of a self-reproducing molecular system, the single-stranded DNA hexamer 3'CCGCGG5' which can line up and ligate its two complementary trimers, 5'CCG3' and 5'CGG3'. But the two ligated trimers constitute the same molecular sequence in the 3' to 5' direction as the initial hexamer, hence this system is autocatalytic. On the other hand the above system is not yet an autonomous agent. At the minimum, autonomous agents, as I have defined them, are a new class of chemical reaction network. At a maximum, they may constitute a proper definition of life itself.

The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels

PubMed Central

2011-01-01

Background The transcription factor Foxg1 is an important regulator of telencephalic cell cycles. Its inactivation causes premature lengthening of telencephalic progenitor cell cycles and increased neurogenic divisions, leading to severe hypoplasia of the telencephalon. These proliferation defects could be a secondary consequence of the loss of Foxg1 caused by the abnormal expression of several morphogens (Fibroblast growth factor 8, bone morphogenetic proteins) in the telencephalon of Foxg1 null mutants. Here we investigated whether Foxg1 has a cell autonomous role in the regulation of telencephalic progenitor proliferation. We analysed Foxg1+/+↔Foxg1-/- chimeras, in which mutant telencephalic cells have the potential to interact with, and to have any cell non-autonomous defects rescued by, normal wild-type cells. Results Our analysis showed that the Foxg1-/- cells are under-represented in the chimeric telencephalon and the proportion of them in S-phase is significantly smaller than that of their wild-type neighbours, indicating that their under-representation is caused by a cell autonomous reduction in their proliferation. We then analysed the expression of the cell-cycle regulator Pax6 and found that it is cell-autonomously downregulated in Foxg1-/- dorsal telencephalic cells. We went on to show that the introduction into Foxg1-/- embryos of a transgene designed to reverse Pax6 expression defects resulted in a partial rescue of the telencephalic progenitor proliferation defects. Conclusions We conclude that Foxg1 exerts control over telencephalic progenitor proliferation by cell autonomous mechanisms that include the regulation of Pax6, which itself is known to regulate proliferation cell autonomously in a regional manner. PMID:21418559

Conditions for Fully Autonomous Anticipation

NASA Astrophysics Data System (ADS)

Collier, John

2006-06-01

Anticipation allows a system to adapt to conditions that have not yet come to be, either externally to the system or internally. Autonomous systems actively control the conditions of their own existence so as to increase their overall viability. This paper will first give minimal necessary and sufficient conditions for autonomous anticipation, followed by a taxonomy of autonomous anticipation. In more complex systems, there can be semi-autonomous subsystems that can anticipate and adapt on their own. Such subsystems can be integrated into a system's overall autonomy, typically with greater efficiency due to modularity and specialization of function. However, it is also possible that semi-autonomous subsystems can act against the viability of the overall system, and have their own functions that conflict with overall system functions.

Both cell-autonomous mechanisms and hormones contribute to sexual development in vertebrates and insects.

PubMed

Bear, Ashley; Monteiro, Antónia

2013-08-01

The differentiation of male and female characteristics in vertebrates and insects has long been thought to proceed via different mechanisms. Traditionally, vertebrate sexual development was thought to occur in two phases: a primary and a secondary phase, the primary phase involving the differentiation of the gonads, and the secondary phase involving the differentiation of other sexual traits via the influence of sex hormones secreted by the gonads. In contrast, insect sexual development was thought to depend exclusively on cell-autonomous expression of sex-specific genes. Recently, however, new evidence indicates that both vertebrates and insects rely on sex hormones as well as cell-autonomous mechanisms to develop sexual traits. Collectively, these new data challenge the traditional vertebrate definitions of primary and secondary sexual development, call for a redefinition of these terms, and indicate the need for research aimed at explaining the relative dependence on cell-autonomous versus hormonally guided sexual development in animals. © 2013 The Authors. BioEssays published by WILEY Periodicals, Inc.

Non-cell-autonomous effects yield lower clonal diversity in expanding tumors.

PubMed

Tissot, Tazzio; Thomas, Frédéric; Roche, Benjamin

2017-09-11

Recent cancer research has investigated the possibility that non-cell-autonomous (NCA) driving tumor growth can support clonal diversity (CD). Indeed, mutations can affect the phenotypes not only of their carriers ("cell-autonomous", CA effects), but also sometimes of other cells (NCA effects). However, models that have investigated this phenomenon have only considered a restricted number of clones. Here, we designed an individual-based model of tumor evolution, where clones grow and mutate to yield new clones, among which a given frequency have NCA effects on other clones' growth. Unlike previously observed for smaller assemblages, most of our simulations yield lower CD with high frequency of mutations with NCA effects. Owing to NCA effects increasing competition in the tumor, clones being already dominant are more likely to stay dominant, and emergent clones not to thrive. These results may help personalized medicine to predict intratumor heterogeneity across different cancer types for which frequency of NCA effects could be quantified.

Convective exosome-tracing microfluidics for analysis of cell-non-autonomous neurogenesis.

PubMed

Oh, Hyun Jeong; Shin, Yoojin; Chung, Seok; Hwang, Do Won; Lee, Dong Soo

2017-01-01

The effective role of exosome delivering neurogenic microRNA (miRNA) enables to induce efficient differentiation process during neurogenesis. The microfludic system capable of visualizing the exosomal behavior such as secretion, migration, and uptake of individual exosomes can be used as a robust technique to understand the exosome-mediated change of cellular behavior. Here, we developed the exosome-tracing microfluidic system to visualize exosomal transport carrying the neurogenic miRNA from leading to neighboring cells, and found a new mode of exosome-mediated cell-non-autonomous neurogenesis. The miR-193a facilitated neurogenesis in F11 cells by blocking proliferation-related target genes. In addition to time-lapse live-cell imaging using microfluidics visualized the convective transport of exosomes from differentiated to undifferentiated cells. Individual exosomes containing miR-193a from differentiated donor cells were taken up by undifferentiated cells to lead them to neurogenesis. Induction of anti-miR-193a was sufficient to block neurogenesis in F11 cells. Inhibition of the exosomal production by manumycin-A and treatment of anti-miR-193a in the differentiated donor cells failed to induce neurogenesis in undifferentiated recipient cells. These findings indicate that exosomes of neural progenitors and neurogenic miRNA within these exosomes propagate cell-non-autonomous differentiation to neighboring progenitors, to delineate the roles of exosome mediating neurogenesis of population of homologous neural progenitor cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

AMPK modulates tissue and organismal aging in a cell-non-autonomous manner

PubMed Central

Ulgherait, Matthew; Rana, Anil; Rera, Michael; Graniel, Jacqueline; Walker, David W.

2014-01-01

AMPK exerts pro-longevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that up-regulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to improved intestinal homeostasis during aging and extended lifespan. Neuronal up-regulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these inter-tissue effects during aging and to prolong lifespan. Furthermore, up-regulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-autonomously in the brain, slows systemic aging and prolongs lifespan. We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a cell-non-autonomous manner. PMID:25199830

Stabilizing Motifs in Autonomous Boolean Networks and the Yeast Cell Cycle Oscillator

NASA Astrophysics Data System (ADS)

Sevim, Volkan; Gong, Xinwei; Socolar, Joshua

2009-03-01

Synchronously updated Boolean networks are widely used to model gene regulation. Some properties of these model networks are known to be artifacts of the clocking in the update scheme. Autonomous updating is a less artificial scheme that allows one to introduce small timing perturbations and study stability of the attractors. We argue that the stabilization of a limit cycle in an autonomous Boolean network requires a combination of motifs such as feed-forward loops and auto-repressive links that can correct small fluctuations in the timing of switching events. A recently published model of the transcriptional cell-cycle oscillator in yeast contains the motifs necessary for stability under autonomous updating [1]. [1] D. A. Orlando, et al. Nature (London), 4530 (7197):0 944--947, 2008.

The double-stranded RNA binding protein RDE-4 can act cell autonomously during feeding RNAi in C. elegans

PubMed Central

Raman, Pravrutha; Zaghab, Soriayah M.; Traver, Edward C.

2017-01-01

Abstract Long double-stranded RNA (dsRNA) can silence genes of matching sequence upon ingestion in many invertebrates and is therefore being developed as a pesticide. Such feeding RNA interference (RNAi) is best understood in the worm Caenorhabditis elegans, where the dsRNA-binding protein RDE-4 initiates silencing by recruiting an endonuclease to process long dsRNA into short dsRNA. These short dsRNAs are thought to move between cells because muscle-specific rescue of rde-4 using repetitive transgenes enables silencing in other tissues. Here, we extend this observation using additional promoters, report an inhibitory effect of repetitive transgenes, and discover conditions for cell-autonomous silencing in animals with tissue-specific rescue of rde-4. While expression of rde-4(+) in intestine, hypodermis, or neurons using a repetitive transgene can enable silencing also in unrescued tissues, silencing can be inhibited wihin tissues that express a repetitive transgene. Single-copy transgenes that express rde-4(+) in body-wall muscles or hypodermis, however, enable silencing selectively in the rescued tissue but not in other tissues. These results suggest that silencing by the movement of short dsRNA between cells is not an obligatory feature of feeding RNAi in C. elegans. We speculate that similar control of dsRNA movement could modulate tissue-specific silencing by feeding RNAi in other invertebrates. PMID:28541563

In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons.

PubMed

Thomas, Elizabeth A; Coppola, Giovanni; Tang, Bin; Kuhn, Alexandre; Kim, SoongHo; Geschwind, Daniel H; Brown, Timothy B; Luthi-Carter, Ruth; Ehrlich, Michelle E

2011-03-15

Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared with those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support. While genes related to excitotoxicity, dopamine signaling and trophic support were altered in both DE5 and R6/2 mice, which may be either cell autonomous or non-cell autonomous, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell-autonomous mechanisms. Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt, in the absence of expression in cortical neurons.

Huntingtin Acts Non Cell-Autonomously on Hippocampal Neurogenesis and Controls Anxiety-Related Behaviors in Adult Mouse

PubMed Central

Pla, Patrick; Orvoen, Sophie; Benstaali, Caroline; Dodier, Sophie; Gardier, Alain M.; David, Denis J.; Humbert, Sandrine; Saudou, Frédéric

2013-01-01

Huntington’s disease (HD) is a fatal neurodegenerative disease, characterized by motor defects and psychiatric symptoms, including mood disorders such as anxiety and depression. HD is caused by an abnormal polyglutamine (polyQ) expansion in the huntingtin (HTT) protein. The development and analysis of various mouse models that express pathogenic polyQ-HTT revealed a link between mutant HTT and the development of anxio-depressive behaviors and various hippocampal neurogenesis defects. However, it is unclear whether such phenotype is linked to alteration of HTT wild-type function in adults. Here, we report the analysis of a new mouse model in which HTT is inducibly deleted from adult mature cortical and hippocampal neurons using the CreERT2/Lox system. These mice present defects in both the survival and the dendritic arborization of hippocampal newborn neurons. Our data suggest that these non-cell autonomous effects are linked to defects in both BDNF transport and release upon HTT silencing in hippocampal neurons, and in BDNF/TrkB signaling. The controlled deletion of HTT also had anxiogenic-like effects. Our results implicate endogenous wild-type HTT in adult hippocampal neurogenesis and in the control of mood disorders. PMID:24019939

Olfactory ensheathing cells but not fibroblasts reduce the duration of autonomic dysreflexia in spinal cord injured rats.

PubMed

Cloutier, Frank; Kalincik, Tomas; Lauschke, Jenny; Tuxworth, Gervase; Cavanagh, Brenton; Meedeniya, Adrian; Mackay-Sim, Alan; Carrive, Pascal; Waite, Phil

2016-12-01

Autonomic dysreflexia is a common complication after high level spinal cord injury and can be life-threatening. We have previously shown that the acute transplantation of olfactory ensheathing cells into the lesion site of rats transected at the fourth thoracic spinal cord level reduced autonomic dysreflexia up to 8weeks after spinal cord injury. This beneficial effect was correlated with changes in the morphology of sympathetic preganglionic neurons despite the olfactory cells surviving no longer than 3weeks. Thus the transitory presence of olfactory ensheathing cells at the injury site initiated long-term functional as well as morphological changes in the sympathetic preganglionic neurons. The primary aim of the present study was to evaluate whether olfactory ensheathing cells survive after transplantation within the parenchyma close to sympathetic preganglionic neurons and whether, in this position, they still reduce the duration of autonomic dysreflexia and modulate sympathetic preganglionic neuron morphology. The second aim was to quantify the density of synapses on the somata of sympathetic preganglionic neurons with the hypothesis that the reduction of autonomic dysreflexia requires synaptic changes. As a third aim, we evaluated the cell type-specificity of olfactory ensheathing cells by comparing their effects with a control group transplanted with fibroblasts. Animals transplanted with OECs had a faster recovery from hypertension induced by colorectal distension at 6 and 7weeks but not at 8weeks after T4 spinal cord transection. Olfactory ensheathing cells survived for at least 8weeks and were observed adjacent to sympathetic preganglionic neurons whose overall number of primary dendrites was reduced and the synaptic density on the somata increased, both caudal to the lesion site. Our results showed a long term cell type-specific effects of olfactory ensheathing cells on sympathetic preganglionic neurons morphology and on the synaptic density on their

Interferon-inducible effector mechanisms in cell-autonomous immunity

PubMed Central

MacMicking, John D.

2014-01-01

Interferons (IFNs) induce the expression of hundreds of genes as part of an elaborate antimicrobial programme designed to combat infection in all nucleated cells — a process termed cell-autonomous immunity. As described in this Review, recent genomic and subgenomic analyses have begun to assign functional properties to novel IFN-inducible effector proteins that restrict bacteria, protozoa and viruses in different subcellular compartments and at different stages of the pathogen life cycle. Several newly described host defence factors also participate in canonical oxidative and autophagic pathways by spatially coordinating their activities to enhance microbial killing. Together, these IFN-induced effector networks help to confer vertebrate host resistance to a vast and complex microbial world. PMID:22531325

The double-stranded RNA binding protein RDE-4 can act cell autonomously during feeding RNAi in C. elegans.

PubMed

Raman, Pravrutha; Zaghab, Soriayah M; Traver, Edward C; Jose, Antony M

2017-08-21

Long double-stranded RNA (dsRNA) can silence genes of matching sequence upon ingestion in many invertebrates and is therefore being developed as a pesticide. Such feeding RNA interference (RNAi) is best understood in the worm Caenorhabditis elegans, where the dsRNA-binding protein RDE-4 initiates silencing by recruiting an endonuclease to process long dsRNA into short dsRNA. These short dsRNAs are thought to move between cells because muscle-specific rescue of rde-4 using repetitive transgenes enables silencing in other tissues. Here, we extend this observation using additional promoters, report an inhibitory effect of repetitive transgenes, and discover conditions for cell-autonomous silencing in animals with tissue-specific rescue of rde-4. While expression of rde-4(+) in intestine, hypodermis, or neurons using a repetitive transgene can enable silencing also in unrescued tissues, silencing can be inhibited wihin tissues that express a repetitive transgene. Single-copy transgenes that express rde-4(+) in body-wall muscles or hypodermis, however, enable silencing selectively in the rescued tissue but not in other tissues. These results suggest that silencing by the movement of short dsRNA between cells is not an obligatory feature of feeding RNAi in C. elegans. We speculate that similar control of dsRNA movement could modulate tissue-specific silencing by feeding RNAi in other invertebrates. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

PubMed

Kamel, Jordan T; Goodman, David J; Howe, Kathy; Cook, Mark J; Ward, Glenn M; Roberts, Leslie J

2015-09-01

This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure. Copyright © 2015 John Wiley & Sons, Ltd.

Cell-autonomous excitation of midbrain dopamine neurons by endocannabinoid-dependent lipid signaling

PubMed Central

Gantz, Stephanie C.; Bean, Bruce P.

2017-01-01

SUMMARY The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing. In voltage-clamp experiments, 2-AG reduced A-type potassium current (IA) through a cannabinoid receptor-independent mechanism mimicked by arachidonic acid, which has no activity on cannabinoid receptors. Activation of orexin, neurotensin, and metabotropic glutamate Gq/11-linked receptors mimicked the effects of exogenous 2-AG and their actions were prevented by inhibiting the 2-AG-synthesizing enzyme diacylglycerol lipase α. The results show that 2-AG and related lipid signaling molecules can directly tune neuronal excitability in a cell-autonomous manner by modulating IA. PMID:28262417

Structural centrosome aberrations promote non-cell-autonomous invasiveness.

PubMed

Ganier, Olivier; Schnerch, Dominik; Oertle, Philipp; Lim, Roderick Yh; Plodinec, Marija; Nigg, Erich A

2018-05-02

Centrosomes are the main microtubule-organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein-like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP-induced structural centrosome aberrations trigger the escape ("budding") of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP-induced centrosome aberrations trigger a re-organization of the cytoskeleton, which stabilizes microtubules and weakens E-cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non-cell-autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

PubMed

Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

2010-01-01

The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

Necroptosis promotes cell-autonomous activation of proinflammatory cytokine gene expression.

PubMed

Zhu, Kezhou; Liang, Wei; Ma, Zaijun; Xu, Daichao; Cao, Shuangyi; Lu, Xiaojuan; Liu, Nan; Shan, Bing; Qian, Lihui; Yuan, Junying

2018-04-27

Necroptosis, a form of regulated necrotic cell death, is mediated by receptor interacting protein 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). However, the mechanism by which necroptosis promotes inflammation is still unclear. Here we report that the expression of cytokines is robustly upregulated in a cell-autonomous manner during necroptosis induced by tumor necrosis factor alpha (TNFα). We demonstrate that TNFα-induced necroptosis leads to two waves of cytokine production. The first wave, more transient and weaker than the second, is in response to TNFα alone; whereas the second wave depends upon the necroptotic signaling. We show that necroptosis promotes the transcription of TNFα-target genes in a cell-intrinsic manner. The activation of both NF-κB and p38 by the necroptotic machinery, RIPK1, RIPK3, and MLKL, is involved in mediating the robust induction of cytokine expression in the second wave. In contrast, necroptosis induced by direct oligomerization of MLKL promotes cytokine production at much lower levels than that of necroptosis induced with TNFα. Thus, we conclude that TNFα-induced necroptosis signaling events mediated by RIPK1 and RIPK3 activation, in addition to the MLKL oligomerization, promotes the expression of cytokines involving multiple intracellular signaling mechanisms including NF-κB pathway and p38. These findings reveal that the necroptotic cell death machinery mounts an immune response by promoting cell-autonomous production of cytokines. Our study provides insights into the mechanism by which necroptosis promotes inflammation in human diseases.

Cadherin-2 Is Required Cell Autonomously for Collective Migration of Facial Branchiomotor Neurons.

PubMed

Rebman, Jane K; Kirchoff, Kathryn E; Walsh, Gregory S

2016-01-01

Collective migration depends on cell-cell interactions between neighbors that contribute to their overall directionality, yet the mechanisms that control the coordinated migration of neurons remains to be elucidated. During hindbrain development, facial branchiomotor neurons (FBMNs) undergo a stereotypic tangential caudal migration from their place of birth in rhombomere (r)4 to their final location in r6/7. FBMNs engage in collective cell migration that depends on neuron-to-neuron interactions to facilitate caudal directionality. Here, we demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for directional and collective migration of FBMNs. We generated stable transgenic zebrafish expressing dominant-negative Cadherin-2 (Cdh2ΔEC) driven by the islet1 promoter. Cell-autonomous inactivation of Cadherin-2 function led to non-directional migration of FBMNs and a defect in caudal tangential migration. Additionally, mosaic analysis revealed that Cdh2ΔEC-expressing FBMNs are not influenced to migrate caudally by neighboring wild-type FBMNs due to a defect in collective cell migration. Taken together, our data suggest that Cadherin-2 plays an essential cell-autonomous role in mediating the collective migration of FBMNs.

Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens

PubMed Central

Randow, Felix; MacMicking, John D.; James, Leo C.

2013-01-01

Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages—the majority of which fall outside the traditional province of the immune system—to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens. PMID:23661752

Cellular self-defense: how cell-autonomous immunity protects against pathogens.

PubMed

Randow, Felix; MacMicking, John D; James, Leo C

2013-05-10

Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages-the majority of which fall outside the traditional province of the immune system-to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens.

Autoimmune autonomic ganglionopathy

PubMed Central

Wang, Z.; Low, P.A.; Jordan, J.; Freeman, R.; Gibbons, C.H.; Schroeder, C.; Sandroni, P.; Vernino, S.

2008-01-01

Background Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (AChRs) that mediate fast synaptic transmission in autonomic ganglia. Previous clinical studies and observations in animal models suggest that AAG is an antibody-mediated neurologic disorder. Methods Using whole-cell patch clamp techniques, we recorded ganglionic AChR currents in cultured human IMR-32 cells and examined the effects of bath application of IgG derived from patients with AAG. Results IgG from seven patients with AAG all produced a progressive decline in whole-cell ganglionic AChR current, whereas IgG from control subjects had no effect. The effect was abolished at low temperature. Fab antibody fragments had no effect unless a secondary antibody was added concurrently. IgG from one patient also produced a more immediate reduction of ganglionic AChR current. Conclusions The characteristics of antibody-mediated inhibition of ganglionic acetylcholine receptor (AChR) current are consistent with modulation and blocking of the membrane AChR, analogous to the effects of muscle AChR antibodies in myasthenia gravis. Our observations demonstrate that antibodies in patients with autoimmune autonomic ganglionopathy (AAG) cause physiologic changes in ganglionic AChR function and confirm that AAG is an antibody-mediated disorder. PMID:17536048

The cytoskeleton in cell-autonomous immunity: structural determinants of host defence

PubMed Central

Mostowy, Serge; Shenoy, Avinash R.

2016-01-01

Host cells use antimicrobial proteins, pathogen-restrictive compartmentalization and cell death in their defence against intracellular pathogens. Recent work has revealed that four components of the cytoskeleton — actin, microtubules, intermediate filaments and septins, which are well known for their roles in cell division, shape and movement — have important functions in innate immunity and cellular self-defence. Investigations using cellular and animal models have shown that these cytoskeletal proteins are crucial for sensing bacteria and for mobilizing effector mechanisms to eliminate them. In this Review, we highlight the emerging roles of the cytoskeleton as a structural determinant of cell-autonomous host defence. PMID:26292640

Autonomous assembly of epithelial structures by subrenal implantation of dissociated embryonic inner-ear cells.

PubMed

Wang, Li; Zhang, Kaiqing; Zhu, Helen He; Gao, Wei-Qiang

2015-05-27

Microenvironment and cell-cell interactions play an important role during embryogenesis and are required for the stemness and differentiation of stem cells. The inner-ear sensory epithelium, containing hair cells and supporting cells, is derived from the stem cells within the otic vesicle at early embryonic stages. However, whether or not such microenvironment or cell-cell interactions within the embryonic otic tissue have the capacity to regulate the proliferation and differentiation of stem cells and to autonomously reassemble the cells into epithelial structures is unknown. Here, we report that on enzymatic digestion and dissociation to harvest all the single cells from 13.5-day-old rat embryonic (E13.5) inner-ear tissue as well as on implantation of these cells under renal capsules; the dissociated cells are able to reassemble themselves to form epithelial structures as early as 7 days after implantation. By 25 days after implantation, more mature epithelial structures are formed. Immunostaining with cell-type-specific markers reveals that hair cells and supporting cells are not only formed, but are also well aligned with the hair cells located in the apical layer surrounded by the supporting cells. These findings suggest that microenvironment and cell-cell interactions within the embryonic inner-ear tissue have the autonomous signals to induce the formation of sensory epithelial structures. This method may also provide a useful system to study the potential of stem cells to differentiate into hair cells in vivo.

Overexpression of Hif-1α in Mesenchymal Stem Cells Affects Cell-Autonomous Angiogenic and Osteogenic Parameters.

PubMed

Lampert, F M; Kütscher, C; Stark, G B; Finkenzeller, G

2016-03-01

Reconstruction of large bone defects still represents a major medical challenge. In recent years tissue engineering has developed techniques based on adult mesenchymal stem cells (MSCs) that could represent an attractive therapeutical option to treat large bone defects in the future. It has been demonstrated in various animal models that ex vivo expanded MSCs are capable of promoting the regeneration of skeletal defects after implantation. However, for the efficient regeneration of bone in tissue engineering applications, a rapid vascularization of implanted grafts is essential to ensure the survival of cells in the early post-implantational phase. A promising strategy to enhance vascularization of MSC-containing implants could consist of overexpression of the angiogenic master transcription factor Hypoxia-inducible factor 1 (Hif-1) in the MSCs in order to induce angiogenesis and support osteogenesis. In the present study, we overexpressed Hif-1α in MSCs by using recombinant adenoviruses and investigated cell-autonomous effects. Overexpression of Hif-1α enhanced proliferation, migration, cell survival and expression of pro-angiogenic genes. Other parameters such as expression of the osteogenic markers BMP-2 and RunX2 were decreased. Hif-1α overexpression had no effect on invasion, senescence and osteogenic differentiation of MSCs. Our experiments revealed multifarious effects of Hif-1α overexpression on cell-autonomous parameters. Therefore, Hif-1α overexpression may represent a therapeutic option to improve cellular functions of MSCs to treat critical sized bone defects. © 2015 Wiley Periodicals, Inc.

Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children

PubMed Central

Kroenke, Candyce H; Epel, Elissa; Adler, Nancy; Bush, Nicole R.; Obradović, Jelena; Lin, Jue; Blackburn, Elizabeth; Stamperdahl, Juliet Lise; Boyce, W. Thomas

2011-01-01

Objective To examine associations between autonomic nervous system and adrenocortical reactivity to laboratory stressors and buccal cell telomere length (BTL) in children. Methods The study sample comprised 78 five- and six-year-old children from a longitudinal cohort study of kindergarten social hierarchies, biological responses to adversity, and child health. Buccal cell samples and reactivity measures were collected in the spring of the kindergarten year. BTL was measured by realtime PCR, as the telomere-to-single copy gene (T/S) ratio. Parents provided demographic information; parents and teachers reported children’s internalizing and externalizing behavior problems. Components of children’s autonomic (heart rate (HR), respiratory sinus arrhythmia (RSA), pre-ejection period (PEP)) and adrenocortical (salivary cortisol) responses were monitored during standardized laboratory challenges. We examined relations between reactivity, internalizing and externalizing behavior, and BTL, adjusted for age, race, and gender. Results Heart rate and cortisol reactivity were inversely related to BTL, PEP was positively related to BTL, and RSA was unrelated. Internalizing behaviors were also inversely related to BTL (standardized β=−0.33, p=0.004). Split at the median of reactivity parameters, children with high sympathetic activation (decreasing PEP) and high parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL. However, children with both this profile and high cortisol reactivity (N=12) had significantly shorter BTL (0.80 vs. 1.00, χ2=7.6, p=0.006), compared with other children. Conclusions Autonomic and adrenocortical reactivity in combination were associated with shorter buccal cell telomere length in children. These data suggest that psychophysiological processes may influence, and that BTL may be a useful marker of, early biological aging. PMID:21873585

An Autonomous BMP2 Regulatory Element in Mesenchymal Cells

PubMed Central

Kruithof, Boudewijn P.T.; Fritz, David T.; Liu, Yijun; Garsetti, Diane E.; Frank, David B.; Pregizer, Steven K.; Gaussin, Vinciane; Mortlock, Douglas P.; Rogers, Melissa B.

2014-01-01

BMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3′untranslated region (UTR) of the Bmp2 mRNA mediate a post-transcriptional block of protein synthesis. Interaction of cell and developmental stage-specific trans-regulatory factors with the 3′UTR is a nimble and versatile mechanism for modulating this potent morphogen in different cell types. We show here, that an ultra-conserved sequence in the 3′UTR functions independently of promoter, coding region, and 3′UTR context in primary and immortalized tissue culture cells and in transgenic mice. Our findings indicate that the ultra-conserved sequence is an autonomously functioning post-transcriptional element that may be used to modulate the level of BMP2 and other proteins while retaining tissue specific regulatory elements. PMID:21268088

The THO Complex Non-Cell-Autonomously Represses Female Germline Specification through the TAS3-ARF3 Module.

PubMed

Su, Zhenxia; Zhao, Lihua; Zhao, Yuanyuan; Li, Shaofang; Won, SoYoun; Cai, Hanyang; Wang, Lulu; Li, Zhenfang; Chen, Piaojuan; Qin, Yuan; Chen, Xuemei

2017-06-05

In most sexually reproducing plants, a single somatic, sub-epidermal cell in an ovule is selected to differentiate into a megaspore mother cell, which is committed to giving rise to the female germline. However, it remains unclear how intercellular signaling among somatic cells results in only one cell in the sub-epidermal layer differentiating into the megaspore mother cell. Here we uncovered a role of the THO complex in restricting the megaspore mother cell fate to a single cell. Mutations in TEX1, HPR1, and THO6, components of the THO/TREX complex, led to the formation of multiple megaspore mother cells, which were able to initiate gametogenesis. We demonstrated that TEX1 repressed the megaspore mother cell fate by promoting the biogenesis of TAS3-derived trans-acting small interfering RNA (ta-siRNA), which represses ARF3 expression. The TEX1 protein was present in epidermal cells, but not in the germline, and, through TAS3-derived ta-siRNA, restricted ARF3 expression to the medio domain of ovule primordia. Expansion of ARF3 expression into lateral epidermal cells in a TAS3 ta-siRNA-insensitive mutant led to the formation of supernumerary megaspore mother cells, suggesting that TEX1- and TAS3-mediated restriction of ARF3 expression limits excessive megaspore mother cell formation non-cell-autonomously. Our findings reveal the role of a small-RNA pathway in the regulation of female germline specification in Arabidopsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

BRCA1 haploinsufficiency cell-autonomously activates RANKL expression and generates denosumab-responsive breast cancer-initiating cells.

PubMed

Cuyàs, Elisabet; Corominas-Faja, Bruna; Martín, María Muñoz-San; Martin-Castillo, Begoña; Lupu, Ruth; Brunet, Joan; Bosch-Barrera, Joaquim; Menendez, Javier A

2017-05-23

Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties. Using isogenic pairs of normal-like human breast epithelial cells in which the inactivation of a single BRCA1 allele results in genomic instability, we assessed the impact of BRCA1 haploinsufficiency on the expression status of RANK and RANKL. RANK expression remained unaltered but RANKL was dramatically up-regulated in BRCA1mut/+ haploinsufficient cells relative to isogenic BRCA1+/+ parental cells. Neutralizing RANKL with denosumab significantly abrogated the ability of BRCA1 haploinsufficient cells to survive and proliferate as floating microtumors or "mammospheres" under non-adherent/non-differentiating conditions, an accepted surrogate of the relative proportion and survival of CSCs. Intriguingly, CSC-like states driven by epithelial-to-mesenchymal transition or HER2 overexpression traits responded to some extent to denosumab. We propose that breast epithelium-specific mono-allelic inactivation of BRCA1 might suffice to cell-autonomously generate RANKL-addicted, denosumab-responsive CSC-like states. The convergent addiction to a hyperactive RANKL/RANK axis of CSC-like states from genetically diverse breast cancer subtypes might inaugurate a new era of cancer prevention and treatment based on denosumab as a CSC-targeted agent.

F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner

PubMed Central

Yumimoto, Kanae; Akiyoshi, Sayuri; Ueo, Hiroki; Sagara, Yasuaki; Onoyama, Ichiro; Ueo, Hiroaki; Ohno, Shinji; Mori, Masaki; Mimori, Koshi; Nakayama, Keiichi I.

2015-01-01

The gene encoding F-box protein FBXW7 is frequently mutated in many human cancers. Although most previous studies have focused on the tumor-suppressive capacity of FBXW7 in tumor cells themselves, we determined that FBXW7 in the host microenvironment also suppresses cancer metastasis. Deletion of Fbxw7 in murine BM-derived stromal cells induced accumulation of NOTCH and consequent transcriptional activation of Ccl2. FBXW7-deficient mice exhibited increased serum levels of the chemokine CCL2, which resulted in the recruitment of both monocytic myeloid-derived suppressor cells and macrophages, thereby promoting metastatic tumor growth. Administration of a CCL2 receptor antagonist blocked the enhancement of metastasis in FBXW7-deficient mice. Furthermore, in human breast cancer patients, FBXW7 expression in peripheral blood was associated with serum CCL2 concentration and disease prognosis. Together, these results suggest that FBXW7 antagonizes cancer development in not only a cell-autonomous manner, but also a non-cell-autonomous manner, and that modulation of the FBXW7/NOTCH/CCL2 axis may provide a potential approach to suppression of cancer metastasis. PMID:25555218

Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes

PubMed Central

Eng, George; Lee, Benjamin W.; Protas, Lev; Gagliardi, Mark; Brown, Kristy; Kass, Robert S.; Keller, Gordon; Robinson, Richard B.; Vunjak-Novakovic, Gordana

2016-01-01

The therapeutic success of human stem cell-derived cardiomyocytes critically depends on their ability to respond to and integrate with the surrounding electromechanical environment. Currently, the immaturity of human cardiomyocytes derived from stem cells limits their utility for regenerative medicine and biological research. We hypothesize that biomimetic electrical signals regulate the intrinsic beating properties of cardiomyocytes. Here we show that electrical conditioning of human stem cell-derived cardiomyocytes in three-dimensional culture promotes cardiomyocyte maturation, alters their automaticity and enhances connexin expression. Cardiomyocytes adapt their autonomous beating rate to the frequency at which they were stimulated, an effect mediated by the emergence of a rapidly depolarizing cell population, and the expression of hERG. This rate-adaptive behaviour is long lasting and transferable to the surrounding cardiomyocytes. Thus, electrical conditioning may be used to promote cardiomyocyte maturation and establish their automaticity, with implications for cell-based reduction of arrhythmia during heart regeneration. PMID:26785135

Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children.

PubMed

Kroenke, Candyce H; Epel, Elissa; Adler, Nancy; Bush, Nicole R; Obradovic, Jelena; Lin, Jue; Blackburn, Elizabeth; Stamperdahl, Juliet Lise; Boyce, W Thomas

2011-09-01

To examine associations between autonomic nervous system and adrenocortical reactivity to laboratory stressors and buccal cell telomere length (BTL) in children. The study sample comprised 78 children, aged 5 to 6 years, from a longitudinal cohort study of kindergarten social hierarchies, biologic responses to adversity, and child health. Buccal cell samples and reactivity measures were collected in the spring of the kindergarten year. BTL was measured by real-time polymerase chain reaction, as the telomere-to-single-copy gene ratio. Parents provided demographic information; parents and teachers reported children's internalizing and externalizing behavior problems. Components of children's autonomic (heart rate, respiratory sinus arrhythmia [RSA], and preejection period [PEP]) and adrenocortical (salivary cortisol) responses were monitored during standardized laboratory challenges. We examined relationships between reactivity, internalizing and externalizing behaviors, and BTL, adjusted for age, race, and sex. Heart rate and cortisol reactivity were inversely related to BTL, PEP was positively related to BTL, and RSA was unrelated to BTL. Internalizing behaviors were also inversely related to BTL (standardized β = -0.33, p = .004). Split at the median of reactivity parameters, children with high sympathetic activation (decreasing PEP), and parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL. However, children with both this profile and high cortisol reactivity (n = 12) had significantly shorter BTL (0.80 versus 1.00; χ² = 7.6, p = .006), compared with other children. The combination of autonomic and adrenocortical reactivity was associated with shorter BTL in children. These data suggest that psychophysiological processes may influence, and that BTL may be a useful marker of, early biologic aging.

Autonomic nervous system involvement in sickle cell disease.

PubMed

Coates, Thomas D; Chalacheva, Patjanaporn; Zeltzer, Lonnie; Khoo, Michael C K

2018-01-01

Sickle cell disease (SCD) is a genetic disorder of hemoglobin producing hemoglobin-S (HbS) and resulting in recurrent severe episodes of pain, organ damage and premature death due to vaso- occlusion. Deoxy HbS polymerizes, causing red cells to become rigid and lodge in the microvasculature if they do not escape into larger vessels before this transformation occurs. The mechanism that triggers this transition from steady state to vaso-occlusive crisis (VOC) is not known. Patients state that cold, emotional stress, and pain itself can trigger these events. In spite of the connection between these symptoms and the autonomic nervous system (ANS), and the fact that the ANS regulates regional microvascular blood flow, the role of the ANS in sickle pathophysiology has not been significantly investigated. We will briefly review the mechanism of SCD vaso-occlusion, the dysautonomia associated with SCD and sickle trait, and the role that the ANS may play in the genesis of sickle vaso-occlusive crisis.

HIF-1α regulates epithelial inflammation by cell autonomous NFκB activation and paracrine stromal remodeling

PubMed Central

Scortegagna, Marzia; Cataisson, Christophe; Martin, Rebecca J.; Hicklin, Daniel J.; Schreiber, Robert D.; Yuspa, Stuart H.

2008-01-01

Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non–cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor κ B (NFκB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1–induced NFκB activation was composed of 2 elements, IκB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFκB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFα) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFα immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFκB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression. PMID:18199827

Drosophila heart cell movement to the midline occurs through both cell autonomous migration and dorsal closure.

PubMed

Haack, Timm; Schneider, Matthias; Schwendele, Bernd; Renault, Andrew D

2014-12-15

The Drosophila heart is a linear organ formed by the movement of bilaterally specified progenitor cells to the midline and adherence of contralateral heart cells. This movement occurs through the attachment of heart cells to the overlying ectoderm which is undergoing dorsal closure. Therefore heart cells are thought to move to the midline passively. Through live imaging experiments and analysis of mutants that affect the speed of dorsal closure we show that heart cells in Drosophila are autonomously migratory and part of their movement to the midline is independent of the ectoderm. This means that heart formation in flies is more similar to that in vertebrates than previously thought. We also show that defects in dorsal closure can result in failure of the amnioserosa to properly degenerate, which can physically hinder joining of contralateral heart cells leading to a broken heart phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

Loss of MeCP2 disrupts cell autonomous and autocrine BDNF signaling in mouse glutamatergic neurons

PubMed Central

Sampathkumar, Charanya; Wu, Yuan-Ju; Vadhvani, Mayur; Trimbuch, Thorsten; Eickholt, Britta; Rosenmund, Christian

2016-01-01

Mutations in the MECP2 gene cause the neurodevelopmental disorder Rett syndrome (RTT). Previous studies have shown that altered MeCP2 levels result in aberrant neurite outgrowth and glutamatergic synapse formation. However, causal molecular mechanisms are not well understood since MeCP2 is known to regulate transcription of a wide range of target genes. Here, we describe a key role for a constitutive BDNF feed forward signaling pathway in regulating synaptic response, general growth and differentiation of glutamatergic neurons. Chronic block of TrkB receptors mimics the MeCP2 deficiency in wildtype glutamatergic neurons, while re-expression of BDNF quantitatively rescues MeCP2 deficiency. We show that BDNF acts cell autonomous and autocrine, as wildtype neurons are not capable of rescuing growth deficits in neighboring MeCP2 deficient neurons in vitro and in vivo. These findings are relevant for understanding RTT pathophysiology, wherein wildtype and mutant neurons are intermixed throughout the nervous system. DOI: http://dx.doi.org/10.7554/eLife.19374.001 PMID:27782879

Power optimization in body sensor networks: the case of an autonomous wireless EMG sensor powered by PV-cells.

PubMed

Penders, J; Pop, V; Caballero, L; van de Molengraft, J; van Schaijk, R; Vullers, R; Van Hoof, C

2010-01-01

Recent advances in ultra-low-power circuits and energy harvesters are making self-powered body sensor nodes a reality. Power optimization at the system and application level is crucial in achieving ultra-low-power consumption for the entire system. This paper reviews system-level power optimization techniques, and illustrates their impact on the case of autonomous wireless EMG monitoring. The resulting prototype, an Autonomous wireless EMG sensor power by PV-cells, is presented.

Cell-Autonomous Control of IL-7 Response Revealed In a Novel Stage of Precursor B Cells

PubMed Central

Sandoval, Gabriel J.; Graham, Daniel B.; Bhattacharya, Deepta; Sleckman, Barry P.; Xavier, Ramnik J.; Swat, Wojciech

2013-01-01

During early stages of B-lineage differentiation in bone marrow, signals emanating from IL-7 receptor and pre-B cell receptor (pre-BCR) are thought to synergistically induce proliferative expansion of progenitor cells. Paradoxically, loss of pre-BCR signaling components is associated with leukemia in both mice and humans. Exactly how progenitor B cells perform the task of balancing proliferative burst dependent on IL-7 with the termination of IL-7 signals and the initiation of LC gene rearrangement remains to be elucidated. In this report, we provide genetic and functional evidence that the cessation of IL-7 response of pre-B cells is controlled via a cell-autonomous mechanism that operates at a discreet developmental transition inside Fraction C’ (Large Pre-BII) marked by transient expression of c-Myc. Our data indicates that pre-BCR cooperates with IL-7R in expanding pre-B cell pool, but it is also critical to control differentiation program shutting off c-Myc gene in large pre-B cells. PMID:23420891

A mechanistic framework for noncell autonomous stem cell induction in Arabidopsis.

PubMed

Daum, Gabor; Medzihradszky, Anna; Suzaki, Takuya; Lohmann, Jan U

2014-10-07

Cell-cell communication is essential for multicellular development and, consequently, evolution has brought about an array of distinct mechanisms serving this purpose. Consistently, induction and maintenance of stem cell fate by noncell autonomous signals is a feature shared by many organisms and may depend on secreted factors, direct cell-cell contact, matrix interactions, or a combination of these mechanisms. Although many basic cellular processes are well conserved between animals and plants, cell-to-cell signaling is one function where substantial diversity has arisen between the two kingdoms of life. One of the most striking differences is the presence of cytoplasmic bridges, called plasmodesmata, which facilitate the exchange of molecules between neighboring plant cells and provide a unique route for cell-cell communication in the plant lineage. Here, we provide evidence that the stem cell inducing transcription factor WUSCHEL (WUS), expressed in the niche, moves to the stem cells via plasmodesmata in a highly regulated fashion and that this movement is required for WUS function and, thus, stem cell activity in Arabidopsis thaliana. We show that cell context-independent mobility is encoded in the WUS protein sequence and mediated by multiple domains. Finally, we demonstrate that parts of the protein that restrict movement are required for WUS homodimerization, suggesting that formation of WUS dimers might contribute to the regulation of apical stem cell activity.

Agent Technology, Complex Adaptive Systems, and Autonomic Systems: Their Relationships

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Rash, James; Rouff, Chistopher; Hincheny, Mike

2004-01-01

To reduce the cost of future spaceflight missions and to perform new science, NASA has been investigating autonomous ground and space flight systems. These goals of cost reduction have been further complicated by nanosatellites for future science data-gathering which will have large communications delays and at times be out of contact with ground control for extended periods of time. This paper describes two prototype agent-based systems, the Lights-out Ground Operations System (LOGOS) and the Agent Concept Testbed (ACT), and their autonomic properties that were developed at NASA Goddard Space Flight Center (GSFC) to demonstrate autonomous operations of future space flight missions. The paper discusses the architecture of the two agent-based systems, operational scenarios of both, and the two systems autonomic properties.

Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity.

PubMed

Marusyk, Andriy; Tabassum, Doris P; Altrock, Philipp M; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia

2014-10-02

Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumours. The mechanisms responsible for the coexistence of distinct sub-clones and the biological consequences of this coexistence remain poorly understood. Here we used a mouse xenograft model to investigate the impact of sub-clonal heterogeneity on tumour phenotypes and the competitive expansion of individual clones. We found that tumour growth can be driven by a minor cell subpopulation, which enhances the proliferation of all cells within a tumour by overcoming environmental constraints and yet can be outcompeted by faster proliferating competitors, resulting in tumour collapse. We developed a mathematical modelling framework to identify the rules underlying the generation of intra-tumour clonal heterogeneity. We found that non-cell-autonomous driving of tumour growth, together with clonal interference, stabilizes sub-clonal heterogeneity, thereby enabling inter-clonal interactions that can lead to new phenotypic traits.

Framing the ultimatum game: gender differences and autonomic responses.

PubMed

Sarlo, Michela; Lotto, Lorella; Palomba, Daniela; Scozzari, Simona; Rumiati, Rino

2013-01-01

The present study aimed at investigating whether the way offers are framed in the Ultimatum Game (UG) affects behavioral and autonomic responses in men and women. The "I give you" and "I take" expressions were used as gain and loss frames, respectively. Skin conductance and heart rate were recorded as indices of autonomic activation in response to unfair, mid-value, and fair offers. Acceptance rates were higher in men than in women under the gain frame. Moreover, men showed higher acceptance rates under the gain than under the loss frame with mid-value offers, whereas women's choices were not affected by frame. On the physiological level, men produced differential autonomic response patterns during decision-making when offers were presented under gain and loss framing. The "I take" frame, by acting as a loss frame, elicited in men the characteristic defensive response pattern that is evoked by aversive stimulation, in which increases in skin conductance are coupled with increases in heart rate. On the other hand, the "I give you" frame, by acting as a gain frame, elicited in men increases in skin conductance associated with prevailing heart rate deceleratory responses, reflecting a state of enhanced attention and orienting. In contrast, women's autonomic reactivity was not affected by frame, consistent with behavioral results. Phasic changes in heart rate were crucial in revealing differential functional significance of skin conductance responses under different frames in men, thus questioning the assumption that this autonomic measure can be used as an index of negative emotional arousal in the UG.

Amnioserosa cell constriction but not epidermal actin cable tension autonomously drives dorsal closure.

PubMed

Pasakarnis, Laurynas; Frei, Erich; Caussinus, Emmanuel; Affolter, Markus; Brunner, Damian

2016-11-01

Tissue morphogenesis requires coordination of multiple force-producing components. During dorsal closure in fly embryogenesis, an epidermis opening closes. A tensioned epidermal actin/MyosinII cable, which surrounds the opening, produces a force that is thought to combine with another MyosinII force mediating apical constriction of the amnioserosa cells that fill the opening. A model proposing that each force could autonomously drive dorsal closure was recently challenged by a model in which the two forces combine in a ratchet mechanism. Acute force elimination via selective MyosinII depletion in one or the other tissue shows that the amnioserosa tissue autonomously drives dorsal closure while the actin/MyosinII cable cannot. These findings exclude both previous models, although a contribution of the ratchet mechanism at dorsal closure onset remains likely. This shifts the current view of dorsal closure being a combinatorial force-component system to a single tissue-driven closure event.

Cell-autonomous defense, re-organization and trafficking of membranes in plant-microbe interactions.

PubMed

Dörmann, Peter; Kim, Hyeran; Ott, Thomas; Schulze-Lefert, Paul; Trujillo, Marco; Wewer, Vera; Hückelhoven, Ralph

2014-12-01

Plant cells dynamically change their architecture and molecular composition following encounters with beneficial or parasitic microbes, a process referred to as host cell reprogramming. Cell-autonomous defense reactions are typically polarized to the plant cell periphery underneath microbial contact sites, including de novo cell wall biosynthesis. Alternatively, host cell reprogramming converges in the biogenesis of membrane-enveloped compartments for accommodation of beneficial bacteria or invasive infection structures of filamentous microbes. Recent advances have revealed that, in response to microbial encounters, plasma membrane symmetry is broken, membrane tethering and SNARE complexes are recruited, lipid composition changes and plasma membrane-to-cytoskeleton signaling is activated, either for pre-invasive defense or for microbial entry. We provide a critical appraisal on recent studies with a focus on how plant cells re-structure membranes and the associated cytoskeleton in interactions with microbial pathogens, nitrogen-fixing rhizobia and mycorrhiza fungi. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Long-Term Dynamics of Autonomous Fractional Differential Equations

NASA Astrophysics Data System (ADS)

Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

Programming Enzyme-Initiated Autonomous DNAzyme Nanodevices in Living Cells.

PubMed

Chen, Feng; Bai, Min; Cao, Ke; Zhao, Yue; Cao, Xiaowen; Wei, Jing; Wu, Na; Li, Jiang; Wang, Lihua; Fan, Chunhai; Zhao, Yongxi

2017-12-26

Molecular nanodevices are computational assemblers that switch defined states upon external stimulation. However, interfacing artificial nanodevices with natural molecular machineries in living cells remains a great challenge. Here, we delineate a generic method for programming assembly of enzyme-initiated DNAzyme nanodevices (DzNanos). Two programs including split assembly of two partzymes and toehold exchange displacement assembly of one intact DNAzyme initiated by telomerase are computed. The intact one obtains higher assembly yield and catalytic performance ascribed to proper conformation folding and active misplaced assembly. By employing MnO 2 nanosheets as both DNA carriers and source of Mn 2+ as DNAzyme cofactor, we find that this DzNano is well assembled via a series of conformational states in living cells and operates autonomously with sustained cleavage activity. Other enzymes can also induce corresponding DzNano assembly with defined programming modules. These DzNanos not only can monitor enzyme catalysis in situ but also will enable the implementation of cellular stages, behaviors, and pathways for basic science, diagnostic, and therapeutic applications as genetic circuits.

Cardiomyocyte Circadian Oscillations Are Cell-Autonomous, Amplified by β-Adrenergic Signaling, and Synchronized in Cardiac Ventricle Tissue

PubMed Central

Welsh, David K.

2016-01-01

Circadian clocks impact vital cardiac parameters such as blood pressure and heart rate, and adverse cardiac events such as myocardial infarction and sudden cardiac death. In mammals, the central circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, synchronizes cellular circadian clocks in the heart and many other tissues throughout the body. Cardiac ventricle explants maintain autonomous contractions and robust circadian oscillations of clock gene expression in culture. In the present study, we examined the relationship between intrinsic myocardial function and circadian rhythms in cultures from mouse heart. We cultured ventricular explants or dispersed cardiomyocytes from neonatal mice expressing a PER2::LUC bioluminescent reporter of circadian clock gene expression. We found that isoproterenol, a β-adrenoceptor agonist known to increase heart rate and contractility, also amplifies PER2 circadian rhythms in ventricular explants. We found robust, cell-autonomous PER2 circadian rhythms in dispersed cardiomyocytes. Single-cell rhythms were initially synchronized in ventricular explants but desynchronized in dispersed cells. In addition, we developed a method for long-term, simultaneous monitoring of clock gene expression, contraction rate, and basal intracellular Ca2+ level in cardiomyocytes using PER2::LUC in combination with GCaMP3, a genetically encoded fluorescent Ca2+ reporter. In contrast to robust PER2 circadian rhythms in cardiomyocytes, we detected no rhythms in contraction rate and only weak rhythms in basal Ca2+ level. In summary, we found that PER2 circadian rhythms of cardiomyocytes are cell-autonomous, amplified by adrenergic signaling, and synchronized by intercellular communication in ventricle explants, but we detected no robust circadian rhythms in contraction rate or basal Ca2+. PMID:27459195

Thymus-autonomous T cell development in the absence of progenitor import.

