Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

PubMed Central

Fung, Samantha J.; Joshi, Dipesh; Allen, Katherine M.; Sivagnanasundaram, Sinthuja; Rothmond, Debora A.; Saunders, Richard; Noble, Pamela L.; Webster, Maree J.; Shannon Weickert, Cynthia

2011-01-01

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia. PMID:21966452

Grape seed extract enhances neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice.

PubMed

Yoo, Dae Young; Kim, Woosuk; Yoo, Ki-Yeon; Lee, Choong Hyun; Choi, Jung Hoon; Yoon, Yeo Sung; Kim, Dong-Woo; Won, Moo-Ho; Hwang, In Koo

2011-05-01

The effects of grape seed extract (GSE), a major source of phenolic compounds, were examined on cell proliferation, neuroblast differentiation and integration into granule cells in the hippocampal dentate gyrus (DG) of middle-aged (12 month-old) mice using Ki67, doublecortin (DCX) immunohistochemistry and 5'-bromo-2-deoxyguanosine (BrdU)/calbindin D-28k (CB) double immunofluorescence study, respectively. GSE (25, 50 and 100 mg/kg) was administered orally for 28 days, and the animals were treated with 50 mg/kg BrdU intraperitoneally on the day of first GSE treatment. In the vehicle-treated group, Ki67 and DCX immunoreactivity was detected in the subgranular zone of the DG (SZDG). GSE treatment dose-dependently increased the number of Ki67 and DCX immunoreactive cells, particularly the number of DCX immunoreactive neuroblasts with well-developed (tertiary) dendrites. GSE also dose-dependently increased DCX protein levels. In addition, GSE treatment increased significantly the number of BrdU/CB double labeled granule cells. These results suggest that GSE significantly increases cell proliferation, neuroblast differentiation and integration into granule cells in the DG, and the consumption of GSE enhances the plasticity of hippocampus in middle-aged mice. Copyright © 2010 John Wiley & Sons, Ltd.

Doublecortin is expressed in trigeminal motoneurons that innervate the velar musculature of lampreys: considerations on the evolution and development of the trigeminal system.

PubMed

Barreiro-Iglesias, Antón; Romaus-Sanjurjo, Daniel; Senra-Martínez, Pablo; Anadón, Ramón; Rodicio, María Celina

2011-01-01

Studies in lampreys have revealed interesting aspects of the evolution of the trigeminal system and the jaw. In the present study, we found a marker that distinguishes subpopulations of trigeminal motoneurons innervating two different kinds of oropharyngeal muscles. Immunofluorescence with an antibody against doublecortin (DCX; a neuron-specific phosphoprotein) enabled identification of the trigeminal motoneurons that innervate the velar musculature of larval and recently transformed sea lampreys. DCX-immunoreactive (-ir) motoneurons were observed in the rostro-lateral part of the trigeminal motor nucleus of these animals, but not in lampreys 1 month or more after metamorphosis. Combined double DCX/tubulin and serotonin/tubulin immunofluorescence and tract-tracing experiments with neurobiotin (NB) were also performed in larvae for further characterization of this system. Rich innervation by DCX-ir fibers was observed on the muscle fibers of the velum but not on the upper lip or lower lip muscles, which were innervated by tubulin-ir/DCX-negative fibers. No double-labelled DCX-ir motoneurons were observed in experiments in which the tracer NB was applied to the upper lip. Innervation of velar muscles by serotonergic fibers is also reported. The present results indicate that development of the trigeminal motoneurons innervating the velum differs from that of the trigeminal motoneurons innervating the lips, which is probably related to the dramatic regression of the velum during metamorphosis. The absence of data on a similar subsystem in the trigeminal motor nucleus of gnathostomes suggests that they may be lamprey-specific motoneurons. These results provide support for the "heterotopic theory" of jaw evolution and are inconsistent with the theories of a velar origin for the gnathostome jaw. © 2011 Wiley Periodicals, Inc.

Materials Testing on the DC-X and DC-XA

NASA Technical Reports Server (NTRS)

Smith, Dane; Carroll, Carol; Marschall, Jochen; Pallix, Joan

1997-01-01

Flight testing of thermal protection materials has been carried out over a two year period on the base heat shield of the Delta Clipper (DC-X and DC-XA), as well on a body flap. The purpose was to use the vehicle as a test bed for materials and more efficient repair or maintenance processes which would be potentially useful for application on new entry vehicles (i.e., X-33, RLV, planetary probes), as well as on the existing space shuttle orbiters. Panels containing Thermal Protection Systems (TPS) and/or structural materials were constructed either at NASA Ames Research Center or at McDonnell Douglas Aerospace (MDA) and attached between two of the four thrusters in the base heat shield of the DC-X or DC-XA. Three different panels were flown on DC-X flights 6, 7, and 8. A total of 7 panels were flown on DC-XA flights 1, 2, and 3. The panels constructed at Ames contained a variety of ceramic TPS including flexible blankets, tiles with high emissivity coatings, lightweight ceramic ablators and other ceramic composites. The MDS test panels consisted primarily of a variety of metallic composites. This report focuses on the ceramic TPS test results.

Chronic tinnitus and unipolar brush cell alterations in the cerebellum and dorsal cochlear nucleus.

PubMed

Brozoski, Thomas; Brozoski, Daniel; Wisner, Kurt; Bauer, Carol

2017-07-01

Animal model research has shown that the central features of tinnitus, the perception of sound without an acoustic correlate, include elevated spontaneous and stimulus-driven activity, enhanced burst-mode firing, decreased variance of inter-spike intervals, and distortion of tonotopic frequency representation. Less well documented are cell-specific correlates of tinnitus. Unipolar brush cell (UBC) alterations in animals with psychophysical evidence of tinnitus has recently been reported. UBCs are glutamatergic interneurons that appear to function as local-circuit signal amplifiers. UBCs are abundant in the dorsal cochlear nucleus (DCN) and very abundant in the flocculus (FL) and paraflocculus (PFL) of the cerebellum. In the present research, two indicators of UBC structure and function were examined: Doublecortin (DCX) and epidermal growth factor receptor substrate 8 (Eps8). DCX is a protein that binds to microtubules where it can modify their assembly and growth. Eps8 is a cell-surface tyrosine kinase receptor mediating the response to epidermal growth factor; it appears to have a role in actin polymerization as well as cytoskeletal protein interactions. Both functions could contribute to synaptic remodeling. In the present research UBC Eps8 and DCX immunoreactivity (IR) were determined in 4 groups of rats distinguished by their exposure to high-level sound and psychophysical performance: Unexposed, exposed to high-level sound with behavioral evidence of tinnitus, and two exposed groups without behavioral evidence of tinnitus. Compared to unexposed controls, exposed animals with tinnitus had Eps8 IR elevated in their PFL; other structures were not affected, nor was DCX IR affected. This was interpreted as UBC upregulation in animals with tinnitus. Exposure that failed to produce tinnitus did not increase either Eps8 or DCX IR. Rather Eps8 IR was decreased in the FL and DCN of one subgroup (Least-Tinnitus), while DCX IR decreased in the FL of the other subgroup (No-Tinnitus). Neuron degeneration was also documented in the cochlear nucleus and PFL of exposed animals, both with and without tinnitus. Degeneration was not found in unexposed animals. Implications for tinnitus neuropathy are discussed in the context of synaptic remodeling and cerebellar sensory modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Seasonal neuronal plasticity in song-control and auditory forebrain areas in subtropical nonmigratory and palearctic-indian migratory male songbirds.

PubMed

Surbhi; Rastogi, Ashutosh; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2016-10-01

This study examines whether differences in annual life-history states (LHSs) among the inhabitants of two latitudes would have an impact on the neuronal plasticity of the song-control system in songbirds. At the times of equinoxes and solstices during the year (n = 4 per year) corresponding to different LHSs, we measured the volumetric changes and expression of doublecortin (DCX; an endogenous marker of the neuronal recruitment) in the song-control nuclei and higher order auditory forebrain regions of the subtropical resident Indian weaverbirds (Ploceus philippinus) and Palearctic-Indian migratory redheaded buntings (Emberiza bruniceps). Area X in basal ganglia, lateral magnocellular nucleus of the anterior nidopallium (LMAN), HVC (proper name), and robust nucleus of the arcopallium (RA) were enlarged during the breeding LHS. Both round and fusiform DCX-immunoreactive (DCX-ir) cells were found in area X and HVC but not in LMAN or RA, with a significant seasonal difference. Also, as shown by increase in volume and by dense, round DCX-ir cells, the neuronal incorporation was increased in HVC alone during the breeding LHS. This suggests differences in the response of song-control nuclei to photoperiod-induced changes in LHSs. Furthermore, DCX immunoreactivity indicated participation of the cortical caudomedial nidopallium and caudomedial mesopallium in the song-control system, albeit with differences between the weaverbirds and the buntings. Overall, these results show seasonal neuronal plasticity in the song-control system closely associated with annual reproductive LHS in both of the songbirds. Differences between species probably account for the differences in the photoperiod-response system between the relative refractory weaverbirds and absolute refractory redheaded buntings. J. Comp. Neurol. 524:2914-2929, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Defensive behaviors and prosencephalic neurogenesis in pigeons (Columba livia) are affected by environmental enrichment in adulthood.

PubMed

Melleu, F F; Pinheiro, M V; Lino-de-Oliveira, C; Marino-Neto, J

2016-05-01

Neurogenesis in the adult brain appears to be phylogenetically conserved across the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons are observed in several prosencephalic areas, suggesting that neurogenesis may participate in the control of different behaviors. The mechanisms controlling neurogenesis and its relevance to defensive behaviors in non-oscine birds remain elusive. Herein, the contribution of the environment to behavior and neurogenesis of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed in standard (SE) or enriched environment (EE) for 42 days, were exposed to an unfamiliar environment (UE) followed by presentation to a novel object (NO). Video recordings of UE+NO tests were analyzed and scored for latency, duration and frequency of angular head movements, peeping, grooming, immobility and locomotion. Twenty-four hours later, pigeons were submitted to the tonic immobility test (TI) and number of trials for TI and TI duration were scored, followed by euthanasia 2 h later. Brains were immunohistochemically processed to reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed in SE, the pigeons housed in EE responded to a NO with more immobility. In addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum than those housed in SE. There was no correlation between the number of DCX-ir cells and the scores of immobility in behavioral tests. Together, these data suggest that enrichment favored behavioral inhibition and neurogenesis in the adult pigeons through different, parallel mechanisms.

Effects of infrasound on cell proliferation in the dentate gyrus of adult rats.

PubMed

Liu, Juanfang; Lin, Tian; Yan, Xiaodong; Jiang, Wen; Shi, Ming; Ye, Ruidong; Rao, Zhiren; Zhao, Gang

2010-06-02

Adult rats were used to identify the effects of infrasound on neurogenesis in the hippocampal dentate gyrus. After 7 consecutive days' exposure to infrasound of 16 Hz at 130 dB, immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) was preformed. Compared with those in normal groups, the numbers of BrdU+ and DCX+/BrdU+ cells in the subgranular zone in infrasound groups were significantly decreased at 3, 6, 10 and 14 days and returned to normal at 18 days. The percentage of BrdU+ cells that were co-labeled with DCX showed no significant differences between the infrasound and normal groups. These data suggest that infrasound inhibits the cell proliferation in adult rat dentate gyrus but has no effects on early migration and differentiation of these newborn cells.

Environmental enrichment brings a beneficial effect on beam walking and enhances the migration of doublecortin-positive cells following striatal lesions in rats.

PubMed

Urakawa, S; Hida, H; Masuda, T; Misumi, S; Kim, T-S; Nishino, H

2007-02-09

Rats raised in an enriched environment (enriched rats) have been reported to show less motor dysfunction following brain lesions, but the neuronal correlates of this improvement have not been well clarified. The present study aimed to elucidate the effect of chemical brain lesions and environmental enrichment on motor function and lesion-induced neurogenesis. Three week-old, recently weaned rats were divided into two groups: one group was raised in an enriched environment and the other group was raised in a standard cage for 5 weeks. Striatal damage was induced at an age of 8 weeks by injection of the neuro-toxins 6-hydroxydopamine (6-OHDA) or quinolinic acid (QA) into the striatum, or by injection of 6-OHDA into the substantia nigra (SN), which depleted nigrostriatal dopaminergic innervation. Enriched rats showed better performance on beam walking compared with those raised in standard conditions, but both groups showed similar forelimb use asymmetry in a cylinder test. The number of bromodeoxyuridine-labeled proliferating cells in the subventricular zone was increased by a severe striatal lesion induced by QA injection 1 week after the lesion, but decreased by injection of 6-OHDA into the SN. Following induction of lesions by striatal injection of 6-OHDA or QA, the number of cells positive for doublecortin (DCX) was strongly increased in the striatum; however, there was no change in the number of DCX-positive cells following 6-OHDA injection into the SN. Environmental enrichment enhanced the increase of DCX-positive cells with migrating morphology in the dorsal striatum. In enriched rats, DCX-positive cells traversed the striatal parenchyma far from the corpus callosum and lateral ventricle. DCX-positive cells co-expressed an immature neuronal marker, polysialylated neural cell adhesion molecule, but were negative for a glial marker. These data suggest that environmental enrichment improves motor performance on beam walking and enhances neuronal migration toward a lesion area in the striatum.

Effects of Environmental Enrichment on Doublecortin and BDNF Expression along the Dorso-Ventral Axis of the Dentate Gyrus.

PubMed

Gualtieri, Fabio; Brégère, Catherine; Laws, Grace C; Armstrong, Elena A; Wylie, Nicholas J; Moxham, Theo T; Guzman, Raphael; Boswell, Timothy; Smulders, Tom V

2017-01-01

Adult hippocampal neurogenesis (AHN) in the dentate gyrus is known to respond to environmental enrichment, chronic stress, and many other factors. The function of AHN may vary across the septo-temporal axis of the hippocampus, as different subdivisions are responsible for different functions. The dorsal pole regulates cognitive-related behaviors, while the ventral pole mediates mood-related responses through the hypothalamic-pituitary-adrenal (HPA) axis. In this study, we investigate different methods of quantifying the effect of environmental enrichment on AHN in the dorsal and ventral parts of the dentate gyrus (dDG and vDG). To this purpose, 11-week-old female CD-1 mice were assigned for 8 days to one of two conditions: the Environmental Enrichment (E) group received (i) running wheels, (ii) larger cages, (iii) plastic tunnels, and (iv) bedding with male urine, while the Control (C) group received standard housing. Dorsal CA ( Cornu Ammonis ) and DG regions were larger in the E than the C animals. Distance run linearly predicted the volume of the dorsal hippocampus, as well as of the intermediate and ventral CA regions. In the dDG, the amount of Doublecortin (DCX) immunoreactivity was significantly higher in E than in C mice. Surprisingly, this pattern was the opposite in the vDG (C > E). Real-time PCR measurement of Dcx mRNA and DCX protein analysis using ELISA showed the same pattern. Brain Derived Neurotrophic Factor (BDNF) immunoreactivity and mRNA displayed no difference between E and C, suggesting that upregulation of DCX was not caused by changes in BDNF levels. BDNF levels were higher in vDG than in dDG, as measured by both methods. Bdnf expression in vDG correlated positively with the distance run by individual E mice. The similarity in the patterns of immunoreactivity, mRNA and protein for differential DCX expression and for BDNF distribution suggests that the latter two methods might be effective tools for more rapid quantification of AHN.