PubMed

Martins, Vera C; Ruggiero, Eliana; Schlenner, Susan M; Madan, Vikas; Schmidt, Manfred; Fink, Pamela J; von Kalle, Christof; Rodewald, Hans-Reimer

2012-07-30

Thymus function is thought to depend on a steady supply of T cell progenitors from the bone marrow. The notion that the thymus lacks progenitors with self-renewal capacity is based on thymus transplantation experiments in which host-derived thymocytes replaced thymus-resident cells within 4 wk. Thymus grafting into T cell-deficient mice resulted in a wave of T cell export from the thymus, followed by colonization of the thymus by host-derived progenitors, and cessation of T cell development. Compound Rag2(-/-)γ(c)(-/-)Kit(W/Wv) mutants lack competitive hematopoietic stem cells (HSCs) and are devoid of T cell progenitors. In this study, using this strain as recipients for wild-type thymus grafts, we noticed thymus-autonomous T cell development lasting several months. However, we found no evidence for export of donor HSCs from thymus to bone marrow. A diverse T cell antigen receptor repertoire in progenitor-deprived thymus grafts implied that many thymocytes were capable of self-renewal. Although the process was most efficient in Rag2(-/-)γ(c)(-/-)Kit(W/Wv) hosts, γ(c)-mediated signals alone played a key role in the competition between thymus-resident and bone marrow-derived progenitors. Hence, the turnover of each generation of thymocytes is not only based on short life span but is also driven via expulsion of resident thymocytes by fresh progenitors entering the thymus.

RoBlock: a prototype autonomous manufacturing cell

NASA Astrophysics Data System (ADS)

Baekdal, Lars K.; Balslev, Ivar; Eriksen, Rene D.; Jensen, Soren P.; Jorgensen, Bo N.; Kirstein, Brian; Kristensen, Bent B.; Olsen, Martin M.; Perram, John W.; Petersen, Henrik G.; Petersen, Morten L.; Ruhoff, Peter T.; Skjolstrup, Carl E.; Sorensen, Anders S.; Wagenaar, Jeroen M.

2000-10-01

RoBlock is the first phase of an internally financed project at the Institute aimed at building a system in which two industrial robots suspended from a gantry, as shown below, cooperate to perform a task specified by an external user, in this case, assembling an unstructured collection of colored wooden blocks into a specified 3D pattern. The blocks are identified and localized using computer vision and grasped with a suction cup mechanism. Future phases of the project will involve other processes such as grasping and lifting, as well as other types of robot such as autonomous vehicles or variable geometry trusses. Innovative features of the control software system include: The use of an advanced trajectory planning system which ensures collision avoidance based on a generalization of the method of artificial potential fields, the use of a generic model-based controller which learns the values of parameters, including static and kinetic friction, of a detailed mechanical model of itself by comparing actual with planned movements, the use of fast, flexible, and robust pattern recognition and 3D-interpretation strategies, integration of trajectory planning and control with the sensor systems in a distributed Java application running on a network of PC's attached to the individual physical components. In designing this first stage, the aim was to build in the minimum complexity necessary to make the system non-trivially autonomous and to minimize the technological risks. The aims of this project, which is planned to be operational during 2000, are as follows: To provide a platform for carrying out experimental research in multi-agent systems and autonomous manufacturing systems, to test the interdisciplinary cooperation architecture of the Maersk Institute, in which researchers in the fields of applied mathematics (modeling the physical world), software engineering (modeling the system) and sensor/actuator technology (relating the virtual and real worlds) could

RB inactivation in keratin 18 positive thymic epithelial cells promotes non-cell autonomous T cell hyperproliferation in genetically engineered mice.

PubMed

Song, Yurong; Sullivan, Teresa; Klarmann, Kimberly; Gilbert, Debra; O'Sullivan, T Norene; Lu, Lucy; Wang, Sophie; Haines, Diana C; Van Dyke, Terry; Keller, Jonathan R

2017-01-01

Thymic epithelial cells (TEC), as part of thymic stroma, provide essential growth factors/cytokines and self-antigens to support T cell development and selection. Deletion of Rb family proteins in adult thymic stroma leads to T cell hyperplasia in vivo. To determine whether deletion of Rb specifically in keratin (K) 18 positive TEC was sufficient for thymocyte hyperplasia, we conditionally inactivated Rb and its family members p107 and p130 in K18+ TEC in genetically engineered mice (TgK18GT121; K18 mice). We found that thymocyte hyperproliferation was induced in mice with Rb inactivation in K18+ TEC, while normal T cell development was maintained; suggesting that inactivation of Rb specifically in K18+ TEC was sufficient and responsible for the phenotype. Transplantation of wild type bone marrow cells into mice with Rb inactivation in K18+ TEC resulted in donor T lymphocyte hyperplasia confirming the non-cell autonomous requirement for Rb proteins in K18+ TEC in regulating T cell proliferation. Our data suggests that thymic epithelial cells play an important role in regulating lymphoid proliferation and thymus size.

Cell-autonomous CCL5 transcription by memory CD8 T cells is regulated by IL-4.

PubMed

Marçais, Antoine; Coupet, Charles-Antoine; Walzer, Thierry; Tomkowiak, Martine; Ghittoni, Raffaella; Marvel, Jacqueline

2006-10-01

Immunological memory is associated with the display of improved effector functions. The maintenance by CD8 memory cells of high levels of untranslated CCL5 mRNA allows these cells to immediately secrete this chemokine upon Ag stimulation. Untranslated mRNA storage is a newly described process supporting the immediate display of an effector function by memory lymphocytes. We have tested the capacity of different cytokines to regulate the memorization of CCL5 by memory CD8 T cells. We found that IL-4 treatment of murine CD8 T cells impairs immediate CCL5 secretion capacity by inhibiting CCL5 mRNA transcription through a STAT6-dependent pathway. The inhibition by IL-4 is reversible, as memory CD8 T cells reconstitute their CCL5 mRNA stores and reacquire their immediate CCL5 secretion capacity when IL-4 is withdrawn. This recovery is cell autonomous because it proceeds in culture medium in the absence of exogenous growth factors, suggesting that CCL5 expression by memory CD8 T cells is a default process. Overall, these results indicate that the expression of CCL5 is an intrinsic property acquired by memory CD8 T cells that is regulated by environmental factors.

Multiple circadian transcriptional elements cooperatively regulate cell-autonomous transcriptional oscillation of Period3, a mammalian clock gene.

PubMed

Matsumura, Ritsuko; Akashi, Makoto

2017-09-29

Cell-autonomous oscillation in clock gene expression drives circadian rhythms. The development of comprehensive analytical techniques, such as bioinformatics and ChIP-sequencing, has enabled the genome-wide identification of potential circadian transcriptional elements that regulate the transcriptional oscillation of clock genes. However, detailed analyses using traditional biochemical and molecular-biological approaches, such as binding and reporter assays, are still necessary to determine whether these potential circadian transcriptional elements are actually functional and how significantly they contribute to driving transcriptional oscillation. Here, we focused on the molecular mechanism of transcriptional oscillations in the mammalian clock gene Period3 ( Per3 ). The PER3 protein is essential for robust peripheral clocks and is a key component in circadian output processes. We found three E box-like elements located upstream of human Per3 transcription start sites that additively contributed to cell-autonomous transcriptional oscillation. However, we also found that Per3 is still expressed in a circadian manner when all three E box-like elements are functionally impaired. We noted that Per3 transcription was activated by the synergistic actions of two D box-like elements and the three E box-like elements, leading to a drastic increase in circadian amplitude. Interestingly, circadian expression of Per3 was completely disrupted only when all five transcriptional elements were functionally impaired. These results indicate that three E box-like and two D box-like elements cooperatively and redundantly regulate cell-autonomous transcriptional oscillation of Per3 . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Autonomous and Autonomic Swarms

NASA Technical Reports Server (NTRS)

Hinchey, Michael G.; Rash, James L.; Truszkowski, Walter F.; Rouff, Christopher A.; Sterritt, Roy

2005-01-01

A watershed in systems engineering is represented by the advent of swarm-based systems that accomplish missions through cooperative action by a (large) group of autonomous individuals each having simple capabilities and no global knowledge of the group s objective. Such systems, with individuals capable of surviving in hostile environments, pose unprecedented challenges to system developers. Design and testing and verification at much higher levels will be required, together with the corresponding tools, to bring such systems to fruition. Concepts for possible future NASA space exploration missions include autonomous, autonomic swarms. Engineering swarm-based missions begins with understanding autonomy and autonomicity and how to design, test, and verify systems that have those properties and, simultaneously, the capability to accomplish prescribed mission goals. Formal methods-based technologies, both projected and in development, are described in terms of their potential utility to swarm-based system developers.

Autonomic regulation of hepatic glucose production.

PubMed

Bisschop, Peter H; Fliers, Eric; Kalsbeek, Andries

2015-01-01

Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine-based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process. © 2014 American Physiological Society.

Human Induced Hepatic Lineage-Oriented Stem Cells: Autonomous Specification of Human iPS Cells toward Hepatocyte-Like Cells without Any Exogenous Differentiation Factors

PubMed Central

Yanagi, Satoshi; Kato, Chika; Takashima, Ryokichi; Kobayashi, Eiji; Hagiwara, Keitaro; Ochiya, Takahiro

2015-01-01

Preparing targeted cells for medical applications from human induced pluripotent stem cells (hiPSCs) using growth factors, compounds, or gene transfer has been challenging. Here, we report that human induced hepatic lineage-oriented stem cells (hiHSCs) were generated and expanded as a new type of hiPSC under non-typical coculture with feeder cells in a chemically defined hiPSC medium at a very high density. Self-renewing hiHSCs expressed markers of both human embryonic stem cells (hESCs) and hepatocytes. Those cells were highly expandable, markedly enhancing gene expression of serum hepatic proteins and cytochrome P450 enzymes with the omission of FGF-2 from an undefined hiPSC medium. The hepatic specification of hiHSCs was not attributable to the genetic and epigenetic backgrounds of the starting cells, as they were established from distinct donors and different types of cells. Approximately 90% of hiHSCs autonomously differentiated to hepatocyte-like cells, even in a defined minimum medium without any of the exogenous growth factors necessary for hepatic specification. After 12 days of this culture, the differentiated cells significantly enhanced gene expression of serum hepatic proteins (ALB, SERPINA1, TTR, TF, FABP1, FGG, AGT, RBP4, and AHSG), conjugating enzymes (UGT2B4, UGT2B7, UGT2B10, GSTA2, and GSTA5), transporters (SULT2A1, SLC13A5, and SLCO2B1), and urea cycle-related enzymes (ARG1 and CPS1). In addition, the hepatocyte-like cells performed key functions of urea synthesis, albumin secretion, glycogen storage, indocyanine green uptake, and low-density lipoprotein uptake. The autonomous hepatic specification of hiHSCs was due to their culture conditions (coculture with feeder cells in a defined hiPSC medium at a very high density) in self-renewal rather than in differentiation. These results suggest the feasibility of preparing large quantities of hepatocytes as a convenient and inexpensive hiPSC differentiation. Our study also suggests the necessity of

A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes

PubMed Central

Nakahata, Yasukazu; Yoshida, Mayumi; Takano, Atsuko; Soma, Haruhiko; Yamamoto, Takuro; Yasuda, Akio; Nakatsu, Toru; Takumi, Toru

2008-01-01

Background The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-box (CACGTG). The non-canonical E-boxes or E-box-like sequences have also been reported to be necessary for circadian oscillation. Results We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-box or a non-canonical E-box and an E-box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-box or E-box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-box-like elements in their promoter region. Conclusion We propose a novel possible mechanism regulated by double E-box-like elements, not to a single E-box, for circadian transcriptional oscillation. The direct repeat of the E-box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes. PMID:18177499

TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans

PubMed Central

McCallum, Katie C.; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A.

2016-01-01

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. PMID:26920757

TRX-1 Regulates SKN-1 Nuclear Localization Cell Non-autonomously in Caenorhabditis elegans.

PubMed

McCallum, Katie C; Liu, Bin; Fierro-González, Juan Carlos; Swoboda, Peter; Arur, Swathi; Miranda-Vizuete, Antonio; Garsin, Danielle A

2016-05-01

The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins, TRX-2 and TRX-3, do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK-signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, classical SKN-1 transcriptional activity associated with stress response remains largely unaffected. Interestingly, RNA-Seq analysis revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport being most prevalent. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Copyright © 2016 by the Genetics Society of America.

Role of redox signaling in the autonomous proliferative response of endothelial cells to hypoxia.

PubMed

Schäfer, M; Schäfer, C; Ewald, N; Piper, H M; Noll, Th

2003-05-16

Endothelial cells exhibit an autonomous proliferative response to hypoxia, independent of paracrine effectors. In cultured endothelial cells of porcine aorta, we analyzed the signaling of this response, with a focus on the roles of redox signaling and the MEK/ERK pathway. Transient hypoxia (1 hour) stimulated proliferation by 61+/-4% (n=16; P<0.05 versus control), quantified after 24 hours normoxic postincubation. Hypoxia induced an activation of ERK2 and of NAD(P)H oxidase and a burst of reactive oxygen species (ROS), determined by DCF fluorescence. To inhibit the MEK/ERK pathway, we used PD 98059 (PD, 20 micromol/L); to downregulate NAD(P)H oxidase, we applied p22phox antisense oligonucleotides; and to inhibit mitochondrial ROS generation, we used the ubiquinone derivate mitoQ (MQ, 10 micromol/L). All three inhibitions suppressed the proliferative response: PD inhibited NAD(P)H oxidase activation; p22phox antisense transfection did not inhibit ERK2 activation, but suppressed ROS production; and MQ inhibited ERK2 activation and ROS production. The autonomous proliferative response depends on the MEK/ERK pathway and redox signaling steps upstream and downstream of ERK. Located upstream is ROS generation by mitochondria, downstream is NAD(P)H oxidase.

From Extended Nanofluidics to an Autonomous Solar-Light-Driven Micro Fuel-Cell Device.

PubMed

Pihosh, Yuriy; Uemura, Jin; Turkevych, Ivan; Mawatari, Kazuma; Kazoe, Yutaka; Smirnova, Adelina; Kitamori, Takehiko

2017-07-03

Autonomous micro/nano mechanical, chemical, and biomedical sensors require persistent power sources scaled to their size. Realization of autonomous micro-power sources is a challenging task, as it requires combination of wireless energy supply, conversion, storage, and delivery to the sensor. Herein, we realized a solar-light-driven power source that consists of a micro fuel cell (μFC) and a photocatalytic micro fuel generator (μFG) integrated on a single microfluidic chip. The μFG produces hydrogen by photocatalytic water splitting under solar light. The hydrogen fuel is then consumed by the μFC to generate electricity. Importantly, the by-product water returns back to the photocatalytic μFG via recirculation loop without losses. Both devices rely on novel phenomena in extended-nano-fluidic channels that ensure ultra-fast proton transport. As a proof of concept, we demonstrate that μFG/μFC source achieves remarkable energy density of ca. 17.2 mWh cm -2 at room temperature. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photonic Microhand with Autonomous Action.

PubMed

Martella, Daniele; Nocentini, Sara; Nuzhdin, Dmitry; Parmeggiani, Camilla; Wiersma, Diederik S

2017-11-01

Grabbing and holding objects at the microscale is a complex function, even for microscopic living animals. Inspired by the hominid-type hand, a microscopic equivalent able to catch microelements is engineered. This microhand is light sensitive and can be either remotely controlled by optical illumination or can act autonomously and grab small particles on the basis of their optical properties. Since the energy is delivered optically, without the need for wires or batteries, the artificial hand can be shrunk down to the micrometer scale. Soft material is used, in particular, a custom-made liquid-crystal network that is patterned by a photolithographic technique. The elastic reshaping properties of this material allow finger movement, using environmental light as the only energy source. The hand can be either controlled externally (via the light field), or else the conditions in which it autonomously grabs a particle in its vicinity can be created. This microrobot has the unique feature that it can distinguish between particles of different colors and gray levels. The realization of this autonomous hand constitutes a crucial element in the development of microscopic creatures that can perform tasks without human intervention and self-organized automation at the micrometer scale. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.

PubMed

Liao, W; Bisgrove, B W; Sawyer, H; Hug, B; Bell, B; Peters, K; Grunwald, D J; Stainier, D Y

1997-01-01

The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood

Autonomous Instrument Placement for Mars Exploration Rovers

NASA Technical Reports Server (NTRS)

Leger, P. Chris; Maimone, Mark

2009-01-01

Autonomous Instrument Placement (AutoPlace) is onboard software that enables a Mars Exploration Rover to act autonomously in using its manipulator to place scientific instruments on or near designated rock and soil targets. Prior to the development of AutoPlace, it was necessary for human operators on Earth to plan every motion of the manipulator arm in a time-consuming process that included downlinking of images from the rover, analysis of images and creation of commands, and uplinking of commands to the rover. AutoPlace incorporates image analysis and planning algorithms into the onboard rover software, eliminating the need for the downlink/uplink command cycle. Many of these algorithms are derived from the existing groundbased image analysis and planning algorithms, with modifications and augmentations for onboard use.

A translational in vivo model of trigeminal autonomic cephalalgias: therapeutic characterization.

PubMed

Akerman, Simon; Holland, Philip R; Summ, Oliver; Lasalandra, Michele P; Goadsby, Peter J

2012-12-01

Trigeminal autonomic cephalalgias are highly disabling primary headache disorders, characterized by severe unilateral head pain and associated ipsilateral cranial autonomic features. There is limited understanding of their pathophysiology and how and where treatments act to reduce symptoms; this is significantly hindered by a lack of animal models. We have developed the first animal model to explore trigeminal autonomic cephalalgias, using stimulation within the brainstem, at the level of the superior salivatory nucleus, to activate the trigeminal autonomic reflex arc. Using electrophysiological recording of neurons of the trigeminocervical complex and laser Doppler blood flow changes around the ipsilateral lacrimal duct, superior salivatory nucleus stimulation exhibited both neuronal trigeminovascular and cranial autonomic manifestations. These responses were specifically inhibited by the autonomic ganglion blocker hexamethonium bromide. These data demonstrate that brainstem activation may be the driver of both sensory and autonomic symptoms in these disorders, and part of this activation may be via the parasympathetic outflow to the cranial vasculature. Additionally, both sensory and autonomic manifestations were significantly inhibited by highly effective treatments for trigeminal autonomic cephalalgias, such as oxygen, indomethacin and triptans, and some part of their therapeutic action appears to be specifically on the parasympathetic outflow to the cranial vasculature. Treatments more used to migraine, such as naproxen and a calcitonin gene-related peptide receptor inhibitor, olcegepant, were less effective in this model. This is the first model to represent the phenotype of trigeminal autonomic cephalalgias and their response to therapies, and indicates the parasympathetic pathway may be uniquely involved in their pathophysiology and targeted to relieve symptoms.

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons.

PubMed

Heilman, Patrick L; Song, SungWon; Miranda, Carlos J; Meyer, Kathrin; Srivastava, Amit K; Knapp, Amy; Wier, Christopher G; Kaspar, Brian K; Kolb, Stephen J

2017-11-01

Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional protein chaperone. Mutations in HSPB1 result in the development of a late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences of HSPB1 mutations associated with hereditary neuropathy are unknown. HSPB1 also displays neuroprotective properties in many neuronal disease models, including the motor neuron disease amyotrophic lateral sclerosis (ALS). HSPB1 is upregulated in SOD1-ALS animal models during disease progression, predominately in glial cells. Glial cells are known to contribute to motor neuron loss in ALS through a non-cell autonomous mechanism. In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a central role in motor neuron health and maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

Adaxial cell migration in the zebrafish embryo is an active cell autonomous property that requires the Prdm1a transcription factor.

PubMed

Ono, Yosuke; Yu, Weimiao; Jackson, Harriet E; Parkin, Caroline A; Ingham, Philip W

2015-01-01

Adaxial cells, the progenitors of slow-twitch muscle fibres in zebrafish, exhibit a stereotypic migratory behaviour during somitogenesis. Although this process is known to be disrupted in various mutants, its precise nature has remained unclear. Here, using in vivo imaging and chimera analysis, we show that adaxial cell migration is a cell autonomous process, during which cells become polarised and extend filopodia at their leading edge. Loss of function of the Prdm1a transcription factor disrupts the polarisation and migration of adaxial cells, reflecting a role that is independent of its repression of sox6 expression. Expression of the M- and N-cadherins, previously implicated in driving adaxial cell migration, is largely unaffected by loss of Prdm1a function, suggesting that differential cadherin expression is not sufficient for adaxial cell migration. Copyright © 2015 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Critically Reflective Work Behaviour within Autonomous Professionals' Learning Communities

ERIC Educational Resources Information Center

de Groot, Esther; van den Berg, B. A. M.; Endedijk, M. D.; van Beukelen, P.; Simons, P. R. J.

2011-01-01

Informal learning communities in which participants show critically reflective work behaviour (CRWB) have the potential to support lifelong learning. In practice this behaviour does not always occur in groups of autonomous professionals. This study explores design principles (DPs) that could act as social affordances for CRWB, within the context…

Advanced Modular "All in One" Battery System with Intelligent Autonomous Cell Balancing Management

NASA Astrophysics Data System (ADS)

Petitdidier, X.; Pasquier, E.; Defer, M.; Koch, M.; Knorr, W.

2008-09-01

A new generation of energy storage systems based on Li-ion technology emerged at the end of the last century.To perform the first tests in safe conditions, Saft designed a simple electronic.Today, all Li-ion batteries for autonomous applications such as drones, launchers, missiles, torpedoes and "human" applications such as cellular, laptop, hybrid vehicle and nearly sub-marines need a Battery Management System.The minimum in terms of functions is the overcharge and over-discharge protections.For a battery made of 2 cells connected in series or more, a balancing system is added to maintain the available energy during all the life of the battery. For stringent/demanding applications, the state of charge and state of health are calculated by one or more computers.It is now time to take benefit of the past 10 years of Saft's experience in the domain to re-evaluate the constraints of Li-ion batteries and provide customers with improved products by optimizing the battery management.Benefits of electronic for satellite applications:• Full control over battery.• Confidence whatever the possible change of conditions in environment.• The battery system can resist long exposure to gradient conditions with mitigated and stabilized impact on performances.• The balancing function allow to use all the energy of all the cells: optimize of installed energy (compact design, mass saving). It started out with the basic fact that electrochemists are not intended to be space rated electronic experts and vice versa, even if Saft has a good heritage in the electronic battery management system. Consequently, considering heritage and expertise in their respective core businesses, Saft and ASP teamed up.It became necessary to provide an "all in one" modular energy storage system with intelligent autonomous cell balancing management.

Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock

PubMed Central

Webb, Alexis B; Lengyel, Iván M; Jörg, David J; Valentin, Guillaume; Jülicher, Frank; Morelli, Luis G; Oates, Andrew C

2016-01-01

In vertebrate development, the sequential and rhythmic segmentation of the body axis is regulated by a “segmentation clock”. This clock is comprised of a population of coordinated oscillating cells that together produce rhythmic gene expression patterns in the embryo. Whether individual cells autonomously maintain oscillations, or whether oscillations depend on signals from neighboring cells is unknown. Using a transgenic zebrafish reporter line for the cyclic transcription factor Her1, we recorded single tailbud cells in vitro. We demonstrate that individual cells can behave as autonomous cellular oscillators. We described the observed variability in cell behavior using a theory of generic oscillators with correlated noise. Single cells have longer periods and lower precision than the tissue, highlighting the role of collective processes in the segmentation clock. Our work reveals a population of cells from the zebrafish segmentation clock that behave as self-sustained, autonomous oscillators with distinctive noisy dynamics. DOI: http://dx.doi.org/10.7554/eLife.08438.001 PMID:26880542

Checkpoints couple transcription network oscillator dynamics to cell-cycle progression.

PubMed

Bristow, Sara L; Leman, Adam R; Simmons Kovacs, Laura A; Deckard, Anastasia; Harer, John; Haase, Steven B

2014-09-05

The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae. The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. A recent proposal suggests CDK acts as a master regulator of cell-cycle processes that have the potential for autonomous oscillatory behavior. Here we find that mitotic CDK is not sufficient for fully inhibiting transcript oscillations in arrested cells. We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression. Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest.

Multiresolution motion planning for autonomous agents via wavelet-based cell decompositions.

PubMed

Cowlagi, Raghvendra V; Tsiotras, Panagiotis

2012-10-01

We present a path- and motion-planning scheme that is "multiresolution" both in the sense of representing the environment with high accuracy only locally and in the sense of addressing the vehicle kinematic and dynamic constraints only locally. The proposed scheme uses rectangular multiresolution cell decompositions, efficiently generated using the wavelet transform. The wavelet transform is widely used in signal and image processing, with emerging applications in autonomous sensing and perception systems. The proposed motion planner enables the simultaneous use of the wavelet transform in both the perception and in the motion-planning layers of vehicle autonomy, thus potentially reducing online computations. We rigorously prove the completeness of the proposed path-planning scheme, and we provide numerical simulation results to illustrate its efficacy.

The Autonomic Symptom Profile: a new instrument to assess autonomic symptoms

NASA Technical Reports Server (NTRS)

Suarez, G. A.; Opfer-Gehrking, T. L.; Offord, K. P.; Atkinson, E. J.; O'Brien, P. C.; Low, P. A.

1999-01-01

OBJECTIVE: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. BACKGROUND: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. METHODS: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. RESULTS: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (+/-SD) overall COMPASS score was 9.8 (+/-9) in controls, 25.9 (+/-17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (+/-24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. CONCLUSIONS: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

New transmitters and new targets in the autonomic nervous system.

PubMed

Barajas-López, C; Huizinga, J D

1993-12-01

Several recent findings have made research into the autonomic nervous system even more exciting, such as the revelation that nitric oxide is a major neurotransmitter, the delineation of the physiological roles for purines and vasoactive intestinal peptide, and the discovery that the interstitial cells of Cajal are major target cells for enteric innervation. Nitric oxide is probably the major neurotransmitter evoking inhibitory junction potentials in smooth muscle. ATP is a mediator of non-adrenergic non-cholinergic enteric innervation, as well as being a fast neurotransmitter in peripheral and autonomic neuro-neuronal synapses. The interactions between enteric nerves and both immune cells and interstitial cells of Cajal (as pacemaker cells of gut smooth muscle) are forcing a rethink of many aspects of gut physiology.

Autonomic neuropathies

NASA Technical Reports Server (NTRS)

Low, P. A.

1998-01-01

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Pejvakin, a Candidate Stereociliary Rootlet Protein, Regulates Hair Cell Function in a Cell-Autonomous Manner

PubMed Central

Kazmierczak, Piotr; Harris, Suzan L.; Shah, Prahar; Puel, Jean-Luc; Lenoir, Marc

2017-01-01

Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and colocalizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations. Hair cells of pejvakin-deficient mice develop normal rootlets, but hair bundle morphology and mechanotransduction are affected before the onset of hearing. Some mechanotransducing shorter row stereocilia are missing, whereas the remaining ones exhibit overextended tips and a greater variability in height and width. Unlike previous studies of Pjvk alleles with neuronal dysfunction, our findings reveal a cell-autonomous role of pejvakin in maintaining stereocilia architecture that is critical for hair cell function. SIGNIFICANCE STATEMENT Two missense mutations in the Pejvakin (PJVK or DFNB59) gene were first identified in patients with audiological hallmarks of auditory neuropathy spectrum disorder, whereas all other PJVK alleles cause hearing loss of cochlear origin. These findings suggest that complex pathogenetic mechanisms underlie human deafness DFNB59. In contrast to recent studies, we demonstrate that pejvakin in auditory neurons is not essential for normal hearing in mice. Moreover, pejvakin localizes to stereociliary rootlets in hair cells and is required for stereocilia maintenance and mechanosensory function of the hair bundle. Delineating the site of the lesion and the mechanisms underlying DFNB59 will allow clinicians to predict the efficacy of different therapeutic approaches, such as determining compatibility for cochlear implants. PMID:28209736

The autonomic laboratory

NASA Technical Reports Server (NTRS)

Low, P. A.; Opfer-Gehrking, T. L.

1999-01-01

The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

Autonomic deficit not the cause of death in West Nile virus neurological disease.

PubMed

Wang, Hong; Siddharthan, Venkatraman; Hall, Jeffery O; Morrey, John D

2014-02-01

Some West Nile virus (WNV)-infected patients have been reported to manifest disease signs consistent with autonomic dysfunction. Moreover, WNV infection in hamsters causes reduced electromyography amplitudes of the gastrointestinal tract and diaphragm, and they have reduced heart rate variability (HRV), a read-out for the parasympathetic autonomic function. HRV was measured in both hamsters and mice using radiotelemetry to identify autonomic deficits. To identify areas of WNV infection within the medulla oblongata mapping to the dorsal motor nucleus of vagus (DMNV) and the nucleus ambiguus (NA), fluorogold dye was injected into the cervical trunk of the vagus nerve of hamsters. As a measurement of the loss of parasympathetic function, tachycardia was monitored contiguously over the time course of the disease. Decrease of HRV did not occur in all animals that died, which is not consistent with autonomic function being the mechanism of death. Fluorogold-stained cells in the DMNV were not stained for WNV envelope protein. Fourteen percent of WNV-stained cells were co-localized with fluorogold-stained cells in the NA. These data, however, did not suggest a fatal loss of autonomic functions because tachycardia was not observed in WNV-infected hamsters. Parasympathetic autonomic function deficit was not a likely mechanism of death in WNV-infected rodents and possibly in human patients with fatal WN neurological disease.

Nature's Autonomous Oscillators

NASA Technical Reports Server (NTRS)

Mayr, H. G.; Yee, J.-H.; Mayr, M.; Schnetzler, R.

2012-01-01

Nonlinearity is required to produce autonomous oscillations without external time dependent source, and an example is the pendulum clock. The escapement mechanism of the clock imparts an impulse for each swing direction, which keeps the pendulum oscillating at the resonance frequency. Among nature's observed autonomous oscillators, examples are the quasi-biennial oscillation and bimonthly oscillation of the Earth atmosphere, and the 22-year solar oscillation. The oscillations have been simulated in numerical models without external time dependent source, and in Section 2 we summarize the results. Specifically, we shall discuss the nonlinearities that are involved in generating the oscillations, and the processes that produce the periodicities. In biology, insects have flight muscles, which function autonomously with wing frequencies that far exceed the animals' neural capacity; Stretch-activation of muscle contraction is the mechanism that produces the high frequency oscillation of insect flight, discussed in Section 3. The same mechanism is also invoked to explain the functioning of the cardiac muscle. In Section 4, we present a tutorial review of the cardio-vascular system, heart anatomy, and muscle cell physiology, leading up to Starling's Law of the Heart, which supports our notion that the human heart is also a nonlinear oscillator. In Section 5, we offer a broad perspective of the tenuous links between the fluid dynamical oscillators and the human heart physiology.

Autonomic headache with autonomic seizures: a case report.

PubMed

Ozge, Aynur; Kaleagasi, Hakan; Yalçin Tasmertek, Fazilet

2006-10-01

The aim of the report is to present a case of an autonomic headache associated with autonomic seizures. A 19-year-old male who had had complex partial seizures for 15 years was admitted with autonomic complaints and left hemicranial headache, independent from seizures, that he had had for 2 years and were provoked by watching television. Brain magnetic resonance imaging showed right hippocampal sclerosis and electroencephalography revealed epileptic activity in right hemispheric areas. Treatment with valproic acid decreased the complaints. The headache did not fulfil the criteria for the diagnosis of trigeminal autonomic cephalalgias, and was different from epileptic headache, which was defined as a pressing type pain felt over the forehead for several minutes to a few hours. Although epileptic headache responds to anti-epileptics and the complaints of the present case decreased with antiepileptics, it has been suggested that the headache could be a non-trigeminal autonomic headache instead of an epileptic headache.

Homeostatic systems, biocybernetics, and autonomic neuroscience.

PubMed

Goldstein, David S; Kopin, Irwin J

2017-12-01

In this review we describe a series of major concepts introduced during the past 150years that have contributed to our current understanding about how physiological processes required for well-being and survival are regulated. One can theorize that hierarchical networks involving input-output relationships continuously orchestrate and learn adaptive patterns of observable behaviors, cognition, memory, mood, and autonomic systems. Taken together, these networks function as "good regulators" determining levels of internal variables and act as if there were homeostatic comparators ("homeostats"). The consequences of models with vs. without homeostats remain the same in terms of allostatic load and the eventual switch from stabilizing negative feedback loops to destabilizing, pathogenic positive feedback loops. Understanding this switch seems important for comprehending senescence-related, neurodegenerative disorders that involve the autonomic nervous system. Our general proposal is that disintegration of homeostatic systems causes disorders of regulation in degenerative diseases and that medical cybernetics can inspire and rationalize new approaches to treatment and prevention. Published by Elsevier B.V.

Cell-Autonomous Regulation of Dendritic Spine Density by PirB.

PubMed

Vidal, George S; Djurisic, Maja; Brown, Kiana; Sapp, Richard W; Shatz, Carla J

2016-01-01

Synapse density on cortical pyramidal neurons is modulated by experience. This process is highest during developmental critical periods, when mechanisms of synaptic plasticity are fully engaged. In mouse visual cortex, the critical period for ocular dominance (OD) plasticity coincides with the developmental pruning of synapses. At this time, mice lacking paired Ig-like receptor B (PirB) have excess numbers of dendritic spines on L5 neurons; these spines persist and are thought to underlie the juvenile-like OD plasticity observed in adulthood. Here we examine whether PirB is required specifically in excitatory neurons to exert its effect on dendritic spine and synapse density during the critical period. In mice with a conditional allele of PirB (PirB fl/fl ), PirB was deleted only from L2/3 cortical pyramidal neurons in vivo by timed in utero electroporation of Cre recombinase. Sparse mosaic expression of Cre produced neurons lacking PirB in a sea of wild-type neurons and glia. These neurons had significantly elevated dendritic spine density, as well as increased frequency of miniature EPSCs, suggesting that they receive a greater number of synaptic inputs relative to Cre - neighbors. The effect of cell-specific PirB deletion on dendritic spine density was not accompanied by changes in dendritic branching complexity or axonal bouton density. Together, results imply a neuron-specific, cell-autonomous action of PirB on synaptic density in L2/3 pyramidal cells of visual cortex. Moreover, they are consistent with the idea that PirB functions normally to corepress spine density and synaptic plasticity, thereby maintaining headroom for cells to encode ongoing experience-dependent structural change throughout life.

The Caenorhabditis elegans Ephrin EFN-4 Functions Non-cell Autonomously with Heparan Sulfate Proteoglycans to Promote Axon Outgrowth and Branching

PubMed Central

Schwieterman, Alicia A.; Steves, Alyse N.; Yee, Vivian; Donelson, Cory J.; Bentley, Melissa R.; Santorella, Elise M.; Mehlenbacher, Taylor V.; Pital, Aaron; Howard, Austin M.; Wilson, Melissa R.; Ereddia, Danielle E.; Effrein, Kelsie S.; McMurry, Jonathan L.; Ackley, Brian D.; Chisholm, Andrew D.; Hudson, Martin L.

2016-01-01

The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. PMID:26645816

Autonomous System Technologies for Resilient Airspace Operations

NASA Technical Reports Server (NTRS)

Houston, Vincent E.; Le Vie, Lisa R.

2017-01-01

Increasing autonomous systems within the aircraft cockpit begins with an effort to understand what autonomy is and developing the technology that encompasses it. Autonomy allows an agent, human or machine, to act independently within a circumscribed set of goals; delegating responsibility to the agent(s) to achieve overall system objective(s). Increasingly Autonomous Systems (IAS) are the highly sophisticated progression of current automated systems toward full autonomy. Working in concert with humans, these types of technologies are expected to improve the safety, reliability, costs, and operational efficiency of aviation. IAS implementation is imminent, which makes the development and the proper performance of such technologies, with respect to cockpit operation efficiency, the management of air traffic and data communication information, vital. A prototype IAS agent that attempts to optimize the identification and distribution of "relevant" air traffic data to be utilized by human crews during complex airspace operations has been developed.

Genetic programs can be compressed and autonomously decompressed in live cells

NASA Astrophysics Data System (ADS)

Lapique, Nicolas; Benenson, Yaakov

2018-04-01

Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes1-13 and genetically encoded circuits in live cells14-21. Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity22 of two bits per nucleotide23. In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum24. We hypothesize that the biological function of a genetic program can be preserved while reducing the length of its DNA encoding and increasing the information content per nucleotide. Here we support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we choose an RNAi cell classifier circuit25 that comprises redundant DNA sequences and is therefore amenable for compression, as are many other complex gene circuits15,18,26-28. In one example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs. The compression principles applied to gene circuits can enable fitting complex genetic programs into DNA delivery vehicles with limited cargo capacity, and storing compressed and biologically inert programs in vivo for on-demand activation.

A dye-sensitized solar cell acting as the electrical reading box of an immunosensor: Application to CEA determination.

PubMed

Truta, Liliana A A N A; Moreira, Felismina T C; Sales, M Goreti F

2018-06-01

Monitoring cancer biomarkers in biological fluids has become a key tool for disease diagnosis, which should be of easy access anywhere in the world. The possibility of reducing basic requirements in the field of electrochemical biosensing may open doors in this direction. This work proposes for this purpose an innovative electrochemical immunosensing system using a photovoltaic cell as an electrical reading box. Immunosensing ensures accuracy, the electrochemical-ground of the device ensures sensitivity and detectability, and the photovoltaic cell drives the system towards electrical autonomy. As proof-of-concept, Carcinoembryonic antigen (CEA) was used herein, a cancer biomarker of clinical relevance. In brief, a conductive glass with a fluorine doped tin oxide film was used as conductive support and modified with anti-CEA by means of a bottom-up approach. All stages involved in the biochemical modification of the FTO surface were followed by electrochemical techniques, namely electrochemical impedance spectroscopy and cyclic voltammetry. This electrode acted as counter electrode of a dye-sensitized solar cells, and the electrical output of this cell was monitored for the different concentrations of CEA. Under optimized conditions, the device displayed a linear behaviour against CEA concentration, from 5 pg/mL to 15 ng/mL. The immunosensor was applied to the analysis of CEA in urine from healthy individual and spiked with the antigen. Overall, the presented approach demonstrates that photovoltaic cells may be employed as an electrical reading box of electrochemical biosensors, yielding a new direction towards autonomous electrochemical biosensing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Tissue-autonomous promotion of palisade cell development by phototropin 2 in Arabidopsis.

PubMed

Kozuka, Toshiaki; Kong, Sam-Geun; Doi, Michio; Shimazaki, Ken-ichiro; Nagatani, Akira

2011-10-01

Light is an important environmental information source that plants use to modify their growth and development. Palisade parenchyma cells in leaves develop cylindrical shapes in response to blue light; however, the photosensory mechanism for this response has not been elucidated. In this study, we analyzed the palisade cell response in phototropin-deficient mutants. First, we found that two different light-sensing mechanisms contributed to the response in different proportions depending on the light intensity. One response observed under lower intensities of blue light was mediated exclusively by a blue light photoreceptor, phototropin 2 (PHOT2). Another response was elicited under higher intensities of light in a phototropin-independent manner. To determine the tissue in which PHOT2 perceives the light stimulus to regulate the response, green fluorescent protein (GFP)-tagged PHOT2 (P2G) was expressed under the control of tissue-specific promoters in the phot1 phot2 mutant background. The results revealed that the expression of P2G in the mesophyll, but not in the epidermis, promoted palisade cell development. Furthermore, a constitutively active C-terminal kinase fragment of PHOT2 fused to GFP (P2CG) promoted the development of cylindrical palisade cells in the proper direction without the directional cue provided by light. Hence, in response to blue light, PHOT2 promotes the development of cylindrical palisade cells along a predetermined axis in a tissue-autonomous manner.

Autonomous Agents on Expedition: Humans and Progenitor Ants and Planetary Exploration

NASA Astrophysics Data System (ADS)

Rilee, M. L.; Clark, P. E.; Curtis, S. A.; Truszkowski, W. F.

2002-01-01

The Autonomous Nano-Technology Swarm (ANTS) is an advanced mission architecture based on a social insect analog of many specialized spacecraft working together to achieve mission goals. The principal mission concept driving the ANTS architecture is a Main Belt Asteroid Survey in the 2020s that will involve a thousand or more nano-technology enabled, artificially intelligent, autonomous pico-spacecraft (< 1 kg). The objective of this survey is to construct a compendium of composition, shape, and other physical parameter observations of a significant fraction of asteroid belt objects. Such an atlas will be of primary scientific importance for the understanding of Solar System origins and evolution and will lay the foundation for future exploration and capitalization of space. As the capabilities enabling ANTS are developed over the next two decades, these capabilities will need to be proven. Natural milestones for this process include the deployment of progenitors to ANTS on human expeditions to space and remote missions with interfaces for human interaction and control. These progenitors can show up in a variety of forms ranging from spacecraft subsystems and advanced handheld sensors, through complete prototypical ANTS spacecraft. A critical capability to be demonstrated is reliable, long-term autonomous operations across the ANTS architecture. High level, mission-oriented behaviors are to be managed by a control / communications layer of the swarm, whereas common low level functions required of all spacecraft, e.g. attitude control and guidance and navigation, are handled autonomically on each spacecraft. At the higher levels of mission planning and social interaction deliberative techniques are to be used. For the asteroid survey, ANTS acts as a large community of cooperative agents while for precursor missions there arises the intriguing possibility of Progenitor ANTS and humans acting together as agents. For optimal efficiency and responsiveness for individual

Autonomous multifunctional nanobrushes-autonomous materials

NASA Astrophysics Data System (ADS)

Ghasemi-Nejhad, Mehrdad N.; Tius, Marcus A.

2007-04-01

In this work, taking advantage of carbon nanotubes' small size, and exceptional mechanical, chemical and electrical properties, we report on a series of nano-synthesis procedures that combine conventional chemical vapor deposition and selective substrate area growth followed by chemical functionalizations to fabricate functionalized nano-brushes from aligned carbon nanotube arrays and chemically selective functional groups. The high aspect ratio and small dimension, mechanical stability and flexibility, surface chemical and adhesive characteristics of carbon nanotubes provide opportunities to create nano-brushes with selected chemical functionalities. The nano-brushes are made from aligned multi-walled carbon nanotube bristles grafted onto long SiC fiber handles in various configurations and functionalized with various chemical functional groups. These nano-brushes can easily be manipulated physically, either manually or with the aid of motors. Here, we explain the autonomous characteristics of the functionalized nano-brushes employing functional chemical groups such that the nano-brush can potentially collect various metal particles, ions, and contaminants from liquid solutions and the air environment, autonomously. These functionalized multiwalled carbon nanotube based nano-brushes can work swiftly in both liquid and air environments. With surface modification and functionalization, the nanotube nano-brushes can potentially become a versatile nano-devices in many chemical and biological applications, where they can autonomously pick up the particles they encounter since they can be chemically programmed to function as Autonomous Chemical Nano Robots (ACNR).

Genetic autonomic disorders.

PubMed

Axelrod, Felicia B

2013-03-01

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms. Copyright © 2013 Elsevier Inc. All rights reserved.

Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction.

PubMed

Vincent, Ann; Whipple, Mary O; Low, Phillip A; Joyner, Michael; Hoskin, Tanya L

2016-05-01

Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia; however, no study to date has assessed these variables simultaneously with comprehensive measures. To characterize physical fitness and autonomic function with the use of clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Cross-sectional, observational, controlled study. Community sample of patients with fibromyalgia and healthy controls. Thirty patients with fibromyalgia and 30 pain and fatigue-free controls. Participants completed a battery of self-report questionnaires and physiological measures, including clinically validated measures of physical fitness and autonomic function. Six-Minute Walk Test total distance, maximal oxygen consumption as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire, and self-reported autonomic symptoms via the 31-item Composite Autonomic Symptom Score questionnaire. Autonomic function, as assessed by self-report, was significantly different between patients and controls (P < .0001); in contrast, the only difference between patients and controls on the Autonomic Reflex Screen was in the adrenergic domain (P = .022), and these abnormalities were mild. Self-reported physical activity was not significantly different between patients and controls (P = .99), but levels of moderate and vigorous physical activity as measured by actigraphy were significantly lower in patients (P = .012 and P = .047, respectively). Exercise capacity (6-Minute Walk) was poorer in patients (P = .0006), but there was no significant difference in maximal volume of oxygen consumption (P = .07). Patients with fibromyalgia report more severe symptoms across all domains, including physical

Patients with Fibromyalgia Have Significant Autonomic Symptoms but Modest Autonomic Dysfunction

PubMed Central

Vincent, Ann; Whipple, Mary O.; Low, Phillip A.; Joyner, Michael; Hoskin, Tanya L.

2015-01-01

Background Research suggests that disordered autonomic function may be one contributor to deconditioning reported in fibromyalgia, however no study to date has simultaneously assessed these variables utilizing comprehensive measures. Objective To characterize physical fitness and autonomic function using clinically validated measures and subjective questionnaires between patients with fibromyalgia and healthy controls. Design Cross-sectional, observational, controlled study Setting Community sample of patients with fibromyalgia and healthy controls Participants 30 patients with fibromyalgia and 30 pain and fatigue-free controls Methods: Participants completed a battery of self-report questionnaires and physiological measures including clinically validated measures of physical fitness and autonomic function. Main Outcome Measurements 6 Minute Walk Test total distance, VO2 max as assessed by cardiopulmonary exercise testing, total steps using activity monitor, Composite Autonomic Scoring Scale as assessed by Autonomic Reflex Screen, total metabolic equivalents per week using the International Physical Activity Questionnaire and self-reported autonomic symptoms using the 31-item Composite Autonomic Symptom Score questionnaire. Results Autonomic function, as assessed by self-report, was significantly different between patients and controls (p<.0001); in contrast, the only difference between patients and controls on the Autonomic Reflex Screen was in the adrenergic domain (p=.022), and these abnormalities were mild. Self-reported physical activity was not significantly different between patients and controls (p=.99), but levels of moderate and vigorous physical activity as measured by actigraphy, were significantly lower in patients (p=.012 and p=.047, respectively). Exercise capacity (6 Minute Walk) was poorer in patients (p=.0006), but there was no significant difference in maximal volume of oxygen consumption (p=.07). Conclusions Patients with fibromyalgia report

Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.

PubMed

Baghdadi, Meryem B; Castel, David; Machado, Léo; Fukada, So-Ichiro; Birk, David E; Relaix, Frederic; Tajbakhsh, Shahragim; Mourikis, Philippos

2018-05-01

The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix 1-3 . Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells 4-9 , the composition and source of molecules that maintain the stem cell niche remain largely unknown. Here we show that adult muscle satellite (stem) cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, we identified NOTCH1/RBPJ-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, we show that Collagen V (COLV) produced by satellite cells is a critical component of the quiescent niche, as depletion of COLV by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of COLV with satellite cells is mediated by the Calcitonin receptor, for which COLV acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in COLV-null satellite cells. This study reveals a Notch-COLV-Calcitonin receptor signalling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion, and raises the possibility that similar reciprocal mechanisms act in diverse stem cell populations.

Room Temperature Operable Autonomously Moving Bio-Microrobot Powered by Insect Dorsal Vessel Tissue

PubMed Central

Akiyama, Yoshitake; Hoshino, Takayuki; Iwabuchi, Kikuo; Morishima, Keisuke

2012-01-01

Living muscle tissues and cells have been attracting attention as potential actuator candidates. In particular, insect dorsal vessel tissue (DVT) seems to be well suited for a bio-actuator since it is capable of contracting autonomously and the tissue itself and its cells are more environmentally robust under culturing conditions compared with mammalian tissues and cells. Here we demonstrate an autonomously moving polypod microrobot (PMR) powered by DVT excised from an inchworm. We fabricated a prototype of the PMR by assembling a whole DVT onto an inverted two-row micropillar array. The prototype moved autonomously at a velocity of 3.5×10−2 µm/s, and the contracting force of the whole DVT was calculated as 20 µN. Based on the results obtained by the prototype, we then designed and fabricated an actual PMR. We were able to increase the velocity significantly for the actual PMR which could move autonomously at a velocity of 3.5 µm/s. These results indicate that insect DVT has sufficient potential as the driving force for a bio-microrobot that can be utilized in microspaces. PMID:22808004

Differential effects of LifeAct-GFP and actin-GFP on cell mechanics assessed using micropipette aspiration.

PubMed

Sliogeryte, Kristina; Thorpe, Stephen D; Wang, Zhao; Thompson, Clare L; Gavara, Nuria; Knight, Martin M

2016-01-25

The actin cytoskeleton forms a dynamic structure involved in many fundamental cellular processes including the control of cell morphology, migration and biomechanics. Recently LifeAct-GFP (green fluorescent protein) has been proposed for visualising actin structure and dynamics in live cells as an alternative to actin-GFP which has been shown to affect cell mechanics. Here we compare the two approaches in terms of their effect on cellular mechanical behaviour. Human mesenchymal stem cells (hMSCs) were analysed using micropipette aspiration and the effective cellular equilibrium and instantaneous moduli calculated using the standard linear solid model. We show that LifeAct-GFP provides clearer visualisation of F-actin organisation and dynamics. Furthermore, LifeAct-GFP does not alter effective cellular mechanical properties whereas actin-GFP expression causes an increase in the cell modulus. Interestingly, LifeAct-GFP expression did produce a small (~10%) increase in the percentage of cells exhibiting aspiration-induced membrane bleb formation, whilst actin-GFP expression reduced blebbing. Further studies examined the influence of LifeAct-GFP in other cell types, namely chondrogenically differentiated hMSCs and murine chondrocytes. LifeAct-GFP also had no effect on the moduli of these non-blebbing cells for which mechanical properties are largely dependent on the actin cortex. In conclusion we show that LifeAct-GFP enables clearer visualisation of actin organisation and dynamics without disruption of the biomechanical properties of either the whole cell or the actin cortex. Thus the study provides new evidence supporting the use of LifeAct-GFP rather than actin-GFP for live cell microscopy and the study of cellular mechanobiology. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cell-autonomous mechanisms of chronological aging in the yeast Saccharomyces cerevisiae.