Dcx Re-expression Reduces Subcortical Band Heterotopia and Seizure Threshold in an Animal Model of Neuronal Migration Disorder

PubMed Central

Manent, Jean-Bernard; Wang, Yu; Chang, YoonJeung; Paramasivam, Murugan; LoTurco, Joseph J

2009-01-01

Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration, and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. PMID:19098909

Epileptogenesis following Kainic Acid-Induced Status Epilepticus in Cyclin D2 Knock-Out Mice with Diminished Adult Neurogenesis

PubMed Central

Kondratiuk, Ilona; Plucinska, Gabriela; Miszczuk, Diana; Wozniak, Grazyna; Szydlowska, Kinga; Kaczmarek, Leszek; Filipkowski, Robert K.; Lukasiuk, Katarzyna

2015-01-01

The goal of this study was to determine whether a substantial decrease in adult neurogenesis influences epileptogenesis evoked by the intra-amygdala injection of kainic acid (KA). Cyclin D2 knockout (cD2 KO) mice, which lack adult neurogenesis almost entirely, were used as a model. First, we examined whether status epilepticus (SE) evoked by an intra-amygdala injection of KA induces cell proliferation in cD2 KO mice. On the day after SE, we injected BrdU into mice for 5 days and evaluated the number of DCX- and DCX/BrdU-immunopositive cells 3 days later. In cD2 KO control animals, only a small number of DCX+ cells was observed. The number of DCX+ and DCX/BrdU+ cells/mm of subgranular layer in cD2 KO mice increased significantly following SE (p<0.05). However, the number of newly born cells was very low and was significantly lower than in KA-treated wild type (wt) mice. To evaluate the impact of diminished neurogenesis on epileptogenesis and early epilepsy, we performed video-EEG monitoring of wt and cD2 KO mice for 16 days following SE. The number of animals with seizures did not differ between wt (11 out of 15) and cD2 KO (9 out of 12) mice. The median latency to the first spontaneous seizure was 4 days (range 2 – 10 days) in wt mice and 8 days (range 2 – 16 days) in cD2 KO mice and did not differ significantly between groups. Similarly, no differences were observed in median seizure frequency (wt: 1.23, range 0.1 – 3.4; cD2 KO: 0.57, range 0.1 – 2.0 seizures/day) or median seizure duration (wt: 51 s, range 23 – 103; cD2 KO: 51 s, range 23 – 103). Our results indicate that SE-induced epileptogenesis is not disrupted in mice with markedly reduced adult neurogenesis. However, we cannot exclude the contribution of reduced neurogenesis to the chronic epileptic state. PMID:26020770

Effects of Environmental Enrichment on Doublecortin and BDNF Expression along the Dorso-Ventral Axis of the Dentate Gyrus

PubMed Central

Gualtieri, Fabio; Brégère, Catherine; Laws, Grace C.; Armstrong, Elena A.; Wylie, Nicholas J.; Moxham, Theo T.; Guzman, Raphael; Boswell, Timothy; Smulders, Tom V.

2017-01-01

Adult hippocampal neurogenesis (AHN) in the dentate gyrus is known to respond to environmental enrichment, chronic stress, and many other factors. The function of AHN may vary across the septo-temporal axis of the hippocampus, as different subdivisions are responsible for different functions. The dorsal pole regulates cognitive-related behaviors, while the ventral pole mediates mood-related responses through the hypothalamic-pituitary-adrenal (HPA) axis. In this study, we investigate different methods of quantifying the effect of environmental enrichment on AHN in the dorsal and ventral parts of the dentate gyrus (dDG and vDG). To this purpose, 11-week-old female CD-1 mice were assigned for 8 days to one of two conditions: the Environmental Enrichment (E) group received (i) running wheels, (ii) larger cages, (iii) plastic tunnels, and (iv) bedding with male urine, while the Control (C) group received standard housing. Dorsal CA (Cornu Ammonis) and DG regions were larger in the E than the C animals. Distance run linearly predicted the volume of the dorsal hippocampus, as well as of the intermediate and ventral CA regions. In the dDG, the amount of Doublecortin (DCX) immunoreactivity was significantly higher in E than in C mice. Surprisingly, this pattern was the opposite in the vDG (C > E). Real-time PCR measurement of Dcx mRNA and DCX protein analysis using ELISA showed the same pattern. Brain Derived Neurotrophic Factor (BDNF) immunoreactivity and mRNA displayed no difference between E and C, suggesting that upregulation of DCX was not caused by changes in BDNF levels. BDNF levels were higher in vDG than in dDG, as measured by both methods. Bdnf expression in vDG correlated positively with the distance run by individual E mice. The similarity in the patterns of immunoreactivity, mRNA and protein for differential DCX expression and for BDNF distribution suggests that the latter two methods might be effective tools for more rapid quantification of AHN. PMID:28966570

A novel DCX missense mutation in a family with X-linked lissencephaly and subcortical band heterotopia syndrome inherited from a low-level somatic mosaic mother: Genetic and functional studies.

PubMed

Tsai, Meng-Han; Kuo, Pei-Wen; Myers, Candace T; Li, Shih-Wen; Lin, Wei-Che; Fu, Ting-Ying; Chang, Hsin-Yun; Mefford, Heather C; Chang, Yao-Chung; Tsai, Jin-Wu

2016-09-01

To study the genetics and functional alteration of a family with X-linked lissencephaly and subcortical band heterotopia. Five affected patients (one male with lissencephaly, four female with subcortical band heterotopia) and their relatives were studied. Sanger sequencing of DCX gene, allele specific PCR and molecular inversion probe technique were performed. Mutant and wild type of the gene products, namely doublecortin, were expressed in cells followed by immunostaining to explore the localization of doublecortin and microtubules in cells. In vitro microtubule-binding protein spin-down assay was performed to quantify the binding ability of doublecortin to microtubules. We identified a novel DCX mutation c.785A > G, p.Asp262Gly that segregated with the affected members of the family. Allele specific PCR and molecular inversion probe technique demonstrated that the asymptomatic female carrier had an 8% mutant allele fraction in DNA derived from peripheral leukocytes. This mother had 7 children, 4 of whom were affected and all four affected siblings carried the mutation. Functional study showed that the mutant doublecortin protein had a significant reduction of its ability to bind microtubules. Low level mosaicism could be a cause of inherited risk from asymptomatic parents for DCX related lissencephaly-subcortical band heterotopia spectrum. This is particularly important in terms of genetic counselling for recurrent risk of future pregnancies. The reduced binding affinity of mutant doublecortin may contribute to developmental malformation of the cerebral cortex. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

PubMed Central

Yan, Bing Chun; Yoo, Ki-Yeon; Park, Joon Ha; Lee, Choong Hyun; Choi, Jung Hoon

2011-01-01

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice. PMID:22025974

Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

PubMed Central

Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J.; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

2016-01-01

Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα−/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα−/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα−/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα−/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments. PMID:27013951

Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches.

PubMed

Pérez-Martín, Margarita; Rivera, Patricia; Blanco, Eduardo; Lorefice, Clara; Decara, Juan; Pavón, Francisco J; Serrano, Antonia; Rodríguez de Fonseca, Fernando; Suárez, Juan

2016-01-01

Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα(-/-) mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα(-/-) mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα(-/-)-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα(-/-) mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.

Experimental epidural hematoma causes cerebral infarction and activates neocortical glial and neuronal genesis in adult guinea pigs.

PubMed

Pan, Aihua; Li, Ming; Gao, Jun-Yan; Xue, Zhi-Qin; Li, Zhiyuan; Yuan, Xian-Yui; Luo, Duan-Wu; Luo, Xue-Gang; Yan, Xiao-Xin

2013-02-01

Epidural hematoma (EDH) is a type of life-threatening traumatic brain injury. Little is known about the extent to which EDH may cause neural damage and regenerative response in the cerebral cortex. Here we attempted to explore these issues by using guinea pigs as an experimental model. Unilateral EDH was induced by injection of 0.1 ml autologous blood into the extradural space, with experimental effects examined at 7, 14, 30, and 60 days postlesion. An infarct developed in the cortex deep to the EDH largely after 7 days postlesion, with neuronal death occurred from layers I to V in the central infarct region, as evidenced by loss of immunoreactivity (IR) for neuron-specific nuclear antigen (NeuN). Glial fibrillary acidic protein (GFAP) IR appeared as a cellular band surrounding the infarct and extending into the periinfarct cortex along the pia. Doublecortin (DCX) IR emerged in these same areas, with labeled cells appearing as astrocytic and neuronal profiles. DCX/GFAP colocalization was found in these regions commonly at 7 and 14 days postlesion, whereas DCX/NeuN-colabeled neurons were detectable at 30 and 60 days postlesion. Subpopulations of GFAP-, DCX-, or NeuN-immunoreactive cells colocalized with the endogenous proliferative marker Ki-67 or bromodeoxyuridine (BrdU) after pulse-chase with this birth-dating marker. The results suggest that experimental EDH can cause severe neuronal loss, induce significant glial activation, and promote a certain degree of local neuronal genesis in adult guinea pig neocortex. These findings point to potential therapeutic targets for improving neuronal recovery in clinical management of EDH. Copyright © 2012 Wiley Periodicals, Inc.

Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering.

PubMed

Vukovic, Jana; Borlikova, Gilyana G; Ruitenberg, Marc J; Robinson, Gregory J; Sullivan, Robert K P; Walker, Tara L; Bartlett, Perry F

2013-04-10

It is now widely accepted that hippocampal neurogenesis underpins critical cognitive functions, such as learning and memory. To assess the behavioral importance of adult-born neurons, we developed a novel knock-in mouse model that allowed us to specifically and reversibly ablate hippocampal neurons at an immature stage. In these mice, the diphtheria toxin receptor (DTR) is expressed under control of the doublecortin (DCX) promoter, which allows for specific ablation of immature DCX-expressing neurons after administration of diphtheria toxin while leaving the neural precursor pool intact. Using a spatially challenging behavioral test (a modified version of the active place avoidance test), we present direct evidence that immature DCX-expressing neurons are required for successful acquisition of spatial learning, as well as reversal learning, but are not necessary for the retrieval of stored long-term memories. Importantly, the observed learning deficits were rescued as newly generated immature neurons repopulated the granule cell layer upon termination of the toxin treatment. Repeat (or cyclic) depletion of immature neurons reinstated behavioral deficits if the mice were challenged with a novel task. Together, these findings highlight the potential of stimulating neurogenesis as a means to enhance learning.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

PubMed

Herrera-Pérez, J J; Martínez-Mota, L; Jiménez-Rubio, G; Ortiz-López, L; Cabrera-Muñoz, E A; Galindo-Sevilla, N; Zambrano, E; Hernández-Luis, F; Ramírez-Rodríguez, G B; Flores-Ramos, M

2017-03-15

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

SDF1 Reduces Interneuron Leading Process Branching through Dual Regulation of Actin and Microtubules

PubMed Central

Lysko, Daniel E.; Putt, Mary

2014-01-01

Normal cerebral cortical function requires a highly ordered balance between projection neurons and interneurons. During development these two neuronal populations migrate from distinct progenitor zones to form the cerebral cortex, with interneurons originating in the more distant ganglionic eminences. Moreover, deficits in interneurons have been linked to a variety of neurodevelopmental disorders underscoring the importance of understanding interneuron development and function. We, and others, have identified SDF1 signaling as one important modulator of interneuron migration speed and leading process branching behavior in mice, although how SDF1 signaling impacts these behaviors remains unknown. We previously found SDF1 inhibited leading process branching while increasing the rate of migration. We have now mechanistically linked SDF1 modulation of leading process branching behavior to a dual regulation of both actin and microtubule organization. We find SDF1 consolidates actin at the leading process tip by de-repressing calpain protease and increasing proteolysis of branched-actin-supporting cortactin. Additionally, SDF1 stabilizes the microtubule array in the leading process through activation of the microtubule-associated protein doublecortin (DCX). DCX stabilizes the microtubule array by bundling microtubules within the leading process, reducing branching. These data provide mechanistic insight into the regulation of interneuron leading process dynamics during neuronal migration in mice and provides insight into how cortactin and DCX, a known human neuronal migration disorder gene, participate in this process. PMID:24695713

Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation.

PubMed

Lee, Hae-June; Kim, Joong-Sun; Song, Myoung-Sub; Seo, Heung-Sik; Yang, Miyoung; Kim, Jong Choon; Jo, Sung-Kee; Shin, Taekyun; Moon, Changjong; Kim, Sung-Ho

2010-03-01

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.

Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice

PubMed Central

Yun, Sanghee; Donovan, Michael H.; Ross, Michele N.; Richardson, Devon R.; Reister, Robin; Farnbauch, Laure A.; Fischer, Stephanie J.; Riethmacher, Dieter; Gershenfeld, Howard K.; Lagace, Diane C.; Eisch, Amelia J.

2016-01-01

Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient–rather than permanent–inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreERT2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12–30 days post-TAM displayed indices of a stress-induced anxiety phenotype–longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype–longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety and a depressive phenotype, and recovery of DCX+ cell number corresponds to normalization of these behaviors. PMID:26795203

Developmental and Adult GAP-43 Deficiency in Mice Dynamically Alters Hippocampal Neurogenesis and Mossy Fiber Volume

PubMed Central

Latchney, Sarah E.; Masiulis, Irene; Zaccaria, Kimberly J.; Lagace, Diane C.; Powell, Craig M.; McCasland, James S.; Eisch, Amelia J.