PubMed

Arlia-Ciommo, Anthony; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

2014-05-27

A body of evidence supports the view that the signaling pathways governing cellular aging - as well as mechanisms of their modulation by longevity-extending genetic, dietary and pharmacological interventions - are conserved across species. The scope of this review is to critically analyze recent advances in our understanding of cell-autonomous mechanisms of chronological aging in the budding yeast Saccharomyces cerevisiae . Based on our analysis, we propose a concept of a biomolecular network underlying the chronology of cellular aging in yeast. The concept posits that such network progresses through a series of lifespan checkpoints. At each of these checkpoints, the intracellular concentrations of some key intermediates and products of certain metabolic pathways - as well as the rates of coordinated flow of such metabolites within an intricate network of intercompartmental communications - are monitored by some checkpoint-specific "master regulator" proteins. The concept envisions that a synergistic action of these master regulator proteins at certain early-life and late-life checkpoints modulates the rates and efficiencies of progression of such processes as cell metabolism, growth, proliferation, stress resistance, macromolecular homeostasis, survival and death. The concept predicts that, by modulating these vital cellular processes throughout lifespan (i.e., prior to an arrest of cell growth and division, and following such arrest), the checkpoint-specific master regulator proteins orchestrate the development and maintenance of a pro- or anti-aging cellular pattern and, thus, define longevity of chronologically aging yeast.

Is there consistency and specificity of autonomic changes during emotional episodes? Guidance from the conceptual act theory and psychophysiology

PubMed Central

Quigley, Karen S.; Barrett, Lisa Feldman

2014-01-01

The consistency and specificity of autonomic nervous system (ANS) responses during emotional episodes remains a topic of debate with relevance for emotional concordance. We present a recent model of how mental states are constructed, the Conceptual Act Theory (CAT), and then review findings from existing meta-analyses and a qualitative review along with studies using pattern classification of multivariate ANS patterns to determine if there is across-study evidence for consistency and specificity of ANS responses during emotional episodes. We conclude that there is thus far minimal evidence for ANS response consistency and specificity across studies. We then review the current understanding of the functional and anatomical features of ANS including its efferent and afferent connections with the central nervous system, which suggests the need to reformulate how we conceptualize ANS response consistency and specificity. We conclude by showing how this reformulation is consistent with the CAT, and how we suggest the model to propose when we would and would not expect to see consistency and specificity in ANS responses, and concordance more generally, during emotional episodes. PMID:24388802

Autonomic responses to cold face stimulation in sickle cell disease: a time-varying model analysis.

PubMed

Chalacheva, Patjanaporn; Kato, Roberta M; Sangkatumvong, Suvimol; Detterich, Jon; Bush, Adam; Wood, John C; Meiselman, Herbert; Coates, Thomas D; Khoo, Michael C K

2015-07-14

Sickle cell disease (SCD) is characterized by sudden onset of painful vaso-occlusive crises (VOC), which occur on top of the underlying chronic blood disorder. The mechanisms that trigger VOC remain elusive, but recent work suggests that autonomic dysfunction may be an important predisposing factor. Heart-rate variability has been employed in previous studies, but the derived indices have provided only limited univariate information about autonomic cardiovascular control in SCD. To circumvent this limitation, a time-varying modeling approach was applied to investigate the functional mechanisms relating blood pressure (BP) and respiration to heart rate and peripheral vascular resistance in healthy controls, untreated SCD subjects and SCD subjects undergoing chronic transfusion therapy. Measurements of respiration, heart rate, continuous noninvasive BP and peripheral vascular resistance were made before, during and after the application of cold face stimulation (CFS), which perturbs both the parasympathetic and sympathetic nervous systems. Cardiac baroreflex sensitivity estimated from the model was found to be impaired in nontransfused SCD subjects, but partially restored in SCD subjects undergoing transfusion therapy. Respiratory-cardiac coupling gain was decreased in SCD and remained unchanged by chronic transfusion. These results are consistent with autonomic dysfunction in the form of impaired parasympathetic control and sympathetic overactivity. As well, CFS led to a significant reduction in vascular resistance baroreflex sensitivity in the nontransfused SCD subjects but not in the other groups. This blunting of the baroreflex control of peripheral vascular resistance during elevated sympathetic drive could be a potential factor contributing to the triggering of VOC in SCD. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor.

PubMed

Bernard, Clémence; Vincent, Clémentine; Testa, Damien; Bertini, Eva; Ribot, Jérôme; Di Nardo, Ariel A; Volovitch, Michel; Prochiantz, Alain

2016-05-01

During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment. In the visual cortex, critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor, which regulates the maturation of parvalbumin-expressing inhibitory interneurons (PV cells). In adult mice, the maintenance of a non-plastic adult state requires continuous Otx2 import by PV cells. An important source of extra-cortical Otx2 is the choroid plexus, which secretes Otx2 into the cerebrospinal fluid. Otx2 secretion and internalization requires two small peptidic domains that are part of the DNA-binding domain. Thus, mutating these "transfer" sequences also modifies cell autonomous transcription, precluding this approach to obtain a cell autonomous-only mouse. Here, we develop a mouse model with inducible secretion of an anti-Otx2 single-chain antibody to trap Otx2 in the extracellular milieu. Postnatal secretion of this single-chain antibody by PV cells delays PV maturation and reduces plasticity gene expression. Induced adult expression of this single-chain antibody in cerebrospinal fluid decreases Otx2 internalization by PV cells, strongly induces plasticity gene expression and reopens physiological plasticity. We provide the first mammalian genetic evidence for a signaling mechanism involving intercellular transfer of a homeoprotein transcription factor. Our single-chain antibody mouse model is a valid strategy for extracellular neutralization that could be applied to other homeoproteins and signaling molecules within and beyond the nervous system.

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously

PubMed Central

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Choi, Giltsu

2016-01-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. PMID:27758895

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.

PubMed

Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B

2011-07-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration

PubMed Central

Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B.

2011-01-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons. PMID:21693519

Micronuclear DNA of Oxytricha nova contains sequences with autonomously replicating activity in Saccharomyces cerevisiae.

PubMed Central

Colombo, M M; Swanton, M T; Donini, P; Prescott, D M

1984-01-01

Oxytricha nova is a hypotrichous ciliate with micronuclei and macronuclei. Micronuclei, which contain large, chromosomal-sized DNA, are genetically inert but undergo meiosis and exchange during cell mating. Macronuclei, which contain only small, gene-sized DNA molecules, provide all of the nuclear RNA needed to run the cell. After cell mating the macronucleus is derived from a micronucleus, a derivation that includes excision of the genes from chromosomes and elimination of the remaining DNA. The eliminated DNA includes all of the repetitious sequences and approximately 95% of the unique sequences. We cloned large restriction fragments from the micronucleus that confer replication ability on a replication-deficient plasmid in Saccharomyces cerevisiae. Sequences that confer replication ability are called autonomously replicating sequences. The frequency and effectiveness of autonomously replicating sequences in micronuclear DNA are similar to those reported for DNAs of other organisms introduced into yeast cells. Of the 12 micronuclear fragments with autonomously replicating sequence activity, 9 also showed homology to macronuclear DNA, indicating that they contain a macronuclear gene sequence. We conclude from this that autonomously replicating sequence activity is nonrandomly distributed throughout micronuclear DNA and is preferentially associated with those regions of micronuclear DNA that contain genes. Images PMID:6092934

Tissue-Autonomous Promotion of Palisade Cell Development by Phototropin 2 in Arabidopsis[W

PubMed Central

Kozuka, Toshiaki; Kong, Sam-Geun; Doi, Michio; Shimazaki, Ken-ichiro; Nagatani, Akira

2011-01-01

Light is an important environmental information source that plants use to modify their growth and development. Palisade parenchyma cells in leaves develop cylindrical shapes in response to blue light; however, the photosensory mechanism for this response has not been elucidated. In this study, we analyzed the palisade cell response in phototropin-deficient mutants. First, we found that two different light-sensing mechanisms contributed to the response in different proportions depending on the light intensity. One response observed under lower intensities of blue light was mediated exclusively by a blue light photoreceptor, phototropin 2 (PHOT2). Another response was elicited under higher intensities of light in a phototropin-independent manner. To determine the tissue in which PHOT2 perceives the light stimulus to regulate the response, green fluorescent protein (GFP)–tagged PHOT2 (P2G) was expressed under the control of tissue-specific promoters in the phot1 phot2 mutant background. The results revealed that the expression of P2G in the mesophyll, but not in the epidermis, promoted palisade cell development. Furthermore, a constitutively active C-terminal kinase fragment of PHOT2 fused to GFP (P2CG) promoted the development of cylindrical palisade cells in the proper direction without the directional cue provided by light. Hence, in response to blue light, PHOT2 promotes the development of cylindrical palisade cells along a predetermined axis in a tissue-autonomous manner. PMID:21972260

Distinct palisade tissue development processes promoted by leaf autonomous signalling and long-distance signalling in Arabidopsis thaliana.

PubMed

Munekage, Yuri Nakajima; Inoue, Shio; Yoneda, Yuki; Yokota, Akiho

2015-06-01

Plants develop palisade tissue consisting of cylindrical mesophyll cells located at the adaxial side of leaves in response to high light. To understand high light signalling in palisade tissue development, we investigated leaf autonomous and long-distance signal responses of palisade tissue development using Arabidopsis thaliana. Illumination of a developing leaf with high light induced cell height elongation, whereas illumination of mature leaves with high light increased cell density and suppressed cell width expansion in palisade tissue of new leaves. Examination using phototropin1 phototropin2 showed that blue light signalling mediated by phototropins was involved in cell height elongation of the leaf autonomous response rather than the cell density increase induced by long-distance signalling. Hydrogen peroxide treatment induced cylindrical palisade tissue cell formation in both a leaf autonomous and long-distance manner, suggesting involvement of oxidative signals. Although constitutive expression of transcription factors involved in systemic-acquired acclimation to excess light, ZAT10 and ZAT12, induced cylindrical palisade tissue cell formation, knockout of these genes did not affect cylindrical palisade tissue cell formation. We conclude that two distinct signalling pathways - leaf autonomous signalling mostly dependent on blue light signalling and long-distance signalling from mature leaves that sense high light and oxidative stress - control palisade tissue development in A. thaliana. © 2014 John Wiley & Sons Ltd.

INL Autonomous Navigation System

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

2005-03-30

The INL Autonomous Navigation System provides instructions for autonomously navigating a robot. The system permits high-speed autonomous navigation including obstacle avoidance, waypoing navigation and path planning in both indoor and outdoor environments.

Control of non-apoptotic nurse cell death by engulfment genes in Drosophila.

PubMed

Timmons, Allison K; Mondragon, Albert A; Meehan, Tracy L; McCall, Kimberly

2017-04-03

Programmed cell death occurs as a normal part of oocyte development in Drosophila. For each egg that is formed, 15 germline-derived nurse cells transfer their cytoplasmic contents into the oocyte and die. Disruption of apoptosis or autophagy only partially inhibits the death of the nurse cells, indicating that other mechanisms significantly contribute to nurse cell death. Recently, we demonstrated that the surrounding stretch follicle cells non-autonomously promote nurse cell death during late oogenesis and that phagocytosis genes including draper, ced-12, and the JNK pathway are crucial for this process. When phagocytosis genes are inhibited in the follicle cells, events specifically associated with death of the nurse cells are impaired. Death of the nurse cells is not completely blocked in draper mutants, suggesting that other engulfment receptors are involved. Indeed, we found that the integrin subunit, αPS3, is enriched on stretch follicle cells during late oogenesis and is required for elimination of the nurse cells. Moreover, double mutant analysis revealed that integrins act in parallel to draper. Death of nurse cells in the Drosophila ovary is a unique example of programmed cell death that is both non-apoptotic and non-cell autonomously controlled.

Autonomic Function in Infancy.

ERIC Educational Resources Information Center

Fox, Nathan A.; Fitzgerald, Hiram E.

1990-01-01

Reviews research that uses autonomic responses of human infants as dependent measures. Focuses on the history of research on the autonomic nervous system, measurement issues, and autonomic correlates of infant behavior and systems. (RJC)

Autonomic Modification of Intestinal Smooth Muscle Contractility

ERIC Educational Resources Information Center

Montgomery, Laura E. A.; Tansey, Etain A.; Johnson, Chris D.; Roe, Sean M.; Quinn, Joe G.

2016-01-01

Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe…

Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo.

PubMed

Yaniv, Yael; Ahmet, Ismayil; Tsutsui, Kenta; Behar, Joachim; Moen, Jack M; Okamoto, Yosuke; Guiriba, Toni-Rose; Liu, Jie; Bychkov, Rostislav; Lakatta, Edward G

2016-08-01

We aimed to determine how age-associated changes in mechanisms extrinsic and intrinsic to pacemaker cells relate to basal beating interval variability (BIV) reduction in vivo. Beating intervals (BIs) were measured in aged (23-25 months) and adult (3-4 months) C57BL/6 male mice (i) via ECG in vivo during light anesthesia in the basal state, or in the presence of 0.5 mg mL(-1) atropine + 1 mg mL(-1) propranolol (in vivo intrinsic conditions), and (ii) via a surface electrogram, in intact isolated pacemaker tissue. BIV was quantified in both time and frequency domains using linear and nonlinear indices. Although the average basal BI did not significantly change with age under intrinsic conditions in vivo and in the intact isolated pacemaker tissue, the average BI was prolonged in advanced age. In vivo basal BIV indices were found to be reduced with age, but this reduction diminished in the intrinsic state. However, in pacemaker tissue BIV indices increased in advanced age vs. adults. In the isolated pacemaker tissue, the sensitivity of the average BI and BIV in response to autonomic receptor stimulation or activation of mechanisms intrinsic to pacemaker cells by broad-spectrum phosphodiesterase inhibition declined in advanced age. Thus, changes in mechanisms intrinsic to pacemaker cells increase the average BIs and BIV in the mice of advanced age. Autonomic neural input to pacemaker tissue compensates for failure of molecular intrinsic mechanisms to preserve average BI. But this compensation reduces the BIV due to both the imbalance of autonomic neural input to the pacemaker cells and altered pacemaker cell responses to neural input. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The effects of views of nature on autonomic control.

PubMed

Gladwell, V F; Brown, D K; Barton, J L; Tarvainen, M P; Kuoppa, P; Pretty, J; Suddaby, J M; Sandercock, G R H

2012-09-01

Previously studies have shown that nature improves mood and self-esteem and reduces blood pressure. Walking within a natural environment has been suggested to alter autonomic nervous system control, but the mechanisms are not fully understood. Heart rate variability (HRV) is a non-invasive method of assessing autonomic control and can give an insight into vagal modulation. Our hypothesis was that viewing nature alone within a controlled laboratory environment would induce higher levels of HRV as compared to built scenes. Heart rate (HR) and blood pressure (BP) were measured during viewing different scenes in a controlled environment. HRV was used to investigate alterations in autonomic activity, specifically parasympathetic activity. Each participant lay in the semi-supine position in a laboratory while we recorded 5 min (n = 29) of ECG, BP and respiration as they viewed two collections of slides (one containing nature views and the other built scenes). During viewing of nature, markers of parasympathetic activity were increased in both studies. Root mean squared of successive differences increased 4.2 ± 7.7 ms (t = 2.9, p = 0.008) and natural logarithm of high frequency increased 0.19 ± 0.36 ms(2) Hz(-1) (t = 2.9, p = 0.007) as compared to built scenes. Mean HR and BP were not significantly altered. This study provides evidence that autonomic control of the heart is altered by the simple act of just viewing natural scenes with an increase in vagal activity.

Distinct mechanisms act in concert to mediate cell cycle arrest.

PubMed

Toettcher, Jared E; Loewer, Alexander; Ostheimer, Gerard J; Yaffe, Michael B; Tidor, Bruce; Lahav, Galit

2009-01-20

In response to DNA damage, cells arrest at specific stages in the cell cycle. This arrest must fulfill at least 3 requirements: it must be activated promptly; it must be sustained as long as damage is present to prevent loss of genomic information; and after the arrest, cells must re-enter into the appropriate cell cycle phase to ensure proper ploidy. Multiple molecular mechanisms capable of arresting the cell cycle have been identified in mammalian cells; however, it is unknown whether each mechanism meets all 3 requirements or whether they act together to confer specific functions to the arrest. To address this question, we integrated mathematical models describing the cell cycle and the DNA damage signaling networks and tested the contributions of each mechanism to cell cycle arrest and re-entry. Predictions from this model were then tested with quantitative experiments to identify the combined action of arrest mechanisms in irradiated cells. We find that different arrest mechanisms serve indispensable roles in the proper cellular response to DNA damage over time: p53-independent cyclin inactivation confers immediate arrest, whereas p53-dependent cyclin downregulation allows this arrest to be sustained. Additionally, p21-mediated inhibition of cyclin-dependent kinase activity is indispensable for preventing improper cell cycle re-entry and endoreduplication. This work shows that in a complex signaling network, seemingly redundant mechanisms, acting in a concerted fashion, can achieve a specific cellular outcome.

'Educated' dendritic cells act as messengers from memory to naive T helper cells.

PubMed

Alpan, Oral; Bachelder, Eric; Isil, Eda; Arnheiter, Heinz; Matzinger, Polly

2004-06-01

Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we found that the conversion of a naive T cell occurs only if it can interact with the same antigen-presenting cell, although not necessarily the same antigen, as the effector T cell. Using a two-step culture system in vitro, we found that antigen-presenting dendritic cells can act as 'temporal bridges' to relay information from orally immunized memory CD4 T cells to naive CD4 T cells. The orally immunized T cells use IL-4 and IL-10 (but not CD40 ligand) to 'educate' dendritic cells, which in turn induce naive T cells to produce the same cytokines as those produced by the orally immunized memory T cells.

Asteroid Exploration with Autonomic Systems

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Rash, James; Rouff, Christopher; Hinchey, Mike

2004-01-01

NASA is studying advanced technologies for a future robotic exploration mission to the asteroid belt. The prospective ANTS (Autonomous Nano Technology Swarm) mission comprises autonomous agents including worker agents (small spacecra3) designed to cooperate in asteroid exploration under the overall authoriq of at least one ruler agent (a larger spacecraft) whose goal is to cause science data to be returned to Earth. The ANTS team (ruler plus workers and messenger agents), but not necessarily any individual on the team, will exhibit behaviors that qualify it as an autonomic system, where an autonomic system is defined as a system that self-reconfigures, self-optimizes, self-heals, and self-protects. Autonomic system concepts lead naturally to realistic, scalable architectures rich in capabilities and behaviors. In-depth consideration of a major mission like ANTS in terms of autonomic systems brings new insights into alternative definitions of autonomic behavior. This paper gives an overview of the ANTS mission and discusses the autonomic properties of the mission.

Epidermal Phytochrome B Inhibits Hypocotyl Negative Gravitropism Non-Cell-Autonomously.

PubMed

Kim, Jaewook; Song, Kijong; Park, Eunae; Kim, Keunhwa; Bae, Gabyong; Choi, Giltsu

2016-11-01

Seedling hypocotyls display negative gravitropism in the dark but agravitropism in the light. The Arabidopsis thaliana pif quadruple mutant (pifQ), which lacks four PHYTOCHROME-INTERACTING FACTORS (PIFs), is agravitropic in the dark. Endodermis-specific expression of PIF1 rescues gravitropism in pifQ mutant seedlings. Since phytochromes induce light responses by inhibiting PIFs and the COP1-SPA ubiquitin E3 ligase complex in the nucleus, we asked whether phyB can cell autonomously inhibit hypocotyl negative gravitropism in the endodermis. We found that while epidermis-specific expression of PHYB rescues hypocotyl negative gravitropism and all other phyB mutant phenotypes, endodermis-specific expression of PHYB does not. Epidermal phyB induces the phosphorylation and degradation of endodermal PIFs in response to red light. This induces a global gene expression pattern similar to that induced by red light treatment of seedlings expressing PHYB under the control of its own endogenous promoter. Our results imply that epidermal phyB generates an unidentified mobile signal that travels to the endodermis where it promotes PIF degradation and inhibits hypocotyl negative gravitropism. © 2016 American Society of Plant Biologists. All rights reserved.

Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.

PubMed

Mah, In Kyoung; Soloff, Rachel; Izuhara, Audrey K; Lakeland, Daniel L; Wang, Charles; Mariani, Francesca V

2016-08-01

Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation. A failure to cavitate could be due to an overgrowth of interior cells or to an inability of interior cells to die. Null cells however, do not have a marked change in proliferation rate and are still capable of undergoing cell death, suggesting that alterations in these processes are not the predominant cause of the failed cavitation. Overexpression of BMP4 or EZRIN can partially rescue the phenotype possibly by promoting cell death, polarity, and differentiation. However, neither is sufficient to provide the required cues to generate a polarized epithelium and fully rescue cavitation. Interestingly, when wildtype and Prkci(-/-) ES cells are mixed together, a polarized ectodermal epithelium forms and cavitation is rescued, likely due to the ability of wildtype cells to produce non-autonomous polarity cues. We conclude that Prkci is not required for cells to respond to these cues, though it is required to produce them. Together these findings indicate that environmental cues can facilitate the formation of polarized epithelia and that cavitation requires the proper coordination of multiple basic cellular processes including proliferation, differentiation, cell death, and apical-basal polarization. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence for vestibular regulation of autonomic functions in a mouse genetic model

NASA Technical Reports Server (NTRS)

Murakami, Dean M.; Erkman, Linda; Hermanson, Ola; Rosenfeld, Michael G.; Fuller, Charles A.

2002-01-01

Physiological responses to changes in the gravitational field and body position, as well as symptoms of patients with anxiety-related disorders, have indicated an interrelationship between vestibular function and stress responses. However, the relative significance of cochlear and vestibular information in autonomic regulation remains unresolved because of the difficulties in distinguishing the relative contributions of other proprioceptive and interoceptive inputs, including vagal and somatic information. To investigate the role of cochlear and vestibular function in central and physiological responses, we have examined the effects of increased gravity in wild-type mice and mice lacking the POU homeodomain transcription factor Brn-3.1 (Brn-3bPou4f3). The only known phenotype of the Brn-3.1(-/-) mouse is related to hearing and balance functions, owing to the failure of cochlear and vestibular hair cells to differentiate properly. Here, we show that normal physiological responses to increased gravity (2G exposure), such as a dramatic drop in body temperature and concomitant circadian adjustment, were completely absent in Brn-3.1(-/-) mice. In line with the lack of autonomic responses, the massive increase in neuronal activity after 2G exposure normally detected in wild-type mice was virtually abolished in Brn-3.1(-/-) mice. Our results suggest that cochlear and vestibular hair cells are the primary regulators of autonomic responses to altered gravity and provide genetic evidence that these cells are sufficient to alter neural activity in regions involved in autonomic and neuroendocrine control.

Autonomous and Autonomic Systems: A Paradigm for Future Space Exploration Missions

NASA Technical Reports Server (NTRS)

Truszkowski, Walter F.; Hinchey, Michael G.; Rash, James L.; Rouff, Christopher A.

2004-01-01

NASA increasingly will rely on autonomous systems concepts, not only in the mission control centers on the ground, but also on spacecraft and on rovers and other assets on extraterrestrial bodies. Automomy enables not only reduced operations costs, But also adaptable goal-driven functionality of mission systems. Space missions lacking autonomy will be unable to achieve the full range of advanced mission objectives, given that human control under dynamic environmental conditions will not be feasible due, in part, to the unavoidably high signal propagation latency and constrained data rates of mission communications links. While autonomy cost-effectively supports accomplishment of mission goals, autonomicity supports survivability of remote mission assets, especially when human tending is not feasible. Autonomic system properties (which ensure self-configuring, self-optimizing self-healing, and self-protecting behavior) conceptually may enable space missions of a higher order into any previously flown. Analysis of two NASA agent-based systems previously prototyped, and of a proposed future mission involving numerous cooperating spacecraft, illustrates how autonomous and autonomic system concepts may be brought to bear on future space missions.

An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

PubMed Central

Lakhal-Littleton, Samira; Wolna, Magda; Chung, Yu Jin; Christian, Helen C; Heather, Lisa C; Brescia, Marcella; Ball, Vicky; Diaz, Rebeca; Santos, Ana; Biggs, Daniel; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

2016-01-01

Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain. DOI: http://dx.doi.org/10.7554/eLife.19804.001 PMID:27897970

Mineralocorticoid Receptor Activation Contributes to the Supine Hypertension of Autonomic Failure.

PubMed

Arnold, Amy C; Okamoto, Luis E; Gamboa, Alfredo; Black, Bonnie K; Raj, Satish R; Elijovich, Fernando; Robertson, David; Shibao, Cyndya A; Biaggioni, Italo

2016-02-01

Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that plasma angiotensin II is elevated and acts at AT1 (angiotensin type 1) receptors to contribute to hypertension in these patients. Because aldosterone and angiotensin II can also bind mineralocorticoid receptors to elevate blood pressure, we hypothesized that mineralocorticoid receptor activation plays a role in the hypertension of autonomic failure. To test this hypothesis, we determined the acute effects of the mineralocorticoid receptor antagonist eplerenone (50 mg, oral) versus placebo on supine blood pressure in a randomized, double-blind, crossover study. Medications were given at 8:00 pm with blood pressure recorded every 2 hours for 12 hours. Ten primary autonomic failure patients with supine hypertension completed this study (7 pure autonomic failure, 2 multiple system atrophy, 1 parkinson's disease; 7 male; 70±2 years of age). Eplerenone maximally reduced supine systolic blood pressure by 32±6 mm Hg at 8 hours after administration (versus 8±10 mm Hg placebo, P=0.016), with no effect on nocturia (12-hour urine volume: 985±134 mL placebo versus 931±94 mL eplerenone, P=0.492; nocturnal weight loss: -1.19±0.15 kg placebo versus -1.18±0.15 kg eplerenone, P=0.766). These findings suggest that inappropriate mineralocorticoid receptor activation contributes to the hypertension of autonomic failure, likely independent of canonical mineralocorticoid effects, and provides rationale for use of eplerenone in these patients. © 2015 American Heart Association, Inc.

Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus

PubMed Central

Teixeira, Catia M.; Kron, Michelle M.; Masachs, Nuria; Zhang, Helen; Lagace, Diane C.; Martinez, Albert; Reillo, Isabel; Duan, Xin; Bosch, Carles; Pujadas, Lluis; Brunso, Lucas; Song, Hongjun; Eisch, Amelia J.; Borrell, Victor; Howell, Brian W.; Parent, Jack M.; Soriano, Eduardo

2012-01-01

Adult hippocampal neurogenesis is thought to be essential for learning and memory and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of disabled-1 (Dab1), an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain- and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. PMID:22933789

When helping helps: autonomous motivation for prosocial behavior and its influence on well-being for the helper and recipient.

PubMed

Weinstein, Netta; Ryan, Richard M

2010-02-01

Self-determination theory posits that the degree to which a prosocial act is volitional or autonomous predicts its effect on well-being and that psychological need satisfaction mediates this relation. Four studies tested the impact of autonomous and controlled motivation for helping others on well-being and explored effects on other outcomes of helping for both helpers and recipients. Study 1 used a diary method to assess daily relations between prosocial behaviors and helper well-being and tested mediating effects of basic psychological need satisfaction. Study 2 examined the effect of choice on motivation and consequences of autonomous versus controlled helping using an experimental design. Study 3 examined the consequences of autonomous versus controlled helping for both helpers and recipients in a dyadic task. Finally, Study 4 manipulated motivation to predict helper and recipient outcomes. Findings support the idea that autonomous motivation for helping yields benefits for both helper and recipient through greater need satisfaction. Limitations and implications are discussed. Copyright 2009 APA, all rights reserved

[Occupational health in the Autonomous Community of the Basque Country. OSALAN-Instituto Vasco de Seguridad y Salud Laborales].

PubMed

Martínez Castillo, A; Achutegui Basagoiti, G

1996-01-01

O.S.A.L.A.N.-Instituto Vasco de Seguridad y Salud Laborales is an autonomous administrative body depending on the Basque Government, ascribed to the Dept. of Justice, Economy, Work and Social Security, which is in charge of managing the general occupational health policies in the Autonomous Community of the Basque Country. Its objectives are: To promote an ongoing improvement in safety and occupational health for all the workers in the Basque Autonomous Region, through the management of programmes in matters affecting safety, hygiene, the environment and occupational health. To co-ordinate and concentrate the different activities related to occupational health, unifying and giving coherence to the functions which were previously the jurisdiction of different departments. Making companies aware of national and E.U. regulations, taking the measures that are set out by the European Directives and the Prevention of Occupational Hazards Act and the rest of the employment regulations, establishing the training and information channels required for promoting and applying these in the companies. It acts: from an overall perspective as regards the prevention of occupational hazards, thanks to co-ordination with all the disciplines involved, applying a multi-disciplinary treatment to the study of each and every one of the occupational hazard factors, which is aimed at the prevention of risks at their source. Providing companies with the ideal means for managing the safety and health of their workers. Promoting the implementation of systems which guarantee an ongoing improvement in occupational safety and health in the companies of the Basque Autonomous Region. Providing the technical and research support that makes it possible to tackle prevention efficiently. The provision established in the Creation Act (O.S.A.L.A.N.) should also be mentioned, as regards its application in public administration and the field of social economy, which was later endorsed and ratified through

Genetics Home Reference: hereditary sensory and autonomic neuropathy type II

MedlinePlus

... and autonomic neurons. It is involved in the recycling of worn-out cell parts (autophagy), specifically a ... endoplasmic reticulum . When the RETREG1 protein is nonfunctional, recycling of the endoplasmic reticulum is impaired. The buildup ...

Immunosuppression after Sepsis: Systemic Inflammation and Sepsis Induce a Loss of Naïve T-Cells but No Enduring Cell-Autonomous Defects in T-Cell Function

PubMed Central

Markwart, Robby; Condotta, Stephanie A.; Requardt, Robert P.; Borken, Farina; Schubert, Katja; Weigel, Cynthia; Bauer, Michael; Griffith, Thomas S.; Förster, Martin; Brunkhorst, Frank M.; Badovinac, Vladimir P.; Rubio, Ignacio

2014-01-01

Sepsis describes the life-threatening systemic inflammatory response (SIRS) of an organism to an infection and is the leading cause of mortality on intensive care units (ICU) worldwide. An acute episode of sepsis is characterized by the extensive release of cytokines and other mediators resulting in a dysregulated immune response leading to organ damage and/or death. This initial pro-inflammatory burst often transits into a state of immune suppression characterised by loss of immune cells and T-cell dysfunction at later disease stages in sepsis survivors. However, despite these appreciations, the precise nature of the evoked defect in T-cell immunity in post-acute phases of SIRS remains unknown. Here we present an in-depth functional analysis of T-cell function in post-acute SIRS/sepsis. We document that T-cell function is not compromised on a per cell basis in experimental rodent models of infection-free SIRS (LPS or CpG) or septic peritonitis. Transgenic antigen-specific T-cells feature an unaltered cytokine response if challenged in vivo and ex vivo with cognate antigens. Isolated CD4+/CD8+ T-cells from post-acute septic animals do not exhibit defects in T-cell receptor-mediated activation at the the level of receptor-proximal signalling, activation marker upregulation or expansion. However, SIRS/sepsis induced transient lymphopenia and gave rise to an environment of immune attenuation at post acute disease stages. Thus, systemic inflammation has an acute impact on T-cell numbers and adaptive immunity, but does not cause major cell-autonomous enduring functional defects in T-cells. PMID:25541945

The power of combining adoptive cell therapy (ACT) and pathogen-boosted vaccination to treat solid tumors.

PubMed

Zander, Ryan; Cui, Weiguo

2017-10-03

Recent advancements in adoptive cell therapy (ACT) are opening up new frontiers for cancer immunotherapy. CAR T cells targeting CD19 have emerged as a remarkable T cell-based therapy for the successful treatment of certain types of leukemia and lymphomas. Despite these clinical successes, as well as significant breakthroughs in T cell engineering, the treatment of solid tumors with ACT remains a relentless challenge. Thus, the current consensus of the field is that an urgent need exists for the design of innovative approaches that can improve the efficacy of ACT in treating solid cancers while maintaining a high degree of reliability and safety.

AmpA protein functions by different mechanisms to influence early cell type specification and to modulate cell adhesion and actin polymerization in Dictyostelium discoideum

PubMed Central

Cost, Hoa N.; Noratel, Elizabeth F.; Blumberg, Daphne D.

2013-01-01

The Dictyostelium discoideum ampA gene encodes a multifunctional regulator protein that modulates cell–cell and cell–substrate adhesions and actin polymerization during growth and is necessary for correct cell type specification and patterning during development. Insertional inactivation of the ampA gene results in defects that define two distinct roles for the ampA gene during development. AmpA is necessary in a non-cell autonomous manner to prevent premature expression of a prespore gene marker. It is also necessary in a cell autonomous manner for the anterior like cells, which express the ampA gene, to migrate to the upper cup during culmination. It is also necessary to prevent excessive cell–cell agglutination when cells are developed in a submerged suspension culture. Here, we demonstrate that a supernatant source of AmpA protein, added extracellularly, can prevent the premature mis-expression of the prespore marker. Synthetic oligopeptides are used to identify the domain of the AmpA protein that is important for preventing cells from mis-expressing the prespore gene. We further demonstrate that a factor capable of inducing additional cells to express the prespore gene marker accumulates extracellularly in the absence of AmpA protein. While the secreted AmpA acts extracellularly to suppress prespore gene expression, the effects of AmpA on cell agglutination and on actin polymerization in growing cells are not due to an extracellular role of secreted AmpA protein. Rather, these effects appear to reflect a distinct cell autonomous role of the ampA gene. Finally, we show that secretion of AmpA protein is brought about by elevating the levels of expression of ampA so that the protein accumulates to an excessive level. PMID:23911723

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease

PubMed Central

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-01-01

Abstract Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD. PMID:26986144

Association Between Autonomic Impairment and Structural Deficit in Parkinson Disease.

PubMed

Chen, Meng-Hsiang; Lu, Cheng-Hsien; Chen, Pei-Chin; Tsai, Nai-Wen; Huang, Chih-Cheng; Chen, Hsiu-Ling; Yang, I-Hsiao; Yu, Chiun-Chieh; Lin, Wei-Che

2016-03-01

Patients with Parkinson disease (PD) have impaired autonomic function and altered brain structure. This study aimed to evaluate the relationship of gray matter volume (GMV) determined by voxel-based morphometry (VBM) to autonomic impairment in patients with PD. Whole-brain VBM analysis was performed on 3-dimensional T1-weighted images in 23 patients with PD and 15 sex- and age-matched healthy volunteers. The relationship of cardiovascular autonomic function (determined by survey) to baroreflex sensitivity (BRS) (determined from changes in heart rate and blood pressure during the early phase II of the Valsalva maneuver) was tested using least-squares regression analysis. The differences in GMV, autonomic parameters, and clinical data were correlated after adjusting for age and sex. Compared with controls, patients with PD had low BRS, suggesting worse cardiovascular autonomic function, and smaller GMV in several brain locations, including the right amygdala, left hippocampal formation, bilateral insular cortex, bilateral caudate nucleus, bilateral cerebellum, right fusiform, and left middle frontal gyri. The decreased GMVs of the selected brain regions were also associated with increased presence of epithelial progenitor cells (EPCs) in the circulation. In patients with PD, decrease in cardiovascular autonomic function and increase in circulating EPC level are associated with smaller GMV in several areas of the brain. Because of its possible role in the modulation of the circulatory EPC pool and baroreflex control, the left hippocampal formation may be a bio-target for disease-modifying therapy and treatment monitoring in PD.

Autonomous Repair Mechanism of Creep Damage in Fe-Au and Fe-Au-B-N Alloys

NASA Astrophysics Data System (ADS)

Zhang, S.; Kwakernaak, C.; Tichelaar, F. D.; Sloof, W. G.; Kuzmina, M.; Herbig, M.; Raabe, D.; Brück, E.; van der Zwaag, S.; van Dijk, N. H.

2015-12-01

The autonomous repair mechanism of creep cavitation during high-temperature deformation has been investigated in Fe-Au and Fe-Au-B-N alloys. Combined electron-microscopy techniques and atom probe tomography reveal how the improved creep properties result from Au precipitation within the creep cavities, preferentially formed on grain boundaries oriented perpendicular to the applied stress. The selective precipitation of Au atoms at the free creep cavity surface results in pore filling, and thereby, autonomous repair of the creep damage. The large difference in atomic size between the Au and Fe strongly hampers the nucleation of precipitates in the matrix. As a result, the matrix acts as a reservoir for the supersaturated solute until damage occurs. Grain boundaries and dislocations are found to act as fast transport routes for solute gold from the matrix to the creep cavities. The mechanism responsible for the self-healing can be characterized by a simple model for cavity growth and cavity filling.

Overview of the Autonomic Nervous System

MedlinePlus

... be reversible or progressive. Anatomy of the autonomic nervous system The autonomic nervous system is the part of ... organs they connect with. Function of the autonomic nervous system The autonomic nervous system controls internal body processes ...

Towards autonomous fuzzy control

NASA Technical Reports Server (NTRS)

Shenoi, Sujeet; Ramer, Arthur

1993-01-01

The efficient implementation of on-line adaptation in real time is an important research problem in fuzzy control. The goal is to develop autonomous self-organizing controllers employing system-independent control meta-knowledge which enables them to adjust their control policies depending on the systems they control and the environments in which they operate. An autonomous fuzzy controller would continuously observe system behavior while implementing its control actions and would use the outcomes of these actions to refine its control policy. It could be designed to lie dormant when its control actions give rise to adequate performance characteristics but could rapidly and autonomously initiate real-time adaptation whenever its performance degrades. Such an autonomous fuzzy controller would have immense practical value. It could accommodate individual variations in system characteristics and also compensate for degradations in system characteristics caused by wear and tear. It could also potentially deal with black-box systems and control scenarios. On-going research in autonomous fuzzy control is reported. The ultimate research objective is to develop robust and relatively inexpensive autonomous fuzzy control hardware suitable for use in real time environments.

An intelligent algorithm for autonomous scientific sampling with the VALKYRIE cryobot

NASA Astrophysics Data System (ADS)

Clark, Evan B.; Bramall, Nathan E.; Christner, Brent; Flesher, Chris; Harman, John; Hogan, Bart; Lavender, Heather; Lelievre, Scott; Moor, Joshua; Siegel, Vickie

2018-07-01

The development of algorithms for agile science and autonomous exploration has been pursued in contexts ranging from spacecraft to planetary rovers to unmanned aerial vehicles to autonomous underwater vehicles. In situations where time, mission resources and communications are limited and the future state of the operating environment is unknown, the capability of a vehicle to dynamically respond to changing circumstances without human guidance can substantially improve science return. Such capabilities are difficult to achieve in practice, however, because they require intelligent reasoning to utilize limited resources in an inherently uncertain environment. Here we discuss the development, characterization and field performance of two algorithms for autonomously collecting water samples on VALKYRIE (Very deep Autonomous Laser-powered Kilowatt-class Yo-yoing Robotic Ice Explorer), a glacier-penetrating cryobot deployed to the Matanuska Glacier, Alaska (Mission Control location: 61°42'09.3''N 147°37'23.2''W). We show performance on par with human performance across a wide range of mission morphologies using simulated mission data, and demonstrate the effectiveness of the algorithms at autonomously collecting samples with high relative cell concentration during field operation. The development of such algorithms will help enable autonomous science operations in environments where constant real-time human supervision is impractical, such as penetration of ice sheets on Earth and high-priority planetary science targets like Europa.

Agent Based Software for the Autonomous Control of Formation Flying Spacecraft

NASA Technical Reports Server (NTRS)

How, Jonathan P.; Campbell, Mark; Dennehy, Neil (Technical Monitor)

2003-01-01

Distributed satellite systems is an enabling technology for many future NASA/DoD earth and space science missions, such as MMS, MAXIM, Leonardo, and LISA [1, 2, 3]. While formation flying offers significant science benefits, to reduce the operating costs for these missions it will be essential that these multiple vehicles effectively act as a single spacecraft by performing coordinated observations. Autonomous guidance, navigation, and control as part of a coordinated fleet-autonomy is a key technology that will help accomplish this complex goal. This is no small task, as most current space missions require significant input from the ground for even relatively simple decisions such as thruster burns. Work for the NMP DS1 mission focused on the development of the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. NMRA integrates traditional real-time monitoring and control with components for constraint-based planning, robust multi-threaded execution, and model-based diagnosis and reconfiguration. The complexity of using an autonomous approach for space flight software was evident when most of its capabilities were stripped off prior to launch (although more capability was uplinked subsequently, and the resulting demonstration was very successful).

Hepatitis C Virus Cell-Cell Transmission and Resistance to Direct-Acting Antiviral Agents

PubMed Central

Heydmann, Laura; Barth, Heidi; Soulier, Eric; Habersetzer, François; Doffoël, Michel; Bukh, Jens; Patel, Arvind H.; Zeisel, Mirjam B.; Baumert, Thomas F.

2014-01-01

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs. PMID:24830295

Autonomous Navigation Using Celestial Objects

NASA Technical Reports Server (NTRS)

Folta, David; Gramling, Cheryl; Leung, Dominic; Belur, Sheela; Long, Anne

1999-01-01

In the twenty-first century, National Aeronautics and Space Administration (NASA) Enterprises envision frequent low-cost missions to explore the solar system, observe the universe, and study our planet. Satellite autonomy is a key technology required to reduce satellite operating costs. The Guidance, Navigation, and Control Center (GNCC) at the Goddard Space Flight Center (GSFC) currently sponsors several initiatives associated with the development of advanced spacecraft systems to provide autonomous navigation and control. Autonomous navigation has the potential both to increase spacecraft navigation system performance and to reduce total mission cost. By eliminating the need for routine ground-based orbit determination and special tracking services, autonomous navigation can streamline spacecraft ground systems. Autonomous navigation products can be included in the science telemetry and forwarded directly to the scientific investigators. In addition, autonomous navigation products are available onboard to enable other autonomous capabilities, such as attitude control, maneuver planning and orbit control, and communications signal acquisition. Autonomous navigation is required to support advanced mission concepts such as satellite formation flying. GNCC has successfully developed high-accuracy autonomous navigation systems for near-Earth spacecraft using NASA's space and ground communications systems and the Global Positioning System (GPS). Recently, GNCC has expanded its autonomous navigation initiative to include satellite orbits that are beyond the regime in which use of GPS is possible. Currently, GNCC is assessing the feasibility of using standard spacecraft attitude sensors and communication components to provide autonomous navigation for missions including: libration point, gravity assist, high-Earth, and interplanetary orbits. The concept being evaluated uses a combination of star, Sun, and Earth sensor measurements along with forward-link Doppler

Adaptive Perception for Autonomous Vehicles

DTIC Science & Technology

1994-05-02

AD-A282 780 Adaptive Perception for Autonomous Vehicles Alonzo Kelly CMU-RI-TR-94-1 8 D IC SELECTF - pUG01 �j ~G U The Robotics Inttt ’I 94-2i...way of doing range image perception. Adaptive Perception for Autonomous Vehicles page 1. LZ Commentary The throughput problem of autonomous navigaticn...idea will be applied to the problem of terrain mapping in outdoor rough terrain. Adaptive Perception for Autonomous Vehicles page 2. 2. Analytical

brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish

PubMed Central

Bergeron, Sadie A.; Tyurina, Oksana V.; Miller, Emily; Bagas, Andrea; Karlstrom, Rolf O.

2011-01-01

The transmembrane protein Brother of Cdo (Boc) has been implicated in Shh-mediated commissural axon guidance, and can both positively and negatively regulate Hedgehog (Hh) target gene transcription, however, little is known about in vivo requirements for Boc during vertebrate embryogenesis. The zebrafish umleitung (umlty54) mutant was identified by defects in retinotectal axon projections. Here, we show that the uml locus encodes Boc and that Boc function is cell-autonomously required for Hh-mediated neural patterning. Our phenotypic analysis suggests that Boc is required as a positive regulator of Hh signaling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might negatively regulate Hh signals in the lower jaw. This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis. PMID:21115611

Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens.

PubMed Central

Chen, J D; Van Dyke, T

1991-01-01

The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis. Images PMID:1658622

A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

PubMed Central

Khavandgar, Zohreh; Poirier, Christophe; Clarke, Christopher J.; Li, Jingjing; Wang, Nicholas; McKee, Marc D.; Hannun, Yusuf A.

2011-01-01

A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phosphodiesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However, we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues. PMID:21788370

Towards an Autonomic Cluster Management System (ACMS) with Reflex Autonomicity

NASA Technical Reports Server (NTRS)

Truszkowski, Walt; Hinchey, Mike; Sterritt, Roy

2005-01-01

Cluster computing, whereby a large number of simple processors or nodes are combined together to apparently function as a single powerful computer, has emerged as a research area in its own right. The approach offers a relatively inexpensive means of providing a fault-tolerant environment and achieving significant computational capabilities for high-performance computing applications. However, the task of manually managing and configuring a cluster quickly becomes daunting as the cluster grows in size. Autonomic computing, with its vision to provide self-management, can potentially solve many of the problems inherent in cluster management. We describe the development of a prototype Autonomic Cluster Management System (ACMS) that exploits autonomic properties in automating cluster management and its evolution to include reflex reactions via pulse monitoring.

Endothelial Cell Autonomous Role of Akt1: Regulation of Vascular Tone and Ischemia-Induced Arteriogenesis.

PubMed

Lee, Monica Y; Gamez-Mendez, Ana; Zhang, Jiasheng; Zhuang, Zhenwu; Vinyard, David J; Kraehling, Jan; Velazquez, Heino; Brudvig, Gary W; Kyriakides, Themis R; Simons, Michael; Sessa, William C

2018-04-01

The importance of PI3K/Akt signaling in the vasculature has been demonstrated in several models, as global loss of Akt1 results in impaired postnatal ischemia- and VEGF-induced angiogenesis. The ubiquitous expression of Akt1, however, raises the possibility of cell-type-dependent Akt1-driven actions, thereby necessitating tissue-specific characterization. Herein, we used an inducible, endothelial-specific Akt1-deleted adult mouse model (Akt1iECKO) to characterize the endothelial cell autonomous functions of Akt1 in the vascular system. Endothelial-targeted ablation of Akt1 reduces eNOS (endothelial nitric oxide synthase) phosphorylation and promotes both increased vascular contractility in isolated vessels and elevated diastolic blood pressures throughout the diurnal cycle in vivo. Furthermore, Akt1iECKO mice subject to the hindlimb ischemia model display impaired blood flow and decreased arteriogenesis. Endothelial Akt1 signaling is necessary for ischemic resolution post-injury and likely reflects the consequence of NO insufficiency critical for vascular repair. © 2018 American Heart Association, Inc.

Skeletal muscle-specific eukaryotic translation initiation factor 2α phosphorylation controls amino acid metabolism and fibroblast growth factor 21-mediated non-cell-autonomous energy metabolism.

PubMed

Miyake, Masato; Nomura, Akitoshi; Ogura, Atsushi; Takehana, Kenji; Kitahara, Yoshihiro; Takahara, Kazuna; Tsugawa, Kazue; Miyamoto, Chinobu; Miura, Naoko; Sato, Ryosuke; Kurahashi, Kiyoe; Harding, Heather P; Oyadomari, Miho; Ron, David; Oyadomari, Seiichi

2016-02-01

The eukaryotic translation initiation factor 2α (eIF2α) phosphorylation-dependent integrated stress response (ISR), a component of the unfolded protein response, has long been known to regulate intermediary metabolism, but the details are poorly worked out. We report that profiling of mRNAs of transgenic mice harboring a ligand-activated skeletal muscle-specific derivative of the eIF2α protein kinase R-like ER kinase revealed the expected up-regulation of genes involved in amino acid biosynthesis and transport but also uncovered the induced expression and secretion of a myokine, fibroblast growth factor 21 (FGF21), that stimulates energy consumption and prevents obesity. The link between the ISR and FGF21 expression was further reinforced by the identification of a small-molecule ISR activator that promoted Fgf21 expression in cell-based screens and by implication of the ISR-inducible activating transcription factor 4 in the process. Our findings establish that eIF2α phosphorylation regulates not only cell-autonomous proteostasis and amino acid metabolism, but also affects non-cell-autonomous metabolic regulation by induced expression of a potent myokine. © FASEB.

Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit

PubMed Central

Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

2016-01-01

The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. DOI: http://dx.doi.org/10.7554/eLife.14277.001 PMID:27240166

Autonomous Soaring Flight Results

NASA Technical Reports Server (NTRS)

Allen, Michael J.

2006-01-01

A viewgraph presentation on autonomous soaring flight results for Unmanned Aerial Vehicles (UAV)'s is shown. The topics include: 1) Background; 2) Thermal Soaring Flight Results; 3) Autonomous Dolphin Soaring; and 4) Future Plans.

Continuous, real-time bioimaging of chemical bioavailability and toxicology using autonomously bioluminescent human cell lines

NASA Astrophysics Data System (ADS)

Xu, Tingting; Close, Dan M.; Webb, James D.; Price, Sarah L.; Ripp, Steven A.; Sayler, Gary S.

2013-05-01

Bioluminescent imaging is an emerging biomedical surveillance strategy that uses external cameras to detect in vivo light generated in small animal models of human physiology or in vitro light generated in tissue culture or tissue scaffold mimics of human anatomy. The most widely utilized of reporters is the firefly luciferase (luc) gene; however, it generates light only upon addition of a chemical substrate, thus only generating intermittent single time point data snapshots. To overcome this disadvantage, we have demonstrated substrate-independent bioluminescent imaging using an optimized bacterial bioluminescence (lux) system. The lux reporter produces bioluminescence autonomously using components found naturally within the cell, thereby allowing imaging to occur continuously and in real-time over the lifetime of the host. We have validated this technology in human cells with demonstrated chemical toxicological profiling against exotoxin exposures at signal strengths comparable to existing luc systems (~1.33 × 107 photons/second). As a proof-in-principle demonstration, we have engineered breast carcinoma cells to express bioluminescence for real-time screening of endocrine disrupting chemicals and validated detection of 17β-estradiol (EC50 = ~ 10 pM). These and other applications of this new reporter technology will be discussed as potential new pathways towards improved models of target chemical bioavailability, toxicology, efficacy, and human safety.

Peritoneal and hematogenous metastases of ovarian cancer cells are both controlled by the p90RSK through a self-reinforcing cell autonomous mechanism.

PubMed

Torchiaro, Erica; Lorenzato, Annalisa; Olivero, Martina; Valdembri, Donatella; Gagliardi, Paolo Armando; Gai, Marta; Erriquez, Jessica; Serini, Guido; Di Renzo, Maria Flavia

2016-01-05

The molecular mechanisms orchestrating peritoneal and hematogenous metastases of ovarian cancer cells are assumed to be distinct. We studied the p90RSK family of serine/threonine kinases that lie downstream the RAS-ERK/MAPK pathway and modulate a variety of cellular processes including cell proliferation, survival, motility and invasiveness. We found the RSK1 and RSK2 isoforms expressed in a number of human ovarian cancer cell lines, where they played redundant roles in sustaining in vitro motility and invasiveness. In vivo, silencing of both RSK1 and RSK2 almost abrogated short-term and long-term metastatic engraftment of ovarian cancer cells in the peritoneum. In addition, RSK1/RSK2 silenced cells failed to colonize the lungs after intravenous injection and to form hematogenous metastasis from subcutaneous xenografts. RSK1/RSK2 suppression resulted in lessened ovarian cancer cell spreading on endogenous fibronectin (FN). Mechanistically, RSK1/RSK2 knockdown diminished FN transcription, α5β1 integrin activation and TGF-β1 translation. Reduced endogenous FN deposition and TGF-β1 secretion depended on the lack of activating phosphorylation of the transcription/translation factor YB-1 by p90RSK. Altogether data show how p90RSK activates a self-reinforcing cell autonomous pro-adhesive circuit necessary for metastatic seeding of ovarian cancer cells. Thus, p90RSK inhibitors might hinder both the hematogenous and the peritoneal metastatic spread of human ovarian cancer.

Comparison of three control methods for an autonomous vehicle

NASA Astrophysics Data System (ADS)

Deshpande, Anup; Mathur, Kovid; Hall, Ernest

2010-01-01

The desirability and challenge of developing a completely autonomous vehicle and the rising need for more efficient use of energy by automobiles motivate this research- a study for an optimum solution to computer control of energy efficient vehicles. The purpose of this paper is to compare three control methods - mechanical, hydraulic and electric that have been used to convert an experimental all terrain vehicle to drive by wire which would eventually act as a test bed for conducting research on various technologies for autonomous operation. Computer control of basic operations in a vehicle namely steering, braking and speed control have been implemented and will be described in this paper. The output from a 3 axis motion controller is used for this purpose. The motion controller is interfaced with a software program using WSDK (Windows Servo Design Kit) as an intermediate tuning layer for tuning and parameter settings in autonomous operation. The software program is developed in C++. The voltage signal sent to the motion controller can be varied through the control program for desired results in controlling the steering motor, activating the hydraulic brakes and varying the vehicle's speed. The vehicle has been tested for its basic functionality which includes testing of street legal operations and also a 1000 mile test while running in a hybrid mode. The vehicle has also been tested for control when it is interfaced with devices such as a keyboard, joystick and sensors under full autonomous operation. The vehicle is currently being tested in various safety studies and is being used as a test bed for experiments in control courses and research studies. The significance of this research is in providing a greater understanding of conventional driving controls and the possibility of improving automobile safety by removing human error in control of a motor vehicle.

Neuronal autoantibodies in epilepsy patients with peri-ictal autonomic findings.

PubMed

Baysal-Kirac, Leyla; Tuzun, Erdem; Erdag, Ece; Ulusoy, Canan; Vanli-Yavuz, Ebru Nur; Ekizoglu, Esme; Peach, Sian; Sezgin, Mine; Bebek, Nerses; Gurses, Candan; Gokyigit, Aysen; Vincent, Angela; Baykan, Betul

2016-03-01

Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3%) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29%), contactin-associated protein-like 2 (CASPR2) in 5 (29%), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18%), glutamic acid decarboxylase (GAD) in 2 (12%), glycine receptor (GLYR) in one (6%) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6%). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.

Development of a Commercially Viable, Modular Autonomous Robotic Systems for Converting any Vehicle to Autonomous Control

NASA Technical Reports Server (NTRS)

Parish, David W.; Grabbe, Robert D.; Marzwell, Neville I.

1994-01-01

A Modular Autonomous Robotic System (MARS), consisting of a modular autonomous vehicle control system that can be retrofit on to any vehicle to convert it to autonomous control and support a modular payload for multiple applications is being developed. The MARS design is scalable, reconfigurable, and cost effective due to the use of modern open system architecture design methodologies, including serial control bus technology to simplify system wiring and enhance scalability. The design is augmented with modular, object oriented (C++) software implementing a hierarchy of five levels of control including teleoperated, continuous guidepath following, periodic guidepath following, absolute position autonomous navigation, and relative position autonomous navigation. The present effort is focused on producing a system that is commercially viable for routine autonomous patrolling of known, semistructured environments, like environmental monitoring of chemical and petroleum refineries, exterior physical security and surveillance, perimeter patrolling, and intrafacility transport applications.

Autonomously folded α-helical lockers promote RNAi*

NASA Astrophysics Data System (ADS)

Guyader, Christian P. E.; Lamarre, Baptiste; de Santis, Emiliana; Noble, James E.; Slater, Nigel K.; Ryadnov, Maxim G.

2016-10-01

RNAi is an indispensable research tool with a substantial therapeutic potential. However, the complete transition of the approach to an applied capability remains hampered due to poorly understood relationships between siRNA delivery and gene suppression. Here we propose that interfacial tertiary contacts between α-helices can regulate siRNA cytoplasmic delivery and RNAi. We introduce a rationale of helical amphipathic lockers that differentiates autonomously folded helices, which promote gene silencing, from helices folded with siRNA, which do not. Each of the helical designs can deliver siRNA into cells via energy-dependent endocytosis, while only autonomously folded helices with pre-locked hydrophobic interfaces were able to promote statistically appreciable gene silencing. We propose that it is the amphipathic locking of interfacing helices prior to binding to siRNA that enables RNAi. The rationale offers structurally balanced amphipathic scaffolds to advance the exploitation of functional RNAi.

Autonomously folded α-helical lockers promote RNAi*

PubMed Central

Guyader, Christian P. E.; Lamarre, Baptiste; De Santis, Emiliana; Noble, James E.; Slater, Nigel K.; Ryadnov, Maxim G.

2016-01-01

RNAi is an indispensable research tool with a substantial therapeutic potential. However, the complete transition of the approach to an applied capability remains hampered due to poorly understood relationships between siRNA delivery and gene suppression. Here we propose that interfacial tertiary contacts between α-helices can regulate siRNA cytoplasmic delivery and RNAi. We introduce a rationale of helical amphipathic lockers that differentiates autonomously folded helices, which promote gene silencing, from helices folded with siRNA, which do not. Each of the helical designs can deliver siRNA into cells via energy-dependent endocytosis, while only autonomously folded helices with pre-locked hydrophobic interfaces were able to promote statistically appreciable gene silencing. We propose that it is the amphipathic locking of interfacing helices prior to binding to siRNA that enables RNAi. The rationale offers structurally balanced amphipathic scaffolds to advance the exploitation of functional RNAi. PMID:27721465

Autonomously folded α-helical lockers promote RNAi.

PubMed

Guyader, Christian P E; Lamarre, Baptiste; De Santis, Emiliana; Noble, James E; Slater, Nigel K; Ryadnov, Maxim G

2016-10-10

RNAi is an indispensable research tool with a substantial therapeutic potential. However, the complete transition of the approach to an applied capability remains hampered due to poorly understood relationships between siRNA delivery and gene suppression. Here we propose that interfacial tertiary contacts between α-helices can regulate siRNA cytoplasmic delivery and RNAi. We introduce a rationale of helical amphipathic lockers that differentiates autonomously folded helices, which promote gene silencing, from helices folded with siRNA, which do not. Each of the helical designs can deliver siRNA into cells via energy-dependent endocytosis, while only autonomously folded helices with pre-locked hydrophobic interfaces were able to promote statistically appreciable gene silencing. We propose that it is the amphipathic locking of interfacing helices prior to binding to siRNA that enables RNAi. The rationale offers structurally balanced amphipathic scaffolds to advance the exploitation of functional RNAi.

Insights into the background of autonomic medicine.

PubMed

Laranjo, Sérgio; Geraldes, Vera; Oliveira, Mário; Rocha, Isabel

2017-10-01

Knowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

NASA Astrophysics Data System (ADS)

van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

2014-04-01

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity.

PubMed

van de Pavert, Serge A; Ferreira, Manuela; Domingues, Rita G; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R; Habani, Yasmin; Haak, Esther; Santori, Fabio R; Littman, Dan R; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J Pedro; Mebius, Reina E; Veiga-Fernandes, Henrique

2014-04-03

The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

Parvalbumin-expressing interneurons can act solo while somatostatin-expressing interneurons act in chorus in most cases on cortical pyramidal cells.

PubMed

Safari, Mir-Shahram; Mirnajafi-Zadeh, Javad; Hioki, Hiroyuki; Tsumoto, Tadaharu

2017-10-06

Neural circuits in the cerebral cortex consist primarily of excitatory pyramidal (Pyr) cells and inhibitory interneurons. Interneurons are divided into several subtypes, in which the two major groups are those expressing parvalbumin (PV) or somatostatin (SOM). These subtypes of interneurons are reported to play distinct roles in tuning and/or gain of visual response of pyramidal cells in the visual cortex. It remains unclear whether there is any quantitative and functional difference between the PV → Pyr and SOM → Pyr connections. We compared unitary inhibitory postsynaptic currents (uIPSCs) evoked by electrophysiological activation of single presynaptic interneurons with population IPSCs evoked by photo-activation of a mass of interneurons in vivo and in vitro in transgenic mice in which PV or SOM neurons expressed channelrhodopsin-2, and found that at least about 14 PV neurons made strong connections with a postsynaptic Pyr cell while a much larger number of SOM neurons made weak connections. Activation or suppression of single PV neurons modified visual responses of postsynaptic Pyr cells in 6 of 7 pairs whereas that of single SOM neurons showed no significant modification in 8 of 11 pairs, suggesting that PV neurons can act solo whereas most of SOM neurons may act in chorus on Pyr cells.

Autonomic Nervous System Disorders

MedlinePlus

Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers.

PubMed

Wu, Zhen; Zhang, Zhen; Guo, Rui; Gros-Louis, Julie

2017-01-01

Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human's tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children's happiness when sharing was autonomous (the recipient did not contribute to getting the reward) with when sharing was obligated (the recipient and the actor jointly earned the reward). We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children's affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers' prosocial behaviors.

Motivation Counts: Autonomous But Not Obligated Sharing Promotes Happiness in Preschoolers

PubMed Central

Wu, Zhen; Zhang, Zhen; Guo, Rui; Gros-Louis, Julie

2017-01-01

Research has demonstrated that prosocial sharing is emotionally rewarding, which leads to further prosocial actions; such a positive feedback loop suggests a proximal mechanism of human’s tendency to act prosocially. However, it leaves open a question as to how the emotional benefits from sharing develop in young children and whether sharing under pressure promotes happiness as well. The current study directly compared 3- and 5-year-old Chinese children’s happiness when sharing was autonomous (the recipient did not contribute to getting the reward) with when sharing was obligated (the recipient and the actor jointly earned the reward). We found that children shared more items overall when sharing was obligated than autonomous, demonstrating their conformity to social norms of merit-based sharing. In children who eventually shared with others, 5-year-olds gave out more stickers in the obligated sharing condition than in the autonomous sharing condition, but 3-year-olds shared the same amount between the conditions, suggesting that 5-year-olds adhered to the merit-based sharing norm more strictly than 3-year-olds. Moreover, in the autonomous sharing condition, children displayed greater happiness when they shared with the recipient than when they kept stickers for themselves, suggesting that costly prosocial giving benefited children with positive mood; however, children did not gain happiness when they shared with the recipient in the obligated sharing condition. These findings demonstrate that children’s affective benefits depend on the motivation underlying their prosocial behavior, and further imply that normative force and emotional gains may independently drive preschoolers’ prosocial behaviors. PMID:28620328

A Robust Compositional Architecture for Autonomous Systems

NASA Technical Reports Server (NTRS)

Brat, Guillaume; Deney, Ewen; Farrell, Kimberley; Giannakopoulos, Dimitra; Jonsson, Ari; Frank, Jeremy; Bobby, Mark; Carpenter, Todd; Estlin, Tara

2006-01-01

Space exploration applications can benefit greatly from autonomous systems. Great distances, limited communications and high costs make direct operations impossible while mandating operations reliability and efficiency beyond what traditional commanding can provide. Autonomous systems can improve reliability and enhance spacecraft capability significantly. However, there is reluctance to utilizing autonomous systems. In part this is due to general hesitation about new technologies, but a more tangible concern is that of reliability of predictability of autonomous software. In this paper, we describe ongoing work aimed at increasing robustness and predictability of autonomous software, with the ultimate goal of building trust in such systems. The work combines state-of-the-art technologies and capabilities in autonomous systems with advanced validation and synthesis techniques. The focus of this paper is on the autonomous system architecture that has been defined, and on how it enables the application of validation techniques for resulting autonomous systems.

Autonomous support for microorganism research in space

NASA Technical Reports Server (NTRS)

Fleet, Mary L.; Miller, Mark S.; Shipley, Derek, E.; Smith, Jeff D.

1992-01-01

A preliminary design for performing on orbit, autonomous research on microorganisms and cultured cells/tissues is presented. An understanding of gravity and its effects on cells is crucial for space exploration as well as for terrestrial applications. The payload is designed to be compatible with the Commercial Experiment Transporter (COMET) launch vehicle, an orbiter middeck locker interface, and with Space Station Freedom. Uplink/downlink capabilities and sample return through controlled reentry are available for all carriers. Autonomous testing activities are preprogrammed with in-flight reprogrammability. Sensors for monitoring temperature, pH, light, gravity levels, vibrations, and radiation are provided for environmental regulation and experimental data collection. Additional experimental data acquisition includes optical density measurement, microscopy, video, and film photography. On-board full data storage capabilities are provided. A fluid transfer mechanism is utilized for inoculation, sampling, and nutrient replenishment of experiment cultures. In addition to payload design, representative experiments were developed to ensure scientific objectives remained compatible with hardware capabilities. The project is defined to provide biological data pertinent to extended duration crewed space flight including crew health issues and development of a Controlled Ecological Life Support System (CELSS). In addition, opportunities are opened for investigations leading to commercial applications of space, such as pharmaceutical development, modeling of terrestrial diseases, and material processing.

Autonomous support for microorganism research in space

NASA Technical Reports Server (NTRS)

Luttges, M. W.; Klaus, D. M.; Fleet, M. L.; Miller, M. S.; Shipley, D. E.; Smith, J. D.

1992-01-01

A preliminary design for performing on-orbit, autonomous research on microorganisms and cultured cells/tissues is presented. An understanding of gravity and its effects on cells is crucial for space exploration as well as for terrestrial applications. The payload is designed to be compatible with the COMmercial Experiment Transported (COMET) launch vehicle, an orbiter middeck locker interface, and with Space Station Freedom. Uplink/downlink capabilities and sample return through controlled reentry are available for all carriers. Autonomous testing activities are preprogrammed with inflight reprogrammability. Sensors for monitoring temperature, pH, light, gravity levels, vibration, and radiation are provided for environmental regulation and experimental data collection. Additional experiment data acquisition includes optical density measurement, microscopy, video, and file photography. Onboard full data storage capabilities are provided. A fluid transfer mechanism is utilized for inoculation, sampling, and nutrient replenishment of experiment cultures. In addition to payload design, representative experiments were developed to ensure scientific objectives remained compatible with hardware capabilities. The project is defined to provide biological data pertinent to extended duration crewed space flight including crew health issues and development of a Controlled Ecological Life Support System (CELSS). In addition, opportunities are opened for investigations leading to commercial applications of space, such as pharmaceutical development, modeling of terrestrial diseases, and material processing.

Terrain Navigation Concepts for Autonomous Vehicles,

DTIC Science & Technology

1984-06-01

AD-fi144 994 TERRAIN NAVIGATION CONCEPTS FOR AUTONOMOUS VEHICLES (U) i/i I ARMY ENGINEER OPOGRAPHIC LABS FORT BELVOIR VA R D LEIGHTY JUN 84 ETL-R@65...FUNCTIONS The pacing problem for developing autonomous vehicles that can efficiently move to designated locations in the real world in the perfor- mance...autonomous functions can serve as general terrain navigation requirements for our discussion of autonomous vehicles . LEIGHTY Can we build a vehicular system

Microglia PACAP and glutamate: Friends or foes in seizure-induced autonomic dysfunction and SUDEP?

PubMed

Bhandare, Amol M; Kapoor, Komal; Farnham, Melissa M J; Pilowsky, Paul M

2016-06-01

Seizure-induced cardiorespiratory autonomic dysfunction is a major cause of sudden unexpected death in epilepsy (SUDEP), and the underlying mechanism is unclear. Seizures lead to increased synthesis, and release of glutamate, pituitary adenylate cyclase activating polypeptide (PACAP), and other neurotransmitters, and cause extensive activation of microglia at multiple regions in the brain including central autonomic cardiorespiratory brainstem nuclei. Glutamate contributes to neurodegeneration, and inflammation in epilepsy. PACAP has neuroprotective, and anti-inflammatory properties, whereas microglia are key players in inflammatory responses in CNS. Seizure-induced increase in PACAP is neuroprotective. PACAP produces neuroprotective effects acting on microglial PAC1 and VPAC1 receptors. Microglia also express glutamate transporters, and their expression can be increased by PACAP in response to harmful or stressful situations such as seizures. Here we discuss the mechanism of autonomic cardiorespiratory dysfunction in seizure, and the role of PACAP, glutamate and microglia in regulating cardiorespiratory brainstem neurons in their physiological state that could provide future therapeutic options for SUDEP. Copyright © 2016 Elsevier B.V. All rights reserved.

Autonomic Computing: Freedom or a Threat?

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

Fink, Glenn A.; Frincke, Deb

2007-12-01

No longer is the question whether autonomic computing will gain general acceptance but when. Experts expect autonomic computing to be widely used within 10 years. When it does become mainstream, how will autonomics change system administration and corporations, and will the change be for better or worse? The answer depends on how well we anticipate the limitations of what autonomic systems are suited to do, whether we can collectively address the vulnerabilities of autonomic approaches as we draw upon the advantages, and whether administrators, companies, partners, and users are prepared for the transition. This article presents some design considerations tomore » address the first two issues and some suggested survival techniques for the third.« less

Design of an autonomous lunar construction utility vehicle

NASA Technical Reports Server (NTRS)

1990-01-01

In order to prepare a site for a lunar base, an autonomously operated construction vehicle is necessary. Discussed here is a Lunar Construction Utility Vehicle (LCUV), which uses interchangeable construction implements. Design of an elastic loop track system has advanced to the testing stage. A standard coupling device has been designed to insure a proper connection between the different construction tools and the LCUV. Autonomous control of the track drive motors was simulated successfully through the use of a joystick and a computer interface. A study of hydrogen-oxygen fuel cells produced estimates of reactant and product requirements and identified multilayer insulation needs. Research on the 100-kW heat rejection system determined that it is necessary to transport the radiator panel on a utility trailer. Extensive logistical support for the 720 hour use cycle requires further study.

In serum veritas—in serum sanitas? Cell non-autonomous aging compromises differentiation and survival of mesenchymal stromal cells via the oxidative stress pathway

PubMed Central

Geißler, S; Textor, M; Schmidt-Bleek, K; Klein, O; Thiele, M; Ellinghaus, A; Jacobi, D; Ode, A; Perka, C; Dienelt, A; Klose, J; Kasper, G; Duda, G N; Strube, P

2013-01-01

Even tissues capable of complete regeneration, such as bone, show an age-related reduction in their healing capacity. Here, we hypothesized that this decline is primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic environment. We demonstrate that culture of mesenchymal stromal cells (MSCs) in serum from aged Sprague–Dawley rats negatively affects their survival and differentiation ability. Proteome analysis and further cellular investigations strongly suggest that serum from aged animals not only changes expression of proteins related to mitochondria, unfolded protein binding or involved in stress responses, it also significantly enhances intracellular reactive oxygen species production and leads to the accumulation of oxidatively damaged proteins. Conversely, reduction of oxidative stress levels in vitro markedly improved MSC function. These results were validated in an in vivo model of compromised bone healing, which demonstrated significant increase regeneration in aged animals following oral antioxidant administration. These observations indicate the high impact of extrinsic aging on cellular functions and the process of endogenous (bone) regeneration. Thus, addressing the cell environment by, for example, systemic antioxidant treatment is a promising approach to enhance tissue regeneration and to regain cellular function especially in elderly patients. PMID:24357801

Autonomous navigation system and method

DOEpatents

Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID

2009-09-08

A robot platform includes perceptors, locomotors, and a system controller, which executes instructions for autonomously navigating a robot. The instructions repeat, on each iteration through an event timing loop, the acts of defining an event horizon based on the robot's current velocity, detecting a range to obstacles around the robot, testing for an event horizon intrusion by determining if any range to the obstacles is within the event horizon, and adjusting rotational and translational velocity of the robot accordingly. If the event horizon intrusion occurs, rotational velocity is modified by a proportion of the current rotational velocity reduced by a proportion of the range to the nearest obstacle and translational velocity is modified by a proportion of the range to the nearest obstacle. If no event horizon intrusion occurs, translational velocity is set as a ratio of a speed factor relative to a maximum speed.

An Autonomous Flight Safety System

NASA Technical Reports Server (NTRS)

Bull, James B.; Lanzi, Raymond J.

2007-01-01

The Autonomous Flight Safety System (AFSS) being developed by NASA s Goddard Space Flight Center s Wallops Flight Facility and Kennedy Space Center has completed two successful developmental flights and is preparing for a third. AFSS has been demonstrated to be a viable architecture for implementation of a completely vehicle based system capable of protecting life and property in event of an errant vehicle by terminating the flight or initiating other actions. It is capable of replacing current human-in-the-loop systems or acting in parallel with them. AFSS is configured prior to flight in accordance with a specific rule set agreed upon by the range safety authority and the user to protect the public and assure mission success. This paper discusses the motivation for the project, describes the method of development, and presents an overview of the evolving architecture and the current status.

Full autonomous microline trace robot

NASA Astrophysics Data System (ADS)

Yi, Deer; Lu, Si; Yan, Yingbai; Jin, Guofan

2000-10-01

Optoelectric inspection may find applications in robotic system. In micro robotic system, smaller optoelectric inspection system is preferred. However, as miniaturizing the size of the robot, the number of the optoelectric detector becomes lack. And lack of the information makes the micro robot difficult to acquire its status. In our lab, a micro line trace robot has been designed, which autonomous acts based on its optoelectric detection. It has been programmed to follow a black line printed on the white colored ground. Besides the optoelectric inspection, logical algorithm in the microprocessor is also important. In this paper, we propose a simply logical algorithm to realize robot's intelligence. The robot's intelligence is based on a AT89C2051 microcontroller which controls its movement. The technical details of the micro robot are as follow: dimension: 30mm*25mm*35*mm; velocity: 60mm/s.

Essential Kinematics for Autonomous Vehicles

DTIC Science & Technology

1994-05-02

AD-.A282 456 Essential Kinematics for Autonomous Vehicles Alonzo Kelly DTICCMU-RI-TR-94- 14 AU 031994 F The Robotics Institute Carnegie Mellon...kit of concepts and techniques that will equip the reader to master a large class of kinematic modelling problems. Control of autonomous vehicles in 3D...transformation from system ’a’ to system b’. Essential Kinematics for Autonomous Vehicles page 1. The specification of derivatives will be necessarily

[Times of gender equity: a description of the inequalities between autonomous communities, Spain 2006-2014].

PubMed

Fernández-Sáez, José; Ruiz-Cantero, María Teresa; Guijarro-Garvi, Marta; Rodenas-Calatayud, Carmen; Martí-Sempere, Mónica; Jiménez-Alegre, María Dolores

2016-01-01

Gender equity (GE) is a structural determinant of health inequalities. In this light, our objective is to show the evolution of gender equity in the Spanish autonomous communities since 2006, prior to the enactment of the Equality Act (2007) and the economic crisis (2008), until 2014. Ecological study of gender equity in the 17 Spanish autonomous communities from 2006-2011-2014. We have calculated: 1) modified gender equity index (MGEI) for the autonomous communities (0=equity, ±1=inequity); 2) interregional and temporal convergences in gender equity. The MGEI in the autonomous communities in 2014 has negative values close to 0 (inequity towards women). There is no interregional convergence due to the dispersion increase (2006: 0.1503; 2011: 0.2280; 2014: 0.4964), and no temporal convergence due to the lack of progress of the autonomous communities with poor gender equity. The gender gap in economic activity continues to be unfavourable to women, decreasing in all communities between 2006 and 2011 but increasing in six communities in 2014. The gender gap in education from 2006-2011-2014 has positive values close to 0 (unfavourable to men), while the gender gap in empowerment is unfavourable to women, representing the most significant gender equity disparity. Inter-community dispersion of economic activity and education did not change between 2006 and 2014, while inter-community dispersion of empowerment increased. The level of gender equity achieved in the Spanish autonomous communities in 2006 was lost during the economic crisis, as gender equity disparities between the communities had increased by 2014. Gender inequity continues to be unfavourable to women. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

Impact of the Affordable Care Act on stem cell transplantation.

PubMed

Farnia, Stephanie; Gedan, Alicia; Boo, Michael

2014-03-01

The Patient Protection and Affordable Care Act, signed into law in 2010, will have a wide-reaching impact on the health care system in the United States when it is fully implemented in 2014. Patients will see increased access to care coupled with new insurance coverage protections as well as a minimum set of benefits mandated in each state known as essential health benefits. Providers are likely to see new forms of payment reform, particularly in the Medicare program, and narrower commercial provider networks. In addition, the composition of the health insurance market will broaden with the introduction of health insurance exchanges and expanded Medicaid populations in many states. Furthermore, the Patient Protection and Affordable Care Act calls for quality initiatives such as comparative effectiveness research to increase effective, appropriate and high-value care. This paper will review the main provisions of the Patient Protection and Affordable Care Act with specific attention to their impact on the field of Stem Cell Transplantation.

A comparison of the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts after calving in cows also given internal teat sealants.

PubMed

Whitfield, L K; Laven, R A

2018-01-01

To compare, in cows treated with an internal teat sealant, the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts (SCC) after calving. Cows from a spring-calving, pasture-based dairy farm in the Manawatu-Whanganui region of New Zealand were randomly allocated to receive either a short-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=291) or a long-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=288) at the end of lactation. Cows were managed on-farm with routine husbandry procedures through the dry period and following calving. A multivariable logistic regression model was used to determine the association between length of action of dry-cow therapy and the proportion of cows with a SCC >150,000 cells/mL at the first herd test after calving. Age of cow, mean SCC for the preceding season and interval from calving to the first post-calving herd test were all associated with the proportion of cows with an individual SCC >150,000 cells/mL at the first herd test (p<0.001) Treatment with the short-acting dry-cow therapy was not associated with decreased odds of cows having a SCC >150,000 cells/mL at the first herd test compared with treatment with long-acting dry-cow therapy (OR=0.724; 95% CI=0.40-1.30). In this herd, which routinely used internal teat sealants, the use of short-acting cloxacillin-based dry-cow therapy did not result in an increased proportion of cows with elevated SSC post-calving. This was a single farm, single year study but indicates that in this herd, changing from a long-acting to a short-acting antimicrobial may have no impact on the prevalence of subclinical mastitis.

Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

NASA Astrophysics Data System (ADS)

Di Pendina, G.; Zianbetov, E.; Beigne, E.

2015-05-01

Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

Why Computer-Based Systems Should be Autonomic

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2005-01-01

The objective of this paper is to discuss why computer-based systems should be autonomic, where autonomicity implies self-managing, often conceptualized in terms of being self-configuring, self-healing, self-optimizing, self-protecting and self-aware. We look at motivations for autonomicity, examine how more and more systems are exhibiting autonomic behavior, and finally look at future directions.

The use of mesenchymal stem cells (MSCs) for amyotrophic lateral sclerosis (ALS) therapy - a perspective on cell biological mechanisms.

PubMed

Tang, Bor Luen

2017-10-26

Recent clinical trials of mesenchymal stem cells (MSCs) transplantation have demonstrated procedural safety and clinical proof of principle with a modest indication of benefit in patients with amyotrophic lateral sclerosis (ALS). While replacement therapy remained unrealistic, the clinical efficacy of this therapeutic option could be potentially enhanced if we could better decipher the mechanisms underlying some of the beneficial effects of transplanted cells, and work toward augmenting or combining these in a strategic manner. Novel ways whereby MSCs could act in modifying disease progression should also be explored. In this review, I discuss the known, emerging and postulated mechanisms of action underlying effects that transplanted MSCs may exert to promote motor neuron survival and/or to encourage regeneration in ALS. I shall also speculate on how transplanted cells may alter the diseased environment so as to minimize non-neuron cell autonomous damages by immune cells and astrocytes.

Decentralized Control of Autonomous Vehicles

DTIC Science & Technology

2003-01-01

Autonomous Vehicles by John S. Baras, Xiaobo Tan, Pedram Hovareshti CSHCN TR 2003-8 (ISR TR 2003-14) Report Documentation Page Form ApprovedOMB No. 0704...AND SUBTITLE Decentralized Control of Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Decentralized Control of Autonomous Vehicles ∗ John S. Baras, Xiaobo Tan, and Pedram

Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus

PubMed Central

Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

2016-01-01

RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh. RACB is required for positioning of the nucleus near the site of attack from Bgh. We therefore suggest that Bgh profits from RACB’s function in cell polarity rather than from immunity-regulating functions of RACB. PMID:27056842

Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus.

PubMed

Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

2016-05-01

RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh RACB is required for positioning of the nucleus near the site of attack from Bgh We therefore suggest that Bgh profits from RACB's function in cell polarity rather than from immunity-regulating functions of RACB. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Public Health, Ethics, and Autonomous Vehicles

PubMed Central

2017-01-01

With the potential to save nearly 30 000 lives per year in the United States, autonomous vehicles portend the most significant advance in auto safety history by shifting the focus from minimization of postcrash injury to collision prevention. I have delineated the important public health implications of autonomous vehicles and provided a brief analysis of a critically important ethical issue inherent in autonomous vehicle design. The broad expertise, ethical principles, and values of public health should be brought to bear on a wide range of issues pertaining to autonomous vehicles. PMID:28207327

Public Health, Ethics, and Autonomous Vehicles.

PubMed

Fleetwood, Janet

2017-04-01

With the potential to save nearly 30 000 lives per year in the United States, autonomous vehicles portend the most significant advance in auto safety history by shifting the focus from minimization of postcrash injury to collision prevention. I have delineated the important public health implications of autonomous vehicles and provided a brief analysis of a critically important ethical issue inherent in autonomous vehicle design. The broad expertise, ethical principles, and values of public health should be brought to bear on a wide range of issues pertaining to autonomous vehicles.

Autonomous Commanding of the WIRE Spacecraft

NASA Technical Reports Server (NTRS)

Prior, Mike; Walyus, Keith; Saylor, Rick

1999-01-01

This paper presents the end-to-end design architecture for an autonomous commanding capability to be used on the Wide Field Infrared Explorer (WIRE) mission for the uplink of command loads during unattended station contacts. The WIRE mission is the fifth and final mission of NASA's Goddard Space Flight Center Small Explorer (SMEX) series to be launched in March of 1999. Its primary mission is the targeting of deep space fields using an ultra-cooled infrared telescope. Due to its mission design WIRE command loads are large (approximately 40 Kbytes per 24 hours) and must be performed daily. To reduce the cost of mission operations support that would be required in order to uplink command loads, the WIRE Flight Operations Team has implemented an autonomous command loading capability. This capability allows completely unattended operations over a typical two- day weekend period. The key factors driving design and implementation of this capability were: 1) Integration with already existing ground system autonomous capabilities and systems, 2) The desire to evolve autonomous operations capabilities based upon previous SMEX operations experience 3) Integration with ground station operations - both autonomous and man-tended, 4) Low cost and quick implementation, and 5) End-to-end system robustness. A trade-off study was performed to examine these factors in light of the low-cost, higher-risk SMEX mission philosophy. The study concluded that a STOL (Spacecraft Test and Operations Language) based script, highly integrated with other scripts used to perform autonomous operations, was best suited given the budget and goals of the mission. Each of these factors is discussed to provide an overview of the autonomous operations capabilities implemented for the mission. The capabilities implemented on the WIRE mission are an example of a low-cost, robust, and efficient method for autonomous command loading when implemented with other autonomous features of the ground system. They

A Multi-Robot Sense-Act Approach to Lead to a Proper Acting in Environmental Incidents

PubMed Central

Conesa-Muñoz, Jesús; Valente, João; del Cerro, Jaime; Barrientos, Antonio; Ribeiro, Angela

2016-01-01

Many environmental incidents affect large areas, often in rough terrain constrained by natural obstacles, which makes intervention difficult. New technologies, such as unmanned aerial vehicles, may help address this issue due to their suitability to reach and easily cover large areas. Thus, unmanned aerial vehicles may be used to inspect the terrain and make a first assessment of the affected areas; however, nowadays they do not have the capability to act. On the other hand, ground vehicles rely on enough power to perform the intervention but exhibit more mobility constraints. This paper proposes a multi-robot sense-act system, composed of aerial and ground vehicles. This combination allows performing autonomous tasks in large outdoor areas by integrating both types of platforms in a fully automated manner. Aerial units are used to easily obtain relevant data from the environment and ground units use this information to carry out interventions more efficiently. This paper describes the platforms and sensors required by this multi-robot sense-act system as well as proposes a software system to automatically handle the workflow for any generic environmental task. The proposed system has proved to be suitable to reduce the amount of herbicide applied in agricultural treatments. Although herbicides are very polluting, they are massively deployed on complete agricultural fields to remove weeds. Nevertheless, the amount of herbicide required for treatment is radically reduced when it is accurately applied on patches by the proposed multi-robot system. Thus, the aerial units were employed to scout the crop and build an accurate weed distribution map which was subsequently used to plan the task of the ground units. The whole workflow was executed in a fully autonomous way, without human intervention except when required by Spanish law due to safety reasons. PMID:27517934

Cell autonomous expression of inflammatory genes in biologically aged fibroblasts associated with elevated NF-kappaB activity.

PubMed

Kriete, Andres; Mayo, Kelli L; Yalamanchili, Nirupama; Beggs, William; Bender, Patrick; Kari, Csaba; Rodeck, Ulrich

2008-07-16

Chronic inflammation is a well-known corollary of the aging process and is believed to significantly contribute to morbidity and mortality of many age-associated chronic diseases. However, the mechanisms that cause age-associated inflammatory changes are not well understood. Particularly, the contribution of cell stress responses to age-associated inflammation in 'non-inflammatory' cells remains poorly defined. The present cross-sectional study focused on differences in molecular signatures indicative of inflammatory states associated with biological aging of human fibroblasts from donors aged 22 to 92 years. Gene expression profiling revealed elevated steady-state transcript levels consistent with a chronic inflammatory state in fibroblast cell-strains obtained from older donors. We also observed enhanced NF-kappaB DNA binding activity in a subset of strains, and the NF-kappaB profile correlated with mRNA expression levels characteristic of inflammatory processes, which include transcripts coding for cytokines, chemokines, components of the complement cascade and MHC molecules. This intrinsic low-grade inflammatory state, as it relates to aging, occurs in cultured cells irrespective of the presence of other cell types or the in vivo context. Our results are consistent with the view that constitutive activation of inflammatory pathways is a phenomenon prevalent in aged fibroblasts. It is possibly part of a cellular survival process in response to compromised mitochondrial function. Importantly, the inflammatory gene expression signature described here is cell autonomous, i.e. occurs in the absence of prototypical immune or pro-inflammatory cells, growth factors, or other inflammatory mediators.

[Trigemino-autonomic headache syndromes].

PubMed

Busch, V; May, A

2003-01-01

This review describes the characteristics of some rare severe primary headache syndromes without any structural lesions, which are summarized as the trigemino-autonomic headaches. Pain in these syndromes is associated with autonomic symptoms such as conjunctival injection, lacrimation, rhinorrhoe, ptosis or eyelid edema. This article summarizes the diagnostics, epidemiology and therapy of these conditions.

Design and Fabrication of an MRI-Compatible, Autonomous Incubation System.

PubMed

Khalilzad-Sharghi, Vahid; Xu, Huihui

2015-10-01

Tissue engineers have long sought access to an autonomous, imaging-compatible tissue incubation system that, with minimum operator handling, can provide real-time visualization and quantification of cells, tissue constructs, and organs. This type of screening system, capable of operating noninvasively to validate tissue, can overcome current limitations like temperature shock, unsustainable cellular environments, sample contamination, and handling/stress. However, this type of system has been a major challenge, until now. Here, we describe the design, fabrication, and characterization of an innovative, autonomous incubation system that is compatible with a 9.4 T magnetic resonance imaging (MRI) scanner. Termed the e-incubator (patent pending; application number: 13/953,984), this microcontroller-based system is integrated into an MRI scanner and noninvasively screens cells and tissue cultures in an environment where temperature, pH, and media/gas handling are regulated. The 4-week study discussed herein details the continuous operation of the e-incubator for a tissue-engineered osteogenic construct, validated by LIVE/DEAD(®) cell assays and histology. The evolving MR quantitative parameters of the osteogenic construct were used as biomarkers for bone tissue engineering and to further validate the quality of the product noninvasively before harvesting. Importantly, the e-incubator reliably facilitates culturing cells and tissue constructs to create engineered tissues and/or investigate disease therapies.

Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia

PubMed Central

Wang, Manqi; Wang, Qian; Whim, Matthew D.

2016-01-01

During fasting, activation of the counter-regulatory response (CRR) prevents hypoglycemia. A major effector arm is the autonomic nervous system that controls epinephrine release from adrenal chromaffin cells and, consequently, hepatic glucose production. However, whether modulation of autonomic function determines the relative strength of the CRR, and thus the ability to withstand food deprivation and maintain euglycemia, is not known. Here we show that fasting leads to altered transmission at the preganglionic → chromaffin cell synapse. The dominant effect is a presynaptic, long-lasting increase in synaptic strength. Using genetic and pharmacological approaches we show this plasticity requires neuropeptide Y, an adrenal cotransmitter and the activation of adrenal Y5 receptors. Loss of neuropeptide Y prevents a fasting-induced increase in epinephrine release and results in hypoglycemia in vivo. These findings connect plasticity within the sympathetic nervous system to a physiological output and indicate the strength of the final synapse in this descending pathway plays a decisive role in maintaining euglycemia. PMID:27092009

Materials learning from life: concepts for active, adaptive and autonomous molecular systems.

PubMed

Merindol, Rémi; Walther, Andreas

2017-09-18

Bioinspired out-of-equilibrium systems will set the scene for the next generation of molecular materials with active, adaptive, autonomous, emergent and intelligent behavior. Indeed life provides the best demonstrations of complex and functional out-of-equilibrium systems: cells keep track of time, communicate, move, adapt, evolve and replicate continuously. Stirred by the understanding of biological principles, artificial out-of-equilibrium systems are emerging in many fields of soft matter science. Here we put in perspective the molecular mechanisms driving biological functions with the ones driving synthetic molecular systems. Focusing on principles that enable new levels of functionalities (temporal control, autonomous structures, motion and work generation, information processing) rather than on specific material classes, we outline key cross-disciplinary concepts that emerge in this challenging field. Ultimately, the goal is to inspire and support new generations of autonomous and adaptive molecular devices fueled by self-regulating chemistry.

Autonomic Computing for Spacecraft Ground Systems

NASA Technical Reports Server (NTRS)

Li, Zhenping; Savkli, Cetin; Jones, Lori

2007-01-01

Autonomic computing for spacecraft ground systems increases the system reliability and reduces the cost of spacecraft operations and software maintenance. In this paper, we present an autonomic computing solution for spacecraft ground systems at NASA Goddard Space Flight Center (GSFC), which consists of an open standard for a message oriented architecture referred to as the GMSEC architecture (Goddard Mission Services Evolution Center), and an autonomic computing tool, the Criteria Action Table (CAT). This solution has been used in many upgraded ground systems for NASA 's missions, and provides a framework for developing solutions with higher autonomic maturity.

Basic emotions induced by odorants: a new approach based on autonomic pattern results.

PubMed

Vernet-Maury, E; Alaoui-Ismaïli, O; Dittmar, A; Delhomme, G; Chanel, J

1999-02-15

The aim of this study was to link the effects of odorants with the emotional process, through autonomic nervous system (ANS) responses. Taking Ekman's data and our previous results into account, we tried to verify a possible evocation by odorants of some basic emotions, i.e. anger, fear, sadness, surprise, disgust and happiness. The question investigated was: would it be possible to associate any of these emotions with a pattern of autonomic responses? A total of 15 subjects inhaled five odorants: lavender, ethyl aceto acetate, camphor, acetic acid and butyric acid acting as olfactory stimuli. After inhaling the odorant, subjects were requested to fill out an 11-point hedonic scale to rate its 'pleasantness' vs. 'unpleasantness'. ANS parameters monitored were skin potential and resistance, skin blood flow and temperature, instantaneous respiratory frequency and instantaneous heart rate. Simultaneous recording of these six autonomic parameters permitted the analysis of phasic responses through specific ANS patterns. An analysis of variance made it possible to differentiate among the five odorants. Two-by-two odorant comparisons for autonomic responses using Tukey's HSD multiple comparison test only permitted differentiation between 'pleasant' and 'unpleasant' odors. Camphor was differentiated from both types. For instance, long duration responses were associated with 'unpleasant' odors whereas camphor elicited intermediate responses. Taking into account each subject's preferential channel, it was possible to associate each ANS pattern with a basic emotion by means of a decision tree. The computation of subjects' responses made it possible to associate an odorant with a basic emotion, over the whole group: lavender elicited mostly 'happiness', as did, to a lesser degree ethyl aceto acetate; camphor induced either 'happiness', 'surprise' or 'sadness' according to subjects' past histories; butyric and acetic acids mainly induced negative emotions: 'anger' and 'disgust

High-frequency transformation of a methylotrophic yeast, Candida boidinii, with autonomously replicating plasmids which are also functional in Saccharomyces cerevisiae.

PubMed

Sakai, Y; Goh, T K; Tani, Y

1993-06-01

We have developed a transformation system which uses autonomous replicating plasmids for a methylotrophic yeast, Candida boidinii. Two autonomous replication sequences, CARS1 and CARS2, were newly cloned from the genome of C. boidinii. Plasmids having both a CARS fragment and the C. boidinii URA3 gene transformed C. boidinii ura3 cells to Ura+ phenotype at frequencies of up to 10(4) CFU/micrograms of DNA. From Southern blot analysis, CARS plasmids seemed to exist in polymeric forms as well as in monomeric forms in C. boidinii cells. The C. boidinii URA3 gene was overexpressed in C. boidinii on these CARS vectors. CARS1 and CARS2 were found to function as an autonomous replicating element in Saccharomyces cerevisiae as well. Different portions of the CARS1 sequence were needed for autonomous replicating activity in C. boidinii and S. cerevisiae. C. boidinii could also be transformed with vectors harboring a CARS fragment and the S. cerevisiae URA3 gene.

Current challenges in autonomous vehicle development

NASA Astrophysics Data System (ADS)

Connelly, J.; Hong, W. S.; Mahoney, R. B., Jr.; Sparrow, D. A.

2006-05-01

The field of autonomous vehicles is a rapidly growing one, with significant interest from both government and industry sectors. Autonomous vehicles represent the intersection of artificial intelligence (AI) and robotics, combining decision-making with real-time control. Autonomous vehicles are desired for use in search and rescue, urban reconnaissance, mine detonation, supply convoys, and more. The general adage is to use robots for anything dull, dirty, dangerous or dumb. While a great deal of research has been done on autonomous systems, there are only a handful of fielded examples incorporating machine autonomy beyond the level of teleoperation, especially in outdoor/complex environments. In an attempt to assess and understand the current state of the art in autonomous vehicle development, a few areas where unsolved problems remain became clear. This paper outlines those areas and provides suggestions for the focus of science and technology research. The first step in evaluating the current state of autonomous vehicle development was to develop a definition of autonomy. A number of autonomy level classification systems were reviewed. The resulting working definitions and classification schemes used by the authors are summarized in the opening sections of the paper. The remainder of the report discusses current approaches and challenges in decision-making and real-time control for autonomous vehicles. Suggested research focus areas for near-, mid-, and long-term development are also presented.

Autonomous search and surveillance with small fixed wing aircraft

NASA Astrophysics Data System (ADS)

McGee, Timothy Garland

Small unmanned aerial vehicles (UAVs) have the potential to act as low cost tools in a variety of both civilian and military applications including traffic monitoring, border patrol, and search and rescue. While most current operational UAV systems require human operators, advances in autonomy will allow these systems to reach their full potential as sensor platforms. This dissertation specifically focuses on developing advanced control, path planning, search, and image processing techniques that allow small fixed wing aircraft to autonomously collect data. The problems explored were motivated by experience with the development and experimental flight testing of a fleet of small autonomous fixed wing aircraft. These issues, which have not been fully addressed in past work done on ground vehicles or autonomous helicopters, include the influence of wind and turning rate constraints, the non-negligible velocity of ground targets relative to the aircraft velocity, and limitations on sensor size and processing power on small vehicles. Several contributions for the autonomous operation of small fixed wing aircraft are presented. Several sliding surface controllers are designed which extend previous techniques to include variable sliding surface coefficients and the use of spatial vehicle dynamics. These advances eliminate potential singularities in the control laws to follow spatially defined paths and allow smooth transition between controllers. The optimal solution for the problem of path planning through an ordered set of points for an aircraft with a bounded turning rate in the presence of a constant wind is then discussed. Path planning strategies are also explored to guarantee that a searcher will travel within sensing distance of a mobile ground target. This work assumes only a maximum velocity of the target and is designed to succeed for any possible path of the target. Closed-loop approximations of both the path planning and search techniques, using the sliding

Compact autonomous navigation system (CANS)

NASA Astrophysics Data System (ADS)

Hao, Y. C.; Ying, L.; Xiong, K.; Cheng, H. Y.; Qiao, G. D.

2017-11-01

Autonomous navigation of Satellite and constellation has series of benefits, such as to reduce operation cost and ground station workload, to avoid the event of crises of war and natural disaster, to increase spacecraft autonomy, and so on. Autonomous navigation satellite is independent of ground station support. Many systems are developed for autonomous navigation of satellite in the past 20 years. Along them American MANS (Microcosm Autonomous Navigation System) [1] of Microcosm Inc. and ERADS [2] [3] (Earth Reference Attitude Determination System) of Honeywell Inc. are well known. The systems anticipate a series of good features of autonomous navigation and aim low cost, integrated structure, low power consumption and compact layout. The ERADS is an integrated small 3-axis attitude sensor system with low cost and small volume. It has the Earth center measurement accuracy higher than the common IR sensor because the detected ultraviolet radiation zone of the atmosphere has a brightness gradient larger than that of the IR zone. But the ERADS is still a complex system because it has to eliminate many problems such as making of the sapphire sphere lens, birefringence effect of sapphire, high precision image transfer optical fiber flattener, ultraviolet intensifier noise, and so on. The marginal sphere FOV of the sphere lens of the ERADS is used to star imaging that may be bring some disadvantages., i.e. , the image energy and attitude measurements accuracy may be reduced due to the tilt image acceptance end of the fiber flattener in the FOV. Besides Japan, Germany and Russia developed visible earth sensor for GEO [4] [5]. Do we have a way to develop a cheaper/easier and more accurate autonomous navigation system that can be used to all LEO spacecraft, especially, to LEO small and micro satellites? To return this problem we provide a new type of the system—CANS (Compact Autonomous Navigation System) [6].

Reactor Power for Large Displacement Autonomous Underwater Vehicles

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

McClure, Patrick Ray; Reid, Robert Stowers; Poston, David Irvin

This is a PentaChart on reactor power for large displacement autonomous underwater vehicles. Currently AUVs use batteries or combinations of batteries and fuel cells for power. Battery/fuel cell technology is limited by duration. Batteries and cell fuels are a good match for some missions, but other missions could benefit greatly by a longer duration. The goal is the following: to design nuclear systems to power an AUV and meet design constraints including non-proliferation issues, power level, size constraints, and power conversion limitations. The action plan is to continue development of a range of systems for terrestrial systems and focus onmore » a system for Titan Moon as alternative to Pu-238 for NASA.« less

Autonomous planetary rover

NASA Astrophysics Data System (ADS)

Krotkov, Eric; Simmons, Reid; Whittaker, William

1992-02-01

This report describes progress in research on an autonomous robot for planetary exploration performed during 1991 at the Robotics Institute, Carnegie Mellon University. The report summarizes the achievements during calendar year 1991, and lists personnel and publications. In addition, it includes several papers resulting from the research. Research in 1991 focused on understanding the unique capabilities of the Ambler mechanism and on autonomous walking in rough, natural terrain. We also designed a sample acquisition system, and began to configure a successor to the Ambler.

Autonomous Flight Safety System

NASA Technical Reports Server (NTRS)

Simpson, James

2010-01-01

The Autonomous Flight Safety System (AFSS) is an independent self-contained subsystem mounted onboard a launch vehicle. AFSS has been developed by and is owned by the US Government. Autonomously makes flight termination/destruct decisions using configurable software-based rules implemented on redundant flight processors using data from redundant GPS/IMU navigation sensors. AFSS implements rules determined by the appropriate Range Safety officials.

Multiple independent autonomous hydraulic oscillators driven by a common gravity head.

PubMed

Kim, Sung-Jin; Yokokawa, Ryuji; Lesher-Perez, Sasha Cai; Takayama, Shuichi

2015-06-15

Self-switching microfluidic circuits that are able to perform biochemical experiments in a parallel and autonomous manner, similar to instruction-embedded electronics, are rarely implemented. Here, we present design principles and demonstrations for gravity-driven, integrated, microfluidic pulsatile flow circuits. With a common gravity head as the only driving force, these fluidic oscillator arrays realize a wide range of periods (0.4 s-2 h) and flow rates (0.10-63 μl min(-1)) with completely independent timing between the multiple oscillator sub-circuits connected in parallel. As a model application, we perform systematic, parallel analysis of endothelial cell elongation response to different fluidic shearing patterns generated by the autonomous microfluidic pulsed flow generation system.

Analysis of autonomous vehicle policies.

DOT National Transportation Integrated Search

2017-01-01

The rapid development and adoption of connected and autonomous vehicles will transform the U.S. transportation system over the next 30 years. Although the widespread use of fully connected and autonomous vehicles is still several years away, it is no...

Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

DOE PAGES

Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick; ...

2014-10-09

As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg -/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displaysmore » many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg -/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.« less

Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency

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

Barnhoorn, Sander; Uittenboogaard, Lieneke M.; Jaarsma, Dick

As part of the Nucleotide Excision Repair (NER) process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS), or the infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional) Xpg -/- mouse model which—in a C57BL6/FVB F1 hybrid genetic background—displaysmore » many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4–5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities) and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg -/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.« less

Proximal—distal pattern formation in Drosophila: cell autonomous requirement for Distal-less gene activity in limb development

PubMed Central

Cohen, Stephen M.; Jürgens, Gerd

1989-01-01

Limb development in the Drosophila embryo requires a pattern-forming system to organize positional information along the proximal–distal axis of the limb. This system must function in the context of the well characterized anterior–posterior and dorsal–ventral pattern-forming systems that are required to organize the body plan of the embryo. By genetic criteria the Distal-less gene appears to play a central role in limb development. Lack-of-function Distal-less mutations cause the deletion of a specific subset of embryonic peripheral sense organs that represent the evolutionary remnants of larval limbs. Distal-less activity is also required in the imaginal discs for the development of adult limbs. This requirement is cell autonomous and region specific within the developing limb primordium. Production of genetically mosaic imaginal discs, in which clones of cells lack Distal-less activity, indicates the existence of an organized proximal–distal positional information in very young imaginal disc primordia. We suggest that this graded positional information may depend on the activity of the Distal-less gene. Images PMID:16453891

Cell-autonomous-like silencing of GFP-partitioned transgenic Nicotiana benthamiana.