2014-01-01

Growth Associated Protein-43 (GAP-43) is a pre-synaptic protein that plays key roles in axonal growth and guidance and in modulating synapse formation. Previous work has demonstrated that mice lacking one allele of this gene [GAP-43(+/-) mice] exhibit hippocampal structural abnormalities and impaired spatial learning and stress-induced behavioral withdrawal and anxiety (Zaccaria et al., 2010), behaviors that are dependent on proper hippocampal circuitry and function. Given the correlation between hippocampal function, synaptic connectivity, and neurogenesis, we tested if behaviorally-naïve GAP-43(+/-) mice had alterations in either neurogenesis or synaptic connectivity in the hippocampus during early postnatal development and young adulthood, and following behavior testing in older adults. To test our hypothesis, we examined hippocampal cell proliferation (Ki67), number of immature neuroblasts (DCX), and mossy fiber volume (synaptoporin) in behaviorally-naïve postnatal (P) day 9 (P9), P26, and behaviorally-experienced 5-7 month old GAP-43(+/-) and (+/+) littermate mice. P9 GAP-43(+/-) mice had fewer Ki67+ and DCX+ cells compared to (+/+) mice, particularly in the posterior dentate gyrus, and smaller mossy fiber volume in the same region. In young adulthood, however, male GAP-43(+/-) mice had more Ki67+ and DCX+ cells and greater mossy fiber volume in the posterior dentate gyrus relative to male (+/+). These increases were not seen in females. In 5-7 month old GAP-43(+/-) mice whose behaviors were the focus of our prior publication (Zaccaria et al., 2010), there was no global change in number of proliferating or immature neurons relative to (+/+) mice. However, more detailed analysis revealed fewer proliferative DCX+ cells in the anterior dentate gyrus of male GAP-43(+/-) mice compared to male (+/+) mice. This reduction was not observed in females. These results suggest that young GAP-43(+/-) mice have decreased hippocampal neurogenesis and synaptic connectivity, but slightly older mice have greater hippocampal neurogenesis and synaptic connectivity. In conjunction with our previous study, these findings suggest GAP-43 is dynamically involved in early postnatal and adult hippocampal neurogenesis and synaptic connectivity, possibly contributing to the GAP-43(+/-) behavioral phenotype. PMID:24576816

Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice.

PubMed

Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Bae, Chun-Sik; Kim, Joong-Sun; Shin, Taekyun; Moon, Changjong

2012-03-01

Object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice exposed to cranial fast neutron irradiation (0.8 Gy) were examined to evaluate hippocampus-related behavioral dysfunction following acute exposure to relatively low doses of fast neutrons. In addition, hippocampal neurogenesis changes in adult murine brain after cranial irradiation were analyzed using the neurogenesis immunohistochemical markers Ki-67 and doublecortin (DCX). In the object recognition memory test and contextual fear conditioning, mice trained 1 and 7 days after irradiation displayed significant memory deficits compared to the sham-irradiated controls. The number of Ki-67- and DCX-positive cells decreased significantly 24 h post-irradiation. These results indicate that acute exposure of the adult mouse brain to a relatively low dose of fast neutrons interrupts hippocampal functions, including learning and memory, possibly by inhibiting neurogenesis.

Reduced cell proliferation and neuroblast differentiation in the dentate gyrus of high fat diet-fed mice are ameliorated by metformin and glimepiride treatment.

PubMed

Yoo, Dae Young; Kim, Woosuk; Nam, Sung Min; Yoo, Ki-Yeon; Lee, Choong Hyun; Choi, Jung Hoon; Won, Moo-Ho; Hwang, In Koo; Yoon, Yeo Sung

2011-12-01

We investigated the effects of a high-fat diet (HFD) and the subsequent treatment of metformin (met) and glimepiride (glim), which are widely prescribed for type 2 diabetes, on cell proliferation and neuroblast differentiation using Ki67 and doublecortin (DCX) immunohistochemistry, respectively. Animals were fed low-fat diet (LFD) or HFD for 8 weeks. After 5 weeks of the HFD treatment, met alone or met + glim was administered orally once a day for 3 weeks. Body weight and food intake were much higher in the HFD + vehicle-treated group than the LFD-treated group. The administration of met or met + glim to the HFD-treated group resulted in a decrease in weight gain and food intake. Ki67-immunoreactive ((+)) nuclei, DCX(+) neuroblasts and brain-derived neurotrophic factor (BDNF) protein levels were markedly decreased in the dentate gyrus (DG) of the HFD + vehicle-treated group compared to the LFD-treated group. The administration of met or met + glim to the HFD-treated group prevented the reduction of Ki67(+) nuclei, DCX(+) neuroblasts, BDNF levels in the DG. The intraventricular injection of K252a (a BDNF receptor blocker) to the HFD-treated group treated met or met + glim distinctively lowered the reduction of cell proliferation and neuroblast differentiation induced by HFD. These results suggest that a HFD significantly reduces cell proliferation and neuroblast differentiation by reducing BDNF levels and these effects are ameliorated by treatment with met or met + glim.

Extract of Ginkgo biloba promotes neuronal regeneration in the hippocampus after exposure to acrylamide.

PubMed

Huang, Wei-Ling; Ma, Yu-Xin; Fan, Yu-Bao; Lai, Sheng-Min; Liu, Hong-Qing; Liu, Jing; Luo, Li; Li, Guo-Ying; Tian, Su-Min

2017-08-01

Previous studies have demonstrated a neuroprotective effect of extract of Ginkgo biloba against neuronal damage, but have mainly focused on antioxidation of extract of Ginkgo biloba . To date, limited studies have determined whether extrasct of Ginkgo biloba has a protective effect on neuronal damage. In the present study, acrylamide and 30, 60, and 120 mg/kg extract of Ginkgo biloba were administered for 4 weeks by gavage to establish mouse models. Our results showed that 30, 60, and 120 mg/kg extract of Ginkgo biloba effectively alleviated the abnormal gait of poisoned mice, and up-regulated protein expression levels of doublecortin (DCX), brain-derived neurotrophic factor, and growth associated protein-43 (GAP-43) in the hippocampus. Simultaneously, DCX- and GAP-43-immunoreactive cells increased. These findings suggest that extract of Ginkgo biloba can mitigate neurotoxicity induced by acrylamide, and thereby promote neuronal regeneration in the hippocampus of acrylamide-treated mice.

Ambient temperature influences the neural benefits of exercise.

PubMed

Maynard, Mark E; Chung, Chasity; Comer, Ashley; Nelson, Katharine; Tran, Jamie; Werries, Nadja; Barton, Emily A; Spinetta, Michael; Leasure, J Leigh

2016-02-15

Many of the neural benefits of exercise require weeks to manifest. It would be useful to accelerate onset of exercise-driven plastic changes, such as increased hippocampal neurogenesis. Exercise represents a significant challenge to the brain because it produces heat, but brain temperature does not rise during exercise in the cold. This study tested the hypothesis that exercise in cold ambient temperature would stimulate hippocampal neurogenesis more than exercise in room or hot conditions. Adult female rats had exercise access 2h per day for 5 days at either room (20 °C), cold (4.5 °C) or hot (37.5 °C) temperature. To label dividing hippocampal precursor cells, animals received daily injections of BrdU. Brains were immunohistochemically processed for dividing cells (Ki67+), surviving cells (BrdU+) and new neurons (doublecortin, DCX) in the hippocampal dentate gyrus. Animals exercising at room temperature ran significantly farther than animals exercising in cold or hot conditions (room 1490 ± 400 m; cold 440 ± 102 m; hot 291 ± 56 m). We therefore analyzed the number of Ki67+, BrdU+ and DCX+ cells normalized for shortest distance run. Contrary to our hypothesis, exercise in either cold or hot conditions generated significantly more Ki67+, BrdU+ and DCX+ cells compared to exercise at room temperature. Thus, a limited amount of running in either cold or hot ambient conditions generates more new cells than a much greater distance run at room temperature. Taken together, our results suggest a simple means by which to augment exercise effects, yet minimize exercise time. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic exercise prevents repeated restraint stress-provoked enhancement of immobility in forced swimming test in ovariectomized mice.

PubMed

Han, Tae-Kyung; Lee, Jang-Kyu; Leem, Yea-Hyun

2015-06-01

We assessed whether chronic treadmill exercise attenuated the depressive phenotype induced by restraint stress in ovariectomized mice (OVX). Immobility of OVX in the forced swimming test was comparable to that of sham mice (CON) regardless of the postoperative time. Immobility was also no difference between restrained mice (exposure to periodic restraint for 21 days; RST) and control mice (CON) on post-exposure 2nd and 9th day, but not 15th day. In contrast, the immobility of ovariectomized mice with repeated stress (OVX + RST) was profoundly enhanced compared to ovariectomized mice-alone (OVX), and this effect was reversed by chronic exercise (19 m/min, 60 min/day, 5 days/week for 8 weeks; OVX + RST + Ex) or fluoxetine administration (20 mg/kg, OVX + RST + Flu). In parallel with behavioral data, the immunoreactivity of Ki-67 and doublecortin (DCX) in OVX was significantly decreased by repeated stress. However, the reduced numbers of Ki-67- and DCX-positive cells in OVX + RST were restored in response to chronic exercise (OVX + RST + Ex) and fluoxetine (OVX + RST + Flu). In addition, the expression pattern of cAMP response element-binding protein (CREB) and calcium-calmodulin-dependent kinase IV (CaMKIV) was similar to that of the hippocampal proliferation and neurogenesis markers (Ki-67 and DCX, respectively). These results suggest that menopausal depression may be induced by an interaction between repeated stress and low hormone levels, rather than a deficit in ovarian secretion alone, which can be improved by chronic exercise.

Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.

PubMed

Rogers, Danny A; Schor, Nina F

2013-03-10

Peripheral neuroblastic tumors exist as a heterogeneous mixture of neuroblastic (N-type) cells and Schwannian stromal (S-type) cells. These stromal cells not only represent a differentiated and less aggressive fraction of the tumor, but also have properties that can influence the further differentiation of nearby malignant cells. In vitro neuroblastoma cultures exhibit similar heterogeneity with N-type and S-type cells representing the neuroblastic and stromal portions of the tumor, respectively, in behavior, morphology, and molecular expression patterns. In this study, we deplete kinase D-interacting substrate of 220kD (Kidins220) with an shRNA construct and thereby cause morphologic transition of the human SH-SY5Y neuroblastoma cell line from N-type to S-type. The resulting cells have similar morphology and expression profile to SH-EP1 cells, a native S-type cell line from the same parent cell line, and to SH-SY5Y cells treated with BrdU, a treatment that induces S-type morphology. Specifically, both Kidins220-deficient SH-SY5Y cells and native SH-EP1 cells demonstrate down-regulation of the genes DCX and STMN2, markers for the neuronal lineage. We further show that Kidins220, DCX and STMN2 are co-down-regulated in cells of S-type morphology generated by methods other than Kidins220 depletion. Finally, we report that the association of low Kidins220 expression with S-type morphology and low DCX and STMN2 expression is demonstrated in spontaneously occurring human peripheral neuroblastic tumors. We propose that Kidins220 is critical in N- to S-type transition of neural crest tumor cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of pyridoxine on a high-fat diet-induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus.

PubMed

Yoo, Dae Young; Kim, Woosuk; Yoo, Ki-Yeon; Nam, Sung Min; Chung, Jin Young; Yoon, Yeo Sung; Won, Moo-Ho; Hwang, In Koo

2012-08-01

In this study, we challenged pyridoxine to mice fed a high-fat diet (HFD) and investigated the effects of pyridoxine on HFD-induced phenotypes such as blood glucose, reduction of cell proliferation and neuroblast differentiation in the dentate gyrus using Ki67 and doublecortin (DCX), respectively. Mice were fed a commercially available low-fat diet (LFD) as control diet or HFD (60% fat) for 8 weeks. After 5 weeks of LFD or HFD treatment, 350 mg/kg pyridoxine was administered for 3 weeks. The administration of pyridoxine significantly decreased body weight in the HFD-treated group. In addition, there were no significant differences in hepatic histology and pancreatic insulin-immunoreactive (-ir) and glucagon-ir cells of the HFD-treated group after pyridoxine treatment. In the HFD-fed group, Ki67-positive nuclei and DCX-ir neuroblasts were significantly decreased in the dentate gyrus compared with those in the LFD-fed mice. However, the administration of pyridoxine significantly increased Ki67-positive nuclei and DCX-ir neuroblasts in the dentate gyrus in both LFD- and HFD-fed mice. In addition, the administration of pyridoxine significantly increased the protein levels of glutamic acid decarboxylase 67 (GAD67) and brain-derived neurotrophic factor (BDNF) and the immunoreactivity of phosphorylated cyclic AMP response element binding protein (pCREB) compared with the vehicle-treated LFD- and HFD-fed mice. In contrast, the administration of pyridoxine significantly decreased HFD-induced malondialdehyde (MDA) levels in the hippocampus. These results showed that pyridoxine supplement reduced the HFD-induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus via controlling the levels of GAD67, pCREB, BDNF, and MDA. Copyright © 2012 Wiley Periodicals, Inc.

Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

PubMed

Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

2017-11-01

Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

Systemic administration of low dosage of tetanus toxin decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

PubMed Central

Yan, Bing Chun; Kim, In Hye; Park, Joon Ha; Ahn, Ji Hyeon; Cho, Jeong-Hwi; Chen, Bai Hui; Lee, Jae-Chul; Choi, Jung Hoon; Yoo, Ki-Yeon; Lee, Choong Hyun; Cho, Jun Hwi

2013-01-01

In the present study, we investigated the effect of Tetaus toxin (TeT) on cell proliferation and neuroblast differentiation using specific markers: 5-bromo-2-deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an endogenous marker for cell proliferation and doublecortin (DCX) as a marker for neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days after the treatment. In both the TeT-treated groups, no neuronal death occurred in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of neuronal degeneration). In addition, no significant change in glial activation in both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX immunoreactive cells, respectively, were apparently decreased compared to the control group, and the mean number of each in the 10 ng/kg TeT-treated-group was much more decreased. In addition, processes of DCX-immunoreactive cells, which projected into the molecular layer, were short compared to those in the control group. In brief, our present results show that low dosage (10 ng/kg) TeT treatment apparently decreased cell proliferation and neuroblast differentiation in the mouse hippocampal DG without distinct gliosis as well as any loss of adult neurons. PMID:24106509

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.

PubMed

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong Choon; Kang, Seong Soo; Bae, Chun-Sik; Shin, Taekyun; Jin, Jae-Kwang; Kim, Sung Ho; Wang, Hongbing; Moon, Changjong

2008-09-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.

Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis.

PubMed

Shevchouk, Olesya T; Ball, Gregory F; Cornil, Charlotte A; Balthazart, Jacques

2017-01-01

In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers.