PubMed

Sohn, Seong-Han; Frost, Jennifer; Kim, Yoon-Hee; Choi, Seung-Kook; Lee, Yi; Seo, Mi-Suk; Lim, Sun-Hyung; Choi, Yeonhee; Kim, Kook-Hyung; Lomonossoff, George

2014-08-01

We previously reported the novel partitioning of regional GFP-silencing on leaves of 35S-GFP transgenic plants, coining the term "partitioned silencing". We set out to delineate the mechanism of partitioned silencing. Here, we report that the partitioned plants were hemizygous for the transgene, possessing two direct-repeat copies of 35S-GFP. The detection of both siRNA expression (21 and 24 nt) and DNA methylation enrichment specifically at silenced regions indicated that both post-transcriptional gene silencing (PTGS) and transcriptional gene silencing (TGS) were involved in the silencing mechanism. Using in vivo agroinfiltration of 35S-GFP/GUS and inoculation of TMV-GFP RNA, we demonstrate that PTGS, not TGS, plays a dominant role in the partitioned silencing, concluding that the underlying mechanism of partitioned silencing is analogous to RNA-directed DNA methylation (RdDM). The initial pattern of partitioned silencing was tightly maintained in a cell-autonomous manner, although partitioned-silenced regions possess a potential for systemic spread. Surprisingly, transcriptome profiling through next-generation sequencing demonstrated that expression levels of most genes involved in the silencing pathway were similar in both GFP-expressing and silenced regions although a diverse set of region-specific transcripts were detected.This suggests that partitioned silencing can be triggered and regulated by genes other than the genes involved in the silencing pathway. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cardiac Autonomic Balance vs. Cardiac Regulatory Capacity

PubMed Central

Berntson, Gary G.; Norman, Greg J.; Hawkley, Louise C.; Cacioppo, John T.

2013-01-01

The concept of autonomic balance views autonomic states along a bipolar continuum from sympathetic (S) to parasympathetic (P) dominance, whereas regulatory capacity models emphasize overall autonomic flexibility as a marker of the capacity for regulation. These two concepts were evaluated for their utility in characterizing patterns of autonomic control. Measures of P (high frequency heart rate variability, HF) and S (pre-ejection period, PEP) cardiac control were obtained. A measure of cardiac autonomic balance (CAB) was derived as the difference in the normalized P index minus the S index, and a measure of cardiac autonomic regulation (CAR) was derived as the normalized P index plus the S index. Results reveal that CAR, but not CAB, was a significant predictor of the prior occurrence of a myocardial infarction, net of demographic and other variables, whereas CAB, but not CAR, was a significant predictor of concurrent diabetes. PMID:18282204

Multi-organ autonomic dysfunction in Parkinson disease

PubMed Central

2010-01-01

Both pathologic and clinical studies of autonomic pathways have expanded the concept of Parkinson disease (PD) from a movement disorder to a multi-level widespread neurodegenerative process with non-motor features spanning several organ systems. This review integrates neuropathologic findings and autonomic physiology in PD as it relates to end organ autonomic function. Symptoms, pathology and physiology of the cardiovascular, skin/sweat gland, urinary, gastrointestinal, pupillary and neuroendocrine systems can be probed by autopsy, biopsy and non-invasive electrophysiological techniques in vivo which assess autonomic anatomy and function. There is mounting evidence that PD affects a chain of neurons in autonomic pathways. Consequently, autonomic physiology may serve as a window into non-motor PD progression and allow the development of mechanistically based treatment strategies for several non-motor features of PD. End-organ physiologic markers may be used to inform a model of PD pathophysiology and non-motor progression. PMID:20851033

Distinct gene networks modulate floral induction of autonomous maize and photoperiod-dependent teosinte.

PubMed

Minow, Mark A A; Ávila, Luis M; Turner, Katie; Ponzoni, Elena; Mascheretti, Iride; Dussault, Forest M; Lukens, Lewis; Rossi, Vincenzo; Colasanti, Joseph

2018-05-25

Temperate maize was domesticated from its tropical ancestor, teosinte. Whereas temperate maize is an autonomous day-neutral plant, teosinte is an obligate short-day plant that requires uninterrupted long nights to induce flowering. Leaf-derived florigenic signals trigger reproductive growth in both teosinte and temperate maize. To study the genetic mechanisms underlying floral inductive pathways in maize and teosinte, mRNA and small RNA genome-wide expression analyses were conducted on leaf tissue from plants that were induced or not induced to flower. Transcriptome profiles reveal common differentially expressed genes during floral induction, but a comparison of candidate flowering time genes indicates that photoperiod and autonomous pathways act independently. Expression differences in teosinte are consistent with the current paradigm for photoperiod-induced flowering, where changes in circadian clock output trigger florigen production. Conversely, differentially expressed genes in temperate maize link carbon partitioning and flowering, but also show altered expression of circadian clock genes that are distinct from those altered upon photoperiodic induction in teosinte. Altered miRNA399 levels in both teosinte and maize suggest a novel common connection between flowering and phosphorus perception. These findings provide insights into the molecular mechanisms underlying a strengthened autonomous pathway that enabled maize growth throughout temperate regions.

Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

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

Di Pendina, G., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; Zianbetov, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; CNRS, SPINTEC, F-38000 Grenoble

2015-05-07

Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remainingmore » in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.« less

Design of an autonomous Lunar construction utility vehicle

NASA Technical Reports Server (NTRS)

Ash, Robert L.; Chew, Mason; Dixon, Iain (Editor)

1990-01-01

In order to prepare a site for a manned lunar base, an autonomously operated construction vehicle is necessary. A Lunar Construction Utility Vehicle (LCUV), which utilizes interchangeable construction implements, was designed conceptually. Some elements of the machine were studied in greater detail. Design of an elastic loop track system has advanced to the testing stage. A standard coupling device was designed to insure a proper connection between the different construction tools and the LCUV. Autonomous control of the track drive motors was simulated successfully through the use of a joystick and computer interface. A study of hydrogen-oxygen fuel cells has produced estimates of reactant and product size requirements and identified multi-layer insulation techniques. Research on a 100 kW heat rejection system has determined that it is necessary to house a radiator panel on a utility trailer. The impact of a 720 hr use cycle has produced a very large logistical support lien which requires further study.

Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

PubMed Central

Wolf, Yochai; Shemer, Anat; Polonsky, Michal; Gross, Mor; Mildner, Alexander; David, Eyal; Amit, Ido; Heikenwalder, Mathias; Nedospasov, Sergei; Prinz, Marco; Friedman, Nir

2017-01-01

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function. PMID:28330904

Manipulation of norepinephrine metabolism with yohimbine in the treatment of autonomic failure

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Robertson, R. M.; Robertson, D.

1994-01-01

It has been postulated that alpha 2-adrenergic receptors play a modulatory role in the regulation of blood pressure. Activation of alpha 2-receptors located in the central nervous system results in inhibition of sympathetic tone and decrease of blood pressure. This indeed may be the mechanism of action of central sympatholytic antihypertensives such as alpha-methyldopa. Presynaptic alpha 2-receptors also are found in adrenergic nerve terminals. These receptors act as a negative feedback mechanism by inhibiting the release of norepinephrine. The relevance of alpha 2-adrenergic receptors for blood pressure regulation can be explored with yohimbine, a selective antagonist of these receptors. Yohimbine increases blood pressure in resting normal volunteers. This effect is associated with an increase in both sympathetic nerve activity, reflecting an increase in central sympathetic outflow, and in norepinephrine spillover, reflecting potentiation of the release of norepinephrine from adrenergic nerve terminals. These actions, therefore, underscore the importance of alpha 2-adrenergic receptors for blood pressure regulation even under resting conditions. Patients with autonomic failure, even those with severe sympathetic deprivation, are hypersensitive to the pressor effects of yohimbine. This increased responsiveness can be explained by sensitization of adrenergic receptors, analogous to denervation supersensitivity, and by the lack of autonomic reflexes that would normally buffer any increase in blood pressure. Preliminary studies suggest that the effectiveness of yohimbine in autonomic failure can be enhanced with monoamine oxidase inhibitors. Used in combination, yohimbine increases norepinephrine release, whereas monoamine oxidase inhibitors inhibit its degradation. Therefore, yohimbine is not only a useful tool in the study of blood pressure regulation, but may offer a therapeutic option in autonomic dysfunction.

Expanded Perspectives on Autonomous Learners

ERIC Educational Resources Information Center

Oxford, Rebecca L.

2015-01-01

This paper explores two general perspectives on autonomous learners: psychological and sociocultural. These perspectives introduce a range of theoretically grounded facets of autonomous learners, facets such as the self-regulated learner, the emotionally intelligent learner, the self-determined learner, the mediated learner, the socioculturally…

Autonomic symptoms following Zika virus infection.

PubMed

Rodríguez, Yhojan; Rojas, Manuel; Ramírez-Santana, Carolina; Acosta-Ampudia, Yeny; Monsalve, Diana M; Anaya, Juan-Manuel

2018-04-01

To determine if autonomic symptoms are associated with previous Zika virus infection. Case-control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31). Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001). Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.

General autonomic components of motion sickness

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Suter, Steve; Toscano, William B.; Kamiya, Joe; Naifeh, Karen

1986-01-01

This report refers to a body of investigations directed toward the examination of autonomic nervous system responses to motion sickness. Heart rate, respiration rate, finger pulse volume, and basal skin resistance were measured on 127 men and women before, during, and after exposure to a nauseogenic rotating chair test. Significant changes in all autonomic responses were observed across the tests (p less than .05). Significant differences in autonomic responses among groups divided according to motion sickness susceptibility were also observed (p less than .05). Results suggest that the examination of autonomic responses as an objective indicator of motion sickness malaise is warranted and may contribute to the overall understanding of the syndrome.

Central cell-derived peptides regulate early embryo patterning in flowering plants.

PubMed

Costa, Liliana M; Marshall, Eleanor; Tesfaye, Mesfin; Silverstein, Kevin A T; Mori, Masashi; Umetsu, Yoshitaka; Otterbach, Sophie L; Papareddy, Ranjith; Dickinson, Hugh G; Boutiller, Kim; VandenBosch, Kathryn A; Ohki, Shinya; Gutierrez-Marcos, José F

2014-04-11

Plant embryogenesis initiates with the establishment of an apical-basal axis; however, the molecular mechanisms accompanying this early event remain unclear. Here, we show that a small cysteine-rich peptide family is required for formation of the zygotic basal cell lineage and proembryo patterning in Arabidopsis. EMBRYO SURROUNDING FACTOR 1 (ESF1) peptides accumulate before fertilization in central cell gametes and thereafter in embryo-surrounding endosperm cells. Biochemical and structural analyses revealed cleavage of ESF1 propeptides to form biologically active mature peptides. Further, these peptides act in a non-cell-autonomous manner and synergistically with the receptor-like kinase SHORT SUSPENSOR to promote suspensor elongation through the YODA mitogen-activated protein kinase pathway. Our findings demonstrate that the second female gamete and its sexually derived endosperm regulate early embryonic patterning in flowering plants.

Physics Simulation Software for Autonomous Propellant Loading and Gas House Autonomous System Monitoring

NASA Technical Reports Server (NTRS)

Regalado Reyes, Bjorn Constant

2015-01-01

1. Kennedy Space Center (KSC) is developing a mobile launching system with autonomous propellant loading capabilities for liquid-fueled rockets. An autonomous system will be responsible for monitoring and controlling the storage, loading and transferring of cryogenic propellants. The Physics Simulation Software will reproduce the sensor data seen during the delivery of cryogenic fluids including valve positions, pressures, temperatures and flow rates. The simulator will provide insight into the functionality of the propellant systems and demonstrate the effects of potential faults. This will provide verification of the communications protocols and the autonomous system control. 2. The High Pressure Gas Facility (HPGF) stores and distributes hydrogen, nitrogen, helium and high pressure air. The hydrogen and nitrogen are stored in cryogenic liquid state. The cryogenic fluids pose several hazards to operators and the storage and transfer equipment. Constant monitoring of pressures, temperatures and flow rates are required in order to maintain the safety of personnel and equipment during the handling and storage of these commodities. The Gas House Autonomous System Monitoring software will be responsible for constantly observing and recording sensor data, identifying and predicting faults and relaying hazard and operational information to the operators.

Architecture of autonomous systems

NASA Technical Reports Server (NTRS)

Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

1986-01-01

Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

Architecture of autonomous systems

NASA Technical Reports Server (NTRS)

Dikshit, Piyush; Guimaraes, Katia; Ramamurthy, Maya; Agrawala, Ashok; Larsen, Ronald L.

1989-01-01

Automation of Space Station functions and activities, particularly those involving robotic capabilities with interactive or supervisory human control, is a complex, multi-disciplinary systems design problem. A wide variety of applications using autonomous control can be found in the literature, but none of them seem to address the problem in general. All of them are designed with a specific application in mind. In this report, an abstract model is described which unifies the key concepts underlying the design of automated systems such as those studied by the aerospace contractors. The model has been kept as general as possible. The attempt is to capture all the key components of autonomous systems. With a little effort, it should be possible to map the functions of any specific autonomous system application to the model presented here.

Supervised autonomous robotic soft tissue surgery.

PubMed

Shademan, Azad; Decker, Ryan S; Opfermann, Justin D; Leonard, Simon; Krieger, Axel; Kim, Peter C W

2016-05-04

The current paradigm of robot-assisted surgeries (RASs) depends entirely on an individual surgeon's manual capability. Autonomous robotic surgery-removing the surgeon's hands-promises enhanced efficacy, safety, and improved access to optimized surgical techniques. Surgeries involving soft tissue have not been performed autonomously because of technological limitations, including lack of vision systems that can distinguish and track the target tissues in dynamic surgical environments and lack of intelligent algorithms that can execute complex surgical tasks. We demonstrate in vivo supervised autonomous soft tissue surgery in an open surgical setting, enabled by a plenoptic three-dimensional and near-infrared fluorescent (NIRF) imaging system and an autonomous suturing algorithm. Inspired by the best human surgical practices, a computer program generates a plan to complete complex surgical tasks on deformable soft tissue, such as suturing and intestinal anastomosis. We compared metrics of anastomosis-including the consistency of suturing informed by the average suture spacing, the pressure at which the anastomosis leaked, the number of mistakes that required removing the needle from the tissue, completion time, and lumen reduction in intestinal anastomoses-between our supervised autonomous system, manual laparoscopic surgery, and clinically used RAS approaches. Despite dynamic scene changes and tissue movement during surgery, we demonstrate that the outcome of supervised autonomous procedures is superior to surgery performed by expert surgeons and RAS techniques in ex vivo porcine tissues and in living pigs. These results demonstrate the potential for autonomous robots to improve the efficacy, consistency, functional outcome, and accessibility of surgical techniques. Copyright © 2016, American Association for the Advancement of Science.

Autonomously Propelled Motors for Value-Added Product Synthesis and Purification.

PubMed

Srivastava, Sarvesh K; Schmidt, Oliver G

2016-06-27

A proof-of-concept design for autonomous, self-propelling motors towards value-added product synthesis and separation is presented. The hybrid motor design consists of two distinct functional blocks. The first, a sodium borohydride (NaBH4 ) granule, serves both as a reaction prerequisite for the reduction of vanillin and also as a localized solid-state fuel in the reaction mixture. The second capping functional block consisting of a graphene-polymer composite serves as a hydrophobic matrix to attract the reaction product vanillyl alcohol (VA), resulting in facile separation of this edible value-added product. These autonomously propelled motors were fabricated at a length scale down to 400 μm, and once introduced in the reaction environment showed rapid bubble-propulsion followed by high-purity separation of the reaction product (VA) by the virtue of the graphene-polymer cap acting as a mesoporous sponge. The concept has excellent potential towards the synthesis/isolation of industrially important compounds, affinity-based product separation, pollutant remediation (such as heavy metal chelation/adsorption), as well as localized fuel-gradients as an alternative to external fuel dependency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Autonomous Learner Model Resource Book

ERIC Educational Resources Information Center

Betts, George T.; Carey, Robin J.; Kapushion, Blanche M.

2016-01-01

"Autonomous Learner Model Resource Book" includes activities and strategies to support the development of autonomous learners. More than 40 activities are included, all geared to the emotional, social, cognitive, and physical development of students. Teachers may use these activities and strategies with the entire class, small groups, or…

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.

PubMed

Fan, Ling; Chen, Li-Feng; Fan, Jing

2017-12-01

To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency. Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01). There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Effects of Antiretroviral Therapy on Autonomic Function in Early HIV Infection: A Preliminary Report

PubMed Central

Chow, Dominic; Kocher, Morgan; Shikuma, Cecilia; Parikh, Nisha; Grandinetti, Andrew; Nakamoto, Beau; Seto, Todd; Low, Phillip

2012-01-01

Background: A prospective study was conducted in human immunodeficiency virus (HIV)-infected patients as they undergo alterations in their antiretroviral therapy (ART) to determine the effect of ART on autonomic function. Methods: HIV-infected subjects who were either 1) naïve to ART and initiating ART, or 2) receiving ART and in HIV virologic failure for at least 4 months and were about to switch ART were enrolled in this study. Autonomic function assessment (cardiovagal, adrenergic, and sudomotor tests) was performed prior to and 4 months after initiating the new ART. Changes in clinical autonomic symptoms and virologic assessment were assessed. Results: Twelve subjects completed the study: 92% male; median age (Q1, Q3) was 41.0 (28.0, 48.2) years; and 50% White/Non-Hispanic. Seventy-five percent were ART naïve while 25% were failing their ART regimen. The median CD4 count was 336.5 (245.3, 372.3) cells/mm3. All subjects achieved an undetectable HIV viral load by the 4-month follow-up visit. The majority of naïve subjects were started on an ART regimen of tenofovir / emtricitabine / efavirenz. There were no significant differences in autonomic function assessment, as measured by cardiovagal, adrenergic, and sudomotor tests, with regards to ART initiation. Conclusion: This is the first study to examine the effects of initiating ART on autonomic function in early HIV infection. This study found no appreciable differences of ART on the autonomic nervous system when ART is initiated early in the course of HIV disease. ART may not contribute to short-term changes in autonomic function. PMID:22859899

Sustainable and Autonomic Space Exploration Missions

NASA Technical Reports Server (NTRS)

Hinchey, Michael G.; Sterritt, Roy; Rouff, Christopher; Rash, James L.; Truszkowski, Walter

2006-01-01

Visions for future space exploration have long term science missions in sight, resulting in the need for sustainable missions. Survivability is a critical property of sustainable systems and may be addressed through autonomicity, an emerging paradigm for self-management of future computer-based systems based on inspiration from the human autonomic nervous system. This paper examines some of the ongoing research efforts to realize these survivable systems visions, with specific emphasis on developments in Autonomic Policies.

Synthetic Deletion of the Interleukin 23 Receptor (IL-23R) Stalk Region Led to Autonomous IL-23R Homodimerization and Activation.

PubMed

Hummel, Thorben M; Ackfeld, Theresa; Schönberg, Marco; Ciupka, Gregor; Schulz, Falk; Oberdoerster, Anne; Grötzinger, Joachim; Scheller, Jürgen; Floss, Doreen M

2017-09-01

Interleukin 23 (IL-23) regulates the development of TH17 cells, which are important for antimicrobial and antifungal responses and autoimmune and chronic inflammatory diseases. IL-23-induced Jak/STAT signaling is mediated via the heterodimeric IL-23 receptor (IL-23R)-IL-12 receptor β1 (IL-12Rβ1) complex. The typical signal-transducing receptor of the IL-6/IL-12 family contains three extracellular-membrane-proximal fibronectin type III (FNIII) domains, which are not involved in cytokine binding but are mandatory for signal transduction. In place of FNIII-type domains, IL-23R has a structurally undefined stalk. We hypothesized that the IL-23R stalk acts as a spacer to position the cytokine binding domains at a defined distance from the plasma membrane to enable signal transduction. Minor deletions of the murine, but not of the human, IL-23R stalk resulted in unresponsiveness to IL-23. Complete deletion of the human IL-23R stalk and the extended murine IL-23R stalk, including a 20-amino-acid-long duplication of domain 3, however, induced ligand-independent, autonomous receptor activation, as determined by STAT3 phosphorylation and cell proliferation. Ligand-independent, autonomous activity was caused by IL-23R homodimers and was independent of IL-12Rβ1. Our data show that deletion of the stalk results in biologically active IL-23R homodimers, thereby creating an as-yet-undescribed receptor complex of the IL-6/IL-12 cytokine family. Copyright © 2017 American Society for Microbiology.

Autonomous software: Myth or magic?

NASA Astrophysics Data System (ADS)

Allan, A.; Naylor, T.; Saunders, E. S.

2008-03-01

We discuss work by the eSTAR project which demonstrates a fully closed loop autonomous system for the follow up of possible micro-lensing anomalies. Not only are the initial micro-lensing detections followed up in real time, but ongoing events are prioritised and continually monitored, with the returned data being analysed automatically. If the ``smart software'' running the observing campaign detects a planet-like anomaly, further follow-up will be scheduled autonomously and other telescopes and telescope networks alerted to the possible planetary detection. We further discuss the implications of this, and how such projects can be used to build more general autonomous observing and control systems.

Cybersecurity for aerospace autonomous systems

NASA Astrophysics Data System (ADS)

Straub, Jeremy

2015-05-01

High profile breaches have occurred across numerous information systems. One area where attacks are particularly problematic is autonomous control systems. This paper considers the aerospace information system, focusing on elements that interact with autonomous control systems (e.g., onboard UAVs). It discusses the trust placed in the autonomous systems and supporting systems (e.g., navigational aids) and how this trust can be validated. Approaches to remotely detect the UAV compromise, without relying on the onboard software (on a potentially compromised system) as part of the process are discussed. How different levels of autonomy (task-based, goal-based, mission-based) impact this remote characterization is considered.

Chemokines and Heart Disease: A Network Connecting Cardiovascular Biology to Immune and Autonomic Nervous Systems

PubMed Central

Dusi, Veronica; Ghidoni, Alice; Ravera, Alice; De Ferrari, Gaetano M.; Calvillo, Laura

2016-01-01

Among the chemokines discovered to date, nineteen are presently considered to be relevant in heart disease and are involved in all stages of cardiovascular response to injury. Chemokines are interesting as biomarkers to predict risk of cardiovascular events in apparently healthy people and as possible therapeutic targets. Moreover, they could have a role as mediators of crosstalk between immune and cardiovascular system, since they seem to act as a “working-network” in deep linkage with the autonomic nervous system. In this paper we will describe the single chemokines more involved in heart diseases; then we will present a comprehensive perspective of them as a complex network connecting the cardiovascular system to both the immune and the autonomic nervous systems. Finally, some recent evidences indicating chemokines as a possible new tool to predict cardiovascular risk will be described. PMID:27242392

Autonomous control systems - Architecture and fundamental issues

NASA Technical Reports Server (NTRS)

Antsaklis, P. J.; Passino, K. M.; Wang, S. J.

1988-01-01

A hierarchical functional autonomous controller architecture is introduced. In particular, the architecture for the control of future space vehicles is described in detail; it is designed to ensure the autonomous operation of the control system and it allows interaction with the pilot and crew/ground station, and the systems on board the autonomous vehicle. The fundamental issues in autonomous control system modeling and analysis are discussed. It is proposed to utilize a hybrid approach to modeling and analysis of autonomous systems. This will incorporate conventional control methods based on differential equations and techniques for the analysis of systems described with a symbolic formalism. In this way, the theory of conventional control can be fully utilized. It is stressed that autonomy is the design requirement and intelligent control methods appear at present, to offer some of the necessary tools to achieve autonomy. A conventional approach may evolve and replace some or all of the `intelligent' functions. It is shown that in addition to conventional controllers, the autonomous control system incorporates planning, learning, and FDI (fault detection and identification).

Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test.

PubMed

Fukusumi, Hayato; Handa, Yukako; Shofuda, Tomoko; Kanemura, Yonehiro

2018-01-01

Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo . Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue-derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

Is variety a spice of (an active) life?: perceived variety, exercise behavior, and the mediating role of autonomous motivation.

PubMed

Sylvester, Benjamin D; Standage, Martyn; Ark, Tavinder K; Sweet, Shane N; Crocker, Peter R; Zumbo, Bruno D; Beauchamp, Mark R

2014-10-01

In this study, we examined whether perceived variety in exercise prospectively predicts unique variance in exercise behavior when examined alongside satisfaction of the three basic psychological needs (for competence, relatedness, and autonomy) embedded within self-determination theory (Ryan & Deci, 2002), through the mediating role of autonomous and controlled motivation. A convenience sample of community adults (N = 363) completed online questionnaires twice over a 6-week period. The results of structural equation modeling showed perceived variety and satisfaction of the needs for competence and relatedness to be unique indirect positive predictors of exercise behavior (through autonomous motivation) 6 weeks later. In addition, satisfaction of the need for autonomy was found to negatively predict controlled motivation. Perceived variety in exercise complemented satisfaction of the needs for competence, relatedness, and autonomy in predicting motivation and (indirectly) exercise behavior, and may act as a salient mechanism in the prediction of autonomous motivation and behavior in exercise settings.

Electrophysiological and morphological properties of pre-autonomic neurones in the rat hypothalamic paraventricular nucleus

PubMed Central

Stern, Javier E

2001-01-01

The cellular properties of pre-autonomic neurones in the hypothalamic paraventricular nucleus (PVN) were characterized by combining in vivo retrograde tracing techniques, in vitro patch-clamp recordings and three-dimensional reconstruction of recorded neurones in adult hypothalamic slices. The results showed that PVN pre-autonomic neurones constitute a heterogeneous neuronal population. Based on morphological criteria, neurones were classified into three subgroups. Type A neurones (52 %) were located in the ventral parvocellular (PaV) subnucleus, and showed an oblique orientation with respect to the third ventricle (3V). Type B neurones (25 %) were located in the posterior parvocellular (PaPo) subnucleus, and were oriented perpendicularly with respect to the 3V. Type C neurones (23 %) were located in both the PaPo (82 %) and the PaV (18 %) subnuclei, and displayed a concentric dendritic configuration. A morphometric analysis revealed significant differences in the dendritic configuration among neuronal types. Type B neurones had the most complex dendritic arborization, with longer and more branching dendritic trees. Several electrophysiological properties, including cell input resistance and action potential waveforms, differed between cell types, suggesting that the expression and/or properties of a variety of ion channels differ between neuronal types. Common features of PVN pre-autonomic neurones included the expression of a low-threshold spike and strong inward rectification. These properties distinguished them from neighbouring magnocellular vasopressin neurones. In summary, these results indicate that PVN pre-autonomic neurones constitute a heterogeneous neuronal population, and provide a cellular basis for the study of their involvement in the pathophysiology of hypertension and congestive heart failure disorders. PMID:11711570

Connected and autonomous vehicles 2040 vision.

DOT National Transportation Integrated Search

2014-07-01

The Pennsylvania Department of Transportation (PennDOT) commissioned a one-year project, Connected and Autonomous : Vehicles 2040 Vision, with researchers at Carnegie Mellon University (CMU) to assess the implications of connected and : autonomous ve...

AUTONOMOUS AND NONAUTONOMOUS REGULATION OF WNT-MEDIATED NEURONAL POLARITY BY THE C. ELEGANS ROR KINASE CAM-1

PubMed Central

Chien, Shih-Chieh Jason; Gurling, Mark; Kim, Changsung; Craft, Teresa; Forrester, Wayne; Garriga, Gian

2015-01-01

Wnts are a conserved family of secreted glycoproteins that regulate various developmental processes in metazoans. Three of the five C. elegans Wnts, CWN-1, CWN-2 and EGL-20, and the sole Wnt receptor of the Ror kinase family, CAM-1, are known to regulate the anterior polarization of the mechanosensory neuron ALM. Here we show that CAM-1 and the Frizzled receptor MOM-5 act in parallel pathways to control ALM polarity. We also show that CAM-1 has two functions in this process: an autonomous signaling function that promotes anterior polarization and a nonautonomous Wnt-antagonistic function that inhibits anterior polarization. These antagonistic activities can account for the weak ALM phenotypes displayed by cam-1 mutants. Our observations suggest that CAM-1 could function as a Wnt receptor in many developmental processes, but the analysis of cam-1 mutants may fail to reveal CAM-1’s role as a receptor in these processes because of its Wnt-antagonistic activity. In this model, loss of CAM-1 results in increased levels of Wnts that act through other Wnt receptors, masking CAM-1’s autonomous role as a Wnt receptor. PMID:25917219

Autonomous Operations System: Development and Application

NASA Technical Reports Server (NTRS)

Toro Medina, Jaime A.; Wilkins, Kim N.; Walker, Mark; Stahl, Gerald M.

2016-01-01

Autonomous control systems provides the ability of self-governance beyond the conventional control system. As the complexity of mechanical and electrical systems increases, there develops a natural drive for developing robust control systems to manage complicated operations. By closing the bridge between conventional automated systems to knowledge based self-awareness systems, nominal control of operations can evolve into relying on safe critical mitigation processes to support any off-nominal behavior. Current research and development efforts lead by the Autonomous Propellant Loading (APL) group at NASA Kennedy Space Center aims to improve cryogenic propellant transfer operations by developing an automated control and health monitoring system. As an integrated systems, the center aims to produce an Autonomous Operations System (AOS) capable of integrating health management operations with automated control to produce a fully autonomous system.

Autonomous Power System intelligent diagnosis and control

NASA Technical Reports Server (NTRS)

Ringer, Mark J.; Quinn, Todd M.; Merolla, Anthony

1991-01-01

The Autonomous Power System (APS) project at NASA Lewis Research Center is designed to demonstrate the abilities of integrated intelligent diagnosis, control, and scheduling techniques to space power distribution hardware. Knowledge-based software provides a robust method of control for highly complex space-based power systems that conventional methods do not allow. The project consists of three elements: the Autonomous Power Expert System (APEX) for fault diagnosis and control, the Autonomous Intelligent Power Scheduler (AIPS) to determine system configuration, and power hardware (Brassboard) to simulate a space based power system. The operation of the Autonomous Power System as a whole is described and the responsibilities of the three elements - APEX, AIPS, and Brassboard - are characterized. A discussion of the methodologies used in each element is provided. Future plans are discussed for the growth of the Autonomous Power System.

Autonomous power system intelligent diagnosis and control

NASA Technical Reports Server (NTRS)

Ringer, Mark J.; Quinn, Todd M.; Merolla, Anthony

1991-01-01

The Autonomous Power System (APS) project at NASA Lewis Research Center is designed to demonstrate the abilities of integrated intelligent diagnosis, control, and scheduling techniques to space power distribution hardware. Knowledge-based software provides a robust method of control for highly complex space-based power systems that conventional methods do not allow. The project consists of three elements: the Autonomous Power Expert System (APEX) for fault diagnosis and control, the Autonomous Intelligent Power Scheduler (AIPS) to determine system configuration, and power hardware (Brassboard) to simulate a space based power system. The operation of the Autonomous Power System as a whole is described and the responsibilities of the three elements - APEX, AIPS, and Brassboard - are characterized. A discussion of the methodologies used in each element is provided. Future plans are discussed for the growth of the Autonomous Power System.

Autonomous Cryogenic Load Operations: KSC Autonomous Test Engineer

NASA Technical Reports Server (NTRS)

Shrading, Nicholas J.

2012-01-01

The KSC Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20+ years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in. the system, As part.of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display ofthe entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledgebase, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

The NASA/Army Autonomous Rotorcraft Project

NASA Technical Reports Server (NTRS)

Whalley, M.; Freed, M.; Takahashi, M.; Christian, D.; Patterson-Hine, A.; Schulein, G.; Harris, R.

2002-01-01

An overview of the NASA Ames Research Center Autonomous Rotorcraft Project (ARP) is presented. The project brings together several technologies to address NASA and US Army autonomous vehicle needs, including a reactive planner for mission planning and execution, control system design incorporating a detailed understanding of the platform dynamics, and health monitoring and diagnostics. A candidate reconnaissance and surveillance mission is described. The autonomous agent architecture and its application to the candidate mission are presented. Details of the vehicle hardware and software development are provided.

GOATS 2008 Autonomous, Adaptive Multistatic Acoustic Sensing

DTIC Science & Technology

2008-09-30

To develop net-centric, autonomous underwater vehicle sensing concepts for littoral MCM and ASW, exploiting collaborative and environmentally...unlimited 13. SUPPLEMENTARY NOTES code 1 only 14. ABSTRACT To develop net-centric, autonomous underwater vehicle sensing concepts for littoral MCM and...of autonomous underwater vehicle networks as platforms for new sonar concepts exploring the full 3-D acoustic environment of shallow water (SW) and

iACT - An interactive mHealth monitoring system to enhance psychotherapy for adolescents with sickle cell disease

PubMed Central

Cheng, Chihwen; Brown, R. Clark; Cohen, Lindsey L.; Venugopalan, Janani; Stokes, Todd H.

2016-01-01

Sickle cell disease (SCD) is the most common inherited disease, and SCD symptoms impact functioning and well-being. For example, adolescents with SCD have a higher tendency of psychological problems than the general population. Acceptance and Commitment Therapy (ACT), a cognitive-behavioral therapy, is an effective intervention to promote quality of life and functioning in adolescents with chronic illness. However, traditional visit-based therapy sessions are restrained by challenges, such as limited follow-up, insufficient data collection, low treatment adherence, and delayed intervention. In this paper, we present Instant Acceptance and Commitment Therapy (iACT), a system designed to enhance the quality of pediatric ACT. iACT utilizes text messaging technology, which is the most popular cell phone activity among adolescents, to conduct real-time psychotherapy interventions. The system is built on cloud computing technologies, which provides a convenient and cost-effective monitoring environment. To evaluate iACT, a trial with 60 adolescents with SCD is being conducted in conjunction with the Georgia Institute of Technology, Children’s Healthcare of Atlanta, and Georgia State University. PMID:24110179

iACT--an interactive mHealth monitoring system to enhance psychotherapy for adolescents with sickle cell disease.

PubMed

Cheng, Chihwen; Brown, R Clark; Cohen, Lindsey L; Venugopalan, Janani; Stokes, Todd H; Wang, May D

2013-01-01

Sickle cell disease (SCD) is the most common inherited disease, and SCD symptoms impact functioning and well-being. For example, adolescents with SCD have a higher tendency of psychological problems than the general population. Acceptance and Commitment Therapy (ACT), a cognitive-behavioral therapy, is an effective intervention to promote quality of life and functioning in adolescents with chronic illness. However, traditional visit-based therapy sessions are restrained by challenges, such as limited follow-up, insufficient data collection, low treatment adherence, and delayed intervention. In this paper, we present Instant Acceptance and Commitment Therapy (iACT), a system designed to enhance the quality of pediatric ACT. iACT utilizes text messaging technology, which is the most popular cell phone activity among adolescents, to conduct real-time psychotherapy interventions. The system is built on cloud computing technologies, which provides a convenient and cost-effective monitoring environment. To evaluate iACT, a trial with 60 adolescents with SCD is being conducted in conjunction with the Georgia Institute of Technology, Children's Healthcare of Atlanta, and Georgia State University.

Autonomic neuropathy

MedlinePlus

... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman-Cecil ... Editorial team. Autonomic Nervous System Disorders Read more Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more A. ...

Advancing Autonomous Operations for Deep Space Vehicles

NASA Technical Reports Server (NTRS)

Haddock, Angie T.; Stetson, Howard K.

2014-01-01

Starting in Jan 2012, the Advanced Exploration Systems (AES) Autonomous Mission Operations (AMO) Project began to investigate the ability to create and execute "single button" crew initiated autonomous activities [1]. NASA Marshall Space Flight Center (MSFC) designed and built a fluid transfer hardware test-bed to use as a sub-system target for the investigations of intelligent procedures that would command and control a fluid transfer test-bed, would perform self-monitoring during fluid transfers, detect anomalies and faults, isolate the fault and recover the procedures function that was being executed, all without operator intervention. In addition to the development of intelligent procedures, the team is also exploring various methods for autonomous activity execution where a planned timeline of activities are executed autonomously and also the initial analysis of crew procedure development. This paper will detail the development of intelligent procedures for the NASA MSFC Autonomous Fluid Transfer System (AFTS) as well as the autonomous plan execution capabilities being investigated. Manned deep space missions, with extreme communication delays with Earth based assets, presents significant challenges for what the on-board procedure content will encompass as well as the planned execution of the procedures.

Epidermal expression of a sterol biosynthesis gene regulates root growth by a non-cell-autonomous mechanism in Arabidopsis.

PubMed

Short, Eleri; Leighton, Margaret; Imriz, Gul; Liu, Dongbin; Cope-Selby, Naomi; Hetherington, Flora; Smertenko, Andrei; Hussey, Patrick J; Topping, Jennifer F; Lindsey, Keith

2018-05-15

The epidermis is hypothesized to play a signalling role during plant development. One class of mutants showing defects in signal transduction and radial patterning are those in sterol biosynthesis. The expectation is that living cells require sterols, but it is not clear that all cell types express sterol biosynthesis genes. The HYDRA1 ( HYD1 ) gene of Arabidopsis encodes sterol Δ8-Δ7 isomerase, and although hyd1 seedlings are defective in radial patterning across several tissues, we show that the HYD1 gene is expressed most strongly in the root epidermis. Transgenic activation of HYD1 transcription in the epidermis of hyd1 null mutants reveals a major role in root patterning and growth. HYD1 expression in the vascular tissues and root meristem, though not endodermis or pericycle, also leads to some phenotypic rescue. Phenotypic rescue is associated with rescued patterning of the PIN1 and PIN2 auxin efflux carriers. The importance of the epidermis in controlling root growth and development is proposed to be, in part, due to its role as a site for sterol biosynthesis, and auxin is a candidate for the non-cell-autonomous signal. © 2018. Published by The Company of Biologists Ltd.

Engineered cell-cell communication via DNA messaging

PubMed Central

2012-01-01

Background Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically “regulate transcription.” Results We have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis. Conclusions We demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia. PMID:22958599

Information for Successful Interaction with Autonomous Systems

NASA Technical Reports Server (NTRS)

Malin, Jane T.; Johnson, Kathy A.

2003-01-01

Interaction in heterogeneous mission operations teams is not well matched to classical models of coordination with autonomous systems. We describe methods of loose coordination and information management in mission operations. We describe an information agent and information management tool suite for managing information from many sources, including autonomous agents. We present an integrated model of levels of complexity of agent and human behavior, which shows types of information processing and points of potential error in agent activities. We discuss the types of information needed for diagnosing problems and planning interactions with an autonomous system. We discuss types of coordination for which designs are needed for autonomous system functions.

Autonomic control of the eye

PubMed Central

McDougal, David H.; Gamlin, Paul D.

2016-01-01

The autonomic nervous system influences numerous ocular functions. It does this by way of parasympathetic innervation from postganglionic fibers that originate from neurons in the ciliary and pterygopalatine ganglia, and by way of sympathetic innervation from postganglionic fibers that originate from neurons in the superior cervical ganglion. Ciliary ganglion neurons project to the ciliary body and the sphincter pupillae muscle of the iris to control ocular accommodation and pupil constriction, respectively. Superior cervical ganglion neurons project to the dilator pupillae muscle of the iris to control pupil dilation. Ocular blood flow is controlled both via direct autonomic influences on the vasculature of the optic nerve, choroid, ciliary body, and iris, as well as via indirect influences on retinal blood flow. In mammals, this vasculature is innervated by vasodilatory fibers from the pterygopalatine ganglion, and by vasoconstrictive fibers from the superior cervical ganglion. Intraocular pressure is regulated primarily through the balance of aqueous humor formation and outflow. Autonomic regulation of ciliary body blood vessels and the ciliary epithelium is an important determinant of aqueous humor formation; autonomic regulation of the trabecular meshwork and episcleral blood vessels is an important determinant of aqueous humor outflow. These tissues are all innervated by fibers from the pterygopalatine and superior cervical ganglia. In addition to these classical autonomic pathways, trigeminal sensory fibers exert local, intrinsic influences on many of these regions of the eye, as well as on some neurons within the ciliary and pterygopalatine ganglia. PMID:25589275

Autonomic neuropathy in an alcoholic population.

PubMed

Barter, F; Tanner, A R

1987-12-01

Autonomic nervous system integrity has been assessed in 30 alcoholic subjects and 30 age-sex matched controls using five simple tests of cardiovascular responses. There was evidence of parasympathetic neuropathy alone in five of the alcoholic subjects (16%) and of combined parasympathetic and sympathetic neuropathy in an additional six (20%). None of the controls showed any abnormality. Within the alcoholic group, those with autonomic neuropathy were older, were more likely to be female and to have established alcoholic liver disease. Symptoms were a poor guide to the presence or absence of autonomic neuropathy.

Development of Autonomous Aerobraking - Phase 2

NASA Technical Reports Server (NTRS)

Murri, Daniel G.

2013-01-01

Phase 1 of the Development of Autonomous Aerobraking (AA) Assessment investigated the technical capability of transferring the processes of aerobraking maneuver (ABM) decision-making (currently performed on the ground by an extensive workforce and communicated to the spacecraft via the deep space network) to an efficient flight software algorithm onboard the spacecraft. This document describes Phase 2 of this study, which was a 12-month effort to improve and rigorously test the AA Development Software developed in Phase 1. Aerobraking maneuver; Autonomous Aerobraking; Autonomous Aerobraking Development Software; Deep Space Network; NASA Engineering and Safety Center

Autonomous support for microorganism research in space

NASA Astrophysics Data System (ADS)

Fleet, M. L.; Smith, J. D.; Klaus, D. M.; Luttges, M. W.

1993-02-01

A preliminary design for performing on orbit, autonomous research on microorganisms and cultured cells/tissues is presented. The payload is designed to be compatible with the COMercial Experiment Transporter (COMET), an orbiter middeck locker interface and with Space Station Freedom. Uplink/downlink capabilities and sample return through controlled reentry are available for all carriers. Autonomous testing activities are preprogrammed with in-flight reprogrammability. Sensors for monitoring temperature, pH, light, gravity levels, vibrations, and radiation are provided for environmental regulation and experimental data collection. Additional data acquisition includes optical density measurement, microscopy, video, and film photography. On-board data storage capabilities are provided. A fluid transfer mechanism is utilized for inoculation, sampling, and nutrient replenishment of experiment cultures. In addition to payload design, research opportunities are explored to illustrate hardware versatility and function. The project is defined to provide biological data pertinent to extended duration crewed space flight including crew health issues and development of a Controlled Ecological Life Support System (CELSS). In addition, opportunities are opened for investigations leading to commercial applications of space, such as pharmaceutical development, modeling of terrestrial diseases, and material processing.

Autonomous Science Analysis with the New Millennium Program-Autonomous Sciencecraft Experiment

NASA Astrophysics Data System (ADS)

Doggett, T.; Davies, A. G.; Castano, R. A.; Baker, V. R.; Dohm, J. M.; Greeley, R.; Williams, K. K.; Chien, S.; Sherwood, R.

2002-12-01

The NASA New Millennium Program (NMP) is a testbed for new, high-risk technologies, including new software and hardware. The Autonomous Sciencecraft Experiment (ASE) will fly on the Air Force Research Laboratory TechSat-21 mission in 2006 is such a NMP mission, and is managed by the Jet Propulsion Laboratory, California Institute of Technology. TechSat-21 consists of three satellites, each equipped with X-band Synthetic Aperture Radar (SAR) that will occupy a 13-day repeat track Earth orbit. The main science objectives of ASE are to demonstrate that process-related change detection and feature identification can be conducted autonomously during space flight, leading to autonomous onboard retargeting of the spacecraft. This mission will observe transient geological and environmental processes using SAR. Examples of geologic processes that may be observed and investigated include active volcanism, the movement of sand dunes and transient features in desert environments, water flooding, and the formation and break-up of lake ice. Science software onboard the spacecraft will allow autonomous processing and formation of SAR images and extraction of scientific information. The subsequent analyses, performed on images formed onboard from the SAR data, will include feature identification using scalable feature "templates" for each target, change detection through comparison of current and archived images, and science discovery, a search for other features of interest in each image. This approach results in obtaining the same science return for a reduced amount of resource use (such as downlink) when compared to that from a mission operating without ASE technology. Redundant data is discarded. The science-driven goals of ASE will evolve during the ASE mission through onboard replanning software that can re-task satellite operations. If necessary, as a result of a discovery made autonomously by onboard science processing, existing observation sequences will be pre-empted to

DNA "nano-claw": logic-based autonomous cancer targeting and therapy.

PubMed

You, Mingxu; Peng, Lu; Shao, Na; Zhang, Liqin; Qiu, Liping; Cui, Cheng; Tan, Weihong

2014-01-29

Cell types, both healthy and diseased, can be classified by inventories of their cell-surface markers. Programmable analysis of multiple markers would enable clinicians to develop a comprehensive disease profile, leading to more accurate diagnosis and intervention. As a first step to accomplish this, we have designed a DNA-based device, called "Nano-Claw". Combining the special structure-switching properties of DNA aptamers with toehold-mediated strand displacement reactions, this claw is capable of performing autonomous logic-based analysis of multiple cancer cell-surface markers and, in response, producing a diagnostic signal and/or targeted photodynamic therapy. We anticipate that this design can be widely applied in facilitating basic biomedical research, accurate disease diagnosis, and effective therapy.

Cooperative Autonomous Robots for Reconnaissance

DTIC Science & Technology

2009-03-06

REPORT Cooperative Autonomous Robots for Reconnaissance 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: Collaborating mobile robots equipped with WiFi ...Cooperative Autonomous Robots for Reconnaissance Report Title ABSTRACT Collaborating mobile robots equipped with WiFi transceivers are configured as a mobile...equipped with WiFi transceivers are configured as a mobile ad-hoc network. Algorithms are developed to take advantage of the distributed processing

Autonomous quantum Maxwell's demon based on two exchange-coupled quantum dots

NASA Astrophysics Data System (ADS)

Ptaszyński, Krzysztof

2018-01-01

I study an autonomous quantum Maxwell's demon based on two exchange-coupled quantum dots attached to the spin-polarized leads. The principle of operation of the demon is based on the coherent oscillations between the spin states of the system which act as a quantum iSWAP gate. Due to the operation of the iSWAP gate, one of the dots acts as a feedback controller which blocks the transport with the bias in the other dot, thus inducing the electron pumping against the bias; this leads to the locally negative entropy production. Operation of the demon is associated with the information transfer between the dots, which is studied quantitatively by mapping the analyzed setup onto the thermodynamically equivalent auxiliary system. The calculated entropy production in a single subsystem and information flow between the subsystems are shown to obey a local form of the second law of thermodynamics, similar to the one previously derived for classical bipartite systems.

miR126-5p Downregulation Facilitates Axon Degeneration and NMJ Disruption via a Non-Cell-Autonomous Mechanism in ALS.

PubMed

Maimon, Roy; Ionescu, Ariel; Bonnie, Avichai; Sweetat, Sahar; Wald-Altman, Shane; Inbar, Shani; Gradus, Tal; Trotti, Davide; Weil, Miguel; Behar, Oded; Perlson, Eran

2018-06-13

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR126-5p in presymptomatic ALS male mice models, and an increase in its targets: axon destabilizing Type 3 Semaphorins and their coreceptor Neuropilins. Using compartmentalized in vitro cocultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 blocking antibody. Finally, overexpressing miR126-5p is sufficient to transiently rescue axon degeneration and NMJ disruption both in vitro and in vivo Thus, we demonstrate a novel mechanism underlying ALS pathology, in which alterations in miR126-5p facilitate a non-cell-autonomous mechanism of motor neuron degeneration in ALS. SIGNIFICANCE STATEMENT Despite some progress, currently no effective treatment is available for amyotrophic lateral sclerosis (ALS). We suggest a novel regulatory role for miR126-5p in ALS and demonstrate, for the first time, a mechanism by which alterations in miR126-5p contribute to axon degeneration and NMJ disruption observed in ALS. We show that miR126-5p is altered in ALS models and that it can modulate Sema3 and NRP protein expression. Furthermore, NRP1 elevations in motor neurons and muscle secretion of Sema3A contribute to axon degeneration and NMJ disruption in ALS. Finally, overexpressing miR126-5p is sufficient to transiently rescue NMJ disruption and axon degeneration both in vitro and in vivo . Copyright © 2018 Maimon et al.

Advancing Autonomous Operations Technologies for NASA Missions

NASA Technical Reports Server (NTRS)

Cruzen, Craig; Thompson, Jerry Todd

2013-01-01

This paper discusses the importance of implementing advanced autonomous technologies supporting operations of future NASA missions. The ability for crewed, uncrewed and even ground support systems to be capable of mission support without external interaction or control has become essential as space exploration moves further out into the solar system. The push to develop and utilize autonomous technologies for NASA mission operations stems in part from the need to reduce operations cost while improving and increasing capability and safety. This paper will provide examples of autonomous technologies currently in use at NASA and will identify opportunities to advance existing autonomous technologies that will enhance mission success by reducing operations cost, ameliorating inefficiencies, and mitigating catastrophic anomalies.

Advancing Autonomous Operations Technologies for NASA Missions

NASA Technical Reports Server (NTRS)

Cruzen, Craig; Thompson, Jerry T.

2013-01-01

This paper discusses the importance of implementing advanced autonomous technologies supporting operations of future NASA missions. The ability for crewed, uncrewed and even ground support systems to be capable of mission support without external interaction or control has become essential as space exploration moves further out into the solar system. The push to develop and utilize autonomous technologies for NASA mission operations stems in part from the need to reduce cost while improving and increasing capability and safety. This paper will provide examples of autonomous technologies currently in use at NASA and will identify opportunities to advance existing autonomous technologies that will enhance mission success by reducing cost, ameliorating inefficiencies, and mitigating catastrophic anomalies

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Enhanced autonomic shutdown of Li-ion batteries by polydopamine coated polyethylene microspheres

DOE PAGES

Baginska, Marta; Blaiszik, Benjamin J.; Rajh, Tijana; ...