Dual Active Bridge based DC Transformer LabVIEW FPGA Control Code

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

In the area of power electronics control, Field Programmable Gate Arrays (FPGAs) have the capability to outperform their Digital Signal Processor (DSP) counterparts due to the FPGA’s ability to implement true parallel processing and therefore facilitate higher switching frequencies, higher control bandwidth, and/or enhanced functionality. National Instruments (NI) has developed two platforms, Compact RIO (cRIO) and Single Board RIO (sbRIO), which combine a real-time processor with an FPGA. The FPGA can be programmed with a subset of the well-known LabVIEW graphical programming language. The candidate software implements complete control algorithms in LabVIEW FPGA for a DC Transformer (DCX) based onmore » a dual active bridge (DAB). A DCX is an isolated bi-directional DC-DC converter designed to operate at unity conversion ratio, M, defined by where Vin is the primary-side DC bus voltage, Vout is the secondary-side DC bus voltage, and n is the turns ratio of the embedded high frequency transformer (HFX). The DCX based on a DAB incorporates two H-bridges, a resonant inductor, and an HFX to provide this functionality. The candidate software employs phase-shift modulation of the two H-bridges and a feedback loop to regulate the conversion ratio at unity. The software also includes alarm-handling capabilities as well as debugging and tuning tools. The software fits on the Xilinx Virtex V LX110 FPGA embedded in the NI cRIO-9118 FPGA chassis, and with a 40 MHz base clock, supports a modulation update rate of 40 MHz, and user-settable switching frequencies and synchronized control loop update rates of tens of kHz.« less

Dose-response and relative biological effectiveness of fast neutrons: induction of apoptosis and inhibition of neurogenesis in the hippocampus of adult mice.

PubMed

Yang, Miyoung; Kim, Joong-Sun; Song, Myoung-Sub; Kim, Jong-Choon; Shin, Taekyun; Lee, Seung-Sook; Kim, Sung-Ho; Moon, Changjong

2010-06-01

Our study compared the effects of high linear energy transfer (LET) fast neutrons on the induction of apoptosis and reduction of neurogenesis in the hippocampus of adult ICR mice with those of low-LET (60)Co gamma-rays, to evaluate the relative biological effectiveness (RBE) of fast neutrons in the adult hippocampal dentate gyrus (DG). The mice were exposed to 35 MeV fast neutrons or (60)Co gamma-rays. We evaluated acutely the incidence of apoptosis and expression of Ki-67 (a protein marker for cell proliferation originally defined by the monoclonal antibody Kiel-67) and doublecortin (DCX: an immature progenitor neuron marker) in the hippocampus after a single whole-body irradiation. The number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL)-positive apoptotic nuclei in the DG increased and both Ki-67- and DCX-positive cells declined in a dose-dependent pattern, with fast neutrons or gamma-rays. In the hippocampus, which showed an apoptosis frequency between 2 and 8 per DG, the RBE of fast neutrons was approximately 1.9. Additionally, the inhibitory effects of fast neutrons on the expression frequencies of Ki-67 (4-8) and DCX (8-32) were approximately 3.2 and 2.5 times, respectively, the effects of gamma-rays at the same dose. Increased apoptotic cell death and decreased neurogenesis in the hippocampal DG were seen in a dose-dependent pattern after exposure to fast neutrons and gamma-rays. In addition, the different rate of hippocampal neurogenesis between different radiation qualities may be an index of RBE.

Studies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis

PubMed Central

Shevchouk, Olesya T.; Ball, Gregory F.; Cornil, Charlotte A.

2017-01-01

In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β-estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. PMID:28141859

Voluntary Wheel Running Reverses the Decrease in Subventricular Zone Neurogenesis Caused by Corticosterone.

PubMed

Lee, Jada Chia-Di; Yau, Suk-Yu; Lee, Tatia M C; Lau, Benson Wui-Man; So, Kwok-Fai

2016-11-01

Adult neurogenesis within the dentate gyrus (DG) of the hippocampus can be increased by voluntary exercise but is suppressed under stress, such as with corticosterone (CORT). However, the effects of exercise and CORT on the cell proliferation of the other traditional neurogenic site, the subventricular zone (SVZ), have been reported with controversial results. In addition, the cotreatment effects of voluntary exercise and CORT have not been investigated. This study aims to determine whether CORT can suppress cell proliferation in the SVZ and whether this can be reversed by voluntary exercise. In the present study, the effect of chronic (4 weeks) CORT treatment and wheel running simultaneously on the SVZ cell proliferation of adult Sprague-Dawley rats was examined. The results showed that cell proliferation indicated by bromodeoxyuridine (BrdU) was increased by voluntary wheel running, whereas it was decreased by CORT treatment within the SVZ of the rats without running. For the rats with both CORT treatment and wheel running, it was found that the number of BrdU-labeled cells was approximately at the same level as the vehicle control group. Furthermore, these proliferating cells expressed doublecortin (DCX), a migrating neuroblast marker. Wheel running increased the percentage of BrdU-labeled cells expressing DCX in the SVZ, whereas CORT treatment decreased this percentage. Thus, chronic injection of CORT can decrease the number of proliferating cells, while wheel running can reverse the decrease in cell proliferation within the SVZ to normal levels. In addition, CORT can suppress the cell differentiation within the SVZ, and this was alleviated by wheel running as indicated by the double labeling of BrdU and DCX.

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

PubMed Central

Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo

2016-01-01

Purpose Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. Materials and Methods This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Results Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Conclusion Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders. PMID:27593875

Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation.

PubMed

Song, Juhyun; Oh, Yumi; Kim, Jong Youl; Cho, Kyoung Joo; Lee, Jong Eun

2016-11-01

Neural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis. This study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression. Our data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a. Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Understanding the Etiology of Tuberous Sclerosis Complex

DTIC Science & Technology

2012-07-01

catalog #4856), mouse anti-NeuN (1:500; Millipore), GFAP (1:100, DAKO) and DCX (1:500, Santa Cruz Biotechnology). Each staining was replicated in slices...Tramontin, A.D., Quinones-Hinojosa, A., Barbaro, N.M., Gupta, N., Kunwar, S., Lawton, M.T., McDermott, M.W., Parsa, A.T., Manuel -Garcia, V.J. et al

Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

PubMed

Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

2014-04-01

To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male Swiss albino mice by modulating hippocampal insulin signaling pathway.

PubMed

Mehta, Vineet; Singh, Tiratha Raj; Udayabanu, Malairaman

2017-12-01

Chronic stress is associated with impaired neurogenesis, neurodegeneration and behavioral dysfunction, whereas the mechanism underlying stress-mediated neurological complications is still not clear. In the present study, we aimed to investigate whether chronic unpredicted stress (CUS) mediated neurological alterations are associated with impaired hippocampal insulin signaling or not, and studied the effect of quercetin in this scenario. Male Swiss albino mice were subjected to 21day CUS, during which 30mg/kg quercetin treatment was given orally. After 21days, behavioral functions were evaluated in terms of locomotor activity (Actophotometer), muscle coordination (Rota-rod), depression (Tail Suspension Test (TST), Forced Swim Test (FST)) and memory performance (Passive-avoidance step-down task (PASD)). Further, hippocampal insulin signaling was evaluated in terms of protein expression of insulin, insulin receptor (IR) and glucose transporter 4 (GLUT-4) and neurogenesis was evaluated in terms of doublecortin (DCX) expression. 21day CUS significantly impaired locomotion and had no effect on muscle coordination. Stressed animals were depressed and showed markedly impaired memory functions. Quercetin treatment significantly improvement stress-mediated behavior dysfunction as indicated by improved locomotion, lesser immobility time and greater frequency of upward turning in TST and FST and increased transfer latency on the day 2 (short-term memory) and day 5 (long-term memory) in PASD test. We observed significantly higher IR expression and significantly lower GLUT-4 expression in the hippocampus of stressed animals, despite of nonsignificant difference in insulin levels. Further, chronic stress impaired hippocampal neurogenesis, as indicated by the significantly reduced levels of hippocampal DCX expression. Quercetin treatment significantly lowered insulin and IR expression and significantly enhanced GLUT-4 and DCX expression in the hippocampus, when compared to CUS. In conclusion, quercetin treatment efficiently alleviated stress mediated behavioral dysfunction by modulating hippocampal insulin signaling and neurogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons.

PubMed

Orts-Del'Immagine, Adeline; Trouslard, Jérôme; Airault, Coraline; Hugnot, Jean-Philippe; Cordier, Baptiste; Doan, Thierry; Kastner, Anne; Wanaverbecq, Nicolas

2017-02-20

The central canal along the spinal cord (SC.) and medulla is characterized by the presence of a specific population of neurons that contacts the cerebrospinal fluid (CSF). These medullo-spinal CSF-contacting neurons (CSF-cNs) are identified by the selective expression of the polycystin kidney disease 2-like 1 ionic channel (PKD2L1 or polycystin-L). In adult, they have been shown to express doublecortin (DCX) and Nkx6.1, two markers of juvenile neurons along with the neuron-specific nuclear protein (NeuN) typically expressed in mature neurons. They were therefore suggested to remain in a rather incomplete maturation state. The aim of this study was to assess whether such juvenile state is stable in postnatal animals or whether CSF-cNs may reach maturity at older stages than neurons in the parenchyma. We show, in the cervical SC. and the brainstem that, in relation to age, CSF-cN density declines and that their cell bodies become more distant from the cc, except in its ventral part. Moreover, in adults (from 1month) by comparison with neonatal mice, we show that CSF-cNs have evolved to a more mature state, as indicated by the increase in the percentage of cells positive for NeuN and of its level of expression. In parallel, CSF-cNs exhibit, in adult, lower DCX immunoreactivity and do not express PSA-NCAM and TUC4, two neurogenic markers. Nevertheless, CSF-cNs still share in adult characteristics of juvenile neurons such as the presence of phospho-CREB and DCX while NeuN expression remained low. This phenotype persists in 12-month-old animals. Thus, despite a pursuit of neuronal maturation during the postnatal period, CSF-cNs retain a durable low differentiated state. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Behavioral deficits induced by third-trimester equivalent alcohol exposure in male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis but are still rescued with voluntary exercise.

PubMed

Hamilton, G F; Bucko, P J; Miller, D S; DeAngelis, R S; Krebs, C P; Rhodes, J S

2016-11-01

Prenatal alcohol exposure can produce permanent alterations in brain structure and profound behavioral deficits. Mouse models can help discover mechanisms and identify potentially useful interventions. This study examined long-term influences of either a single or repeated alcohol exposure during the third-trimester equivalent on survival of new neurons in the hippocampus, behavioral performance on the Passive avoidance and Rotarod tasks, and the potential role of exercise as a therapeutic intervention. C57BL/6J male mice received either saline or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned on PD21 and received either a running wheel or remained sedentary from PD35-PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine (BrdU) to label dividing cells. Behavioral testing occurred between PD72-79. Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in either experiment. Running significantly increased number of BrdU+ and DCX+ cells in both treatment groups. Alcohol-induced deficits on Rotarod performance and acquisition of the Passive avoidance task (Day 1) were evident only in Experiment 2 and running rescued these deficits. These data suggest neonatal alcohol exposure does not result in long-term impairments in adult hippocampal neurogenesis in the mouse model. Three doses of ethanol were necessary to induce behavioral deficits. Finally, the mechanisms by which exercise ameliorated the neonatal alcohol induced behavioral deficits remain unknown. Copyright © 2016 Elsevier B.V. All rights reserved.

Hippocampal neurogenesis and cortical cellular plasticity in Wahlberg's epauletted fruit bat: a qualitative and quantitative study.

PubMed

Gatome, Catherine W; Mwangi, Deter K; Lipp, Hans-Peter; Amrein, Irmgard

2010-01-01

Species-specific characteristics of neuronal plasticity emerging from comparative studies can address the functional relevance of hippocampal or cortical plasticity in the light of ecological adaptation and evolutionary history of a given species. Here, we present a quantitative and qualitative analysis of neurogenesis in young and adult free-living Wahlberg's epauletted fruit bats. Using the markers for proliferating cell nuclear antigen (PCNA), bromodeoxyuridine (BrdU), doublecortin (DCX) and polysialic acid neural cell adhesion molecule (PSA-NCAM), our findings in the hippocampus, olfactory bulb and cortical regions are described and compared to reports in other mammals. Expressed as a percentage of the total number of granule cells, PCNA- and BrdU-positive cells accounted for 0.04 in young to 0.01% in adult animals; DCX-positive cells for 0.05 (young) to 0.01% (adult); PSA-NCAM-positive cells for 0.1 (young) to 0.02% (adult), and pyknotic cells for 0.007 (young) to 0.005% (adult). The numbers were comparable to other long-lived, late-maturing mammals such as primates. A significant increase in the total granule cell number from young to adult animals demonstrated the successful formation and integration of new cells. In adulthood, granule cell number appeared stable and was surprisingly low in comparison to other species. Observations in the olfactory bulb and rostral migratory stream were qualitatively similar to descriptions in other species. In the ventral horn of the lateral ventricle, we noted prominent expression of DCX and PSA-NCAM forming a temporal migratory stream targeting the piriform cortex, possibly reflecting the importance of olfaction to these species. Low, but persistent hippocampal neurogenesis in non-echolocating fruit bats contrasted the findings in echolocating microbats, in which hippocampal neurogenesis was largely absent. Together with the observed intense cortical plasticity in the olfactory system of fruit bats we suggest a differential influence of sensory modalities on hippocampal and cortical plasticity in this mammalian order. Copyright © 2010 S. Karger AG, Basel.

Environmental Assessment: Single Stage Rocket Technology DC-X Test Program

DTIC Science & Technology

1992-06-01

the National Historic Preservation Act (NHPA) requires Federal agencies to consider the affects of their proposed actions on historic properties, which...activities were coordinated with the New Mexico State Historic * Preservation Office. June 1992 Uncidsifled !2-7 Environmntal Assesmnkw~ SSRTI Habitat... Preservation (ACHP), and the New Mexico State Historic Preservation Office. Compliance with Section 106 of the National Historic Preservation Act for the SSRT

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

PubMed Central

Kalmar, Alain F.; Doorduin, Janine; Struys, Michel M. R. F.; Schoemaker, Regien G.; Absalom, Anthony R.

2018-01-01

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage. PMID:29451906

TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors.