2014-07-17

Thermally triggered autonomic shutdown of a Lithium-ion (Li-ion) battery is demonstrated using polydopamine (PDA)-coated polyethylene microspheres applied onto a battery anode. The microspheres are dispersed in a buffered 10 mM dopamine salt solution and the pH is raised to initiate the polymerization and coat the microspheres. Coated microspheres are then mixed with an aqueous binder, applied onto a battery anode surface, dried, and incorporated into Li-ion coin cells. FTIR and Raman spectroscopy are used to verify the presence of the polydopamine on the surface of the microspheres. Scanning electron microscopy is used to examine microsphere surface morphology and resulting anodemore » coating quality. Charge and discharge capacity, as well as impedance, are measured for Li-ion coin cells as a function of microsphere content. Autonomous shutdown is achieved by applying 1.7 mg cm –2 of PDA-coated microspheres to the electrode. Furthermore, the PDA coating significantly reduces the mass of microspheres for effective shutdown compared to our prior work with uncoated microspheres.« less

Epidermal Notch signalling: differentiation, cancer and adhesion.

PubMed

Watt, Fiona M; Estrach, Soline; Ambler, Carrie A

2008-04-01

The Notch pathway plays an important role in regulating epidermal differentiation. Notch ligands, receptors and effectors are expressed in a complex and dynamic pattern in embryonic and adult skin. Genetic ablation or activation of the pathway reveals that Notch signalling promotes differentiation of the hair follicle, sebaceous gland and interfollicular epidermal lineages and that Notch acts as an epidermal tumour suppressor. Notch signalling interacts with a range of other pathways to fulfil these functions and acts via RBP-Jkappa dependent and independent mechanisms. The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion.

Transposable elements at the center of the crossroads between embryogenesis, embryonic stem cells, reprogramming, and long non-coding RNAs.

PubMed

Hutchins, Andrew Paul; Pei, Duanqing

Transposable elements (TEs) are mobile genomic sequences of DNA capable of autonomous and non-autonomous duplication. TEs have been highly successful, and nearly half of the human genome now consists of various families of TEs. Originally thought to be non-functional, these elements have been co-opted by animal genomes to perform a variety of physiological functions ranging from TE-derived proteins acting directly in normal biological functions, to innovations in transcription factor logic and influence on epigenetic control of gene expression. During embryonic development, when the genome is epigenetically reprogrammed and DNA-demethylated, TEs are released from repression and show embryonic stage-specific expression, and in human and mouse embryos, intact TE-derived endogenous viral particles can even be detected. A similar process occurs during the reprogramming of somatic cells to pluripotent cells: When the somatic DNA is demethylated, TEs are released from repression. In embryonic stem cells (ESCs), where DNA is hypomethylated, an elaborate system of epigenetic control is employed to suppress TEs, a system that often overlaps with normal epigenetic control of ESC gene expression. Finally, many long non-coding RNAs (lncRNAs) involved in normal ESC function and those assisting or impairing reprogramming contain multiple TEs in their RNA. These TEs may act as regulatory units to recruit RNA-binding proteins and epigenetic modifiers. This review covers how TEs are interlinked with the epigenetic machinery and lncRNAs, and how these links influence each other to modulate aspects of ESCs, embryogenesis, and somatic cell reprogramming.

Electrophysiological and morphological properties of pre-autonomic neurones in the rat hypothalamic paraventricular nucleus.

PubMed

Stern, J E

2001-11-15

1. The cellular properties of pre-autonomic neurones in the hypothalamic paraventricular nucleus (PVN) were characterized by combining in vivo retrograde tracing techniques, in vitro patch-clamp recordings and three-dimensional reconstruction of recorded neurones in adult hypothalamic slices. 2. The results showed that PVN pre-autonomic neurones constitute a heterogeneous neuronal population. Based on morphological criteria, neurones were classified into three subgroups. Type A neurones (52 %) were located in the ventral parvocellular (PaV) subnucleus, and showed an oblique orientation with respect to the third ventricle (3V). Type B neurones (25 %) were located in the posterior parvocellular (PaPo) subnucleus, and were oriented perpendicularly with respect to the 3V. Type C neurones (23 %) were located in both the PaPo (82 %) and the PaV (18 %) subnuclei, and displayed a concentric dendritic configuration. 3. A morphometric analysis revealed significant differences in the dendritic configuration among neuronal types. Type B neurones had the most complex dendritic arborization, with longer and more branching dendritic trees. 4. Several electrophysiological properties, including cell input resistance and action potential waveforms, differed between cell types, suggesting that the expression and/or properties of a variety of ion channels differ between neuronal types. 5. Common features of PVN pre-autonomic neurones included the expression of a low-threshold spike and strong inward rectification. These properties distinguished them from neighbouring magnocellular vasopressin neurones. 6. In summary, these results indicate that PVN pre-autonomic neurones constitute a heterogeneous neuronal population, and provide a cellular basis for the study of their involvement in the pathophysiology of hypertension and congestive heart failure disorders.

Trigeminal autonomic cephalgias

PubMed Central

2012-01-01

Summary points 1. Trigeminal autonomic cephalgias (TACs) are headaches/facial pains classified together based on:a suspected common pathophysiology involving the trigeminovascular system, the trigeminoparasympathetic reflex and centres controlling circadian rhythms;a similar clinical presentation of trigeminal pain, and autonomic activation. 2. There is much overlap in the diagnostic features of individual TACs. 3. In contrast, treatment response is relatively specific and aids in establishing a definitive diagnosis. 4. TACs are often presentations of underlying pathology; all patients should be imaged. 5. The aim of the article is to provide the reader with a broad introduction to, and an overview of, TACs. The reading list is extensive for the interested reader. PMID:26516482

Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles

DTIC Science & Technology

2007-11-01

Tolerant Overactuated Autonomous Vehicles Casavola, A.; Garone, E. (2007) Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous ...Adaptive Control Allocation for Fault Tolerant Overactuated Autonomous Vehicles 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Tolerant Overactuated Autonomous Vehicles 3.2 - 2 RTO-MP-AVT-145 UNCLASSIFIED/UNLIMITED Control allocation problem (CAP) - Given a virtual input v(t

Research Institute for Autonomous Precision Guided Systems

DTIC Science & Technology

2007-03-08

research on agile autonomous munitions, in direct support of the Air Force Research Laboratory Munitions Directorate (AFRL/MN). The grant was awarded with a...Flight had (5) research task areas: 1. Aeroforms and Actuation for Small and Micro Agile Air Vehicles 2. Sensing for Autonomous Control and...critical barriers in AAM, but are not covered in the scope of the AVCAAF (Vision-Based Control of Agile, Autonomous Micro Air Vehicles and Small UAVs

Autonomous Locator of Thermals (ALOFT) Autonomous Soaring Algorithm

DTIC Science & Technology

2015-04-03

estimator used on the NRL CICADA Mk 3 micro air vehicle [13]. An extended Kalman filter (EKF) was designed to estimate the airspeed sensor bias and...Boulder, 2007. ALOFT Autonomous Soaring Algorithm 31 13. A.D. Kahn and D.J. Edwards, “Navigation, Guidance and Control for the CICADA Expendable

System Engineering of Autonomous Space Vehicles

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Johnson, Stephen B.; Trevino, Luis

2014-01-01

Human exploration of the solar system requires fully autonomous systems when travelling more than 5 light minutes from Earth. This autonomy is necessary to manage a large, complex spacecraft with limited crew members and skills available. The communication latency requires the vehicle to deal with events with only limited crew interaction in most cases. The engineering of these systems requires an extensive knowledge of the spacecraft systems, information theory, and autonomous algorithm characteristics. The characteristics of the spacecraft systems must be matched with the autonomous algorithm characteristics to reliably monitor and control the system. This presents a large system engineering problem. Recent work on product-focused, elegant system engineering will be applied to this application, looking at the full autonomy stack, the matching of autonomous systems to spacecraft systems, and the integration of different types of algorithms. Each of these areas will be outlined and a general approach defined for system engineering to provide the optimal solution to the given application context.

An introduction to autonomous control systems

NASA Technical Reports Server (NTRS)

Antsaklis, Panos J.; Passino, Kevin M.; Wang, S. J.

1991-01-01

The functions, characteristics, and benefits of autonomous control are outlined. An autonomous control functional architecture for future space vehicles that incorporates the concepts and characteristics described is presented. The controller is hierarchical, with an execution level (the lowest level), coordination level (middle level), and management and organization level (highest level). The general characteristics of the overall architecture, including those of the three levels, are explained, and an example to illustrate their functions is given. Mathematical models for autonomous systems, including 'logical' discrete event system models, are discussed. An approach to the quantitative, systematic modeling, analysis, and design of autonomous controllers is also discussed. It is a hybrid approach since it uses conventional analysis techniques based on difference and differential equations and new techniques for the analysis of the systems described with a symbolic formalism such as finite automata. Some recent results from the areas of planning and expert systems, machine learning, artificial neural networks, and the area restructurable controls are briefly outlined.

Apoptosis and Self-Destruct: A Contribution to Autonomic Agents?

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2004-01-01

Autonomic Computing (AC), a self-managing systems initiative based on the biological metaphor of the autonomic nervous system, is increasingly gaining momentum as the way forward in designing reliable systems. Agent technologies have been identified as a key enabler for engineering autonomicity in systems, both in terms of retrofitting autonomicity into legacy systems and designing new systems. The AC initiative provides an opportunity to consider other biological systems and principles in seeking new design strategies. This paper reports on one such investigation; utilizing the apoptosis metaphor of biological systems to provide a dynamic health indicator signal between autonomic agents.

Advanced Autonomous Systems for Space Operations

NASA Astrophysics Data System (ADS)

Gross, A. R.; Smith, B. D.; Muscettola, N.; Barrett, A.; Mjolssness, E.; Clancy, D. J.

2002-01-01

New missions of exploration and space operations will require unprecedented levels of autonomy to successfully accomplish their objectives. Inherently high levels of complexity, cost, and communication distances will preclude the degree of human involvement common to current and previous space flight missions. With exponentially increasing capabilities of computer hardware and software, including networks and communication systems, a new balance of work is being developed between humans and machines. This new balance holds the promise of not only meeting the greatly increased space exploration requirements, but simultaneously dramatically reducing the design, development, test, and operating costs. New information technologies, which take advantage of knowledge-based software, model-based reasoning, and high performance computer systems, will enable the development of a new generation of design and development tools, schedulers, and vehicle and system health management capabilities. Such tools will provide a degree of machine intelligence and associated autonomy that has previously been unavailable. These capabilities are critical to the future of advanced space operations, since the science and operational requirements specified by such missions, as well as the budgetary constraints will limit the current practice of monitoring and controlling missions by a standing army of ground-based controllers. System autonomy capabilities have made great strides in recent years, for both ground and space flight applications. Autonomous systems have flown on advanced spacecraft, providing new levels of spacecraft capability and mission safety. Such on-board systems operate by utilizing model-based reasoning that provides the capability to work from high-level mission goals, while deriving the detailed system commands internally, rather than having to have such commands transmitted from Earth. This enables missions of such complexity and communication` distances as are not

A Primer on Autonomous Aerial Vehicle Design

PubMed Central

Coppejans, Hugo H. G.; Myburgh, Herman C.

2015-01-01

There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV), such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM) solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers. PMID:26633410

A Primer on Autonomous Aerial Vehicle Design.

PubMed

Coppejans, Hugo H G; Myburgh, Herman C

2015-12-02

There is a large amount of research currently being done on autonomous micro-aerial vehicles (MAV), such as quadrotor helicopters or quadcopters. The ability to create a working autonomous MAV depends mainly on integrating a simultaneous localization and mapping (SLAM) solution with the rest of the system. This paper provides an introduction for creating an autonomous MAV for enclosed environments, aimed at students and professionals alike. The standard autonomous system and MAV automation are discussed, while we focus on the core concepts of SLAM systems and trajectory planning algorithms. The advantages and disadvantages of using remote processing are evaluated, and recommendations are made regarding the viability of on-board processing. Recommendations are made regarding best practices to serve as a guideline for aspirant MAV designers.

Central autonomic nervous system response to autonomic challenges is altered in patients with a previous episode of Takotsubo cardiomyopathy.

PubMed

Pereira, Vitor H; Marques, Paulo; Magalhães, Ricardo; Português, João; Calvo, Lucy; Cerqueira, João J; Sousa, Nuno

2016-04-01

Takotsubo cardiomyopathy is an intriguing disease characterized by acute transient left ventricular dysfunction usually triggered by an episode of severe stress. The excessive levels of catecholamines and the overactivation of the sympathetic system are believed to be the main pathophysiologic mechanisms of Takotsubo cardiomyopathy, but it is unclear whether there is a structural or functional signature of the disease. In this sense, our aim was to characterize the central autonomic system response to autonomic challenges in patients with a previous episode of Takotsubo cardiomyopathy when compared with a control group of healthy volunteers. Functional magnetic resonance imaging (fMRI) was performed in four patients with a previous episode of Takotsubo cardiomyopathy (average age of 67 ± 12 years) and in eight healthy volunteers (average age of 66 ± 5 years) while being submitted to different autonomic challenges (cold exposure and Valsalva manoeuvre). The fMRI analysis revealed a significant variation of the blood oxygen level dependent signal triggered by the Valsalva manoeuvre in specific areas of the brain involved in the cortical control of the autonomic system and significant differences in the pattern of activation of the insular cortex, amygdala and the right hippocampus between patients with Takotsubo cardiomyopathy and controls, even though these regions did not present significant volumetric changes. The central autonomic response to autonomic challenges is altered in patients with Takotsubo cardiomyopathy, thus suggesting a dysregulation of the central autonomic nervous system network. Subsequent studies are needed to unveil whether these alterations are causal or predisposing factors to Takotsubo cardiomyopathy. © The European Society of Cardiology 2015.

Methods of determining complete sensor requirements for autonomous mobility

NASA Technical Reports Server (NTRS)

Curtis, Steven A. (Inventor)

2012-01-01

A method of determining complete sensor requirements for autonomous mobility of an autonomous system includes computing a time variation of each behavior of a set of behaviors of the autonomous system, determining mobility sensitivity to each behavior of the autonomous system, and computing a change in mobility based upon the mobility sensitivity to each behavior and the time variation of each behavior. The method further includes determining the complete sensor requirements of the autonomous system through analysis of the relative magnitude of the change in mobility, the mobility sensitivity to each behavior, and the time variation of each behavior, wherein the relative magnitude of the change in mobility, the mobility sensitivity to each behavior, and the time variation of each behavior are characteristic of the stability of the autonomous system.

Hybrid power systems for autonomous MEMS

NASA Astrophysics Data System (ADS)

Bennett, Daniel M.; Selfridge, Richard H.; Humble, Paul; Harb, John N.

2001-08-01

This paper describes the design of a hybrid power system for use with autonomous MEMS and other microdevices. This hybrid power system includes energy conversion and storage along with an electronic system for managing the collection and distribution of power. It offers flexibility and longevity in a compact package. The hybrid power system couples a silicon solar cell with a microbattery specially designed for MEMS applications. We have designed a control/interface charging circuit to be compatible with a MEMS duty cycle. The design permits short pulses of 'high' power while taking care to avoid excessive charging or discharging of the battery. Charging is carefully controlled to provide a balance between acceptably small charging times and a charging profile that extends battery life. Our report describes the charging of our Ni/Zn microbatteries using solar cells. To date we have demonstrated thousands of charge/discharge cycles of a simulated MEMS duty cycle.

Effects of a small talking facial image on autonomic activity: the moderating influence of dispositional BIS and BAS sensitivities and emotions.

PubMed

Ravaja, Niklas

2004-01-01

We examined the moderating influence of dispositional behavioral inhibition system and behavioral activation system (BAS) sensitivities, Negative Affect, and Positive Affect on the relationship between a small moving vs. static facial image and autonomic responses when viewing/listening to news messages read by a newscaster among 36 young adults. Autonomic parameters measured were respiratory sinus arrhythmia (RSA), low-frequency (LF) component of heart rate variability (HRV), electrodermal activity, and pulse transit time (PTT). The results showed that dispositional BAS sensitivity, particularly BAS Fun Seeking, and Negative Affect interacted with facial image motion in predicting autonomic nervous system activity. A moving facial image was related to lower RSA and LF component of HRV and shorter PTTs as compared to a static facial image among high BAS individuals. Even a small talking facial image may contribute to sustained attentional engagement among high BAS individuals, given that the BAS directs attention toward the positive cue and a moving social stimulus may act as a positive incentive for high BAS individuals.

Autonomous Microstructure EM-APEX Floats

DTIC Science & Technology

2016-01-01

Autonomous Microstructure_EM-APEX_Float 4/8/16 at 3:21 PM 1 Title: Autonomous Microstructure EM-APEX Floats Authors: Ren-Chieh Lien1,2...Street Seattle, WA 98105 rcl@uw.edu Abstract: Fast responding FP-07 thermistors have been incorporated on profiling EM-APEX floats to measure...storage board. The raw and processed temperature observations are stored on a microSD card. Results from eight microstructure EM-APEX floats

Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots.

PubMed

Hess, H; Ross, Jennifer L

2017-09-18

Biological systems have evolved to harness non-equilibrium processes from the molecular to the macro scale. It is currently a grand challenge of chemistry, materials science, and engineering to understand and mimic biological systems that have the ability to autonomously sense stimuli, process these inputs, and respond by performing mechanical work. New chemical systems are responding to the challenge and form the basis for future responsive, adaptive, and active materials. In this article, we describe a particular biochemical-biomechanical network based on the microtubule cytoskeletal filament - itself a non-equilibrium chemical system. We trace the non-equilibrium aspects of the system from molecules to networks and describe how the cell uses this system to perform active work in essential processes. Finally, we discuss how microtubule-based engineered systems can serve as testbeds for autonomous chemical robots composed of biological and synthetic components.

May a unitary autonomic index help assess autonomic cardiac regulation in elite athletes? Preliminary observations on the national Italian Olympic committee team.

PubMed

Sala, Roberto; Malacarne, Mara; Tosi, Fabio; Benzi, Manuela; Solaro, Nadia; Tamorri, Stefano; Spataro, Antonio; Pagani, Massimo; Lucini, Daniela

2017-12-01

Long term endurance training, as occurring in elite athletes, is associated to cardiac neural remodeling in favor of cardioprotective vagal mechanisms, resulting in resting bradycardia and augmented contribution of cardiac parasympathetic nerve activity. Autonomic assessment can be performed by way of heart rate variability. This technique however provides multiple indices, and there is not yet complete agreement on their specific significance. Purpose of the study was to assess whether a rank transformation and radar plot could provide a unitary autonomic index, capable to show a correlation between intensity of individual work and quality of autonomic regulation. We studied 711 (23.6±6.2 years) elite athletes that took part in the selection procedure for the 2016 Rio Olympic Games for the National Italian Olympic Committee (CONI). Indices from Heart Rate Variability HRV obtained at rest, during standing up and during recovery from an exercise test were used to compute a percent ranked unitary autonomic index for sport (ANSIs), taken as proxy of quality of autonomic regulation. Within the observed wide range of energy expenditure, the unitary autonomic index ANSIs appears significantly correlated to individual and discipline specific training workloads (r=0.25, P<0.001 and r=0.78, P<0.001, respectively), correcting for possible age and gender bias. ANSIs also positively correlates to lipid profile. Estimated intensity of physical activity correlates with quality of cardiac autonomic regulation, as expressed by a novel unitary index of cardiac autonomic regulation. ANSIs could provide a novel and convenient approach to individual autonomic evaluation in athletes.

PHM Enabled Autonomous Propellant Loading Operations

NASA Technical Reports Server (NTRS)

Walker, Mark; Figueroa, Fernando

2017-01-01

The utility of Prognostics and Health Management (PHM) software capability applied to Autonomous Operations (AO) remains an active research area within aerospace applications. The ability to gain insight into which assets and subsystems are functioning properly, along with the derivation of confident predictions concerning future ability, reliability, and availability, are important enablers for making sound mission planning decisions. When coupled with software that fully supports mission planning and execution, an integrated solution can be developed that leverages state assessment and estimation for the purposes of delivering autonomous operations. The authors have been applying this integrated, model-based approach to the autonomous loading of cryogenic spacecraft propellants at Kennedy Space Center.

On-Orbit Autonomous Assembly from Nanosatellites

NASA Technical Reports Server (NTRS)

Murchison, Luke S.; Martinez, Andres; Petro, Andrew

2015-01-01

The On-Orbit Autonomous Assembly from Nanosatellites (OAAN) project will demonstrate autonomous control algorithms for rendezvous and docking maneuvers; low-power reconfigurable magnetic docking technology; and compact, lightweight and inexpensive precision relative navigation using carrier-phase differential (CD) GPS with a three-degree of freedom ground demonstration. CDGPS is a specific relative position determination method that measures the phase of the GPS carrier wave to yield relative position data accurate to.4 inch (1 centimeter). CDGPS is a technology commonly found in the surveying industry. The development and demonstration of these technologies will fill a current gap in the availability of proven autonomous rendezvous and docking systems for small satellites.

Development of Autonomous Aerobraking (Phase 1)

NASA Technical Reports Server (NTRS)

Murri, Daniel G.; Powell, Richard W.; Prince, Jill L.

2012-01-01

The NASA Engineering and Safety Center received a request from Mr. Daniel Murri (NASA Technical Fellow for Flight Mechanics) to develop an autonomous aerobraking capability. An initial evaluation for all phases of this assessment was approved to proceed at the NESC Review Board meeting. The purpose of phase 1 of this study was to provide an assessment of the feasibility of autonomous aerobraking. During this phase, atmospheric, aerodynamic, and thermal models for a representative spacecraft were developed for both the onboard algorithm known as Autonomous Aerobraking Development Software, and a ground-based "truth" simulation developed for testing purposes. The results of the phase 1 assessment are included in this report.

Autonomous Control of Space Reactor Systems

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

Belle R. Upadhyaya; K. Zhao; S.R.P. Perillo

2007-11-30

Autonomous and semi-autonomous control is a key element of space reactor design in order to meet the mission requirements of safety, reliability, survivability, and life expectancy. Interrestrial nuclear power plants, human operators are avilable to perform intelligent control functions that are necessary for both normal and abnormal operational conditions.

Dynamic pre-BCR homodimers fine-tune autonomous survival signals in B cell precursor acute lymphoblastic leukemia

PubMed Central

Erasmus, M. Frank; Matlawska-Wasowska, Ksenia; Kinjyo, Ichiko; Mahajan, Avanika; Winter, Stuart S.; Xu, Li; Horowitz, Michael; Lidke, Diane S.; Wilson, Bridget S.

2017-01-01

The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent Quantum Dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions. Receptor motion was correlated at short separation distances, consistent with the formation of dimers and higher-order oligomers. Repeated encounters between diffusing pre-BCRs appeared to reflect transient co-confinement in plasma membrane domains. In human B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells, we showed that frequent, short-lived, homotypic pre-BCR interactions stimulated survival signals, including expression of BCL6, which encodes a transcriptional repressor. These survival signals were blocked by inhibitory monovalent antigen-binding antibody fragments (Fabs) specific for the surrogate light chain components of the pre-BCR or by inhibitors of the tyrosine kinases Lyn and Syk. For comparison, we evaluated pre-BCR aggregation mediated by dimeric galectin-1, which has binding sites for carbohydrate and for the λ5 component of the surrogate light chain. Galectin-1 binding resulted in the formation of large, highly immobile pre-BCR aggregates, which was partially relieved by the addition of lactose to prevent the crosslinking of galectin-BCR complexes to other glycosylated membrane components. Analysis of the pre-BCR and its signaling partners suggested that they could be potential targets for combination therapy in BCP-ALL. PMID:27899526

Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation

PubMed Central

Tape, Christopher J.; Ling, Stephanie; Dimitriadi, Maria; McMahon, Kelly M.; Worboys, Jonathan D.; Leong, Hui Sun; Norrie, Ida C.; Miller, Crispin J.; Poulogiannis, George; Lauffenburger, Douglas A.; Jørgensen, Claus

2016-01-01

Summary Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRASG12D) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRASG12D signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRASG12D engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRASG12D. Consequently, reciprocal KRASG12D produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRASG12D alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. Video Abstract PMID:27087446

Stochastic modeling indicates that aging and somatic evolution in the hematopoetic system are driven by non-cell-autonomous processes.

PubMed

Rozhok, Andrii I; Salstrom, Jennifer L; DeGregori, James

2014-12-01

Age-dependent tissue decline and increased cancer incidence are widely accepted to be rate-limited by the accumulation of somatic mutations over time. Current models of carcinogenesis are dominated by the assumption that oncogenic mutations have defined advantageous fitness effects on recipient stem and progenitor cells, promoting and rate-limiting somatic evolution. However, this assumption is markedly discrepant with evolutionary theory, whereby fitness is a dynamic property of a phenotype imposed upon and widely modulated by environment. We computationally modeled dynamic microenvironment-dependent fitness alterations in hematopoietic stem cells (HSC) within the Sprengel-Liebig system known to govern evolution at the population level. Our model for the first time integrates real data on age-dependent dynamics of HSC division rates, pool size, and accumulation of genetic changes and demonstrates that somatic evolution is not rate-limited by the occurrence of mutations, but instead results from aged microenvironment-driven alterations in the selective/fitness value of previously accumulated genetic changes. Our results are also consistent with evolutionary models of aging and thus oppose both somatic mutation-centric paradigms of carcinogenesis and tissue functional decline. In total, we demonstrate that aging directly promotes HSC fitness decline and somatic evolution via non-cell-autonomous mechanisms.

Swarm autonomic agents with self-destruct capability

NASA Technical Reports Server (NTRS)

Hinchey, Michael G. (Inventor); Sterritt, Roy (Inventor)

2009-01-01

Systems, methods and apparatus are provided through which in some embodiments an autonomic entity manages a system by generating one or more stay alive signals based on the functioning status and operating state of the system. In some embodiments, an evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy. The evolvable neural interface receives and generates heartbeat monitor signals and pulse monitor signals that are used to generate a stay alive signal that is used to manage the operations of the synthetic neural system. In another embodiment an asynchronous Alice signal (Autonomic license) requiring valid credentials of an anonymous autonomous agent is initiated. An unsatisfactory Alice exchange may lead to self-destruction of the anonymous autonomous agent for self-protection.

Swarm autonomic agents with self-destruct capability

NASA Technical Reports Server (NTRS)

Hinchey, Michael G. (Inventor); Sterritt, Roy (Inventor)

2011-01-01

Systems, methods and apparatus are provided through which in some embodiments an autonomic entity manages a system by generating one or more stay alive signals based on the functioning status and operating state of the system. In some embodiments, an evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy. The evolvable neural interface receives and generates heartbeat monitor signals and pulse monitor signals that are used to generate a stay alive signal that is used to manage the operations of the synthetic neural system. In another embodiment an asynchronous Alice signal (Autonomic license) requiring valid credentials of an anonymous autonomous agent is initiated. An unsatisfactory Alice exchange may lead to self-destruction of the anonymous autonomous agent for self-protection.

The Actions of Piperidine Alkaloids at Fetal Muscle-Type and Autonomic-Type Nicotinic Acetylcholine Receptors

USDA-ARS?s Scientific Manuscript database

Piperidine alkaloids are found in many species of plants including Conium maculatum, Nicotiana spp., and Lupinus spp. A pharmacodynamic comparison was made of the alkaloids ammodendrine, anabasine, anabaseine, and coniine in; SH-SY5Y cells which express autonomic-type nicotinic acetylcholine recept...

α2 Integrin, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-3 act sequentially to induce differentiation of mouse embryonic stem cells into odontoblast-like cells

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

Ozeki, Nobuaki; Kawai, Rie; Hase, Naoko

We previously reported that interleukin 1β acts via matrix metalloproteinase (MMP)-3 to regulate cell proliferation and suppress apoptosis in α2 integrin-positive odontoblast-like cells differentiated from mouse embryonic stem (ES) cells. Here we characterize the signal cascade underpinning odontoblastic differentiation in mouse ES cells. The expression of α2 integrin, extracellular matrix metalloproteinase inducer (Emmprin), and MMP-3 mRNA and protein were all potently increased during odontoblastic differentiation. Small interfering RNA (siRNA) disruption of the expression of these effectors potently suppressed the expression of the odontoblastic biomarkers dentin sialophosphoprotein, dentin matrix protein-1 and alkaline phosphatase, and blocked odontoblast calcification. Our siRNA, western blotmore » and blocking antibody analyses revealed a unique sequential cascade involving α2 integrin, Emmprin and MMP-3 that drives ES cell differentiation into odontoblasts. This cascade requires the interaction between α2 integrin and Emmprin and is potentiated by exogenous MMP-3. Finally, although odontoblast-like cells potently express α2, α6, αV, β1, and β3, integrins, we confirmed that β1 integrin acts as the trigger for ES cell differentiation, apparently in complex with α2 integrin. These results demonstrate a unique and unanticipated role for an α2 integrin-, Emmprin-, and MMP-3-mediated signaling cascade in driving mouse ES cell differentiation into odontoblast-like cells. - Highlights: • Odontoblast differentiation requires activation of α2 integrin, Emmprin and MMP-3. • α2 integrin, Emmprin and MMP-3 form a sequential signaling cascade. • β1 integrin acts a specific trigger for odontoblast differentiation. • The role of these effectors is highly novel and unanticipated.« less

Planning Flight Paths of Autonomous Aerobots

NASA Technical Reports Server (NTRS)

Kulczycki, Eric; Elfes, Alberto; Sharma, Shivanjli

2009-01-01

Algorithms for planning flight paths of autonomous aerobots (robotic blimps) to be deployed in scientific exploration of remote planets are undergoing development. These algorithms are also adaptable to terrestrial applications involving robotic submarines as well as aerobots and other autonomous aircraft used to acquire scientific data or to perform surveying or monitoring functions.

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

PubMed Central

Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

2016-01-01

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

Mitochondria released by cells undergoing TNF-α-induced necroptosis act as danger signals.

PubMed

Maeda, A; Fadeel, B

2014-07-03

Necrosis leads to the release of so-called damage-associated molecular patterns (DAMPs), which may provoke inflammatory responses. However, the release of organelles from dying cells, and the consequences thereof have not been documented before. We demonstrate here that mitochondria are released from cells undergoing tumor necrosis factor-α (TNF-α)-induced, receptor-interacting protein (RIP)1-dependent necroptosis, a form of programmed necrosis. The released, purified mitochondria were determined to be intact as they did not emit appreciable amounts of mitochondrial DNA (mtDNA). Pharmacological inhibition of dynamin-related protein 1 (Drp1) prevented mitochondrial fission in TNF-α-triggered cells, but this did not block necroptosis nor the concomitant release of mitochondria. Importantly, primary human macrophages and dendritic cells engulfed mitochondria from necroptotic cells leading to modulation of macrophage secretion of cytokines and induction of dendritic cell maturation. Our results show that intact mitochondria are released from necroptotic cells and suggest that these organelles act as bona fide danger signals.

Adenosine triphosphate acts as a paracrine signaling molecule to reduce the motility of T cells

PubMed Central

Wang, Chiuhui Mary; Ploia, Cristina; Anselmi, Fabio; Sarukhan, Adelaida; Viola, Antonella

2014-01-01

Organization of immune responses requires exchange of information between cells. This is achieved through either direct cell–cell contacts and establishment of temporary synapses or the release of soluble factors, such as cytokines and chemokines. Here we show a novel form of cell-to-cell communication based on adenosine triphosphate (ATP). ATP released by stimulated T cells induces P2X4/P2X7-mediated calcium waves in the neighboring lymphocytes. Our data obtained in lymph node slices suggest that, during T-cell priming, ATP acts as a paracrine messenger to reduce the motility of lymphocytes and that this may be relevant to allow optimal tissue scanning by T cells. PMID:24843045

Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells.

PubMed

Morita, Ken; Noura, Mina; Tokushige, Chieko; Maeda, Shintaro; Kiyose, Hiroki; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Yoshida, Kenichi; Ozaki, Toshifumi; Matsuo, Hidemasa; Ogawa, Seishi; Liu, Pu Paul; Nakahata, Tatsutoshi; Sugiyama, Hiroshi; Adachi, Souichi; Kamikubo, Yasuhiko

2017-11-30

Although runt-related transcription factor 1 (RUNX1) and its associating core binding factor-β (CBFB) play pivotal roles in leukemogenesis, and inhibition of RUNX1 has now been widely recognized as a novel strategy for anti-leukemic therapies, it has been elusive how leukemic cells could acquire the serious resistance against RUNX1-inhibition therapies and also whether CBFB could participate in this process. Here, we show evidence that p53 (TP53) and CBFB are sequentially up-regulated in response to RUNX1 depletion, and their mutual interaction causes the physiological resistance against chemotherapy for acute myeloid leukemia (AML) cells. Mechanistically, p53 induced by RUNX1 gene silencing directly binds to CBFB promoter and stimulates its transcription as well as its translation, which in turn acts as a platform for the stabilization of RUNX1, thereby creating a compensative RUNX1-p53-CBFB feedback loop. Indeed, AML cells derived from relapsed cases exhibited higher CBFB expression levels compared to those from primary AML cells at diagnosis, and these CBFB expressions were positively correlated to those of p53. Our present results underscore the importance of RUNX1-p53-CBFB regulatory loop in the development and/or maintenance of AML cells, which could be targeted at any sides of this triangle in strategizing anti-leukemia therapies.

Drosophila glypican Dally-like acts in FGF-receiving cells to modulate FGF signaling during tracheal morphogenesis

PubMed Central

Yan, Dong; Lin, Xinhua

2007-01-01

Summary Previous studies in Drosophila have shown that heparan sulfate proteoglycans (HSPGs) are involved in both breathless (btl)- and heartless (htl)-mediated FGF signaling during embryogenesis. However, the mechanism(s) by which HSPGs control Btl and Htl signaling is unknown. Here we show that dally-like (dlp, a Drosophila glypican) mutant embryos exhibit severe defects in tracheal morphogenesis and show a reduction in btl-mediated FGF signaling activity. However, htl-dependent mesodermal cell migration is not affected in dlp mutant embryos. Furthermore, expression of Dlp, but not other Drosophila HSPGs, can restore effectively the tracheal morphogenesis in dlp embryos. Rescue experiments in dlp embryos demonstrate that Dlp functions only in Bnl/FGF receiving cells in a cell-autonomous manner, but is not essential for Bnl/FGF expression cells. To further dissect the mechanism(s) of Dlp in Btl signaling, we analyzed the role of Dlp in Btl-mediated air sac tracheoblast formation in wing discs. Mosaic analysis experiments show that removal of HSPG activity in FGF-producing or other surrounding cells does not affect tracheoblasts migration, while HSPG mutant tracheoblast cells fail to receive FGF signaling. Together, our results argue strongly that HSPGs regulate Btl signaling exclusively in FGF-receiving cells as co-receptors, but are not essential for the secretion and distribution of the FGF ligand. This mechanism is distinct from HSPG functions in morphogen distribution, and is likely a general paradigm for HSPG functions in FGF signaling in Drosophila. PMID:17959166

A Model-Driven Architecture Approach for Modeling, Specifying and Deploying Policies in Autonomous and Autonomic Systems

NASA Technical Reports Server (NTRS)

Pena, Joaquin; Hinchey, Michael G.; Sterritt, Roy; Ruiz-Cortes, Antonio; Resinas, Manuel

2006-01-01

Autonomic Computing (AC), self-management based on high level guidance from humans, is increasingly gaining momentum as the way forward in designing reliable systems that hide complexity and conquer IT management costs. Effectively, AC may be viewed as Policy-Based Self-Management. The Model Driven Architecture (MDA) approach focuses on building models that can be transformed into code in an automatic manner. In this paper, we look at ways to implement Policy-Based Self-Management by means of models that can be converted to code using transformations that follow the MDA philosophy. We propose a set of UML-based models to specify autonomic and autonomous features along with the necessary procedures, based on modification and composition of models, to deploy a policy as an executing system.

Autonomous Cryogenics Loading Operations Simulation Software: Knowledgebase Autonomous Test Engineer

NASA Technical Reports Server (NTRS)

Wehner, Walter S., Jr.

2013-01-01

Working on the ACLO (Autonomous Cryogenics Loading Operations) project I have had the opportunity to add functionality to the physics simulation software known as KATE (Knowledgebase Autonomous Test Engineer), create a new application allowing WYSIWYG (what-you-see-is-what-you-get) creation of KATE schematic files and begin a preliminary design and implementation of a new subsystem that will provide vision services on the IHM (Integrated Health Management) bus. The functionality I added to KATE over the past few months includes a dynamic visual representation of the fluid height in a pipe based on number of gallons of fluid in the pipe and implementing the IHM bus connection within KATE. I also fixed a broken feature in the system called the Browser Display, implemented many bug fixes and made changes to the GUI (Graphical User Interface).

Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences.

PubMed

Chen, Sunlu; Zheng, Huizhen; Kishima, Yuji

2017-06-01

The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus-virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.

Demonstration of Autonomous Rendezvous Technology (DART) Project Summary

NASA Technical Reports Server (NTRS)

Rumford, TImothy E.

2003-01-01

Since the 1960's, NASA has performed numerous rendezvous and docking missions. The common element of all US rendezvous and docking is that the spacecraft has always been piloted by astronauts. Only the Russian Space Program has developed and demonstrated an autonomous capability. The Demonstration of Autonomous Rendezvous Technology (DART) project currently funded under NASA's Space Launch Initiative (SLI) Cycle I, provides a key step in establishing an autonomous rendezvous capability for the United States. DART's objective is to demonstrate, in space, the hardware and software necessary for autonomous rendezvous. Orbital Sciences Corporation intends to integrate an Advanced Video Guidance Sensor and Autonomous Rendezvous and Proximity Operations algorithms into a Pegasus upper stage in order to demonstrate the capability to autonomously rendezvous with a target currently in orbit. The DART mission will occur in April 2004. The launch site will be Vandenburg AFB and the launch vehicle will be a Pegasus XL equipped with a Hydrazine Auxiliary Propulsion System 4th stage. All mission objectives will be completed within a 24 hour period. The paper provides a summary of mission objectives, mission overview and a discussion on the design features of the chase and target vehicles.

Examining accident reports involving autonomous vehicles in California

PubMed Central

Nader, Nazanin; Eurich, Sky O.; Tripp, Michelle; Varadaraju, Naresh

2017-01-01

Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017). The data provides important information on autonomous vehicles accidents’ dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama. PMID:28931022

Examining accident reports involving autonomous vehicles in California.

PubMed

Favarò, Francesca M; Nader, Nazanin; Eurich, Sky O; Tripp, Michelle; Varadaraju, Naresh

2017-01-01

Autonomous Vehicle technology is quickly expanding its market and has found in Silicon Valley, California, a strong foothold for preliminary testing on public roads. In an effort to promote safety and transparency to consumers, the California Department of Motor Vehicles has mandated that reports of accidents involving autonomous vehicles be drafted and made available to the public. The present work shows an in-depth analysis of the accident reports filed by different manufacturers that are testing autonomous vehicles in California (testing data from September 2014 to March 2017). The data provides important information on autonomous vehicles accidents' dynamics, related to the most frequent types of collisions and impacts, accident frequencies, and other contributing factors. The study also explores important implications related to future testing and validation of semi-autonomous vehicles, tracing the investigation back to current literature as well as to the current regulatory panorama.

An autonomous flying vehicle for Mars exploration

NASA Astrophysics Data System (ADS)

Bouras, Peter; Fox, Tim

1990-09-01

A remotely reprogrammable, autonomous flying craft for surveying and mapping the Martian surface environment is presented. This solar powered, modified flying wing design could cover about 2000 statute miles while maneuvering at Mach 0.3. The craft is configured to fly one km above the surface, measuring atmospheric properties, performing subsurface mapping, mapping the surface topography, and searching for the presence of water and perhaps life. A 35 kg scientific payload, plus communication and control electronics, are placed spanwise inside the flying wing, removing the requirement for a normal fuselage, and reducing structural needs. Thrust is provided by a two-bladed electrically driven propeller motorized by high-efficiency solar cells.

Tactical Decision Aids High Bandwidth Links Using Autonomous Vehicles

DTIC Science & Technology

2004-01-01

1 Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) A. J. Healey, D. P. Horner, Center for Autonomous Underwater Vehicle...SUBTITLE Tactical Decision Aids (High Bandwidth Links Using Autonomous Vehicles ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Autonomous Vehicle Systems Laboratory Research Capability Expansion Program

DTIC Science & Technology

2017-12-03

currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. University of the Incarnate Word 4301 Broadway, Box #T-2 San Antonio...autonomous control , collaboration, and decision-making in unstructured, dynamic, and uncertain nonlinear environments for autonomous ground and air...vehicle systems. To fulfill the research goal, the PI has initiated fundamental research in the areas of autonomous rotorcraft control and

Autonomous Cryogenic Load Operations: Knowledge-Based Autonomous Test Engineer

NASA Technical Reports Server (NTRS)

Schrading, J. Nicolas

2013-01-01

The Knowledge-Based Autonomous Test Engineer (KATE) program has a long history at KSC. Now a part of the Autonomous Cryogenic Load Operations (ACLO) mission, this software system has been sporadically developed over the past 20 years. Originally designed to provide health and status monitoring for a simple water-based fluid system, it was proven to be a capable autonomous test engineer for determining sources of failure in the system. As part of a new goal to provide this same anomaly-detection capability for a complicated cryogenic fluid system, software engineers, physicists, interns and KATE experts are working to upgrade the software capabilities and graphical user interface. Much progress was made during this effort to improve KATE. A display of the entire cryogenic system's graph, with nodes for components and edges for their connections, was added to the KATE software. A searching functionality was added to the new graph display, so that users could easily center their screen on specific components. The GUI was also modified so that it displayed information relevant to the new project goals. In addition, work began on adding new pneumatic and electronic subsystems into the KATE knowledge base, so that it could provide health and status monitoring for those systems. Finally, many fixes for bugs, memory leaks, and memory errors were implemented and the system was moved into a state in which it could be presented to stakeholders. Overall, the KATE system was improved and necessary additional features were added so that a presentation of the program and its functionality in the next few months would be a success.

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Biologically-Inspired Concepts for Autonomic Self-Protection in Multiagent Systems

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2006-01-01

Biologically-inspired autonomous and autonomic systems (AAS) are essentially concerned with creating self-directed and self-managing systems based on metaphors &om nature and the human body, such as the autonomic nervous system. Agent technologies have been identified as a key enabler for engineering autonomy and autonomicity in systems, both in terms of retrofitting into legacy systems and in designing new systems. Handing over responsibility to systems themselves raises concerns for humans with regard to safety and security. This paper reports on the continued investigation into a strand of research on how to engineer self-protection mechanisms into systems to assist in encouraging confidence regarding security when utilizing autonomy and autonomicity. This includes utilizing the apoptosis and quiescence metaphors to potentially provide a self-destruct or self-sleep signal between autonomic agents when needed, and an ALice signal to facilitate self-identification and self-certification between anonymous autonomous agents and systems.

Autonomous intelligent cruise control system

NASA Astrophysics Data System (ADS)

Baret, Marc; Bomer, Thierry T.; Calesse, C.; Dudych, L.; L'Hoist, P.

1995-01-01

Autonomous intelligent cruise control (AICC) systems are not only controlling vehicles' speed but acting on the throttle and eventually on the brakes they could automatically maintain the relative speed and distance between two vehicles in the same lane. And more than just for comfort it appears that these new systems should improve the safety on highways. By applying a technique issued from the space research carried out by MATRA, a sensor based on a charge coupled device (CCD) was designed to acquire the reflected light on standard-mounted car reflectors of pulsed laser diodes emission. The CCD is working in a unique mode called flash during transfer (FDT) which allows identification of target patterns in severe optical environments. It provides high accuracy for distance and angular position of targets. The absence of moving mechanical parts ensures high reliability for this sensor. The large field of view and the high measurement rate give a global situation assessment and a short reaction time. Then, tracking and filtering algorithms have been developed in order to select the target, on which the equipped vehicle determines its safety distance and speed, taking into account its maneuvering and the behaviors of other vehicles.

Symmetries and solutions of the non-autonomous von Bertalanffy equation

NASA Astrophysics Data System (ADS)

Edwards, Maureen P.; Anderssen, Robert S.

2015-05-01

For growth in a closed environment, which is indicative of the situation in laboratory experiments, autonomous ODE models do not necessarily capture the dynamics under investigation. The importance and impact of a closed environment arise when the question under examination relates, for example, to the number of the surviving microbes, such as in a study of the spoilage and contamination of food, the gene silencing activity of fungi or the production of a chemical compound by bacteria or fungi. Autonomous ODE models are inappropriate as they assume that only the current size of the population controls the growth-decay dynamics. This is reflected in the fact that, asymptotically, their solutions can only grow or decay monotonically or asymptote. Non-autonomous ODE models are not so constrained. A natural strategy for the choice of non-autonomous ODEs is to take appropriate autonomous ones and change them to be non-autonomous through the introduction of relevant non-autonomous terms. This is the approach in this paper with the focus being the von Bertalanffy equation. Since this equation has independent importance in relation to practical applications in growth modelling, it is natural to explore the deeper relationships between the introduced non-autonomous terms through a symmetry analysis, which is the purpose and goal of the current paper. Infinitesimals are derived which allow particular forms of the non-autonomous von Bertalanffy equation to be transformed into autonomous forms for which some new analytic solutions have been found.

Autonomy Level Specification for Intelligent Autonomous Vehicles

DTIC Science & Technology

2003-09-01

Autonomy Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report Hui-Min Huang, Elena Messina, James Albus...Level Specification for Intelligent Autonomous Vehicles : Interim Progress Report 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Autonomous Command Operations of the WIRE Spacecraft

NASA Technical Reports Server (NTRS)

Walyus, Keith; Prior, Mike; Saylor, Richard

1999-01-01

This paper presents operational innovations which will be introduced on NASA's Wide Field Infrared Explorer (WIRE) mission. These innovations include an end-to-end design architecture for an autonomous commanding capability for the uplink of command loads during unattended station contacts. The WIRE mission is the fifth and final mission of NASA's Goddard Space Flight Center Small Explorer (SMEX) series to be launched in March of 1999. Its primary mission is the targeting of deep space fields using an ultra-cooled infrared telescope. Due to its mission design WIRE command loads are large (approximately 40 Kbytes per 24 hours) and must be performed daily. To reduce the cost of mission operations support that would be required in order to uplink command loads, the WIRE Flight Operations Team has implemented all autonomous command loading capability. This capability allows completely unattended operations over a typical two-day weekend period. The key factors driving design and implementation of this capability were: 1) integration with already existing ground system autonomous capabilities and systems, 2) the desire to evolve autonomous operations capabilities based upon previous SMEX operations experience - specifically the TRACE mission, 3) integration with ground station operations - both autonomous and man-tended, 4) low cost and quick implementation, and 5) end-to-end system robustness. A trade-off study was performed to examine these factors in light of the low-cost, higher-risk SMEX mission philosophy. The study concluded that a STOL (Spacecraft Test and Operations Language) based script, highly integrated with other scripts used to perform autonomous operations, was best suited given the budget and goals of the mission. Each of these factors is discussed in addition to use of the TRACE mission as a testbed for autonomous commanding prior to implementation on WIRE. The capabilities implemented on the WIRE mission are an example of a low-cost, robust, and

Multiple Autonomous Vehicles for Minefield Reconnaissance and Mapping

DTIC Science & Technology

1997-12-01

NPS-ME-97-008 NAVAL POSTGRADUATE SCHOOL Monterey, California ItC A D- 19980421 131 =C QUALTY Ui Ji.CTEJ) THESIS MULTIPLE AUTONOMOUS VEHICLES FOR...MULTIPLE AUTONOMOUS VEHICLES FOR MINEFIELD 5. FUNDING NUMBERS RECONNAISSANCE AND MAPPING N0001497WX30039 6. AUTHOR(S) Jack A. Starr 7. PERFORMING... AUTONOMOUS VEHICLES FOR MINEFIELD RECONNAISSANCE AND MAPPING Jack A. Starr Lieutenant, United States Navy B.S., Oregon State University, 1991 Submitted in

Emotions induced by operatic music: psychophysiological effects of music, plot, and acting: a scientist's tribute to Maria Callas.

PubMed

Balteş, Felicia Rodica; Avram, Julia; Miclea, Mircea; Miu, Andrei C

2011-06-01

Operatic music involves both singing and acting (as well as rich audiovisual background arising from the orchestra and elaborate scenery and costumes) that multiply the mechanisms by which emotions are induced in listeners. The present study investigated the effects of music, plot, and acting performance on emotions induced by opera. There were three experimental conditions: (1) participants listened to a musically complex and dramatically coherent excerpt from Tosca; (2) they read a summary of the plot and listened to the same musical excerpt again; and (3) they re-listened to music while they watched the subtitled film of this acting performance. In addition, a control condition was included, in which an independent sample of participants succesively listened three times to the same musical excerpt. We measured subjective changes using both dimensional, and specific music-induced emotion questionnaires. Cardiovascular, electrodermal, and respiratory responses were also recorded, and the participants kept track of their musical chills. Music listening alone elicited positive emotion and autonomic arousal, seen in faster heart rate, but slower respiration rate and reduced skin conductance. Knowing the (sad) plot while listening to the music a second time reduced positive emotions (peacefulness, joyful activation), and increased negative ones (sadness), while high autonomic arousal was maintained. Watching the acting performance increased emotional arousal and changed its valence again (from less positive/sad to transcendent), in the context of continued high autonomic arousal. The repeated exposure to music did not by itself induce this pattern of modifications. These results indicate that the multiple musical and dramatic means involved in operatic performance specifically contribute to the genesis of music-induced emotions and their physiological correlates. Copyright © 2011 Elsevier Inc. All rights reserved.

Human germinal center CD4+CD57+ T cells act differently on B cells than do classical T-helper cells.

PubMed

Bouzahzah, F; Bosseloir, A; Heinen, E; Simar, L J

1995-01-01

We have isolated two subtypes of helper T cells from human tonsils: CD4+CD57+ cells, mostly located in the germinal center (GC), and CD4+CD57- cells, distributed through the interfollicular areas but also present in the GC. In a functional study, we have compared the capacities of these T-cell subtypes to stimulate B cells in cocultures. In order to block T-cell proliferation while maintaining their activation level, we pretreated isolated T cells with mitomycin C prior to culture in the presence of B cells and added polyclonal activators such as PHA and Con A, combined or not with IL-2. Contrary to CD4+ CD57- cells, CD4+CD57+ cells did not markedly enhance B-cell proliferation. Even when sIgD.B cells typical of germinal center cells were tested, the CD4+CD57+ cells had no significant effect. This is in accordance with the location of these cells: They mainly occupy the light zones of the GC where few B cells divide. Even when added to preactivated, actively proliferating cells, CD4+CD57 cells failed to modulate B-cell multiplication. On the supernatants of B-cell-T-cell cocultures, we examined by the ELISA technique the effect of T cells on Ig synthesis. Contrary to CD57+ T cells, whose effect was strong, CD57- T cells weakly stimulated Ig synthesis. More IgM than IgG was generally found. Because CD57 antigen is a typical marker of natural killer cells, we tested the cytolytic activity of tonsillar CD4+CD57+ cells on K562 target cells. Unlike NK cells, neither CD4+CD57+ nor CD4+CD57- cells exhibit any cytotoxicity. Thus, germinal center CD4+CD57+ cells are not cytolytic and do not strongly stimulate either B-cell proliferation or Ig secretion. CD4+CD57- cells, however, enhance B-cell proliferation and differentiation, thus acting like the classical helper cells of the T-dependent areas.