PubMed

Elmi, Muna; Matsumoto, Yoshiki; Zeng, Zhao-jun; Lakshminarasimhan, Pavithra; Yang, Weiwen; Uemura, Akiyoshi; Nishikawa, Shin-ichi; Moshiri, Alicia; Tajima, Nobuyoshi; Agren, Hans; Funa, Keiko

2010-10-01

The orphan nuclear receptor TLX has been proposed to act as a repressor of cell cycle inhibitors to maintain the neural stem cells in an undifferentiated state, and prevents commitment into astrocyte lineages. However, little is known about the mechanism of TLX in neuronal lineage commitment and differentiation. A majority of adult rat hippocampus-derived progenitors (AHPs) cultured in the presence of FGF express a high level of TLX and a fraction of these cells also express the proneural gene MASH1. Upon FGF withdrawal, TLX rapidly decreased, while MASH1 was intensely expressed within 1h, decreasing gradually to disappear at 24h. Adenoviral transduction of TLX in AHP cells in the absence of FGF transiently increased cell proliferation, however, later resulted in neuronal differentiation by inducing MASH1, Neurogenin1, DCX, and MAP2ab. Furthermore, TLX directly targets and activates the MASH1 promoter through interaction with Sp1, recruiting co-activators whereas dismissing the co-repressor HDAC4. Conversely, silencing of TLX in AHPs decreased beta-III tubulin and DCX expression and promoted glial differentiation. Our results thus suggest that TLX not only acts as a repressor of cell cycle and glial differentiation but also activates neuronal lineage commitment in AHPs. Copyright 2010 Elsevier Inc. All rights reserved.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

PubMed

Chiaretti, Antonio; Conti, Giorgio; Falsini, Benedetto; Buonsenso, Danilo; Crasti, Matteo; Manni, Luigi; Soligo, Marzia; Fantacci, Claudia; Genovese, Orazio; Calcagni, Maria Lucia; Di Giuda, Daniela; Mattoli, Maria Vittoria; Cocciolillo, Fabrizio; Ferrara, Pietro; Ruggiero, Antonio; Staccioli, Susanna; Colafati, Giovanna Stefania; Riccardi, Riccardo

2017-01-01

Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

Single Stage Rocket Technology (SSRT) DC-X Test Program Environmental Assessment

DTIC Science & Technology

1992-06-01

23). 2.2.1.5 Cultural Resources Section 106 of the National Historic Preservation Act (NHPA) requires Federal agencies to consider the affects of...were coordinated with the New Mexico State Historic Preservation Office. June 1992 UncLassified 2-7 EaWronmemW~ AWsnevssln SSRT Habitat lor White... Preservation (ACHP), and the New Mexico State Historic Preservation Office. Compliance with Section 106 of the National Historic Preservation Act for the

Advanced Space Transportation Program (ASTP)

NASA Image and Video Library

1995-01-23

Pictured here is a DC-XA Reusable Launch Vehicle (RLV) prototype concept with an RLV logo. The Delta Clipper-Experimental (DC-X) was originally developed by McDornell Douglas for the Department of Defense (DOD). The DC-XA is a single-stage-to-orbit, vertical takeoff/vertical landing, launch vehicle concept, whose development is geared to significantly reduce launch costs and will provide a test bed for NASA Reusable Launch Vehicle (RLV) technology as the Delta Clipper-Experimental Advanced (DC-XA).

The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats.

PubMed

Ghumatkar, Priya; Peshattiwar, Vaibhavi; Patil, Sachin; Muke, Suraj; Whitfield, David; Howlett, David; Francis, Paul; Sathaye, Sadhana

2018-04-23

Considering the deleterious effect of Aβ1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in Aβ1-42-injected Wistar rats. The rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated Aβ1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis. The Western blot revealed that Aβ1-42-injected rats had significantly low levels of synaptophysin as compared to sham control. Phloretin pretreatment significantly protected the presynaptic protein synaptophysin against the effects of Aβ1-42. There were no significant changes in the levels of PSD95 between different groups. The IHC findings showed that Aβ1-42 significantly reduced the Ki67 and DCX in the dentate gyrus as compared to sham control. However, phloretin significantly improved the number of Ki67- and DCX-positive neurons in the dentate gyrus region as compared to Aβ1-42 group. This study demonstrated the protective effect of phloretin on synaptophysin and adult neuronal proliferating cells in Aβ1-42-injected rats. The encouraging findings highlight the potential of phloretin as a dietary supplement targeting key therapeutic mechanisms in neurodegenerative disorders such as AD. © 2018 Royal Pharmaceutical Society.

Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease.

PubMed

Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

2013-01-01

Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer's disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD.

Intranasal Delivery of Plasma and Platelet Growth Factors Using PRGF-Endoret System Enhances Neurogenesis in a Mouse Model of Alzheimer’s Disease

PubMed Central

Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Antequera, Desiree; Padilla, Sabino; Orive, Gorka; Carro, Eva

2013-01-01

Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimer’s disease (AD) induced by a combination of toxic amyloid-β peptide (Aβ) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce Aβ-induced neurodegeneration in a mouse model of AD. PMID:24069173

Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB.

PubMed

Chen, Bai Hui; Ahn, Ji Hyeon; Park, Joon Ha; Song, Minah; Kim, Hyunjung; Lee, Tae-Kyeong; Lee, Jae Chul; Kim, Young-Myeong; Hwang, In Koo; Kim, Dae Won; Lee, Choong-Hyun; Yan, Bing Chun; Kang, Il Jun; Won, Moo-Ho

2018-04-25

Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB. Copyright © 2018 Elsevier B.V. All rights reserved.

Responses of neurogenesis and neuroplasticity related genes to elevated CO2 levels in the brain of three teleost species.

PubMed

Lai, Floriana; Fagernes, Cathrine E; Bernier, Nicholas J; Miller, Gabrielle M; Munday, Philip L; Jutfelt, Fredrik; Nilsson, Göran E

2017-08-01

The continuous increase of anthropogenic CO 2 in the atmosphere resulting in ocean acidification has been reported to affect brain function in some fishes. During adulthood, cell proliferation is fundamental for fish brain growth and for it to adapt in response to external stimuli, such as environmental changes. Here we report the first expression study of genes regulating neurogenesis and neuroplasticity in brains of three-spined stickleback ( Gasterosteus aculeatus ), cinnamon anemonefish ( Amphiprion melanopus ) and spiny damselfish ( Acanthochromis polyacanthus ) exposed to elevated CO 2 The mRNA expression levels of the neurogenic differentiation factor (NeuroD) and doublecortin (DCX) were upregulated in three-spined stickleback exposed to high-CO 2 compared with controls, while no changes were detected in the other species. The mRNA expression levels of the proliferating cell nuclear antigen (PCNA) and the brain-derived neurotrophic factor (BDNF) remained unaffected in the high-CO 2 exposed groups compared to the control in all three species. These results indicate a species-specific regulation of genes involved in neurogenesis in response to elevated ambient CO 2 levels. The higher expression of NeuroD and DCX mRNA transcripts in the brain of high-CO 2 -exposed three-spined stickleback, together with the lack of effects on mRNA levels in cinnamon anemonefish and spiny damselfish, indicate differences in coping mechanisms among fish in response to the predicted-future CO 2 level. © 2017 The Author(s).

Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS Induced Model of Depression in Rat.

PubMed

Kumar, Sourav; Mondal, Amal Chandra

2016-11-01

Major depression is a life threatening neuropsychiatric disorder that produces mental illness and major cause of morbidity. The present study was conducted to evaluate the neuroprotective, neurotrophic and antioxidant potential of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced behavioral depression in rats. Behavioral tests were carried out for investigation of antidepressant like effects of BME, and potential mechanism was assessed by determining neurotrophin level and hippocampal neurogenesis. Depressive-like behavior was assessed by shuttle-box escape test, forced swim test and tail suspension test. Effect of BME on hypothalamic-pituitary-adrenal (HPA) axis was evaluated by measuring the plasma level of adrenocorticotropic hormone (ACTH) and corticosterone. The expression of brain derived neurotrophic factor (BDNF), neuronal marker doublecortin (DCX) in the hippocampus were measured and hippocampal neurogenesis was investigated by 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). In addition, effects of BME on oxidative stress markers were also measured in the hippocampus of CUS exposed rats. The results indicated that BME significantly able to attenuate the depressive-like behaviors, normalized the levels of ACTH, corticosterone, and up-regulate the expression of BDNF, DCX and BrdU/NeuN in CUS induced rats compared to BME treated rats. It is also found that BME significantly increased the activity of antioxidant enzymes on CUS induced rats. These findings revealed that BME exerted neuroprotective effects possibly by promoting hippocampal neurogenesis with elevation of BDNF level and antioxidant defense against oxidative stress.

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

PubMed Central

Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

2014-01-01

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9–10 HVR counterparts. However, voluntary running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats

PubMed Central

Luo, Jing; Zheng, Haiqing; Zhang, Liying; Zhang, Qingjie; Li, Lili; Pei, Zhong; Hu, Xiquan

2017-01-01

Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats. PMID:28230741

Periadolescent ethanol vapor exposure persistently reduces measures of hippocampal neurogenesis that are associated with behavioral outcomes in adulthood.

PubMed

Ehlers, C L; Liu, W; Wills, D N; Crews, F T

2013-08-06

Excessive alcohol consumption is prevalent among adolescents and may result in lasting neurobehavioral consequences. The use of animal models to study adolescent alcohol exposure has the advantage of allowing for the control necessary in order to evaluate the effects of ethanol on the brain and separate such effects from genetic background and other environmental insults. In the present study the effects of moderate ethanol vapor exposure, during adolescence, on measures of neurogenesis and behavioral measures were evaluated at two different times following ethanol withdrawal, in adulthood. The two groups of Wistar rats were both exposed to intermittent ethanol vapor (14 h on/10h off/day) for 35-36 days from PD 23 to PD 58 (average blood ethanol concentration: 163 mg%). In the first group, after rats were withdrawn from vapor they were subsequently assessed for locomotor activity, conflict behavior in the open field, and behaviors in the forced swim test (FST) and then sacrificed at 72 days of age. The second group of rats were withdrawn from vapor and injected for 5 days with Bromo-deoxy-Uridine (BrdU). Over the next 8 weeks they were also assessed for locomotor activity, conflict behavior in the open field, and behaviors in the FST and then sacrificed at 113/114 days of age. All rats were perfused for histochemical analyses. Ethanol vapor-exposed rats displayed hypoactivity in tests of locomotion and less anxiety-like and/or more "disinhibitory" behavior in the open field conflict. Quantitative analyses of immunoreactivity revealed a significant reduction in measures of neurogenesis, progenitor proliferation, as indexed by doublecortin (DCX), Ki67, and increased markers of cell death as indexed by cleaved caspase-3, and Fluoro-Jade at 72 days, and decreases in DCX, and increases in cleaved caspase-3 at 114 days in the ethanol vapor-exposed rats. Progenitor survival, as assessed by BrdU+, was reduced in the vapor-exposed animals that were sacrificed at 114 days. The reduction seen in DCX labeled in cell counts was significantly correlated with hypoactivity at 24h after withdrawal as well as less anxiety-like and/or more "disinhibitory" behavior in the open field conflict test at 2 and 8 weeks following termination of vapor exposure. These studies demonstrate that behavioral measures of disinhibitory behavior correlated with decreases in neurogenesis are all significantly and persistently impacted by periadolescent ethanol exposure and withdrawal in Wistar rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Reusable launch vehicle development research

NASA Technical Reports Server (NTRS)

1995-01-01

NASA has generated a program approach for a SSTO reusable launch vehicle technology (RLV) development which includes a follow-on to the Ballistic Missile Defense Organization's (BMDO) successful DC-X program, the DC-XA (Advanced). Also, a separate sub-scale flight demonstrator, designated the X-33, will be built and flight tested along with numerous ground based technologies programs. For this to be a successful effort, a balance between technical, schedule, and budgetary risks must be attained. The adoption of BMDO's 'fast track' management practices will be a key element in the eventual success of NASA's effort.

Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats.

PubMed

Loxton, David; Canales, Juan J

2017-03-06

A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

PubMed

Lee, Sung-Min; Kim, Bo-Kyun; Kim, Tae-Woon; Ji, Eun-Sang; Choi, Hyun-Hee

2016-06-01

Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis.

PubMed

Hulshof, Henriëtte J; Novati, Arianna; Luiten, Paul G M; den Boer, Johan A; Meerlo, Peter

2012-10-01

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Whole-Body Exposure to 28Si-Radiation Dose-Dependently Disrupts Dentate Gyrus Neurogenesis and Proliferation in the Short Term and New Neuron Survival and Contextual Fear Conditioning in the Long Term.

PubMed

Whoolery, Cody W; Walker, Angela K; Richardson, Devon R; Lucero, Melanie J; Reynolds, Ryan P; Beddow, David H; Clark, K Lyles; Shih, Hung-Ying; LeBlanc, Junie A; Cole, Mara G; Amaral, Wellington Z; Mukherjee, Shibani; Zhang, Shichuan; Ahn, Francisca; Bulin, Sarah E; DeCarolis, Nathan A; Rivera, Phillip D; Chen, Benjamin P C; Yun, Sanghee; Eisch, Amelia J

2017-11-01

Astronauts traveling to Mars will be exposed to chronic low doses of galactic cosmic space radiation, which contains highly charged, high-energy (HZE) particles. 56 Fe-HZE-particle exposure decreases hippocampal dentate gyrus (DG) neurogenesis and disrupts hippocampal function in young adult rodents, raising the possibility of impaired astronaut cognition and risk of mission failure. However, far less is known about how exposure to other HZE particles, such as 28 Si, influences hippocampal neurogenesis and function. To compare the influence of 28 Si exposure on indices of neurogenesis and hippocampal function with previous studies on 56 Fe exposure, 9-week-old C57BL/6J and Nestin-GFP mice (NGFP; made and maintained for 10 or more generations on a C57BL/6J background) received whole-body 28 Si-particle-radiation exposure (0, 0.2 and 1 Gy, 300 MeV/n, LET 67 KeV/μ, dose rate 1 Gy/min). For neurogenesis assessment, the NGFP mice were injected with the mitotic marker BrdU at 22 h postirradiation and brains were examined for indices of hippocampal proliferation and neurogenesis, including Ki67 + , BrdU + , BrdU + NeuN + and DCX + cell numbers at short- and long-term time points (24 h and 3 months postirradiation, respectively). In the short-term group, stereology revealed fewer Ki67 + , BrdU + and DCX + cells in 1-Gy-irradiated group relative to nonirradiated control mice, fewer Ki67 + and DCX + cells in 0.2 Gy group relative to control group and fewer BrdU + and DCX + cells in 1 Gy group relative to 0.2 Gy group. In contrast to the clearly observed radiation-induced, dose-dependent reductions in the short-term group across all markers, only a few neurogenesis indices were changed in the long-term irradiated groups. Notably, there were fewer surviving BrdU + cells in the 1 Gy group relative to 0- and 0.2-Gy-irradiated mice in the long-term group. When the short- and long-term groups were analyzed by sex, exposure to radiation had a similar effect on neurogenesis indices in male and female mice, although only male mice showed fewer surviving BrdU + cells in the long-term group. Fluorescent immunolabeling and confocal phenotypic analysis revealed that most surviving BrdU + cells in the long-term group expressed the neuronal marker NeuN, definitively confirming that exposure to 1 Gy 28 Si radiation decreased the number of surviving adult-generated neurons in male mice relative to both 0- and 0.2-Gy-irradiated mice. For hippocampal function assessment, 9-week-old male C57BL/6J mice received whole-body 28 Si-particle exposure and were then assessed long-term for performance on contextual and cued fear conditioning. In the context test the animals that received 0.2 Gy froze less relative to control animals, suggesting decreased hippocampal-dependent function. However, in the cued fear conditioning test, animals that received 1 Gy froze more during the pretone portion of the test, relative to controls and 0.2-Gy-irradiated mice, suggesting enhanced anxiety. Compared to previously reported studies, these data suggest that 28 Si-radiation exposure damages neurogenesis, but to a lesser extent than 56 Fe radiation and that low-dose 28 Si exposure induces abnormalities in hippocampal function, disrupting fear memory but also inducing anxiety-like behavior. Furthermore, exposure to 28 Si radiation decreased new neuron survival in long-term male groups but not females suggests that sex may be an important factor when performing brain health risk assessment for astronauts traveling in space.