Autonomous execution of the Precision Immobilization Technique

NASA Astrophysics Data System (ADS)

Mascareñas, David D. L.; Stull, Christopher J.; Farrar, Charles R.

2017-03-01

Over the course of the last decade great advances have been made in autonomously driving cars. The technology has advanced to the point that driverless car technology is currently being tested on publicly accessed roadways. The introduction of these technologies onto publicly accessed roadways not only raises questions of safety, but also security. Autonomously driving cars are inherently cyber-physical systems and as such will have novel security vulnerabilities that couple both the cyber aspects of the vehicle including the on-board computing and any network data it makes use of, with the physical nature of the vehicle including its sensors, actuators, and the vehicle chassis. Widespread implementation of driverless car technology will require that both the cyber, as well as physical security concerns surrounding these vehicles are addressed. In this work, we specifically developed a control policy to autonomously execute the Precision Immobilization Technique, a.k.a. the PIT maneuver. The PIT maneuver was originally developed by law enforcement to end high-speed vehicular pursuits in a quasi-safe manner. However, there is still a risk of damage/roll-over to both the vehicle executing the PIT maneuver as well as to the vehicle subject to the PIT maneuver. In law enforcement applications, it would be preferable to execute the PIT maneuver using an autonomous vehicle, thus removing the danger to law-enforcement officers. Furthermore, it is entirely possible that unscrupulous individuals could inject code into an autonomously-driving car to use the PIT maneuver to immobilize other vehicles while maintaining anonymity. For these reasons it is useful to know how the PIT maneuver can be implemented on an autonomous car. In this work a simple control policy based on velocity pursuit was developed to autonomously execute the PIT maneuver using only a vision and range measurements that are both commonly collected by contemporary driverless cars. The ability of this

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.

PubMed

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-05-01

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors.

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

PubMed Central

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-01-01

SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

Software control architecture for autonomous vehicles

NASA Astrophysics Data System (ADS)

Nelson, Michael L.; DeAnda, Juan R.; Fox, Richard K.; Meng, Xiannong

1999-07-01

The Strategic-Tactical-Execution Software Control Architecture (STESCA) is a tri-level approach to controlling autonomous vehicles. Using an object-oriented approach, STESCA has been developed as a generalization of the Rational Behavior Model (RBM). STESCA was initially implemented for the Phoenix Autonomous Underwater Vehicle (Naval Postgraduate School -- Monterey, CA), and is currently being implemented for the Pioneer AT land-based wheeled vehicle. The goals of STESCA are twofold. First is to create a generic framework to simplify the process of creating a software control architecture for autonomous vehicles of any type. Second is to allow for mission specification system by 'anyone' with minimal training to control the overall vehicle functionality. This paper describes the prototype implementation of STESCA for the Pioneer AT.

On the autonomous motion of active drops or bubbles.

PubMed

Ryazantsev, Yuri S; Velarde, Manuel G; Guzman, Eduardo; Rubio, Ramón G; Ortega, Francisco; Montoya, Juan-Jose

2018-05-19

Thermo-capillary stresses on the surface of a drop can be the result of a non-isothermal surface chemical conversion of a reactant dissolved in the host fluid. The strength of heat production (with e.g. absorption) on the surface is ruled by the diffusion of the reactant and depends on the state of motion of the drop. Such thermo-capillary stresses can provoke the motion of the drop or its motionless state in the presence of an external body force. If in the balance of forces, including indeed viscous drag, the net resultant force vanishes there is the possibility of autonomous motion with constant velocity of the drop. Focusing on drops with radii in the millimeter range provided here is a quantitative study of the possibility of such autonomous motion when the drop, considered as active unit, is seat of endo- or exo-thermic reactive processes that dominate its motion. The framework is restricted to Stokes flows in the hydrodynamics, negligible heat Peclet number while the solute Peclet number is considered very high. A boundary layer approximation is used in the description of reactant diffusion. Those processes eventually end up in the action being expressed by surface tension gradients and the Marangoni effect. Explicit expressions of the force acting on the drop and the velocity fields inside and outside the drop are provided. Some significant particular cases are discussed to illustrate the usefulness of the theory. Copyright © 2018. Published by Elsevier Inc.

Autonomic Computing: Panacea or Poppycock?

NASA Technical Reports Server (NTRS)

Sterritt, Roy; Hinchey, Mike

2005-01-01

Autonomic Computing arose out of a need for a means to cope with rapidly growing complexity of integrating, managing, and operating computer-based systems as well as a need to reduce the total cost of ownership of today's systems. Autonomic Computing (AC) as a discipline was proposed by IBM in 2001, with the vision to develop self-managing systems. As the name implies, the influence for the new paradigm is the human body's autonomic system, which regulates vital bodily functions such as the control of heart rate, the body's temperature and blood flow-all without conscious effort. The vision is to create selfivare through self-* properties. The initial set of properties, in terms of objectives, were self-configuring, self-healing, self-optimizing and self-protecting, along with attributes of self-awareness, self-monitoring and self-adjusting. This self-* list has grown: self-anticipating, self-critical, self-defining, self-destructing, self-diagnosis, self-governing, self-organized, self-reflecting, and self-simulation, for instance.

Focus on autonomic dysfunction in familial amyloidotic polyneuropathy (FAP).

PubMed

Obayashi, Konen; Ando, Yukio

2012-06-01

It is well known that autonomic dysfunction in familial amyloidotic polyneuropathy (FAP) is the most serious problem, because it restricts the daily life of these patients. The detail mechanisms of the onset are not well understood in FAP and domino liver transplantation-induced amyloid neuropathy. As autonomic disturbances play an important role in the symptomatology of FAP, further studies of autonomic dysfunction in these patients may lead the pathogenesis of FAP. Autonomic dysfunction is often observed before sensory and motor nerve dysfunction in FAP. This can be attributed to the morphological characteristics of the nerves. Unmyelinated, small myelinated, and large myelinated fibers tend to become impaired in that order. Although the reasons of susceptibility to amyloid infiltration and injury are not known, studies of autopsied FAP patients have revealed heavy infiltration of amyloid in autonomic ganglions. Moreover, spinal ganglion and posterior loot of the spine had severe amyloid deposits than did the anterior root of the spine or the motor nerves. It is well known that autonomic dysfunction is the most serious problem, because it restricts the daily life of FAP patients. However, we have four major questions about autonomic dysfunction in clinical. In this manuscript, we discuss about the answers of these questions.

Unique autonomic responses to pain in yoga practitioners.

PubMed

Cotton, Valerie; Low, Lucie A; Villemure, Chantal; Bushnell, M Catherine

2018-04-03

Autonomic nervous system activity is associated with neurobehavioral aspects of pain. Yogis use breathing, relaxation and mindfulness to tolerate pain, which could influence autonomic responses. To evaluate how the link between autonomic responses and pain is altered by other factors, we compared perceptual and autonomic responses to pain between yogis and controls. Nineteen yogis and 15 controls rated warm and painfully hot stimuli (1-cm thermode on calf), with visual anticipatory cues indicating certainly painful, certainly non-painful or uncertainly either painful or non-painful. Heart rate, skin conductance, respiration, and blood pressure were measured. At baseline, yogis breathed slower and deeper than controls, with no differences in other autonomic measures. During the task, perceptual ratings did not differ between groups in either the certain or uncertain conditions. Nevertheless, yogis had higher phasic skin conductance responses in anticipation of and response to all stimuli, but particularly during painful heat in uncertain contexts (Uncertain: 0.46 ± 0.34μS; Certain: 0.37 ± 0.28μS, t(18) = 3.962, p = 0.001). Furthermore, controls showed a decrease in heart rate to warm (-2.51 ± 2.17 bpm) versus painful stimuli (0.83 ± 1.63 bpm; t(13) = 5.212, p < 0.001) and lower respiratory sinus arrhythmia during pain than warm trials, whereas yogis had similar reactions to painful and non-painful stimuli. Autonomic responses to pain differed in yogis and healthy volunteers, despite similar pain ratings. Thus, autonomic reactivity to pain may be altered by environmental and psychological factors throughout an individual's life.

Autonomous Vehicles and the Net-Centric Battlespace

DTIC Science & Technology

2000-04-01

Autonomous vehicles are playing increasing roles in the air/land/sea network of today’s battlespace. As the Navy’s lead laboratory for command...including remote sensor platforms, communication relays, and work platforms. As these capabilities are developed autonomous vehicles will become an

3-D Vision Techniques for Autonomous Vehicles

DTIC Science & Technology

1988-08-01

TITLE (Include Security Classification) W 3-D Vision Techniques for Autonomous Vehicles 12 PERSONAL AUTHOR(S) Martial Hebert, Takeo Kanade, inso Kweoni... Autonomous Vehicles Martial Hebert, Takeo Kanade, Inso Kweon CMU-RI-TR-88-12 The Robotics Institute Carnegie Mellon University Acession For Pittsburgh

Hard-real-time resource management for autonomous spacecraft

NASA Technical Reports Server (NTRS)

Gat, E.

2000-01-01

This paper describes tickets, a computational mechanism for hard-real-time autonomous resource management. Autonomous spacecraftcontrol can be considered abstractly as a computational process whose outputs are spacecraft commands.

Autonomous Science Operations Technologies for Deep Space Gateway

NASA Astrophysics Data System (ADS)

Barnes, P. K.; Haddock, A. T.; Cruzen, C. A.

2018-02-01

Autonomous Science Operations Technologies for Deep Space Gateway (DSG) is an overview of how the DSG would benefit from autonomous systems utilizing proven technologies performing telemetry monitoring and science operations.

Tracked robot controllers for climbing obstacles autonomously

NASA Astrophysics Data System (ADS)

Vincent, Isabelle

2009-05-01

Research in mobile robot navigation has demonstrated some success in navigating flat indoor environments while avoiding obstacles. However, the challenge of analyzing complex environments to climb obstacles autonomously has had very little success due to the complexity of the task. Unmanned ground vehicles currently exhibit simple autonomous behaviours compared to the human ability to move in the world. This paper presents the control algorithms designed for a tracked mobile robot to autonomously climb obstacles by varying its tracks configuration. Two control algorithms are proposed to solve the autonomous locomotion problem for climbing obstacles. First, a reactive controller evaluates the appropriate geometric configuration based on terrain and vehicle geometric considerations. Then, a reinforcement learning algorithm finds alternative solutions when the reactive controller gets stuck while climbing an obstacle. The methodology combines reactivity to learning. The controllers have been demonstrated in box and stair climbing simulations. The experiments illustrate the effectiveness of the proposed approach for crossing obstacles.

Autonomic Cluster Management System (ACMS): A Demonstration of Autonomic Principles at Work

NASA Technical Reports Server (NTRS)

Baldassari, James D.; Kopec, Christopher L.; Leshay, Eric S.; Truszkowski, Walt; Finkel, David

2005-01-01

Cluster computing, whereby a large number of simple processors or nodes are combined together to apparently function as a single powerful computer, has emerged as a research area in its own right. The approach offers a relatively inexpensive means of achieving significant computational capabilities for high-performance computing applications, while simultaneously affording the ability to. increase that capability simply by adding more (inexpensive) processors. However, the task of manually managing and con.guring a cluster quickly becomes impossible as the cluster grows in size. Autonomic computing is a relatively new approach to managing complex systems that can potentially solve many of the problems inherent in cluster management. We describe the development of a prototype Automatic Cluster Management System (ACMS) that exploits autonomic properties in automating cluster management.

Autonomic Nervous System Reactivity: Children With and Without Sickle Cell Disease

PubMed Central

Treadwell, Marsha J.; Alkon, Abbey; Styles, Lori; Boyce, W. Thomas

2011-01-01

Background Previous studies of healthy children have demonstrated a link between autonomic nervous system (ANS) reactivity and health outcomes, but there is limited research on whether ANS reactivity is similar for children with chronic conditions. Objective To determine if ANS reactivity differs for children with sickle cell disease (SCD) compared to a community sample of children without SCD. Method In two cross-sectional, descriptive studies, 32 public school children without chronic health problems were compared with 33 children with SCD. The children were 5-8 years old and they completed standardized protocols measuring ANS responses (respiratory sinus arrhythmia and pre-ejection period) during rest and challenge conditions in social, cognitive, sensory, and emotion domains. Reactivity was calculated as the difference between challenge response minus rest for each domain and overall. Results There were differences in the distributions of the samples in parent education and child age, so these variables were adjusted for in subsequent analyses. The community sample showed parasympathetic withdrawal (low respiratory sinus arrhythmia scores) and greater parasympathetic reactivity (low respiratory sinus arrhythmia difference scores and percentage of negative scores) compared with the children with SCD in the social (p < .05) and sensory domains (p < .05). The children with SCD showed greater sympathetic reactivity (low preejection period difference scores) compared with the community children in the cognitive domain (p < .05) and a greater percentage of children with SCD versus the community children showed negative pre-ejection period difference scores (sympathetic reactivity) in the social domain (p < .05). The community sample, but not the children with SCD, showed changes in respiratory sinus arrhythmia across domains (p < .05). Discussion Children with SCD may display a different pattern of ANS responses to laboratory challenges compared with children without

Autonomic Management of Space Missions. Chapter 12

NASA Technical Reports Server (NTRS)

Hinchey, Michael G.; Rash, James L.; Truszkowski, Walt; Rouff, Christopher A.; Sterritt, Roy

2006-01-01

With NASA s renewed commitment to outer space exploration, greater emphasis is being placed on both human and robotic exploration. Even when humans are involved in the exploration, human tending of assets becomes cost-prohibitive or in many cases is simply not feasible. In addition, certain exploration missions will require spacecraft that will be capable of venturing where humans cannot be sent. Early space missions were operated manually from ground control centers with little or no automated operations. In the mid-l980s, the high costs of satellite operations prompted NASA, and others, to begin automating as many functions as possible. In our context, a system is autonomous if it can achieve its goals without human intervention. A number of more-or-less automated ground systems exist today, but work continues with the goal being to reduce operations costs to even lower levels. Cost reductions can be achieved in a number of areas. Ground control and spacecraft operations are two such areas where greater autonomy can reduce costs. As a consequence, autonomy is increasingly seen as a critical approach for robotic missions and for some aspects of manned missions. Although autonomy will be critical for the success of future missions (and indeed will enable certain kinds of science data gathering approaches), missions imbued with autonomy must also exhibit autonomic properties. Exploitation of autonomy alone, without emphasis on autonomic properties, will leave spacecraft vulnerable to the dangerous environments in which they must operate. Without autonomic properties, a spacecraft may be unable to recognize negative environmental effects on its components and subsystems, or may be unable to take any action to ameliorate the effects. The spacecraft, though operating autonomously, may then sustain a degradation of performance of components or subsystems, and consequently may have a reduced potential for achieving mission objectives. In extreme cases, lack of autonomic

FGF signaling in the osteoprogenitor lineage non-autonomously regulates postnatal chondrocyte proliferation and skeletal growth

PubMed Central

Karuppaiah, Kannan; Yu, Kai; Lim, Joohyun; Chen, Jianquan; Smith, Craig; Long, Fanxin

2016-01-01

ABSTRACT Fibroblast growth factor (FGF) signaling is important for skeletal development; however, cell-specific functions, redundancy and feedback mechanisms regulating bone growth are poorly understood. FGF receptors 1 and 2 (Fgfr1 and Fgfr2) are both expressed in the osteoprogenitor lineage. Double conditional knockout mice, in which both receptors were inactivated using an osteoprogenitor-specific Cre driver, appeared normal at birth; however, these mice showed severe postnatal growth defects that include an ∼50% reduction in body weight and bone mass, and impaired longitudinal bone growth. Histological analysis showed reduced cortical and trabecular bone, suggesting cell-autonomous functions of FGF signaling during postnatal bone formation. Surprisingly, the double conditional knockout mice also showed growth plate defects and an arrest in chondrocyte proliferation. We provide genetic evidence of a non-cell-autonomous feedback pathway regulating Fgf9, Fgf18 and Pthlh expression, which led to increased expression and signaling of Fgfr3 in growth plate chondrocytes and suppression of chondrocyte proliferation. These observations show that FGF signaling in the osteoprogenitor lineage is obligately coupled to chondrocyte proliferation and the regulation of longitudinal bone growth. PMID:27052727

Autonomous Cryogenics Loading Operations Simulation Software: Knowledgebase Autonomous Test Engineer

NASA Technical Reports Server (NTRS)

Wehner, Walter S.

2012-01-01

The Simulation Software, KATE (Knowledgebase Autonomous Test Engineer), is used to demonstrate the automatic identification of faults in a system. The ACLO (Autonomous Cryogenics Loading Operation) project uses KATE to monitor and find faults in the loading of the cryogenics int o a vehicle fuel tank. The KATE software interfaces with the IHM (Integrated Health Management) systems bus to communicate with other systems that are part of ACLO. One system that KATE uses the IHM bus to communicate with is AIS (Advanced Inspection System). KATE will send messages to AIS when there is a detected anomaly. These messages include visual inspection of specific valves, pressure gauges and control messages to have AIS open or close manual valves. My goals include implementing the connection to the IHM bus within KATE and for the AIS project. I will also be working on implementing changes to KATE's Ul and implementing the physics objects in KATE that will model portions of the cryogenics loading operation.

Cooperative Control of Multiple Unmanned Autonomous Vehicles

DTIC Science & Technology

2005-06-03

I I Final Report 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Cooperative Control of Multiple Unmanned Autonomous Vehicles F49620-01-1-0337 6. AUTHOR(S... Autonomous Vehicles Final Report Kendall E. Nygard Department of Computer Science and Operations Research North Dakota State University Fargo, ND 58105-5164

Autonomic Physiological Response Patterns Related to Intelligence

ERIC Educational Resources Information Center

Melis, Cor; van Boxtel, Anton

2007-01-01

We examined autonomic physiological responses induced by six different cognitive ability tasks, varying in complexity, that were selected on the basis of on Guilford's Structure of Intellect model. In a group of 52 participants, task performance was measured together with nine different autonomic response measures and respiration rate. Weighted…

Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate Actinomyces interactions with streptococci and host cells during oral biofilm development

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

Mishra, Arunima; Devarajan, Bharanidharan; Reardon, Melissa E.

2011-09-06

By combining X-ray crystallography and modelling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbours an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability ofmore » FimA. Remarkably, FimA harbours two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae.« less

Two Autonomous Structural Modules in the Fimbrial Shaft Adhesin FimA Mediate Actinomyces Interactions with Streptococci and Host Cells during Oral Biofilm Development

PubMed Central

Mishra, Arunima; Devarajan, Bharanidharan; Reardon, Melissa E.; Dwivedi, Prabhat; Krishnan, Vengadesan; Cisar, John O.; Das, Asis; Narayana, Sthanam V. L; Ton-That, Hung

2011-01-01

By combining X-ray crystallography and modeling, we describe here the atomic structure of distinct adhesive moieties of FimA, the shaft fimbrillin of Actinomyces type 2 fimbriae, which uniquely mediates the receptor-dependent intercellular interactions between Actinomyces and oral streptococci as well as host cells during the development of oral biofilms. The FimA adhesin is built with three IgG-like domains, each of which harbors an intramolecular isopeptide bond, previously described in several Gram-positive pilins. Genetic and biochemical studies demonstrate that although these isopeptide bonds are dispensable for fimbrial assembly, cell-cell interactions and biofilm formation, they contribute significantly to the proteolytic stability of FimA. Remarkably, FimA harbors two autonomous adhesive modules, which structurally resemble the Staphylococcus aureus Cna B domain. Each isolated module can bind the plasma glycoprotein asialofetuin as well as the polysaccharide receptors present on the surface of oral streptococci and epithelial cells. Thus, FimA should serve as an excellent paradigm for the development of therapeutic strategies and elucidating the precise molecular mechanisms underlying the interactions between cellular receptors and Gram-positive fimbriae. PMID:21696465

Laser Range and Bearing Finder for Autonomous Missions

NASA Technical Reports Server (NTRS)

Granade, Stephen R.

2004-01-01

NASA has recently re-confirmed their interest in autonomous systems as an enabling technology for future missions. In order for autonomous missions to be possible, highly-capable relative sensor systems are needed to determine an object's distance, direction, and orientation. This is true whether the mission is autonomous in-space assembly, rendezvous and docking, or rover surface navigation. Advanced Optical Systems, Inc. has developed a wide-angle laser range and bearing finder (RBF) for autonomous space missions. The laser RBF has a number of features that make it well-suited for autonomous missions. It has an operating range of 10 m to 5 km, with a 5 deg field of view. Its wide field of view removes the need for scanning systems such as gimbals, eliminating moving parts and making the sensor simpler and space qualification easier. Its range accuracy is 1% or better. It is designed to operate either as a stand-alone sensor or in tandem with a sensor that returns range, bearing, and orientation at close ranges, such as NASA's Advanced Video Guidance Sensor. We have assembled the initial prototype and are currently testing it. We will discuss the laser RBF's design and specifications. Keywords: laser range and bearing finder, autonomous rendezvous and docking, space sensors, on-orbit sensors, advanced video guidance sensor

The autonomous sciencecraft constellations

NASA Technical Reports Server (NTRS)

Sherwood, R. L.; Chien, S.; Castano, R.; Rabideau, G.

2003-01-01

The Autonomous Sciencecraft Experiment (ASE) will fly onboard the Air Force TechSat 21 constellation of three spacecraft scheduled for launch in 2006. ASE uses onboard continuous planning, robust task and goal-based execution, model-based mode identification and reconfiguration, and onboard machine learning and pattern recognition to radically increase science return by enabling intelligent downlink selection and autonomous retargeting. In this paper we discuss how these AI technologies are synergistically integrated in a hybrid multi-layer control architecture to enable a virtual spacecraft science agent. Demonstration of these capabilities in a flight environment will open up tremendous new opportunities in planetary science, space physics, and earth science that would be unreachable without this technology.

Contingency Software in Autonomous Systems

NASA Technical Reports Server (NTRS)

Lutz, Robyn; Patterson-Hine, Ann

2006-01-01

This viewgraph presentation reviews the development of contingency software for autonomous systems. Autonomous vehicles currently have a limited capacity to diagnose and mitigate failures. There is a need to be able to handle a broader range of contingencies. The goals of the project are: 1. Speed up diagnosis and mitigation of anomalous situations.2.Automatically handle contingencies, not just failures.3.Enable projects to select a degree of autonomy consistent with their needs and to incrementally introduce more autonomy.4.Augment on-board fault protection with verified contingency scripts

A System for Fast Navigation of Autonomous Vehicles

DTIC Science & Technology

1991-09-01

AD-A243 523 4, jj A System for Fast Navigation of Autonomous Vehicles Sanjiv Singh, Dai Feng, Paul Keller, Gary Shaffer, Wen Fan Shi, Dong Hun Shin...FUNDING NUMBERS A System for Fast Navigation of Autonomous Vehicles 6. AUTHOR(S) S. Singh, D. Feng, P. Keller, G. Shaffer, W.F. Shi, D.H. Shin, J. West...common in the control of autonomous vehicles to establish the necessary kinematic models but to ignore an explicit representation of the vehicle dynamics

ALI (Autonomous Lunar Investigator): Revolutionary Approach to Exploring the Moon with Addressable Reconfigurable Technology

NASA Technical Reports Server (NTRS)

Clark, P. E.; Curtis, S. A.; Rilee, M. L.; Floyd, S. R.

2005-01-01

Addressable Reconfigurable Technology (ART) based structures: Mission Concepts based on Addressable Reconfigurable Technology (ART), originally studied for future ANTS (Autonomous Nanotechnology Swarm) Space Architectures, are now being developed as rovers for nearer term use in lunar and planetary surface exploration. The architecture is based on the reconfigurable tetrahedron as a building block. Tetrahedra are combined to form space-filling networks, shaped for the required function. Basic structural components are highly modular, addressable arrays of robust nodes (tetrahedral apices) from which highly reconfigurable struts (tetrahedral edges), acting as supports or tethers, are efficiently reversibly deployed/stowed, transforming and reshaping the structures as required.

Autonomous power expert system

NASA Technical Reports Server (NTRS)

Ringer, Mark J.; Quinn, Todd M.

1990-01-01

The goal of the Autonomous Power System (APS) program is to develop and apply intelligent problem solving and control technologies to the Space Station Freedom Electrical Power Systems (SSF/EPS). The objectives of the program are to establish artificial intelligence/expert system technology paths, to create knowledge based tools with advanced human-operator interfaces, and to integrate and interface knowledge-based and conventional control schemes. This program is being developed at the NASA-Lewis. The APS Brassboard represents a subset of a 20 KHz Space Station Power Management And Distribution (PMAD) testbed. A distributed control scheme is used to manage multiple levels of computers and switchgear. The brassboard is comprised of a set of intelligent switchgear used to effectively switch power from the sources to the loads. The Autonomous Power Expert System (APEX) portion of the APS program integrates a knowledge based fault diagnostic system, a power resource scheduler, and an interface to the APS Brassboard. The system includes knowledge bases for system diagnostics, fault detection and isolation, and recommended actions. The scheduler autonomously assigns start times to the attached loads based on temporal and power constraints. The scheduler is able to work in a near real time environment for both scheduling and dynamic replanning.

Autonomous power expert system

NASA Technical Reports Server (NTRS)

Ringer, Mark J.; Quinn, Todd M.

1990-01-01

The goal of the Autonomous Power System (APS) program is to develop and apply intelligent problem solving and control technologies to the Space Station Freedom Electrical Power Systems (SSF/EPS). The objectives of the program are to establish artificial intelligence/expert system technology paths, to create knowledge based tools with advanced human-operator interfaces, and to integrate and interface knowledge-based and conventional control schemes. This program is being developed at the NASA-Lewis. The APS Brassboard represents a subset of a 20 KHz Space Station Power Management And Distribution (PMAD) testbed. A distributed control scheme is used to manage multiple levels of computers and switchgear. The brassboard is comprised of a set of intelligent switchgear used to effectively switch power from the sources to the loads. The Autonomous Power Expert System (APEX) portion of the APS program integrates a knowledge based fault diagnostic system, a power resource scheduler, and an interface to the APS Brassboard. The system includes knowledge bases for system diagnostics, fault detection and isolation, and recommended actions. The scheduler autonomously assigns start times to the attached loads based on temporal and power constraints. The scheduler is able to work in a near real time environment for both scheduling an dynamic replanning.

Towards autonomous vehicles.

DOT National Transportation Integrated Search

2013-11-01

We are moving towards an age of autonomous vehicles. Cycles of innovation initiated in the public and private sectors : have led one into another since the 1990s; and out of these efforts have sprung a variety of Advanced Driver Assistance : Systems ...

High-frequency autonomic modulation: a new model for analysis of autonomic cardiac control.

PubMed

Champéroux, Pascal; Fesler, Pierre; Judé, Sebastien; Richard, Serge; Le Guennec, Jean-Yves; Thireau, Jérôme

2018-05-03

Increase in high-frequency beat-to-beat heart rate oscillations by torsadogenic hERG blockers appears to be associated with signs of parasympathetic and sympathetic co-activation which cannot be assessed directly using classic methods of heart rate variability analysis. The present work aimed to find a translational model that would allow this particular state of the autonomic control of heart rate to be assessed. High-frequency heart rate and heart period oscillations were analysed within discrete 10 s intervals in a cohort of 200 healthy human subjects. Results were compared to data collected in non-human primates and beagle dogs during pharmacological challenges and torsadogenic hERG blockers exposure, in 127 genotyped LQT1 patients on/off β-blocker treatment and in subgroups of smoking and non-smoking subjects. Three states of autonomic modulation, S1 (parasympathetic predominance) to S3 (reciprocal parasympathetic withdrawal/sympathetic activation), were differentiated to build a new model of heart rate variability referred to as high-frequency autonomic modulation. The S2 state corresponded to a specific state during which both parasympathetic and sympathetic systems were coexisting or co-activated. S2 oscillations were proportionally increased by torsadogenic hERG-blocking drugs, whereas smoking caused an increase in S3 oscillations. The combined analysis of the magnitude of high-frequency heart rate and high-frequency heart period oscillations allows a refined assessment of heart rate autonomic modulation applicable to long-term ECG recordings and offers new approaches to assessment of the risk of sudden death both in terms of underlying mechanisms and sensitivity. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Autonomous robot software development using simple software components

NASA Astrophysics Data System (ADS)

Burke, Thomas M.; Chung, Chan-Jin

2004-10-01

Developing software to control a sophisticated lane-following, obstacle-avoiding, autonomous robot can be demanding and beyond the capabilities of novice programmers - but it doesn"t have to be. A creative software design utilizing only basic image processing and a little algebra, has been employed to control the LTU-AISSIG autonomous robot - a contestant in the 2004 Intelligent Ground Vehicle Competition (IGVC). This paper presents a software design equivalent to that used during the IGVC, but with much of the complexity removed. The result is an autonomous robot software design, that is robust, reliable, and can be implemented by programmers with a limited understanding of image processing. This design provides a solid basis for further work in autonomous robot software, as well as an interesting and achievable robotics project for students.

The nature of the autonomic dysfunction in multiple system atrophy

NASA Technical Reports Server (NTRS)

Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

2002-01-01

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

Model-Unified Planning and Execution for Distributed Autonomous System Control

NASA Technical Reports Server (NTRS)

Aschwanden, Pascal; Baskaran, Vijay; Bernardini, Sara; Fry, Chuck; Moreno, Maria; Muscettola, Nicola; Plaunt, Chris; Rijsman, David; Tompkins, Paul

2006-01-01

The Intelligent Distributed Execution Architecture (IDEA) is a real-time architecture that exploits artificial intelligence planning as the core reasoning engine for interacting autonomous agents. Rather than enforcing separate deliberation and execution layers, IDEA unifies them under a single planning technology. Deliberative and reactive planners reason about and act according to a single representation of the past, present and future domain state. The domain state behaves the rules dictated by a declarative model of the subsystem to be controlled, internal processes of the IDEA controller, and interactions with other agents. We present IDEA concepts - modeling, the IDEA core architecture, the unification of deliberation and reaction under planning - and illustrate its use in a simple example. Finally, we present several real-world applications of IDEA, and compare IDEA to other high-level control approaches.

The physical examination as a window into autonomic disorders.

PubMed

Cheshire, William P; Goldstein, David S

2018-02-01

Signs of autonomic dysfunction, although at times seemingly mysterious, can contribute to diagnostic clarification and clinical investigation. Even when sophisticated autonomic testing equipment is not readily available, the experienced clinician, through educated observation and inductive reasoning-in conjunction with an intelligently obtained autonomic medical history-can discern much by a careful physical examination. Elements of the autonomic examination include variations in the pulse, postural measurements of blood pressure and heart rate, pupillary light reactions, skin coloration and temperature, patterns of sweating, and other organ-specific physical findings relevant to the individual patient's presentation. Especially important is the often neglected practice of measuring the blood pressure standing up, for orthostatic hypotension cannot be diagnosed by symptoms alone and is a common source of potential morbidity. The examination should be carried out in the context of understanding the syndromic nature of abnormalities of components of the autonomic nervous system.

Vital Signs Evaluation of Human Behaviour via an Autonomous Body Area Network System

NASA Astrophysics Data System (ADS)

Hussin, S.; Takayama, S.

2016-11-01

Enhancing Quality of Life (QOL) has long been an explicit and implicit goal for individuals, nations, and the world. QOL involves diverse multidimensional factors spanning wealth, physical health, social well-being, and international relationships. This study presents a definition of QOL combining the measurement of health-related QOL with an autonomous Body Area Network System (BANs). A method of evaluating vital signs is performed and linked to physical intensity assistance in exercise. Specifically, BAN acts as a supportive system which can assist a user in monitoring his or her body's parameters, providing real-time feedbacks and dynamically sharing information from any location to one or more users.

Longitudinal Control for Mengshi Autonomous Vehicle via Cloud Model

NASA Astrophysics Data System (ADS)

Gao, H. B.; Zhang, X. Y.; Li, D. Y.; Liu, Y. C.

2018-03-01

Dynamic robustness and stability control is a requirement for self-driving of autonomous vehicle. Longitudinal control method of autonomous is a key technique which has drawn the attention of industry and academe. In this paper, we present a longitudinal control algorithm based on cloud model for Mengshi autonomous vehicle to ensure the dynamic stability and tracking performance of Mengshi autonomous vehicle. An experiments is applied to test the implementation of the longitudinal control algorithm. Empirical results show that if the longitudinal control algorithm based Gauss cloud model are applied to calculate the acceleration, and the vehicles drive at different speeds, a stable longitudinal control effect is achieved.

Oncogenic Kit signals on endolysosomes and endoplasmic reticulum are essential for neoplastic mast cell proliferation

PubMed Central

Obata, Yuuki; Toyoshima, Shota; Wakamatsu, Ei; Suzuki, Shunichi; Ogawa, Shuhei; Esumi, Hiroyasu; Abe, Ryo

2014-01-01

Kit is a receptor-type tyrosine kinase found on the plasma membrane. It can transform mast cells through activating mutations. Here, we show that a mutant Kit from neoplastic mast cells from mice, Kit(D814Y), is permanently active and allows cells to proliferate autonomously. It does so by activating two signalling pathways from different intracellular compartments. Mutant Kit from the cell surface accumulates on endolysosomes through clathrin-mediated endocytosis, which requires Kit’s kinase activity. Kit(D814Y) is constitutively associated with phosphatidylinositol 3-kinase, but the complex activates Akt only on the cytoplasmic surface of endolysosomes. It resists destruction because it is under-ubiquitinated. Kit(D814Y) also appears in the endoplasmic reticulum soon after biosynthesis, and there, can activate STAT5 aberrantly. These mechanisms of oncogenic signalling are also seen in rat and human mast cell leukemia cells. Thus, oncogenic Kit signalling occurs from different intracellular compartments, and the mutation acts by altering Kit trafficking as well as activation. PMID:25493654

Integrated System for Autonomous Science

NASA Technical Reports Server (NTRS)

Chien, Steve; Sherwood, Robert; Tran, Daniel; Cichy, Benjamin; Davies, Ashley; Castano, Rebecca; Rabideau, Gregg; Frye, Stuart; Trout, Bruce; Shulman, Seth;

Cooperative Control of Distributed Autonomous Vehicles in Adversarial Environments

DTIC Science & Technology

2006-08-14

COOPERATIVE CONTROL OF DISTRIBUTED AUTONOMOUS VEHICLES IN ADVERSARIAL ENVIRONMENTS Grant #F49620–01–1–0361 Final Report Jeff Shamma Department of...CONTRACT NUMBER F49620-01-1-0361 5b. GRANT NUMBER 4. TITLE AND SUBTITLE COOPERATIVE CONTROL OF DISTRIBUTED AUTONOMOUS VEHICLES IN...single dominant language or a distribution of languages. A relation to multivehicle systems is understanding how highly autonomous vehicles on extended

Communication and Control for Fleets of Autonomous Underwater Vehicles

DTIC Science & Technology

2006-10-30

Washington State University (WSU) on fuzzy logic control systems [2-4] and autonomous vehicles [5-10]. The ALWSE-MC program developed at NAVSEA CSS was...rotating head sonar on crawlers as an additional sensor for navigation. We have previously investigated the use of video cameras on autonomous vehicles for...simulates autonomous vehicles performing mine reconnaissance/mapping, clearance, and surveillance in a littoral region. Three simulations were preformed

Small heat shock proteins mediate cell-autonomous and -nonautonomous protection in a Drosophila model for environmental-stress-induced degeneration.

PubMed

Kawasaki, Fumiko; Koonce, Noelle L; Guo, Linda; Fatima, Shahroz; Qiu, Catherine; Moon, Mackenzie T; Zheng, Yunzhen; Ordway, Richard W

2016-09-01

Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration. In wild-type flies, HS stress causes selective loss of the flight ability and degeneration of three susceptible cell types comprising the flight motor: muscle, motor neurons and associated glia. Other motor behaviors persist and, accordingly, the corresponding cell types controlling leg motor function are resistant to degeneration. Flight motor degeneration was preceded by a failure of muscle proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover, muscle-specific overexpression of a small heat shock protein (HSP), HSP23, promoted proteostasis and protected muscle from HS stress. Notably, neurons and glia were protected as well, indicating that a small HSP can mediate cell-nonautonomous protection. Cell-autonomous protection of muscle was characterized by a distinct distribution of ubiquitinated proteins, including perinuclear localization and clearance of protein aggregates associated with the perinuclear microtubule network. This network was severely disrupted in wild-type preparations prior to degeneration, suggesting that it serves an important role in muscle proteostasis and protection. Finally, studies of resistant leg muscles revealed that they sustain proteostasis and the microtubule

New Small Autonomous Schools District Policy. Revised.

ERIC Educational Resources Information Center

Oakland Unified School District, CA.

Inspired by the gains in student achievement realized by the small schools movement in New York City, the Oakland Unified School District (California) has proposed creating a network of 10 new, small autonomous (NSA) schools over the next 3 years. School size will range between 250 and 500 students, depending on grade level. "Autonomous"…

Improving Human/Autonomous System Teaming Through Linguistic Analysis

NASA Technical Reports Server (NTRS)

Meszaros, Erica L.

2016-01-01

An area of increasing interest for the next generation of aircraft is autonomy and the integration of increasingly autonomous systems into the national airspace. Such integration requires humans to work closely with autonomous systems, forming human and autonomous agent teams. The intention behind such teaming is that a team composed of both humans and autonomous agents will operate better than homogenous teams. Procedures exist for licensing pilots to operate in the national airspace system and current work is being done to define methods for validating the function of autonomous systems, however there is no method in place for assessing the interaction of these two disparate systems. Moreover, currently these systems are operated primarily by subject matter experts, limiting their use and the benefits of such teams. Providing additional information about the ongoing mission to the operator can lead to increased usability and allow for operation by non-experts. Linguistic analysis of the context of verbal communication provides insight into the intended meaning of commonly heard phrases such as "What's it doing now?" Analyzing the semantic sphere surrounding these common phrases enables the prediction of the operator's intent and allows the interface to supply the operator's desired information.

Are Autonomous and Controlled Motivations School-Subjects-Specific?

PubMed

Chanal, Julien; Guay, Frédéric

2015-01-01

This research sought to test whether autonomous and controlled motivations are specific to school subjects or more general to the school context. In two cross-sectional studies, 252 elementary school children (43.7% male; mean age = 10.7 years, SD = 1.3 years) and 334 junior high school children (49.7% male, mean age = 14.07 years, SD = 1.01 years) were administered a questionnaire assessing their motivation for various school subjects. Results based on structural equation modeling using the correlated trait-correlated method minus one model (CTCM-1) showed that autonomous and controlled motivations assessed at the school subject level are not equally school-subject-specific. We found larger specificity effects for autonomous (intrinsic and identified) than for controlled (introjected and external) motivation. In both studies, results of factor loadings and the correlations with self-concept and achievement demonstrated that more evidence of specificity was obtained for autonomous regulations than for controlled ones. These findings suggest a new understanding of the hierarchical and multidimensional academic structure of autonomous and controlled motivations and of the mechanisms involved in the development of types of regulations for school subjects.

Are Autonomous and Controlled Motivations School-Subjects-Specific?

PubMed Central

Chanal, Julien; Guay, Frédéric

2015-01-01

This research sought to test whether autonomous and controlled motivations are specific to school subjects or more general to the school context. In two cross-sectional studies, 252 elementary school children (43.7% male; mean age = 10.7 years, SD = 1.3 years) and 334 junior high school children (49.7% male, mean age = 14.07 years, SD = 1.01 years) were administered a questionnaire assessing their motivation for various school subjects. Results based on structural equation modeling using the correlated trait-correlated method minus one model (CTCM-1) showed that autonomous and controlled motivations assessed at the school subject level are not equally school-subject-specific. We found larger specificity effects for autonomous (intrinsic and identified) than for controlled (introjected and external) motivation. In both studies, results of factor loadings and the correlations with self-concept and achievement demonstrated that more evidence of specificity was obtained for autonomous regulations than for controlled ones. These findings suggest a new understanding of the hierarchical and multidimensional academic structure of autonomous and controlled motivations and of the mechanisms involved in the development of types of regulations for school subjects. PMID:26247788

Comparative anatomy of the autonomic nervous system.

PubMed

Nilsson, Stefan

2011-11-16

This short review aims to point out the general anatomical features of the autonomic nervous systems of non-mammalian vertebrates. In addition it attempts to outline the similarities and also the increased complexity of the autonomic nervous patterns from fish to tetrapods. With the possible exception of the cyclostomes, perhaps the most striking feature of the vertebrate autonomic nervous system is the similarity between the vertebrate classes. An evolution of the complexity of the system can be seen, with the segmental ganglia of elasmobranchs incompletely connected longitudinally, while well developed paired sympathetic chains are present in teleosts and the tetrapods. In some groups the sympathetic chains may be reduced (dipnoans and caecilians), and have yet to be properly described in snakes. Cranial autonomic pathways are present in the oculomotor (III) and vagus (X) nerves of gnathostome fish and the tetrapods, and with the evolution of salivary and lachrymal glands in the tetrapods, also in the facial (VII) and glossopharyngeal (IX) nerves. Copyright © 2010 Elsevier B.V. All rights reserved.

Autonomous Soaring: The Montague Cross Country Challenge

NASA Astrophysics Data System (ADS)

Edwards, Daniel J.

A novel method was developed for locating and allowing gliders to stay in thermals (convective updrafts). The method was applied to a 5 kg, glider, called ALOFT (autonomous locator of thermals), that was entered in the 2008 Montague Cross-Country Challenge held on 13-15 June 2008 in Montague, California. In this competition, RC (remote controlled) gliders in the 5 kg class competed on the basis of speed and distance. ALOFT was the first known autonomously soaring aircraft to enter a soaring competition and its entry provided a valuable comparison between the effectiveness of manual soaring and autonomous soaring. ALOFT placed third in the competition in overall points, outperforming manually-flown aircraft in its ability to center and utilize updrafts, especially at higher altitudes and in the presence of wind, to fly more optimal airspeeds, and to fly directly between turn points. The results confirm that autonomous soaring is a bona fide engineering sub-discipline, which is expected to be of interest to engineers who might find this has some utility in the aviation industry.

Memory and modularity in cell-fate decision making

NASA Astrophysics Data System (ADS)

Norman, Thomas M.; Lord, Nathan D.; Paulsson, Johan; Losick, Richard

2013-11-01

Genetically identical cells sharing an environment can display markedly different phenotypes. It is often unclear how much of this variation derives from chance, external signals, or attempts by individual cells to exert autonomous phenotypic programs. By observing thousands of cells for hundreds of consecutive generations under constant conditions, we dissect the stochastic decision between a solitary, motile state and a chained, sessile state in Bacillus subtilis. We show that the motile state is `memoryless', exhibiting no autonomous control over the time spent in the state. In contrast, the time spent as connected chains of cells is tightly controlled, enforcing coordination among related cells in the multicellular state. We show that the three-protein regulatory circuit governing the decision is modular, as initiation and maintenance of chaining are genetically separable functions. As stimulation of the same initiating pathway triggers biofilm formation, we argue that autonomous timing allows a trial commitment to multicellularity that external signals could extend.

Development Of Autonomous Systems

NASA Astrophysics Data System (ADS)

Kanade, Takeo

1989-03-01

In the last several years at the Robotics Institute of Carnegie Mellon University, we have been working on two projects for developing autonomous systems: Nablab for Autonomous Land Vehicle and Ambler for Mars Rover. These two systems are for different purposes: the Navlab is a four-wheeled vehicle (van) for road and open terrain navigation, and the Ambler is a six-legged locomotor for Mars exploration. The two projects, however, share many common aspects. Both are large-scale integrated systems for navigation. In addition to the development of individual components (eg., construction and control of the vehicle, vision and perception, and planning), integration of those component technologies into a system by means of an appropriate architecture is a major issue.

Conference proceedings of the Northeast Autonomous Vehicle Summit.

DOT National Transportation Integrated Search

2017-05-24

The development of autonomous vehicle technology and potential adoption of autonomous vehicles is occurring at a rapid rate in the United States. As this technology evolves, there are many technical, logistical and legal issues that need to be addres...

Autonomous Rovers for Polar Science Campaigns

NASA Astrophysics Data System (ADS)

Lever, J. H.; Ray, L. E.; Williams, R. M.; Morlock, A. M.; Burzynski, A. M.

2012-12-01

We have developed and deployed two over-snow autonomous rovers able to conduct remote science campaigns on Polar ice sheets. Yeti is an 80-kg, four-wheel-drive (4WD) battery-powered robot with 3 - 4 hr endurance, and Cool Robot is a 60-kg 4WD solar-powered robot with unlimited endurance during Polar summers. Both robots navigate using GPS waypoint-following to execute pre-planned courses autonomously, and they can each carry or tow 20 - 160 kg instrument payloads over typically firm Polar snowfields. In 2008 - 12, we deployed Yeti to conduct autonomous ground-penetrating radar (GPR) surveys to detect hidden crevasses to help establish safe routes for overland resupply of research stations at South Pole, Antarctica, and Summit, Greenland. We also deployed Yeti with GPR at South Pole in 2011 to identify the locations of potentially hazardous buried buildings from the original 1950's-era station. Autonomous surveys remove personnel from safety risks posed during manual GPR surveys by undetected crevasses or buried buildings. Furthermore, autonomous surveys can yield higher quality and more comprehensive data than manual ones: Yeti's low ground pressure (20 kPa) allows it to cross thinly bridged crevasses or other voids without interrupting a survey, and well-defined survey grids allow repeated detection of buried voids to improve detection reliability and map their extent. To improve survey efficiency, we have automated the mapping of detected hazards, currently identified via post-survey manual review of the GPR data. Additionally, we are developing machine-learning algorithms to detect crevasses autonomously in real time, with reliability potentially higher than manual real-time detection. These algorithms will enable the rover to relay crevasse locations to a base station for near real-time mapping and decision-making. We deployed Cool Robot at Summit Station in 2005 to verify its mobility and power budget over Polar snowfields. Using solar power, this zero

Dynamics control of autonomous vehicle at driving limits and experiment on an autonomous formula racing car

NASA Astrophysics Data System (ADS)

Ni, Jun; Hu, Jibin

2017-06-01

In this paper, a novel dynamics controller for autonomous vehicle to simultaneously control it to the driving limits and follow the desired path is proposed. The dynamics controller consists of longitudinal and lateral controllers. In longitudinal controller, the G-G diagram is utilized to describe the driving and handling limits of the vehicle. The accurate G-G diagram is obtained based on phase plane approach and a nonlinear vehicle dynamic model with accurate tyre model. In lateral controller, the tyre cornering stiffness is estimated to improve the robustness of the controller. The stability analysis of the closed-looped error dynamics shows that the controller remains stable against parameters uncertainties in extreme condition such as tyre saturation. Finally, an electric autonomous Formula race car developed by the authors is used to validate the proposed controller. The autonomous driving experiment on an oval race track shows the efficiency and robustness of the proposed controller.

Autonomously Self-Adhesive Hydrogels as Building Blocks for Additive Manufacturing.

PubMed

Deng, Xudong; Attalla, Rana; Sadowski, Lukas P; Chen, Mengsu; Majcher, Michael J; Urosev, Ivan; Yin, Da-Chuan; Selvaganapathy, P Ravi; Filipe, Carlos D M; Hoare, Todd

2018-01-08

We report a simple method of preparing autonomous and rapid self-adhesive hydrogels and their use as building blocks for additive manufacturing of functional tissue scaffolds. Dynamic cross-linking between 2-aminophenylboronic acid-functionalized hyaluronic acid and poly(vinyl alcohol) yields hydrogels that recover their mechanical integrity within 1 min after cutting or shear under both neutral and acidic pH conditions. Incorporation of this hydrogel in an interpenetrating calcium-alginate network results in an interfacially stiffer but still rapidly self-adhesive hydrogel that can be assembled into hollow perfusion channels by simple contact additive manufacturing within minutes. Such channels withstand fluid perfusion while retaining their dimensions and support endothelial cell growth and proliferation, providing a simple and modular route to produce customized cell scaffolds.

NANOS2 acts downstream of glial cell line-derived neurotrophic factor signaling to suppress differentiation of spermatogonial stem cells.

PubMed

Sada, Aiko; Hasegawa, Kazuteru; Pin, Pui Han; Saga, Yumiko

2012-02-01

Stem cells are maintained by both stem cell-extrinsic niche signals and stem cell-intrinsic factors. During murine spermatogenesis, glial cell line-derived neurotrophic factor (GDNF) signal emanated from Sertoli cells and germ cell-intrinsic factor NANOS2 represent key regulators for the maintenance of spermatogonial stem cells. However, it remains unclear how these factors intersect in stem cells to control their cellular state. Here, we show that GDNF signaling is essential to maintain NANOS2 expression, and overexpression of Nanos2 can alleviate the stem cell loss phenotype caused by the depletion of Gfra1, a receptor for GDNF. By using an inducible Cre-loxP system, we show that NANOS2 expression is downregulated upon the conditional knockout (cKO) of Gfra1, while ectopic expression of Nanos2 in GFRA1-negative spermatogonia does not induce de novo GFRA1 expression. Furthermore, overexpression of Nanos2 in the Gfra1-cKO testes prevents precocious differentiation of the Gfra1-knockout stem cells and partially rescues the stem cell loss phenotypes of Gfra1-deficient mice, indicating that the stem cell differentiation can be suppressed by NANOS2 even in the absence of GDNF signaling. Taken together, we suggest that NANOS2 acts downstream of GDNF signaling to maintain undifferentiated state of spermatogonial stem cells. Copyright © 2011 AlphaMed Press.

Control of autonomous ground vehicles: a brief technical review

NASA Astrophysics Data System (ADS)

Babak, Shahian-Jahromi; Hussain, Syed A.; Karakas, Burak; Cetin, Sabri

2017-07-01

This paper presents a brief review of the developments achieved in autonomous vehicle systems technology. A concise history of autonomous driver assistance systems is presented, followed by a review of current state of the art sensor technology used in autonomous vehicles. Standard sensor fusion method that has been recently explored is discussed. Finally, advances in embedded software methodologies that define the logic between sensory information and actuation decisions are reviewed.

Progress towards autonomous, intelligent systems

NASA Technical Reports Server (NTRS)

Lum, Henry; Heer, Ewald

1987-01-01

An aggressive program has been initiated to develop, integrate, and implement autonomous systems technologies starting with today's expert systems and evolving to autonomous, intelligent systems by the end of the 1990s. This program includes core technology developments and demonstration projects for technology evaluation and validation. This paper discusses key operational frameworks in the content of systems autonomy applications and then identifies major technological challenges, primarily in artificial intelligence areas. Program content and progress made towards critical technologies and demonstrations that have been initiated to achieve the required future capabilities in the year 2000 era are discussed.