Sex and seasonal differences in neurogenesis and volume of the song-control system are associated with song in brood-parasitic and non-brood-parasitic icterid songbirds.

PubMed

Guigueno, Mélanie F; Sherry, David F; MacDougall-Shackleton, Scott A

2016-11-01

The song-control system in the brain of songbirds is important for the production and acquisition of song and exhibits both remarkable seasonal plasticity and some of the largest neural sex differences observed in vertebrates. We measured sex and seasonal differences in two nuclei of the song-control system of brood-parasitic brown-headed cowbirds (Molothrus ater) and closely-related non-parasitic red-winged blackbirds (Agelaius phoeniceus). These species differ in both the development and function of song. Brown-headed cowbirds have a larger sex difference in song than red-winged blackbirds. Female cowbirds never sing, whereas female blackbirds do though much less than males. In cowbirds, song primarily functions in mate choice and males modify their song as they approach sexual maturity and interact with females. In red-winged blackbirds, song is used primarily in territorial defence and is crystalized earlier in life. We found that the HVC was more likely to be discernable in breeding female blackbirds than in breeding female cowbirds. Compared to males, females had a smaller HVC and a smaller robust nucleus of the arcopallium (RA). However, females had higher doublecortin immunoreactivity (DCX+) in HVC, a measure of neurogenesis. Consistent with sex differences in song, the sex difference in RA volume was greater in cowbirds than in blackbirds. Males of both species had a smaller HVC with higher DCX+ in post-breeding condition than in breeding condition when song is more plastic. Sex and seasonal differences in the song-control system were closely related to variation in song in these two icterid songbirds. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1226-1240, 2016. © 2016 Wiley Periodicals, Inc.

Hippocampal neurogenesis and volume in migrating and wintering semipalmated sandpipers (Calidris pusilla)

PubMed Central

de Morais Magalhães, Nara Gyzely; Guerreiro Diniz, Daniel; Pereira Henrique, Ediely; Corrêa Pereira, Patrick Douglas; Matos Moraes, Isis Ananda; Damasceno de Melo, Mauro André; Sherry, David Francis; Wanderley Picanço Diniz, Cristovam

2017-01-01

Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla) is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information for navigation. Hippocampal neurogenesis may contribute to hippocampal function and a variety of factors including cognitive activity, exercise, enrichment, diet and stress influence neurogenesis in the hippocampus. We quantified hippocampal neurogenesis and volume in adult migrating and wintering semipalmated sandpipers using stereological counts of doublecortin (DCX) immunolabeled immature neurons. We found that birds captured in the coastal region of Bragança, Brazil during the wintering period had more DCX positive neurons and larger volume in the hippocampus than individuals captured in the Bay of Fundy, Canada during fall migration. We also estimate the number of NeuN immunolabeled cells in migrating and wintering birds and found no significant differences between them. These findings suggest that, at this time window, neurogenesis just replaced neurons that might be lost during the transatlantic flight. Our findings also show that in active fall migrating birds, a lower level of adult hippocampal neurogenesis is associated with a smaller hippocampal formation. High levels of adult hippocampal neurogenesis and a larger hippocampal formation found in wintering birds may be late occurring effects of long distance migratory flight or the result of conditions the birds experienced while wintering. PMID:28591201

Chronic lead exposure reduces doublecortin-expressing immature neurons in young adult guinea pig cerebral cortex.

PubMed

Huang, JuFang; Huang, Kai; Shang, Lei; Wang, Hui; Zhang, Mengqi; Fan, Chun-Ling; Chen, Dan; Yan, Xiaoxin; Xiong, Kun

2012-07-19

Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ). Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 μg/dL at the above time points, respectively, relative to ~3 μg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling. Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death.

Hippocampal neurogenesis and volume in migrating and wintering semipalmated sandpipers (Calidris pusilla).

PubMed

de Morais Magalhães, Nara Gyzely; Guerreiro Diniz, Cristovam; Guerreiro Diniz, Daniel; Pereira Henrique, Ediely; Corrêa Pereira, Patrick Douglas; Matos Moraes, Isis Ananda; Damasceno de Melo, Mauro André; Sherry, David Francis; Wanderley Picanço Diniz, Cristovam

2017-01-01

Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla) is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information for navigation. Hippocampal neurogenesis may contribute to hippocampal function and a variety of factors including cognitive activity, exercise, enrichment, diet and stress influence neurogenesis in the hippocampus. We quantified hippocampal neurogenesis and volume in adult migrating and wintering semipalmated sandpipers using stereological counts of doublecortin (DCX) immunolabeled immature neurons. We found that birds captured in the coastal region of Bragança, Brazil during the wintering period had more DCX positive neurons and larger volume in the hippocampus than individuals captured in the Bay of Fundy, Canada during fall migration. We also estimate the number of NeuN immunolabeled cells in migrating and wintering birds and found no significant differences between them. These findings suggest that, at this time window, neurogenesis just replaced neurons that might be lost during the transatlantic flight. Our findings also show that in active fall migrating birds, a lower level of adult hippocampal neurogenesis is associated with a smaller hippocampal formation. High levels of adult hippocampal neurogenesis and a larger hippocampal formation found in wintering birds may be late occurring effects of long distance migratory flight or the result of conditions the birds experienced while wintering.

Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus.

PubMed

Aguilar-Arredondo, Andrea; Zepeda, Angélica

2018-07-01

The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.

Effect of sub-optimal doses of fluoxetine plus estradiol on antidepressant-like behavior and hippocampal neurogenesis in ovariectomized rats.

PubMed

Vega-Rivera, Nelly M; Fernández-Guasti, Alonso; Ramírez-Rodríguez, Gerardo; Estrada-Camarena, Erika

2015-07-01

Estrogens and antidepressants synergize to reduce depressive symptoms and stimulate neurogenesis and neuroplastic events. The aim of this study was to explore whether the antidepressant-like effect induced by the combination of low doses of estradiol (E2) and fluoxetine (FLX) involves changes in cell proliferation, early survival, morphology and dendrite complexity of hippocampal new-immature neurons. The antidepressant-like effects of E2 and/or FLX were evaluated by the forced swimming test (FST), cell proliferation was determined with the endogenous marker Ki67, survival of newborn cells was established with bromo-deoxiuridine (BrdU) and immature neurons were ascertained by doublecortin (DCX) labeling while their dendrite complexity was evaluated with Sholl analysis. Ovariectomized Wistar rats were randomly assigned to one of the following groups: Vehicle (saline/14 days+Oil/-8h before FST); E2 (saline/14 days + E2 2.5 or 10 μg/rat; -8 h before FST); FLX (1.25 or 10 mg/kg for 14 days + oil -8h before FST), and FLX plus E2 (FLX 1.25 mg/kg for 14 days + E2 2.5 μg/rat -8 h before FST). The combination of sub-threshold doses of FLX plus E2 produced antidepressant-like actions similar to those induced by FLX or E2 given independently at optimal doses. Only FLX at an optimal dose and the combination of FLX plus E2 increased cell proliferation, the number of DCX-labeled immature neurons and the complexity of their dendritic tree, suggesting that these events may be responsible for their antidepressant-like effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice.

PubMed

Chien, Mei-Yin; Chuang, Cheng-Hung; Chern, Chang-Ming; Liou, Kou-Tong; Liu, Der-Zen; Hou, Yu-Chang; Shen, Yuh-Chiang

2016-10-01

Salvianolic acid A (SalA), a chemical type of caffeic acid trimer, has drawn great attention for its potent bioactivities against ischemia-induced injury both in vitro and in vivo. In this study, we evaluated SalA's protective effects against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries in mice. Treatment of the mice with SalA (50 and 100μg/kg, i.v.) at 2h after MCAO enhanced their survival rate, improved their moving activity, and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes such as the extensive breakdown of the blood-brain barrier (BBB), nitrosative stress, and the activation of an inflammatory transcriptional factor p65 nuclear factor-kappa B (NF-κB) and a pro-apoptotic kinase p25/Cdk5. SalA also intensively limited cortical infarction and promoted the expression of neurogenesis protein near the peri-infarct cortex and subgranular zone of the hippocampal dentate gyrus by compromising the activation of GSK3β and p25/Cdk5, which in turn upregulated β-catenin, doublecortin (DCX), and Bcl-2, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor. We conclude that SalA blocks inflammatory responses by impairing NF-κB signaling, thereby limiting inflammation/nitrosative stress and preserving the integrity of the BBB; SalA also concomitantly promotes neurogenesis-related protein expression by compromising GSK3β/Cdk5 activity to enhance the expression levels of β-catenin/DCX and Bcl-2 for neuroprotection. Copyright © 2016 Elsevier Inc. All rights reserved.

PAN-811 prevents chemotherapy-induced cognitive impairment and preserves neurogenesis in the hippocampus of adult rats

PubMed Central

Winocur, Gordon; Wojtowicz, J. Martin; Shevtsova, Olga; Fuller, Steven; Ghanbari, Hossein A.

2018-01-01

Chemotherapy-induced cognitive impairment (CICI) occurs in a substantial proportion of treated cancer patients, with no drug currently available for its therapy. This study investigated whether PAN-811, a ribonucleotide reductase inhibitor, can reduce cognitive impairment and related suppression of neurogenesis following chemotherapy in an animal model. Young adult rats in Chemo and Chemo+PAN-811 groups received 3 intraperitoneal (i.p.) injections of methotrexate (MTX) and 5-fluorouracil (5-FU), and those in Saline and Saline+PAN-811 groups received equal volumes of physiological saline at 10-day intervals. PAN-811 in saline was delivered through i.p. injection, 10 min following each saline (Saline+PAN-811 group) or MTX/5-FU (Chemo+PAN-811 group) treatment, while equal volumes of saline were delivered to Saline and Chemo groups. Over Days 31–66, rats were administered tests of spatial memory, nonmatching-to-sample rule learning, and discrimination learning, which are sensitive to dysfunction in hippocampus, frontal lobe and striatum, respectively. On Day 97, neurogenesis was immnunohistochemically evaluated by counting doublecortin-positive (DCX+) cells in the dentate gyrus (DG). The results demonstrated that the Chemo group was impaired on the three cognitive tasks, but co-administration of PAN-811 significantly reduced all MTX/5-FU-induced cognitive impairments. In addition, MTX/5-FU reduced DCX+ cells to 67% of that in Saline control rats, an effect that was completely blocked by PAN-811 co-administration. Overall, we present the first evidence that PAN-811 protects cognitive functions and preserves neurogenesis from deleterious effects of MTX/5-FU. The current findings provide a basis for rapid clinical translation to determine the effect of PAN-811 on CICI in human. PMID:29370277

Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

NASA Astrophysics Data System (ADS)

Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

2016-12-01

Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

Elimination of Isoxazolyl-Penicillins antibiotics in waters by the ligninolytic native Colombian strain Leptosphaerulina sp. considerations on biodegradation process and antimicrobial activity removal.

PubMed

Copete-Pertuz, Ledys S; Plácido, Jersson; Serna-Galvis, Efraím A; Torres-Palma, Ricardo A; Mora, Amanda

2018-07-15

In this work, Leptosphaerulina sp. (a Colombian native fungus) significantly removed three Isoxazolyl-Penicillin antibiotics (IP): oxacillin (OXA, 16000 μg L -1 ), cloxacillin (CLX, 17500 μg L -1 ) and dicloxacillin (DCX, 19000 μg L -1 ) from water. The biological treatment was performed at pH 5.6, 28 °C, and 160 rpm for 15 days. The biotransformation process and lack of toxicity of the final solutions (antibacterial activity (AA) and cytotoxicity) were tested. The role of enzymes in IP removal was analysed through in vitro studies with enzymatic extracts (crude and pre-purified) from Leptosphaerulina sp., commercial enzymes and enzymatic inhibitors. Furthermore, the applicability of mycoremediation process to a complex matrix (simulated hospital wastewater) was evaluated. IP were considerably abated by the fungus, OXA was the fastest degraded (day 6), followed by CLX (day 7) and DCX (day 8). Antibiotics biodegradation was associated to laccase and versatile peroxidase action. Assays using commercial enzymes (i.e. laccase from Trametes versicolor and horseradish peroxidase) and inhibitors (EDTA, NaCl, sodium acetate, manganese (II) ions) confirmed the significant role of enzymatic transformation. Whereas, biomass sorption was not an important process in the antibiotics elimination. Evaluation of AA against Staphylococcus aureus ATCC 6538 revealed that Leptosphaerulina sp. also eliminated the AA. In addition, the cytotoxicity assay (MTT) on the HepG2 cell line demonstrated that the IP final solutions were non-toxic. Finally, Leptosphaerulina sp. eliminated OXA and its AA from synthetic hospital wastewater at 6 days. All these results evidenced the potential of Leptosphaerulina sp. mycoremediation as a novel environmentally friendly process for the removal of IP from aqueous systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Hippophae rhamnoides L. leaves extract enhances cell proliferation and neuroblast differentiation through upregulation of intrinsic factors in the dentate gyrus of the aged gerbil.