Gas House Autonomous System Monitoring

NASA Technical Reports Server (NTRS)

Miller, Luke; Edsall, Ashley

2015-01-01

Gas House Autonomous System Monitoring (GHASM) will employ Integrated System Health Monitoring (ISHM) of cryogenic fluids in the High Pressure Gas Facility at Stennis Space Center. The preliminary focus of development incorporates the passive monitoring and eventual commanding of the Nitrogen System. ISHM offers generic system awareness, adept at using concepts rather than specific error cases. As an enabler for autonomy, ISHM provides capabilities inclusive of anomaly detection, diagnosis, and abnormality prediction. Advancing ISHM and Autonomous Operation functional capabilities enhances quality of data, optimizes safety, improves cost effectiveness, and has direct benefits to a wide spectrum of aerospace applications.

Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease

PubMed Central

Khaleel, Maha; Sunwoo, John; Shah, Payal; Detterich, Jon A.; Kato, Roberta M.; Thuptimdang, Wanwara; Meiselman, Herbert J.; Sposto, Richard; Tsao, Jennie; Wood, John C.; Zeltzer, Lonnie; Coates, Thomas D.; Khoo, Michael C. K.

2017-01-01

Painful vaso-occlusive crisis (VOC), a complication of sickle cell disease (SCD), occurs when sickled red blood cells obstruct flow in the microvasculature. We postulated that exaggerated sympathetically mediated vasoconstriction, endothelial dysfunction and the synergistic interaction between these two factors act together to reduce microvascular flow, promoting regional vaso-occlusions, setting the stage for VOC. We previously found that SCD subjects had stronger vasoconstriction response to pulses of heat-induced pain compared to controls but the relative degrees to which autonomic dysregulation, peripheral vascular dysfunction and their interaction are present in SCD remain unknown. In the present study, we employed a mathematical model to decompose the total vasoconstriction response to pain into: 1) the neurogenic component, 2) the vascular response to blood pressure, 3) respiratory coupling and 4) neurogenic-vascular interaction. The model allowed us to quantify the contribution of each component to the total vasoconstriction response. The most salient features of the components were extracted to represent biophysical markers of autonomic and vascular impairment in SCD and controls. These markers provide a means of phenotyping severity of disease in sickle-cell anemia that is based more on underlying physiology than on genotype. The marker of the vascular component (BMv) showed stronger contribution to vasoconstriction in SCD than controls (p = 0.0409), suggesting a dominant myogenic response in the SCD subjects as a consequence of endothelial dysfunction. The marker of neurogenic-vascular interaction (BMn-v) revealed that the interaction reinforced vasoconstriction in SCD but produced vasodilatory response in controls (p = 0.0167). This marked difference in BMn-v suggests that it is the most sensitive marker for quantifying combined alterations in autonomic and vascular function in SCD in response to heat-induced pain. PMID:28542469

Alleviating Autonomic Dysreflexia after Spinal Cord Injury

DTIC Science & Technology

2017-12-01

autonomic disorders greatly influence the functional, psychological , and socioeconomic aspects of patients’ lives. Compared to numer- ous...The disruption of descending autonomic pathways renders abnormalities in multiple organ systems including cardiovascular function, respiration...the rise in blood pressure, the integration center in the brainstem transmits signals to the heart via parasympathetic pathways to reduce the heart

Safe and Autonomous Drones for Urban Flight

NASA Technical Reports Server (NTRS)

Krishnakumar, Kalmanje

2016-01-01

Autonomous vehicles are no longer futuristic technology; in fact, there are already cars with self-driving features on the road. Over the next five years, the connected vehicles will disrupt the entire automotive and UAS ecosystems. The industry will undergo fundamental change as semi-autonomous driving and flying emerges, followed by an eventual shift to full autonomy.

Evaluating the autonomic nervous system in patients with laryngopharyngeal reflux.

PubMed

Huang, Wan-Ju; Shu, Chih-Hung; Chou, Kun-Ta; Wang, Yi-Fen; Hsu, Yen-Bin; Ho, Ching-Yin; Lan, Ming-Ying

2013-06-01

The pathogenesis of laryngopharyngeal reflux (LPR) remains unclear. It is linked to but distinct from gastroesophageal reflux disease (GERD), which has been shown to be related to disturbed autonomic regulation. The aim of this study is to investigate whether autonomic dysfunction also plays a role in the pathogenesis of LPR. Case-control study. Tertiary care center. Seventeen patients with LPR and 19 healthy controls, aged between 19 and 50 years, were enrolled in the study. The patients were diagnosed with LPR if they had a reflux symptom index (RSI) ≥ 13 and a reflux finding score (RFS) ≥ 7. Spectral analysis of heart rate variability (HRV) analysis was used to assess autonomic function. Anxiety and depression levels measured by the Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II) were also conducted. In HRV analysis, high frequency (HF) represents the parasympathetic activity of the autonomic nervous system, whereas low frequency (LF) represents the total autonomic activity. There were no significant differences in the LF power and HF power between the 2 groups. However, significantly lower HF% (P = .003) and a higher LF/HF ratio (P = .012) were found in patients with LPR, who demonstrated poor autonomic modulation and higher sympathetic activity. Anxiety was also frequently observed in the patient group. The study suggests that autonomic dysfunction seems to be involved in the pathogenesis of LPR. The potential beneficial effect of autonomic nervous system modulation as a therapeutic modality for LPR merits further investigation.

A photovoltaic-driven and energy-autonomous CMOS implantable sensor.

PubMed

Ayazian, Sahar; Akhavan, Vahid A; Soenen, Eric; Hassibi, Arjang

2012-08-01

An energy-autonomous, photovoltaic (PV)-driven and MRI-compatible CMOS implantable sensor is presented. On-chip P+/N-well diode arrays are used as CMOS-compatible PV cells to harvest μW's of power from the light that penetrates into the tissue. In this 2.5 mm × 2.5 mm sub-μW integrated system, the in-vivo physiological signals are first measured by using a subthreshold ring oscillator-based sensor, the acquired data is then modulated into a frequency-shift keying (FSK) signal, and finally transmitted neuromorphically to the skin surface by using a pair of polarized electrodes.

Autonomous Vehicles: Disengagements, Accidents and Reaction Times.

PubMed

Dixit, Vinayak V; Chand, Sai; Nair, Divya J

2016-01-01

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems.

Autonomous Vehicles: Disengagements, Accidents and Reaction Times

PubMed Central

Dixit, Vinayak V.; Chand, Sai; Nair, Divya J.

2016-01-01

Autonomous vehicles are being viewed with scepticism in their ability to improve safety and the driving experience. A critical issue with automated driving at this stage of its development is that it is not yet reliable and safe. When automated driving fails, or is limited, the autonomous mode disengages and the drivers are expected to resume manual driving. For this transition to occur safely, it is imperative that drivers react in an appropriate and timely manner. Recent data released from the California trials provide compelling insights into the current factors influencing disengagements of autonomous mode. Here we show that the number of accidents observed has a significantly high correlation with the autonomous miles travelled. The reaction times to take control of the vehicle in the event of a disengagement was found to have a stable distribution across different companies at 0.83 seconds on average. However, there were differences observed in reaction times based on the type of disengagements, type of roadway and autonomous miles travelled. Lack of trust caused by the exposure to automated disengagements was found to increase the likelihood to take control of the vehicle manually. Further, with increased vehicle miles travelled the reaction times were found to increase, which suggests an increased level of trust with more vehicle miles travelled. We believe that this research would provide insurers, planners, traffic management officials and engineers fundamental insights into trust and reaction times that would help them design and engineer their systems. PMID:27997566

Autonomous Deep-Space Optical Navigation Project

NASA Technical Reports Server (NTRS)

D'Souza, Christopher

2014-01-01

This project will advance the Autonomous Deep-space navigation capability applied to Autonomous Rendezvous and Docking (AR&D) Guidance, Navigation and Control (GNC) system by testing it on hardware, particularly in a flight processor, with a goal of limited testing in the Integrated Power, Avionics and Software (IPAS) with the ARCM (Asteroid Retrieval Crewed Mission) DRO (Distant Retrograde Orbit) Autonomous Rendezvous and Docking (AR&D) scenario. The technology, which will be harnessed, is called 'optical flow', also known as 'visual odometry'. It is being matured in the automotive and SLAM (Simultaneous Localization and Mapping) applications but has yet to be applied to spacecraft navigation. In light of the tremendous potential of this technique, we believe that NASA needs to design a optical navigation architecture that will use this technique. It is flexible enough to be applicable to navigating around planetary bodies, such as asteroids.

Passive and Self-Powered Autonomous Sensors for Remote Measurements

PubMed Central

Sardini, Emilio; Serpelloni, Mauro

2009-01-01

Autonomous sensors play a very important role in the environmental, structural, and medical fields. The use of this kind of systems can be expanded for several applications, for example in implantable devices inside the human body where it is impossible to use wires. Furthermore, they enable measurements in harsh or hermetic environments, such as under extreme heat, cold, humidity or corrosive conditions. The use of batteries as a power supply for these devices represents one solution, but the size, and sometimes the cost and unwanted maintenance burdens of replacement are important drawbacks. In this paper passive and self-powered autonomous sensors for harsh or hermetical environments without batteries are discussed. Their general architectures are presented. Sensing strategies, communication techniques and power management are analyzed. Then, general building blocks of an autonomous sensor are presented and the design guidelines that such a system must follow are given. Furthermore, this paper reports different proposed applications of autonomous sensors applied in harsh or hermetic environments: two examples of passive autonomous sensors that use telemetric communication are proposed, the first one for humidity measurements and the second for high temperatures. Other examples of self-powered autonomous sensors that use a power harvesting system from electromagnetic fields are proposed for temperature measurements and for airflow speeds. PMID:22399949

[Signs and symptoms of autonomic dysfunction in dysphonic individuals].

PubMed

Park, Kelly; Behlau, Mara

2011-01-01

To verify the occurrence of signs and symptoms of autonomic nervous system dysfunction in individuals with behavioral dysphonia, and to compare it with the results obtained by individuals without vocal complaints. Participants were 128 adult individuals with ages between 14 and 74 years, divided into two groups: behavioral dysphonia (61 subjects) and without vocal complaints (67 subjects). It was administered the Protocol of Autonomic Dysfunction, containing 46 questions: 22 related to the autonomic nervous system and had no direct relationship with voice, 16 related to both autonomic nervous system and voice, six non-relevant questions, and two reliability questions. There was a higher occurrence of reported neurovegetative signs in the group with behavioral dysphonia, in questions related to voice, such as frequent throat clearing, frequent swallowing need, fatigability when speaking, and sore throat. In questions not directly related to voice, dysphonic individuals presented greater occurrence of three out of 22 symptoms: gas, tinnitus and aerophagia. Both groups presented similar results in questions non-relevant to the autonomic nervous system. Reliability questions needed reformulation. Individuals with behavioral dysphonia present higher occurrence of neurovegetative signs and symptoms, particularly those with direct relationship with voice, indicating greater lability of the autonomic nervous system in these subjects.

Passive and self-powered autonomous sensors for remote measurements.

PubMed

Sardini, Emilio; Serpelloni, Mauro

2009-01-01

Autonomous sensors play a very important role in the environmental, structural, and medical fields. The use of this kind of systems can be expanded for several applications, for example in implantable devices inside the human body where it is impossible to use wires. Furthermore, they enable measurements in harsh or hermetic environments, such as under extreme heat, cold, humidity or corrosive conditions. The use of batteries as a power supply for these devices represents one solution, but the size, and sometimes the cost and unwanted maintenance burdens of replacement are important drawbacks. In this paper passive and self-powered autonomous sensors for harsh or hermetical environments without batteries are discussed. Their general architectures are presented. Sensing strategies, communication techniques and power management are analyzed. Then, general building blocks of an autonomous sensor are presented and the design guidelines that such a system must follow are given. Furthermore, this paper reports different proposed applications of autonomous sensors applied in harsh or hermetic environments: two examples of passive autonomous sensors that use telemetric communication are proposed, the first one for humidity measurements and the second for high temperatures. Other examples of self-powered autonomous sensors that use a power harvesting system from electromagnetic fields are proposed for temperature measurements and for airflow speeds.

Abnormal cardiac autonomic regulation in mice lacking ASIC3.

PubMed

Cheng, Ching-Feng; Kuo, Terry B J; Chen, Wei-Nan; Lin, Chao-Chieh; Chen, Chih-Cheng

2014-01-01

Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3) is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3(-/-) mice. Asic3(-/-) mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3(-/-) mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3(-/-) mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

Sexually dimorphic differentiation of a C. elegans hub neuron is cell-autonomously controlled by a conserved transcription factor

PubMed Central

Serrano-Saiz, Esther; Oren-Suissa, Meital; Bayer, Emily A.; Hobert, Oliver

2018-01-01

SUMMARY Functional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex, or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neurons of the nematode C. elegans differentiate in a strikingly sex-specific manner. While in hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, PHC differentiates into a densely connected hub sensory/interneuron in males, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry. We show that the differentiation into such a hub neuron involves the sex-specific scaling of several components of the synaptic vesicle machinery, including the vesicular glutamate transporter eat-4/VGLUT, induction of neuropeptide expression, changes in axonal projection morphology and a switch in neuronal function. We demonstrate that these molecular and anatomical remodeling events are controlled cell-autonomously by the phylogenetically conserved Doublesex homolog dmd-3, which is both required and sufficient for sex-specific PHC differentiation. Cellular specificity of dmd-3 action is ensured by its collaboration with non-sex specific terminal selector-type transcription factors whereas sex-specificity of dmd-3 action is ensured by the hermaphrodite-specific, transcriptional master regulator of hermaphroditic cell identity, tra-1, which represses transcription of dmd-3 in hermaphrodite PHC. Taken together, our studies provide mechanistic insights into how neurons are specified in a sexually dimorphic manner. PMID:28065609

Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1

PubMed Central

Cvetanovic, Marija; Hu, Yuan-Shih; Opal, Puneet

2017-01-01

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by the expansion of a polyglutamine (Q) repeat tract in the protein ataxin-1 (ATXN1). Beginning as a cerebellar ataxic disorder, SCA1 progresses to involve the cerebral cortex, hippocampus, and brainstem. Using SCA1 knock-in mice that mirror the complexity of the human disease, we report a significant decrease in the capacity of adult neuronal progenitor cells (NPCs) to proliferate. Remarkably, a decrease in NPCs proliferation can be observed in vitro, outside the degenerative milieu of surrounding neurons or glia, demonstrating that mutant ATXN1 acting cell autonomously within progenitor cells interferes with their ability to proliferate. Our findings suggest that compromised adult neurogenesis contributes to the progressive pathology of the disease particularly in areas such as the hippocampus and cerebral cortex where stem cells provide neurotropic factors and participate in adult neurogenesis. These findings not only shed light on the biology of the disease but also have therapeutic implications in any future stem cell- based clinical trials. PMID:27306906

Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1.

PubMed

Cvetanovic, Marija; Hu, Yuan-Shih; Opal, Puneet

2017-04-01

Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by the expansion of a polyglutamine (Q) repeat tract in the protein ataxin-1 (ATXN1). Beginning as a cerebellar ataxic disorder, SCA1 progresses to involve the cerebral cortex, hippocampus, and brainstem. Using SCA1 knock-in mice that mirror the complexity of the human disease, we report a significant decrease in the capacity of adult neuronal progenitor cells (NPCs) to proliferate. Remarkably, a decrease in NPCs proliferation can be observed in vitro, outside the degenerative milieu of surrounding neurons or glia, demonstrating that mutant ATXN1 acting cell autonomously within progenitor cells interferes with their ability to proliferate. Our findings suggest that compromised adult neurogenesis contributes to the progressive pathology of the disease particularly in areas such as the hippocampus and cerebral cortex where stem cells provide neurotropic factors and participate in adult neurogenesis. These findings not only shed light on the biology of the disease but also have therapeutic implications in any future stem cell-based clinical trials.

Formal Methods for Autonomic and Swarm-based Systems

NASA Technical Reports Server (NTRS)

Rouff, Christopher; Vanderbilt, Amy; Hinchey, Mike; Truszkowski, Walt; Rash, James

2004-01-01

Swarms of intelligent rovers and spacecraft are being considered for a number of future NASA missions. These missions will provide MSA scientist and explorers greater flexibility and the chance to gather more science than traditional single spacecraft missions. These swarms of spacecraft are intended to operate for large periods of time without contact with the Earth. To do this, they must be highly autonomous, have autonomic properties and utilize sophisticated artificial intelligence. The Autonomous Nano Technology Swarm (ANTS) mission is an example of one of the swarm type of missions NASA is considering. This mission will explore the asteroid belt using an insect colony analogy cataloging the mass, density, morphology, and chemical composition of the asteroids, including any anomalous concentrations of specific minerals. Verifying such a system would be a huge task. This paper discusses ongoing work to develop a formal method for verifying swarm and autonomic systems.

The Prevalence and Severity of Autonomic Dysfunction in Chronic Inflammatory Demyelinating Polyneuropathy

PubMed Central

Pasangulapati, Suresh Babu; Murthy, T. V.; Sivadasan, Ajith; Gideon, L. Rynjah; Prabhakar, A. T.; Sanjith, Aaron; Mathew, Vivek; Alexander, Mathew

2017-01-01

Introduction: In chronic inflammatory demyelinating polyneuropathy (CIDP), emphasis has been on motor disabilities, and autonomic dysfunction in these patients has not been addressed systematically. Materials and Methods: Autonomic function was prospectively analyzed in 38 patients with CIDP. Quantitative autonomic function testing was done using Finometer® PRO and severity of adrenergic and cardiovagal dysfunction graded according to composite autonomic severity score and sudomotor dysfunction assessed using sympathetic skin response. Results: Thirty-four (89%) patients had features of autonomic dysfunction. Thirty-three (86%) patients had cardiovagal dysfunction, 21 (55%) had adrenergic dysfunction, and 24 (63%) had sudomotor dysfunction. Autonomic dysfunction was mild to moderate in the majority (86%). Conclusions: Autonomic dysfunction in CIDP is underreported and potentially amenable to therapy. Our cohort had a high proportion of adrenergic dysfunction compared to previous studies. PMID:28904461

Role of the autonomic nervous system in tumorigenesis and metastasis

PubMed Central

Magnon, Claire

2015-01-01

Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis. PMID:27308436

Role of the autonomic nervous system in tumorigenesis and metastasis.

PubMed

Magnon, Claire

2015-01-01

Convergence of multiple stromal cell types is required to develop a tumorigenic niche that nurtures the initial development of cancer and its dissemination. Although the immune and vascular systems have been shown to have strong influences on cancer, a growing body of evidence points to a role of the nervous system in promoting cancer development. This review discusses past and current research that shows the intriguing role of autonomic nerves, aided by neurotrophic growth factors and axon cues, in creating a favorable environment for the promotion of tumor formation and metastasis.

The hypertension of autonomic failure and its treatment

NASA Technical Reports Server (NTRS)

Shannon, J.; Jordan, J.; Costa, F.; Robertson, R. M.; Biaggioni, I.

1997-01-01

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.

Autonomous interplanetary constellation design

NASA Astrophysics Data System (ADS)

Chow, Cornelius Channing, II

According to NASA's integrated space technology roadmaps, space-based infrastructures are envisioned as necessary ingredients to a sustained effort in continuing space exploration. Whether it be for extra-terrestrial habitats, roving/cargo vehicles, or space tourism, autonomous space networks will provide a vital communications lifeline for both future robotic and human missions alike. Projecting that the Moon will be a bustling hub of activity within a few decades, a near-term opportunity for in-situ infrastructure development is within reach. This dissertation addresses the anticipated need for in-space infrastructure by investigating a general design methodology for autonomous interplanetary constellations; to illustrate the theory, this manuscript presents results from an application to the Earth-Moon neighborhood. The constellation design methodology is formulated as an optimization problem, involving a trajectory design step followed by a spacecraft placement sequence. Modeling the dynamics as a restricted 3-body problem, the investigated design space consists of families of periodic orbits which play host to the constellations, punctuated by arrangements of spacecraft autonomously guided by a navigation strategy called LiAISON (Linked Autonomous Interplanetary Satellite Orbit Navigation). Instead of more traditional exhaustive search methods, a numerical continuation approach is implemented to map the admissible configuration space. In particular, Keller's pseudo-arclength technique is used to follow folding/bifurcating solution manifolds, which are otherwise inaccessible with other parameter continuation schemes. A succinct characterization of the underlying structure of the local, as well as global, extrema is thus achievable with little a priori intuition of the solution space. Furthermore, the proposed design methodology offers benefits in computation speed plus the ability to handle mildly stochastic systems. An application of the constellation design

Autonomic Correlates of Speech Versus Nonspeech Tasks in Children and Adults

PubMed Central

Arnold, Hayley S.; MacPherson, Megan K.; Smith, Anne

2015-01-01

Purpose To assess autonomic arousal associated with speech and nonspeech tasks in school-age children and young adults. Method Measures of autonomic arousal (electrodermal level, electrodermal response amplitude, blood pulse volume, and heart rate) were recorded prior to, during, and after the performance of speech and nonspeech tasks by twenty 7- to 9-year-old children and twenty 18- to 22-year-old adults. Results Across age groups, autonomic arousal was higher for speech tasks compared with nonspeech tasks, based on peak electrodermal response amplitude and blood pulse volume. Children demonstrated greater relative arousal, based on heart rate and blood pulse volume, for nonspeech oral motor tasks than adults but showed similar mean arousal levels for speech tasks as adults. Children demonstrated sex differences in autonomic arousal; specifically, autonomic arousal remained high for school-age boys but not girls in a more complex open-ended narrative task that followed a simple sentence production task. Conclusions Speech tasks elicit greater autonomic arousal than nonspeech tasks, and children demonstrate greater autonomic arousal for nonspeech oral motor tasks than adults. Sex differences in autonomic arousal associated with speech tasks in school-age children are discussed relative to speech-language differences between boys and girls. PMID:24686989

Autonomous Motivation and Fruit/Vegetable Intake in Parent-Adolescent Dyads.

PubMed

Dwyer, Laura A; Bolger, Niall; Laurenceau, Jean-Philippe; Patrick, Heather; Oh, April Y; Nebeling, Linda C; Hennessy, Erin

2017-06-01

Autonomous motivation (motivation to engage in a behavior because of personal choice, interest, or value) is often associated with health behaviors. The present study contributes to research on motivation and eating behaviors by examining (1) how autonomous motivation is correlated within parent-adolescent dyads and (2) whether parent- and adolescent-reported autonomous motivation predicts the parent-adolescent correlation in fruit and vegetable (FV) intake frequency. Data were drawn from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study, a cross-sectional U.S. survey of parent-adolescent dyads led by the National Cancer Institute and fielded between April and October 2014. In 2016, data were analyzed from dyads who had responses on a six-item self-report measure of daily frequency of FV consumption and a two-item self-report measure of autonomous motivation for consuming FVs. Parents' and adolescents' reports of autonomous motivation and FV intake frequency were positively correlated. Both parents' and adolescents' autonomous motivation predicted higher levels of their own FV intake frequency and that of their dyad partner (p-values ≤0.001). These effects of autonomous motivation explained 22.6% of the parent-adolescent correlation in FV intake frequency. Actor effects (one's motivation predicting their own FV intake frequency) were stronger than partner effects (one's motivation predicting their partner's FV intake frequency). Parent-adolescent similarity in autonomous motivation for healthy eating may contribute to similarity in eating behaviors. Future research should further examine how individual-level health behavior correlates influence health behaviors within dyads. Published by Elsevier Inc.

Autonomous Motivation and Fruit/Vegetable Intake in Parent–Adolescent Dyads

PubMed Central

Dwyer, Laura A.; Bolger, Niall; Laurenceau, Jean-Philippe; Patrick, Heather; Oh, April Y.; Nebeling, Linda C.; Hennessy, Erin

2017-01-01

Introduction Autonomous motivation (motivation to engage in a behavior because of personal choice, interest, or value) is often associated with health behaviors. The present study contributes to research on motivation and eating behaviors by examining: (1) how autonomous motivation is correlated within parent–adolescent dyads; and (2) whether parent- and adolescent-reported autonomous motivation predicts the parent–adolescent correlation in fruit and vegetable (FV) intake frequency. Methods Data were drawn from the Family Life, Activity, Sun, Health, and Eating (FLASHE) Study, a cross-sectional U.S. survey of parent–adolescent dyads led by the National Cancer Institute and fielded between April and October 2014. In 2016, data were analyzed from dyads who had responses on a six-item self-report measure of daily frequency of FV consumption and a two-item self-report measure of autonomous motivation for consuming FVs. Results Parents' and adolescents' reports of autonomous motivation and FV intake frequency were positively correlated. Both parents' and adolescents' autonomous motivation predicted higher levels of their own FV intake frequency and that of their dyad partner (p-values ≤0.001). These effects of autonomous motivation explained 22.6% of the parent–adolescent correlation in FV intake frequency. Actor effects (one's motivation predicting their own FV intake frequency) were stronger than partner effects (one's motivation predicting their partner's FV intake frequency). Conclusions Parent–adolescent similarity in autonomous motivation for healthy eating may contribute to similarity in eating behaviors. Future research should further examine how individual-level health behavior correlates influence health behaviors within dyads. PMID:28526363

Systems, methods and apparatus for quiesence of autonomic safety devices with self action

NASA Technical Reports Server (NTRS)

Hinchey, Michael G. (Inventor); Sterritt, Roy (Inventor)

2011-01-01

Systems, methods and apparatus are provided through which in some embodiments an autonomic environmental safety device may be quiesced. In at least one embodiment, a method for managing an autonomic safety device, such as a smoke detector, based on functioning state and operating status of the autonomic safety device includes processing received signals from the autonomic safety device to obtain an analysis of the condition of the autonomic safety device, generating one or more stay-awake signals based on the functioning status and the operating state of the autonomic safety device, transmitting the stay-awake signal, transmitting self health/urgency data, and transmitting environment health/urgency data. A quiesce component of an autonomic safety device can render the autonomic safety device inactive for a specific amount of time or until a challenging situation has passed.

Pelvic autonomic neuromonitoring: present reality, future prospects.

PubMed

Skinner, Stanley A

2014-08-01

Currently, the means to assess the autonomic nervous system primarily depend on end organ functional measurement: intravesical pressure, skin resistance, and penile strain gauge tension, for example. None of these measures has been generally accepted in the operating room. Nevertheless, the segmental and peripheral pelvic autonomic nerve supply is placed at risk during both pelvic and lower spine surgery. In this difficult era of suboptimal post-prostatectomy outcomes, the urological literature does reveal the salutary development of safer dissection techniques about the peri-prostatic and cavernous plexus. Means of reliably specific nerve identification remain elusive. The need for actual nerve monitoring (not just identification) has only recently been proposed. Data from the animal lab reinforce an appreciation of the intimate and elegant interconnectedness of autonomic and somatic structures, particularly at the segmental level. Also, the biochemistry of erectile tissue engorgement (in both sexes) is very well understood (the electrophysiology increasingly so). Understanding these principles should permit parallel investigation and implementation of neurophysiological techniques which both identify and monitor pelvic autonomic function. The predicates for these proposed new approaches in the operating room are discussed in this review.

Cold Regions Issues for Off-Road Autonomous Vehicles

DTIC Science & Technology

2004-04-01

the operation of off-road autonomous vehicles . Low-temperature effects on lubricants, materials, and batteries can impair a robot’s ability to operate...demanding that off-road autonomous vehicles must be designed for and tested in cold regions if they are expected to operate there successfully.

Heterogeneous Teams of Autonomous Vehicles: Advanced Sensing & Control

DTIC Science & Technology

2009-03-01

Final Technical 3. DATES COVERED (From To) 7/1/05-12/31708 4. TITLE AND SUBTITLE Heterogeneous Teams of Autonomous Vehicles Advanced Sensing...assimilating data from underwater and surface autonomous vehicles in addition to the usual sources of Eulerian and Lagrangian systems into a small scale

Vector Pursuit Path Tracking for Autonomous Ground Vehicles

DTIC Science & Technology

2000-08-01

vi INTRODUCTION ...........................................................................................................1...other geometric path-tracking techniques. 1 CHAPTER 1 INTRODUCTION An autonomous vehicle is one that is capable of automatic navigation. It is...Joint Architecture for Unmanned Ground Vehicles ( JAUGS ) working group meeting held at the University of Florida. 5 Figure 1.5: Autonomous

Advanced avionics concepts: Autonomous spacecraft control

NASA Technical Reports Server (NTRS)

1990-01-01

A large increase in space operations activities is expected because of Space Station Freedom (SSF) and long range Lunar base missions and Mars exploration. Space operations will also increase as a result of space commercialization (especially the increase in satellite networks). It is anticipated that the level of satellite servicing operations will grow tenfold from the current level within the next 20 years. This growth can be sustained only if the cost effectiveness of space operations is improved. Cost effectiveness is operational efficiency with proper effectiveness. A concept is presented of advanced avionics, autonomous spacecraft control, that will enable the desired growth, as well as maintain the cost effectiveness (operational efficiency) in satellite servicing operations. The concept of advanced avionics that allows autonomous spacecraft control is described along with a brief description of each component. Some of the benefits of autonomous operations are also described. A technology utilization breakdown is provided in terms of applications.

Draper Laboratory small autonomous aerial vehicle

NASA Astrophysics Data System (ADS)

DeBitetto, Paul A.; Johnson, Eric N.; Bosse, Michael C.; Trott, Christian A.

1997-06-01

The Charles Stark Draper Laboratory, Inc. and students from Massachusetts Institute of Technology and Boston University have cooperated to develop an autonomous aerial vehicle that won the 1996 International Aerial Robotics Competition. This paper describes the approach, system architecture and subsystem designs for the entry. This entry represents a combination of many technology areas: navigation, guidance, control, vision processing, human factors, packaging, power, real-time software, and others. The aerial vehicle, an autonomous helicopter, performs navigation and control functions using multiple sensors: differential GPS, inertial measurement unit, sonar altimeter, and a flux compass. The aerial transmits video imagery to the ground. A ground based vision processor converts the image data into target position and classification estimates. The system was designed, built, and flown in less than one year and has provided many lessons about autonomous vehicle systems, several of which are discussed. In an appendix, our current research in augmenting the navigation system with vision- based estimates is presented.

A subclass of plant heat shock cognate 70 chaperones carries a motif that facilitates trafficking through plasmodesmata

PubMed Central

Aoki, Koh; Kragler, Friedrich; Xoconostle-Cázares, Beatriz; Lucas, William J.

2002-01-01

Plasmodesmata establish a pathway for the trafficking of non-cell-autonomously acting proteins and ribonucleoprotein complexes. Plasmodesmal enriched cell fractions and the contents of enucleate sieve elements, in the form of phloem sap, were used to isolate and characterize heat shock cognate 70 (Hsc70) chaperones associated with this cell-to-cell transport pathway. Three Cucurbita maxima Hsc70 chaperones were cloned and functional and sequence analysis led to the identification of a previously uncharacterized subclass of non-cell-autonomous chaperones. The highly conserved nature of the heat shock protein 70 (Hsp70) family, in conjunction with mutant analysis, permitted the characterization of a motif that allows these Hsc70 chaperones to engage the plasmodesmal non-cell-autonomous translocation machinery. Proof of concept that this motif is necessary for Hsp70 gain-of-movement function was obtained through the engineering of a human Hsp70 that acquired the capacity to traffic through plasmodesmata. These results are discussed in terms of the roles likely played by this subclass of Hsc70 chaperones in the trafficking of non-cell-autonomous proteins. PMID:12456884

Autonomous Science on the EO-1 Mission

NASA Technical Reports Server (NTRS)

Chien, S.; Sherwood, R.; Tran, D.; Castano, R.; Cichy, B.; Davies, A.; Rabideau, G.; Tang, N.; Burl, M.; Mandl, D.;

Research on an autonomous vision-guided helicopter

NASA Technical Reports Server (NTRS)

Amidi, Omead; Mesaki, Yuji; Kanade, Takeo

1994-01-01

Integration of computer vision with on-board sensors to autonomously fly helicopters was researched. The key components developed were custom designed vision processing hardware and an indoor testbed. The custom designed hardware provided flexible integration of on-board sensors with real-time image processing resulting in a significant improvement in vision-based state estimation. The indoor testbed provided convenient calibrated experimentation in constructing real autonomous systems.

Terminal Homing for Autonomous Underwater Vehicle Docking

DTIC Science & Technology

2016-06-01

underwater domain, accurate navigation. Above the water, light and electromagnetic signals travel well through air and space, mediums that allow for a...DISTRIBUTION CODE 13. ABSTRACT The use of docking stations for autonomous underwater vehicles (AUV) provides the ability to keep a vehicle on...Mechanical and Aerospace Engineering iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT The use of docking stations for autonomous underwater

A Queueing Model for Supervisory Control of Unmanned Autonomous Vehicles

DTIC Science & Technology

2013-09-01

Autonomous Vehicles Joseph DiVita, PhD Robert L. Morris Maria Olinda Rodas SSC Pacific Approved...298 (Rev. 8/98) Prescribed by ANSI Std. Z39.18 09–2013 Final A Queueing Model for Supervisory Control of Unmanned Autonomous Vehicles Joseph...Mission Area: Command and Control, Queueing Model; Supervisory Control; Unmanned Autonomous Vehicles M. O. Rodas U U U U 38 (619)

Learner Behaviors and Perceptions of Autonomous Language Learning

ERIC Educational Resources Information Center

Bekleyen, Nilüfer; Selimoglu, Figen

2016-01-01

The purpose of the present study was to investigate the learners' behaviors and perceptions about autonomous language learning at the university level in Turkey. It attempts to reveal what type of perceptions learners held regarding teachers' and their own responsibilities in the language learning process. Their autonomous language learning…

Cardiac Autonomic Control in Individuals With Down Syndrome

ERIC Educational Resources Information Center

Goulopoulou, Styliani; Baynard, Tracy; Collier, Scott; Giannopoulou, Ifigenia; Figueroa, Arturo; Beets, Michael; Pitetti, Kenneth; Fernhall, Bo

2006-01-01

Our goal in this study was to compare cardiac autonomic control at rest between 50 individuals with Down syndrome and 24 control participants without disabilities. Resting autonomic function was assessed using analysis of heart rate variability. Participants with Down syndrome had reduced total heart rate variability, which indicates possible…

Wireless IR Image Transfer System for Autonomous Vehicles

DTIC Science & Technology

2003-12-01

the camera can operate between 0 and 500 C; this uniquely suites it for employment on autonomous vehicles in rugged environments. The camera is...system is suitable for used on autonomous vehicles under varying antenna orientations. • The third is the use of MDS transceivers allows the received

Tele-assistance for semi-autonomous robots

NASA Technical Reports Server (NTRS)

Rogers, Erika; Murphy, Robin R.

1994-01-01

This paper describes a new approach in semi-autonomous mobile robots. In this approach the robot has sufficient computerized intelligence to function autonomously under a certain set of conditions, while the local system is a cooperative decision making unit that combines human and machine intelligence. Communication is then allowed to take place in a common mode and in a common language. A number of exception-handling scenarios that were constructed as a result of experiments with actual sensor data collected from two mobile robots were presented.

Autonomic consequences of arousal from sleep: mechanisms and implications.

PubMed

Horner, R L

1996-12-01

Normal spontaneous arousals from sleep are associated with transient increases in blood pressure, heart rate, and ventilation caused by large transient changes in autonomic output. These autonomic changes are out of proportion to obvious physiological need and are in excess of those observed in later periods of quiet wakefulness. This paper discusses some of the mechanisms underlying the cardio-respiratory consequences of arousal from sleep, and discusses why the normal onset of wakefulness may be associated with such large changes in autonomic output.

Challenges in verification and validation of autonomous systems for space exploration

NASA Technical Reports Server (NTRS)

Brat, Guillaume; Jonsson, Ari

2005-01-01

Space exploration applications offer a unique opportunity for the development and deployment of autonomous systems, due to limited communications, large distances, and great expense of direct operation. At the same time, the risk and cost of space missions leads to reluctance to taking on new, complex and difficult-to-understand technology. A key issue in addressing these concerns is the validation of autonomous systems. In recent years, higher-level autonomous systems have been applied in space applications. In this presentation, we will highlight those autonomous systems, and discuss issues in validating these systems. We will then look to future demands on validating autonomous systems for space, identify promising technologies and open issues.

CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction

PubMed Central

Hermann, Gerlinda E.; Van Meter, Montina J.; Rogers, Richard C.

2014-01-01

The chemokine receptor, CXCR4, plays an essential role in guiding neural development of the CNS. Its natural agonist, CXCL12 [or stromal cell-derived factor-1 (SDF-1)], normally is derived from stromal cells, but is also produced by damaged and virus-infected neurons and glia. Pathologically, this receptor is critical to the proliferation of the HIV virus and initiation of metastatic cell growth in the brain. Anorexia, nausea and failed autonomic regulation of gastrointestinal (GI) function cause morbidity and contribute to the mortality associated with these disease states. Our previous work on the peripheral cytokine, tumor necrosis factor-alpha, demonstrated that similar morbidity factors involving GI dysfunction are attributable to agonist action on neural circuit elements of the dorsal vagal complex (DVC) of the hindbrain. The DVC includes vagal afferent terminations in the solitary nucleus, neurons in the solitary nucleus (NST) and area postrema, and visceral efferent motor neurons in the dorsal motor nucleus (DMN) that are responsible for the neural regulation of digestive functions from the oral cavity to the transverse colon. Immunohistochemical techniques demonstrate a dense concentration of CXCR4 receptors on neurons throughout the DVC and the hypoglossal nucleus. CXCR4-immunoreactivity is also intense on microglia within the DVC, though not on the astrocytes. Physiological studies show that nanoinjection of SDF-1 into the DVC produces a significant reduction in gastric motility in parallel with an elevation in the numbers of cFOS-activated neurons in the NST and DMN. These results suggest that this chemokine receptor may contribute to autonomically mediated pathophysiological events associated with CNS metastasis and infection. PMID:18333961

Sex differences in autonomic function following maximal exercise.

PubMed

Kappus, Rebecca M; Ranadive, Sushant M; Yan, Huimin; Lane-Cordova, Abbi D; Cook, Marc D; Sun, Peng; Harvey, I Shevon; Wilund, Kenneth R; Woods, Jeffrey A; Fernhall, Bo

2015-01-01

Heart rate variability (HRV), blood pressure variability, (BPV) and heart rate recovery (HRR) are measures that provide insight regarding autonomic function. Maximal exercise can affect autonomic function, and it is unknown if there are sex differences in autonomic recovery following exercise. Therefore, the purpose of this study was to determine sex differences in several measures of autonomic function and the response following maximal exercise. Seventy-one (31 males and 40 females) healthy, nonsmoking, sedentary normotensive subjects between the ages of 18 and 35 underwent measurements of HRV and BPV at rest and following a maximal exercise bout. HRR was measured at minute one and two following maximal exercise. Males have significantly greater HRR following maximal exercise at both minute one and two; however, the significance between sexes was eliminated when controlling for VO2 peak. Males had significantly higher resting BPV-low-frequency (LF) values compared to females and did not significantly change following exercise, whereas females had significantly increased BPV-LF values following acute maximal exercise. Although males and females exhibited a significant decrease in both HRV-LF and HRV-high frequency (HF) with exercise, females had significantly higher HRV-HF values following exercise. Males had a significantly higher HRV-LF/HF ratio at rest; however, both males and females significantly increased their HRV-LF/HF ratio following exercise. Pre-menopausal females exhibit a cardioprotective autonomic profile compared to age-matched males due to lower resting sympathetic activity and faster vagal reactivation following maximal exercise. Acute maximal exercise is a sufficient autonomic stressor to demonstrate sex differences in the critical post-exercise recovery period.

Cardiac and autonomic nerve function after reduced-intensity stem cell transplantation for hematologic malignancy in patients with pre-transplant cardiac dysfunction.

PubMed

Nakane, Takahiko; Nakamae, Hirohisa; Muro, Takashi; Yamagishi, Hiroyuki; Kobayashi, Yoshiki; Aimoto, Mizuki; Sakamoto, Erina; Terada, Yoshiki; Nakamae, Mika; Koh, Ki-Ryang; Yamane, Takahisa; Yoshiyama, Minoru; Hino, Masayuki

2009-09-01

Recent reports have shown that cardiomyopathy caused by hemochromatosis in severe aplastic anemia is reversible after reduced-intensity allogeneic stem-cell transplantation (RIST). We comprehensively evaluated cardiac and autonomic nerve function to determine whether cardiac dysfunction due to causes other than hemochromatosis is attenuated after RIST. In five patients with cardiac dysfunction before transplant, we analyzed the changes in cardiac and autonomic nerve function after transplant, using electrocardiography (ECG), echocardiography, radionuclide angiography (RNA), serum markers, and heart rate variability (HRV), before and up to 100 days after transplant. There was no significant improvement in cardiac function in any patient and no significant alteration in ECG, echocardiogram, RNA, or serum markers. However, on time-domain analysis of HRV, the SD of normal-to-normal RR intervals (SDNN) and the coefficient of variation of the RR interval (CVRR) decreased significantly 30 and 60 days after transplant (P = 0.04 and 0.01, respectively). Similarly, on frequency-domain analysis of HRV, low and high frequency power (LF and HF) significantly and temporarily decreased (P = 0.003 and 0.03, respectively). Notably, in one patient who had acute heart failure after transplantation, the values of SDNN, CVRR, r-MSSD, LF, and HF at 30 and 60 days after transplantation were the lowest of all the patients. In conclusion, this study suggests that (a) RIST is well-tolerated in patients with cardiac dysfunction, but we cannot expect improvement in cardiac dysfunction due to causes other than hemochromatosis; and (b) monitoring HRV may be useful in predicting cardiac events after RIST.

Control of autonomous robot using neural networks

NASA Astrophysics Data System (ADS)

Barton, Adam; Volna, Eva

2017-07-01

The aim of the article is to design a method of control of an autonomous robot using artificial neural networks. The introductory part describes control issues from the perspective of autonomous robot navigation and the current mobile robots controlled by neural networks. The core of the article is the design of the controlling neural network, and generation and filtration of the training set using ART1 (Adaptive Resonance Theory). The outcome of the practical part is an assembled Lego Mindstorms EV3 robot solving the problem of avoiding obstacles in space. To verify models of an autonomous robot behavior, a set of experiments was created as well as evaluation criteria. The speed of each motor was adjusted by the controlling neural network with respect to the situation in which the robot was found.

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

Autonomous Space Shuttle

NASA Technical Reports Server (NTRS)

Siders, Jeffrey A.; Smith, Robert H.

2004-01-01

The continued assembly and operation of the International Space Station (ISS) is the cornerstone within NASA's overall Strategic P an. As indicated in NASA's Integrated Space Transportation Plan (ISTP), the International Space Station requires Shuttle to fly through at least the middle of the next decade to complete assembly of the Station, provide crew transport, and to provide heavy lift up and down mass capability. The ISTP reflects a tight coupling among the Station, Shuttle, and OSP programs to support our Nation's space goal . While the Shuttle is a critical component of this ISTP, there is a new emphasis for the need to achieve greater efficiency and safety in transporting crews to and from the Space Station. This need is being addressed through the Orbital Space Plane (OSP) Program. However, the OSP is being designed to "complement" the Shuttle as the primary means for crew transfer, and will not replace all the Shuttle's capabilities. The unique heavy lift capabilities of the Space Shuttle is essential for both ISS, as well as other potential missions extending beyond low Earth orbit. One concept under discussion to better fulfill this role of a heavy lift carrier, is the transformation of the Shuttle to an "un-piloted" autonomous system. This concept would eliminate the loss of crew risk, while providing a substantial increase in payload to orbit capability. Using the guidelines reflected in the NASA ISTP, the autonomous Shuttle a simplified concept of operations can be described as; "a re-supply of cargo to the ISS through the use of an un-piloted Shuttle vehicle from launch through landing". Although this is the primary mission profile, the other major consideration in developing an autonomous Shuttle is maintaining a crew transportation capability to ISS as an assured human access to space capability.

An Efficient Model-Based Image Understanding Method for an Autonomous Vehicle.

DTIC Science & Technology

1997-09-01

The problem discussed in this dissertation is the development of an efficient method for visual navigation of autonomous vehicles . The approach is to... autonomous vehicles . Thus the new method is implemented as a component of the image-understanding system in the autonomous mobile robot Yamabico-11 at

Autonomous Formation Flight

NASA Technical Reports Server (NTRS)

Schkolnik, Gerard S.; Cobleigh, Brent

2004-01-01

NASA's Strategic Plan for the Aerospace Technology Enterprise includes ambitious objectives focused on affordable air travel, reduced emissions, and expanded aviation-system capacity. NASA Dryden Flight Research Center, in cooperation with NASA Ames Research Center, the Boeing Company, and the University of California, Los Angeles, has embarked on an autonomous-formation-flight project that promises to make significant strides towards these goals. For millions of years, birds have taken advantage of the aerodynamic benefit of flying in formation. The traditional "V" formation flown by many species of birds (including gulls, pelicans, and geese) enables each of the trailing birds to fly in the upwash flow field that exists just outboard of the bird immediately ahead in the formation. The result for each trailing bird is a decrease in induced drag and thus a reduction in the energy needed to maintain a given speed. Hence, for migratory birds, formation flight extends the range of the system of birds over the range of birds flying solo. The Autonomous Formation Flight (AFF) Project is seeking to extend this symbiotic relationship to aircraft.

MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

PubMed

Conti, Valentina; Gandaglia, Anna; Galli, Francesco; Tirone, Mario; Bellini, Elisa; Campana, Lara; Kilstrup-Nielsen, Charlotte; Rovere-Querini, Patrizia; Brunelli, Silvia; Landsberger, Nicoletta

2015-01-01

Rett syndrome (RTT) is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.

PubMed

Röhling, Martin; Strom, Alexander; Bönhof, Gidon J; Roden, Michael; Ziegler, Dan

2017-10-23

This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.

Reciprocal phosphorylation and glycosylation recognition motifs control NCAPP1 interaction with pumpkin phloem proteins and their cell-to-cell movement.

PubMed

Taoka, Ken-Ichiro; Ham, Byung-Kook; Xoconostle-Cázares, Beatriz; Rojas, Maria R; Lucas, William J

2007-06-01

In plants, cell-to-cell trafficking of non-cell-autonomous proteins (NCAPs) involves protein-protein interactions, and a role for posttranslational modification has been implicated. In this study, proteins contained in pumpkin (Cucurbita maxima cv Big Max) phloem sap were used as a source of NCAPs to further explore the molecular basis for selective NCAP trafficking. Protein overlay assays and coimmunoprecipitation experiments established that phosphorylation and glycosylation, on both Nicotiana tabacum NON-CELL-AUTONOMOUS PATHWAY PROTEIN1 (Nt-NCAPP1) and the phloem NCAPs, are essential for their interaction. Detailed molecular analysis of a representative phloem NCAP, Cm-PP16-1, identified the specific residues on which glycosylation and phosphorylation must occur for effective binding to NCAPP1. Microinjection studies confirmed that posttranslational modification on these residues is essential for cell-to-cell movement of Cm-PP16-1. Lastly, a glutathione S-transferase (GST)-Cm-PP16-1 fusion protein system was employed to test whether the peptide region spanning these residues was required for cell-to-cell movement. These studies established that a 36-amino acid peptide was sufficient to impart cell-to-cell movement capacity to GST, a normally cell-autonomous protein. These findings are consistent with the hypothesis that a phosphorylation-glycosylation recognition motif functions to control the binding of a specific subset of phloem NCAPs to NCAPP1 and their subsequent transport through plasmodesmata.

[Features of autonomic dysfunction in myofascial pain syndromes cervicobrachial localization].

PubMed

Морозова, О Г; Ярошевский, А А; Липинская, Я В

2015-01-01

The relevance of this study is due to the prevalence of autonomic disorders and musculoskeletal pain, especially among the young people of working age. In recent years, many authors in scientific works have been highlighted aspects of mutual development myofascial and autonomic dysfunction, which is caused by neurophysiological preconditions and anatomical and topographical relationships that need to be considered in the diagnostic and therapeutic approaches. To study the characteristics of the formation and flow of autonomic dysfunction syndrome with paroxysmal and permanent types of flow in patients with myofascial pain syndromes cervicobrachial localization. Using clinical neurological, vertebral neurological, neuropsychological methods of studying the severity of pain (visual analogue scale and Pain questionnaire of Mac Gill) examined 84 patients suffering from autonomic dysfunction on the background of myofascial pain syndromes cervicobrachial localization. To identify the features of vegetative regulation of patients were divided into two groups: group 1 (51 people) - with a permanent type of course; group 2 (33 patients) - a type of paroxysmal of course of autonomic dysfunction. It was found more pronounced disturbances in patients with paroxysmal type of course of autonomic dysfunction. The frequency and severity of autonomic paroxysms associated with the severity of musculo-tonic syndrome and location of active trigger points in the muscles of the neck and shoulder girdle, due to anatomic and topographic features of these muscles, namely the proximity of their location to the sympathetic formations neck. The formation and development of emotional and affective disorders in both groups played a significant role of pain and musculo-tonic syndrome. The syndrome of autonomic dysfunction, in particular its paroxysmal type of flow, on the one hand is a response to the development of myofascial pain syndromes cervicobrachial localization, with another - a factor

GOATS 2008: Autonomous, Adaptive Multistatic Acoustic Sensing

DTIC Science & Technology

2010-09-30

carried out jointly with the NATO Undersea Research Centre in the Tuscan archipelago July 26 – August 16, 2010. MIT operated the Unicorn AUV and...4 trail behavior with the physical Unicorn AUV, and is accidentally passing close the R/V Leonardo, fully autonomously changing its depth from...vehicles. The AUV Unicorn is performing an adaptive thermocline mapping mission, with the vehicle trail shown in green. Note the autonomous collision

JOMAR: Joint Operations with Mobile Autonomous Robots

DTIC Science & Technology

2015-12-21

AFRL-AFOSR-JP-TR-2015-0009 JOMAR: Joint Operations with Mobile Autonomous Robots Edwin Olson UNIVERSITY OF MICHIGAN Final Report 12/21/2015...SUBTITLE JOMAR: Joint Operations with Mobile Autonomous Robots 5a. CONTRACT NUMBER FA23861114024 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...14. ABSTRACT Under this grant, we formulated and implemented a variety of novel algorithms that address core problems in multi- robot systems. These

Testing the Intelligence of Unmanned Autonomous Systems

DTIC Science & Technology

2008-01-01