PubMed

Ahn, Ji Hyeon; Chen, Bai Hui; Park, Joon Ha; Kim, In Hye; Cho, Jeong-Hwi; Lee, Jae-Chul; Yan, Bing Chun; Choi, Jung Hoon; Hwang, In Koo; Park, Ju-Hee; Han, Sang-No; Lee, Yun Lyul; Kim, Myong Jo; Won, Moo-Ho

2014-01-01

Hippophae rhamnoides L. (HL) exerts antioxidant activities against various oxidative stress conditions. In this study, we investigated effects of extract from HL leaves (HLE) on cell proliferation and neuroblast differentiation in the subgranular zone (SGZ) of the dentate gyrus (DG) of aged gerbils. Aged gerbils (24 months) were divided into vehicle (saline)-treated- and HLE-treated-groups. The vehicle and HLE were orally administered with 200 mg/kg once a day for 20 days before sacrifice. Cell proliferation and neuroblast differentiation were examined in the DG using Ki67 and doublecortin (DCX), respectively. We also observed changes in immunoreactivities of superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2), brain-derived neurotrophic factor (BDNF), and phospho-glycogen synthase kinase-3-beta (p-GSK-3β) to examine their relation with neurogenesis using immunohistochemistry. The administration of HLE significantly increased the number of Ki67-positive cells and DCX-positive neuroblasts with well-developed processes in the SGZ of the DG of the HLE-treated-group. In addition, immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in granule and polymorphic cells of the DG in the HLE-treated-group compared with those in the vehicle-treated-group. HLE treatment significantly increased cell proliferation and neuroblast differentiation, showing that immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in the DG. These indicate that increased neuroblast differentiation neurogenesis may be closely related to upregulation of SOD1, SOD2, BDNF, and p-GSK-3β in aged gerbils.

Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

PubMed

Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

2012-09-01

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Ghrelin-induced hippocampal neurogenesis and enhancement of cognitive function are mediated independently of GH/IGF-1 axis: lessons from the spontaneous dwarf rats.

PubMed

Li, Endan; Kim, Yumi; Kim, Sehee; Park, Seungjoon

2013-01-01

We recently have reported that ghrelin modulates adult hippocampal neurogenesis. However, there is a possibility that the action of ghrelin on hippocampal neurogenesis could be, in part, due to the ability of ghrelin to stimulate the GH/insulin-like growth factor (IGF)-1 axis, where both GH and IGF-1 infusions are known to increase hippocampal neurogenesis. To explore this possibility, we assessed the impact of ghrelin on progenitor cell proliferation and differentiation in the dentate gyrus (DG) of spontaneous dwarf rats (SDRs), a dwarf strain with a mutation of the GH gene resulting in total loss of GH. Double immunohistochemical staining revealed that Ki-67-positive progenitor cells and doublecortin (DCX)-positive neuroblasts in the DG of the SDRs expressed ghrelin receptors. We found that ghrelin treatment in the SDRs significantly increased the number of proliferating cell nuclear antigen- and BrdU-labeled cells in the DG. The number of DCX-labeled cells in the DG of ghrelin-treated SDRs was also significantly increased compared with the vehicle-treated controls. To test whether ghrelin has a direct effect on cognitive performance independently of somatotropic axis, hippocampus-dependent learning and memory were assessed using the Y-maze and novel object recognition (NOR) test in the SDRs. Ghrelin treatment for 4 weeks by subcutaneous osmotic pump significantly increased alternation rates in the Y-maze and exploration time for novel object in the NOR test compared to vehicle-treated controls. Our results indicate that ghrelin-induced adult hippocampal neurogenesis and enhancement of cognitive function are mediated independently of somatotropic axis.

The prebiotics 3′Sialyllactose and 6′Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut-brain axis

PubMed Central

Tarr, Andrew J.; Galley, Jeffrey D.; Fisher, Sydney; Chichlowski, Maciej; Berg, Brian M.; Bailey, Michael T.

2015-01-01

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3′Sialyllactose (3′SL) or 6′Sialyllactose (6′SL) for two weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3′SL or 6′SL. In addition, 3′SL and 6′SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis. PMID:26144888

Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats.

PubMed

Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

2016-08-01

Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

PubMed

Val-Laillet, David; Guérin, Sylvie; Coquery, Nicolas; Nogret, Isabelle; Formal, Michèle; Romé, Véronique; Le Normand, Laurence; Meurice, Paul; Randuineau, Gwénaëlle; Guilloteau, Paul; Malbert, Charles-Henri; Parnet, Patricia; Lallès, Jean-Paul; Segain, Jean-Pierre

2018-04-01

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water only [control (C)]. All pigs had blood sampled after 2 and 3 wk of treatment, and were subjected to a brain positron emission tomography after 3 wk. Animals were euthanized after 4 wk to sample pancreas, intestine, and brain for gut physiology and anatomy measurements, as well as hippocampal histology, Ki67, and doublecortin (DCX) immunohistochemistry. SB compared with C treatment triggered basal brain glucose metabolism changes in the nucleus accumbens and hippocampus ( P = 0.003), increased hippocampal granular cell layer volume ( P = 0.006), and neurogenesis (Ki67: P = 0.026; DCX: P = 0.029). After 2 wk of treatment, plasma levels of glucose, insulin, lactate, glucagon-like peptide 1, and peptide tyrosine tyrosine remained unchanged. After 3 wk, plasma levels of lactate were lower in SB compared with C animals ( P = 0.028), with no difference for glucose and insulin. Butyrate intake impacted very little gut anatomy and function. These results demonstrate that oral SB impacted brain functions with little effects on the gut.-Val-Laillet, D., Guérin, S., Coquery, N., Nogret, I., Formal, M., Romé, V., Le Normand, L., Meurice, P., Randuineau, G., Guilloteau, P., Malbert, C.-H., Parnet, P., Lallès, J.-P., Segain, J.-P. Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Characterization and isolation of immature neurons of the adult mouse piriform cortex.

PubMed

Rubio, A; Belles, M; Belenguer, G; Vidueira, S; Fariñas, I; Nacher, J

2016-07-01

Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA-NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar-pyramidal transitional neurons. Most were also immunoreactive for DCX, confirming their immature nature. In agreement with this, detection of PSA-NCAM combined with that of different cell lineage-specific antigens revealed that most PSA-NCAM positive cells did not co-express markers of glial cells or mature neurons. Their time of origin was evaluated by birthdating experiments with halogenated nucleosides performed at different developmental stages and in adulthood. We found that virtually all cells in this paleocortical region, including PSA-NCAM-positive cells, are born during fetal development. In addition, proliferation analyses in adult mice revealed that very few cells were cycling in layer II of the piriform cortex and that none of them was PSA-NCAM-positive. Moreover, we have established conditions to isolate and culture these immature neurons in the adult piriform cortex layer II. We find that although they can survive under certain conditions, they do not proliferate in vitro either. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 748-763, 2016. © 2015 Wiley Periodicals, Inc.

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

PubMed

Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress.

PubMed

Xing, Hang; Zhang, Kuo; Zhang, Ruowen; Shi, Huiyan; Bi, Kaishun; Chen, Xiaohui

2015-12-01

Water extract of the fixed combination of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, traditional name - Zhi-Zi-Hou-Po (ZZHPD) is used for treatment of depressive-like symptoms in traditional Chinese medicine for centuries. The present study aimed to explore antidepressant-like effects and potential mechanisms of ZZHPD in a rat model of chronic unpredictable mild stress (CUMS). Antidepressant-like effects of ZZHPD were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system, neurotrophin and hippocampal neurogenesis. Antidepressant-like effects of ZZHPD (3.66, 7.32 and 14.64 g/kg/day) were estimated through coat state test, sucrose preference test, forced swimming test and open-field test. Effects of ZZHPD on hypothalamic-pituitary-adrenal (HPA) axis were evaluated by hormones measurement and dexamethasone suppression test. In addition, the expression of brain-derived neurotrophic factor (BDNF) in hippocampus was measured, as well as hippocampal neurogenesis was investigated by doublecortin (DCX) and 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). The results demonstrated that ZZHPD significantly reversed the depressive-like behaviors, normalized the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT), restored the negative feedback loop of HPA axis and improved the levels of BDNF, DCX and BrdU/NeuN compared with those in CUMS-induced rats. The above results revealed that ZZHPD exerted antidepressant-like effects possibly by normalizing HPA axis function, increasing expression of BDNF in hippocampus and promoting hippocampal neurogenesis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice.

PubMed

Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling

2016-04-01

Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nitric oxide donor up-regulation of SDF1/CXCR4 and Ang1/Tie2 promotes neuroblast cell migration after stroke.

PubMed

Cui, Xu; Chen, Jieli; Zacharek, Alex; Roberts, Cynthia; Yang, Yuping; Chopp, Michael

2009-01-01

We tested the hypothesis that a nitric oxide donor, DETA-NONOate, up-regulates stromal cell-derived factor-1 (SDF1) and angiopoietin 1 (Ang1) in the ischemic brain and their respective receptors chemokine CXC motif receptor 4 (CXCR4) and Tie2 in the subventricular zone (SVZ) and thereby promote SVZ neuroblast cell migration after stroke. C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAo), and 24 hr later DETA-NONOate (0.4 mg/kg) or phosphate-buffered solution was intravenously administered. Mice were sacrificed at 14 days for histological assessment or sacrificed at 3 days for analysis by real-time polymerase chain reaction and migration after MCAo. To elucidate whether SDF1/CXCR4 and Ang1/Tie2 pathways mediate DETA-NONOate-induced SVZ migration after stroke, SDF1alpha, Ang1 peptide, a specific antagonist of CXCR4 (AMD3100), and a neutralizing antibody of Tie2 (anti-Tie2) were used in vitro. DETA-NONOate significantly increased the percentage area of doublecortin (DCX, a marker of migrating neuroblasts)-immunoreactive cells in the SVZ and ischemic boundary zone. DETA-NONOate significantly increased the expression of SDF1 and Ang1 in the ischemic border and up-regulated CXCR4 and Tie2 in the SVZ compared with MCAo control. DCX-positive cell migration from SVZ explants was significantly increased in the DETA-NONOate treatment group compared with MCAo-alone animals. In vitro, SDF1alpha and Ang1 significantly increased SVZ explants cell migration. In addition, inhibition of CXCR4 or Tie2 significantly attenuated DETA-NONOate-induced SVZ cell migration. Our data indicate that treatment of stroke with a nitric oxide donor up-regulates SDF1/CXCR4 and Ang1/Tie2 pathways and thereby likely increases SVZ neuroblast cell migration. 2008 Wiley-Liss, Inc.

Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

PubMed

Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

2014-11-01

Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

Fluoxetine prevents the memory deficits and reduction in hippocampal cell proliferation caused by valproic acid.

PubMed

Welbat, Jariya Umka; Sangrich, Preeyanuch; Sirichoat, Apiwat; Chaisawang, Pornthip; Chaijaroonkhanarak, Wunnee; Prachaney, Parichat; Pannangrong, Wanassanun; Wigmore, Peter

2016-12-01

Valproic acid (VPA), a commonly used antiepileptic drug, has been reported to cause cognitive impairments in patients. In a previous study, using a rodent model, we showed that VPA treatment impaired cognition which was associated with a reduction in the cell proliferation required for hippocampal neurogenesis. The antidepressant fluoxetine has been shown to increase hippocampal neurogenesis and to reverse the memory deficits found in a number of pathological conditions. In the present study we investigated the protective effects of fluoxetine treatment against the impairments in memory and hippocampal cell proliferation produced by VPA. Male Sprague Dawley rats received daily treatment with fluoxetine (10mg/kg) by oral gavage for 21days. Some rats were co-administered with VPA (300mg/kg, twice daily i.p. injections) for 14days from day 8 to day 21 of the fluoxetine treatment. Spatial memory was tested using the novel object location (NOL) test. The number of proliferating cells present in the sub granular zone of the dentate gyrus was quantified using Ki67 immunohistochemistry at the end of the experiment. Levels of the receptor Notch1, the neurotrophic factor BDNF and the neural differentiation marker DCX were determined by Western blotting. VPA-treated rats showed memory deficits, a decrease in the number of proliferating cells in the sub granular zone and decreases in the levels of Notch1 and BDNF but not DCX compared to control animals. These changes in behavior, cell proliferation and Notch1 and BDNF were prevented in animals which had received both VPA and fluoxetine. Rats receiving fluoxetine alone did not show a significant difference in the number of proliferating cells or behavior compared to controls. These results demonstrated that the spatial memory deficits and reduction of cell proliferation produced by VPA can be ameliorated by the simultaneous administration of the antidepressant fluoxetine. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Advanced structural multimodal imaging of a patient with subcortical band heterotopia.

PubMed

Kini, Lohith G; Nasrallah, Ilya M; Coto, Carlos; Ferraro, Lindsay C; Davis, Kathryn A

2016-12-01

Subcortical band heterotopia (SBH) is a disorder of neuronal migration most commonly due to mutations of the Doublecortin (DCX) gene. A range of phenotypes is seen, with most patients having some degree of epilepsy and intellectual disability. Advanced diffusion and structural magnetic resonance imaging (MRI) sequences may be useful in identifying heterotopias and dysplasias of different sizes in drug-resistant epilepsy. We describe a patient with SBH and drug-resistant epilepsy and investigate neurite density, neurite dispersion, and diffusion parameters as compared to a healthy control through the use of multiple advanced MRI modalities. Neurite density and dispersion in heterotopia was found to be more similar to white matter than gray matter. Neurite density and dispersion maps obtained using diffusion imaging may be able to better characterize different subtypes of heterotopia.

PAN AIR - A Computer Program for Predicting Subsonic or Supersonic Linear Potential Flows about Arbitrary Configurations Using a Higher Order Panel Method. Volume I. Theory Document (Version 1.0)

DTIC Science & Technology

1980-04-15

superinclined panel J.12-12 J.20 Transformation to (s,t) variables and region of integration J.12-13 J.21 Numbering of edges of ’n Hh J.12-13 J.22 A region... JB . 4.12d((C-x) 2+(n-y)2+(ý-z)2)i) (8.4.12) we have • (P) ij 0 (8.4.13) if i+j is even, and i+j > 0. Let us now consider the velocity OD Pij I1 4...came from, since we did not arrive at A through a rigorous procedure. Recall that we claim that AT I [CO] r [Co] o n’o I~~ I, )T-- hh )1T (E.3.16a

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

Kim, Hyeokjin; Chen, Hua; Maksimovic, Dragan

An experimental 30 kW boost composite converter is described in this paper. The composite converter architecture, which consists of a buck module, a boost module, and a dual active bridge module that operates as a DC transformer (DCX), leads to substantial reductions in losses at partial power points, and to significant improvements in weighted efficiency in applications that require wide variations in power and conversion ratio. A comprehensive loss model is developed, accounting for semiconductor conduction and switching losses, capacitor losses, as well as dc and ac losses in magnetic components. Based on the developed loss model, the module andmore » system designs are optimized to maximize efficiency at a 50% power point. Experimental results for the 30 kW prototype demonstrate 98.5%peak efficiency, very high efficiency over wide ranges of power and voltage conversion ratios, as well as excellent agreements between model predictions and measured efficiency curves.« less

Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

NASA Astrophysics Data System (ADS)

Broadwater, Margaret A.

Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol-induced disruption of context fear retention; however, acute ethanol-induced disruptions of context fear did not differ as a function of prior ethanol exposure at either exposure age in adulthood. Together these results reflect differential influence of ethanol on the brain as it changes throughout ontogeny, with the hippocampus seemingly vulnerable to early adolescent exposure, whereas the mPFC may be more affected by ethanol exposure in mid-adolescence through adulthood. These data have implications for alcohol use not only throughout adolescence, but also in adulthood.

Quantitative assessment of fibroblast growth factor receptor 1 expression in neurons and glia.

PubMed

Choubey, Lisha; Collette, Jantzen C; Smith, Karen Müller

2017-01-01

Fibroblast growth factors (FGFs) and their receptors (FGFRs) have numerous functions in the developing and adult central nervous system (CNS). For example, the FGFR1 receptor is important for proliferation and fate specification of radial glial cells in the cortex and hippocampus, oligodendrocyte proliferation and regeneration, midline glia morphology and soma translocation, Bergmann glia morphology, and cerebellar morphogenesis. In addition, FGFR1 signaling in astrocytes is required for postnatal maturation of interneurons expressing parvalbumin (PV). FGFR1 is implicated in synapse formation in the hippocampus, and alterations in the expression of Fgfr1 and its ligand, Fgf2 accompany major depression. Understanding which cell types express Fgfr1 during development may elucidate its roles in normal development of the brain as well as illuminate possible causes of certain neuropsychiatric disorders. Here, we used a BAC transgenic reporter line to trace Fgfr1 expression in the developing postnatal murine CNS. The specific transgenic line employed was created by the GENSAT project, tgFGFR1-EGFPGP338Gsat , and includes a gene encoding enhanced green fluorescent protein ( EGFP ) under the regulation of the Fgfr1 promoter, to trace Fgfr1 expression in the developing CNS. Unbiased stereological counts were performed for several cell types in the cortex and hippocampus. This model reveals that Fgfr1 is primarily expressed in glial cells, in both astrocytes and oligodendrocytes, along with some neurons. Dual labeling experiments indicate that the proportion of GFP+ ( Fgfr1 +) cells that are also GFAP+ increases from postnatal day 7 (P7) to 1 month, illuminating dynamic changes in Fgfr1 expression during postnatal development of the cortex. In postnatal neurogenic areas, GFP expression was also observed in SOX2, doublecortin (DCX), and brain lipid-binding protein (BLBP) expressing cells. Fgfr1 is also highly expressed in DCX positive cells of the dentate gyrus (DG), but not in the rostral migratory stream. Fgfr1 driven GFP was also observed in tanycytes and GFAP+ cells of the hypothalamus, as well as in Bergmann glia and astrocytes of the cerebellum. The tgFGFR1-EGFPGP338Gsat mouse model expresses GFP that is congruent with known functions of FGFR1, including hippocampal development, glial cell development, and stem cell proliferation. Understanding which cell types express Fgfr1 may elucidate its role in neuropsychiatric disorders and brain development.

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function.

PubMed

Moon, Hyo Youl; Becke, Andreas; Berron, David; Becker, Benjamin; Sah, Nirnath; Benoni, Galit; Janke, Emma; Lubejko, Susan T; Greig, Nigel H; Mattison, Julie A; Duzel, Emrah; van Praag, Henriette

2016-08-09

Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here, we show that a muscle secretory factor, cathepsin B (CTSB) protein, is important for the cognitive and neurogenic benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition. Published by Elsevier Inc.

GABA-CREB signalling regulates maturation and survival of newly generated neurons in the adult hippocampus

PubMed Central

Jagasia, Ravi; Steib, Kathrin; Englberger, Elisabeth; Herold, Sabine; Faus-Kessler, Theresa; Saxe, Michael; Gage, Fred H.; Song, Hongjun; Lie, D. Chichung

2009-01-01

Survival and integration of new neurons in the hippocampal circuit are rate-limiting steps in adult hippocampal neurogenesis. Neuronal network activity is a major regulator of these processes, yet little is known about the respective downstream signalling pathways. Here, we investigate the role of CREB signalling in adult hippocampal neurogenesis. CREB is activated in new granule neurons during a distinct developmental period. Loss of CREB function in a cell-autonomous fashion impairs dendritic development, decreases the expression of the neurogenic transcription factor NeuroD and of the neuronal microtubule associated protein, DCX, and compromises the survival of newborn neurons. In addition, GABA-mediated excitation regulates CREB activation at early developmental stages. Importantly, developmental defects following loss of GABA-mediated excitation can be compensated by enhanced CREB signalling. These results indicate that CREB signalling is a central pathway in adult hippocampal neurogenesis, regulating the development and survival of new hippocampal neurons downstream of GABA-mediated excitation. PMID:19553437

Suspension of Mitotic Activity in Dentate Gyrus of the Hibernating Ground Squirrel

PubMed Central

Popov, Victor I.; Kraev, Igor V.; Ignat'ev, Dmitri A.; Stewart, Michael G.

2011-01-01

Neurogenesis occurs in the adult mammalian hippocampus, a region of the brain important for learning and memory. Hibernation in Siberian ground squirrels provides a natural model to study mitosis as the rapid fall in body temperature in 24 h (from 35-36°C to +4–6°C) permits accumulation of mitotic cells at different stages of the cell cycle. Histological methods used to study adult neurogenesis are limited largely to fixed tissue, and the mitotic state elucidated depends on the specific phase of mitosis at the time of day. However, using an immunohistochemical study of doublecortin (DCX) and BrdU-labelled neurons, we demonstrate that the dentate gyrus of the ground squirrel hippocampus contains a population of immature cells which appear to possess mitotic activity. Our data suggest that doublecortin-labelled immature cells exist in a mitotic state and may represent a renewable pool for generation of new neurons within the dentate gyrus. PMID:21773054

GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

PubMed

Morgan-Smith, Meghan; Wu, Yaohong; Zhu, Xiaoqin; Pringle, Julia; Snider, William D

2014-07-29

GSK-3 is an essential mediator of several signaling pathways that regulate cortical development. We therefore created conditional mouse mutants lacking both GSK-3α and GSK-3β in newly born cortical excitatory neurons. Gsk3-deleted neurons expressing upper layer markers exhibited striking migration failure in all areas of the cortex. Radial migration in hippocampus was similarly affected. In contrast, tangential migration was not grossly impaired after Gsk3 deletion in interneuron precursors. Gsk3-deleted neurons extended axons and developed dendritic arbors. However, the apical dendrite was frequently branched while basal dendrites exhibited abnormal orientation. GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling. Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased. Our data demonstrate that GSK-3 signaling is essential for radial migration and dendritic orientation and suggest that GSK-3 mediates these effects by phosphorylating key microtubule regulatory proteins.DOI: http://dx.doi.org/10.7554/eLife.02663.001. Copyright © 2014, Morgan-Smith et al.

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice

PubMed Central

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Shon, Dong-Hwa; Lee, Soon-Tae; Shin, Chang-Yup; Lee, Yuri; Lee, Dong Hun; Chung, Jin Ho

2016-01-01

A decrease in adult neurogenesis is associated with the aging process, and this decrease is closely related to memory impairment. Tomato (Lycopersicon esculentum) is a fruit with diverse bioactive nutrients that is consumed worldwide. In this study, we investigated the cognition-enhancing effect of tomato ethanolic extracts (TEE) in aged mice. Six weeks of oral TEE administration in 12-month-old aged mice significantly increased their exploration time of novel objects when compared to vehicle-treated mice. The TEE supplement increased doublecortin (DCX)-positive cells and postsynaptic density-95 (PSD95) expression in mice hippocampus. Moreover, we found an increased expression of brain-derived neurotrophic factor (BDNF) and subsequently-activated extracellular-signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling pathway in the TEE-supplemented mice hippocampus. In conclusion, the oral administration of TEE exhibits a cognition-enhancing effect, and the putative underlying mechanism is the induction of BDNF signaling-mediated proliferation and synapse formation in the hippocampus. These findings indicate that TEE could be a candidate for treatment of age-related memory impairment and neurodegenerative disorders. PMID:27792185

Lycopersicon esculentum Extract Enhances Cognitive Function and Hippocampal Neurogenesis in Aged Mice.

PubMed

Bae, Jung-Soo; Han, Mira; Shin, Hee Soon; Shon, Dong-Hwa; Lee, Soon-Tae; Shin, Chang-Yup; Lee, Yuri; Lee, Dong Hun; Chung, Jin Ho

2016-10-26

A decrease in adult neurogenesis is associated with the aging process, and this decrease is closely related to memory impairment. Tomato ( Lycopersicon esculentum ) is a fruit with diverse bioactive nutrients that is consumed worldwide. In this study, we investigated the cognition-enhancing effect of tomato ethanolic extracts (TEE) in aged mice. Six weeks of oral TEE administration in 12-month-old aged mice significantly increased their exploration time of novel objects when compared to vehicle-treated mice. The TEE supplement increased doublecortin (DCX)-positive cells and postsynaptic density-95 (PSD95) expression in mice hippocampus. Moreover, we found an increased expression of brain-derived neurotrophic factor (BDNF) and subsequently-activated extracellular-signal-regulated kinase (ERK)/cAMP response element binding (CREB) signaling pathway in the TEE-supplemented mice hippocampus. In conclusion, the oral administration of TEE exhibits a cognition-enhancing effect, and the putative underlying mechanism is the induction of BDNF signaling-mediated proliferation and synapse formation in the hippocampus. These findings indicate that TEE could be a candidate for treatment of age-related memory impairment and neurodegenerative disorders.

Single-stage-to-orbit: Meeting the challenge

NASA Astrophysics Data System (ADS)

Freeman, Delma C., Jr.; Talay, Theodore A.; Austin, Robert Eugene

1995-10-01

There has been and continues to be significant discussion about the viability of fully reusable, single-stage-to-orbit (SSTO) concepts for delivery of payloads to orbit. Often, these discussions have focused in detail on performance and technology requirements relating to the technical feasibility of the concept, with only broad generalizations on how the SSTO will achieve its economic goals of greatly reduced vehicle ground and flight operations costs. With the current industry and NASA Reusable Launch Vehicle Technology Program efforts underway to mature and demonstrate technologies leading to a viable commercial launch system that also satisfies national needs, achieving acceptable recurring costs becomes a significant challenge. This paper reviews the current status of the Reusable Launch Vehicle Technology Program including the DC-XA, X-33, and X-34 flight systems and associated technology programs. The paper also examines lessons learned from the recently completed DC-X reusable rocket demonstrator program. It examines how these technologies and flight systems address the technical and operability challenges of SSTO whose solutions are necessary to reduce costs. The paper also discusses the management and operational approaches that address the challenge of a new cost-effective, reusable launch vehicle system.

Single-stage-to-orbit — Meeting the challenge

NASA Astrophysics Data System (ADS)

Freeman, Delma C.; Talay, Theodore A.; Austin, Robert Eugene

1996-02-01

There has been and continues to be significant discussion about the viability of fully reusable, single-stage-to-orbit (SSTO) concepts for delivery of payloads to orbit. Often, these discussions have focused in detail on performance and technology requirements relating to the technical feasibility of the concept, with only broad generalizations on how the SSTO will achieve its economic goals of greatly reduced vehicle ground and flight operations costs. With the current industry and NASA Reusable Launch Vehicle Technology Program efforts underway to mature and demonstrate technologies leading to a viable commercial launch system that also satisfies national needs, achieving acceptable recurring costs becomes a significant challenge. This paper reviews the current status of the Reusable Launch Vehicle Technology Program including the DC-XA, X-33, X-34 flight systems and associated technology programs. The paper also examines lessons learned from the recently completed DC-X reusable rocket demonstrator program. It examines how these technologies and flight systems address the technical and operability challenges of SSTO whose solutions are necessary to reduce costs. The paper also discusses the management and operational approaches that address the challenge of a new cost-effective, reusable launch vehicle system.

Delta clipper lessons learned for increased operability in reusable space vehicles

NASA Astrophysics Data System (ADS)

Charette, Ray O.; Steinmeyer, Don A.; Smiljanic, Ray R.

1998-01-01

Important lessons were learned from the design, development, and test (DD&T), and operation of the Delta Clipper Experimental (DC-X/XA) Reusable Launch Vehicle (RLV) which apply to increased operability for the operational Reusable Space Vehicles (RSVs). Boeing maintains a continuous process improvement program that provides the opportunity to ``institutionalize'' the results from projects such as Delta Clipper for application to product improvement in future programs. During the design phase, operations and supportability (O&S) were emphasized to ensure aircraft-like operations, traceable to an operational RSV. The operations personnel, flight, and ground crew and crew chief were actively involved in the design, manufacture, and checkout of the systems. Changes and additions to capability were implemented as they evolved from knowledge gained in each phase of development. This paper presents key lessons learned with respect to design and implementation of flight systems, propulsion, airframe, hydraulics, avionics, and ground operations. Information was obtained from discussions with personnel associated with this program concerning their experience and lessons learned. Additionally, field process records and operations timelines were evaluated for applicability to RSVs. The DC-X program pursued reusability in all aspects of the design, a unique approach in rocket system development.

Selected advanced aerodynamic and active control concepts development

NASA Technical Reports Server (NTRS)

1981-01-01

A task for the Energy Efficient Transport program conducted: (1) The design and wind tunnel development of high-aspect-ratio supercritical wings, investigating the cruise speed regime and also high-lift. (2) The preliminary design and evaluation of an aircraft combining a high-aspect-ratio supercritical wing with a winglet. (3) Active Controls: The determination of criteria, configuration, and flying qualities associated with augmented longitudinal stability of a level likely to be acceptable for the next generation transport; and the design of a practical augmentation system. The baseline against which the work was performed and evaluated was the Douglas DC-X-200 twin engine derivative of the DC-10 transport. The supercritical wing development showed that the cruise and buffet requirements could be achieved and that the wing could be designed to realize a sizable advantage over today's technology. Important advances in high lift performance were shown. The design study of an aircraft with supercritical wing and winglet suggested advantages in weight and fuel economy could be realized. The study of augmented stability, conducted with the aid of a motion base simulator, concluded that a negative static margin was acceptable for the baseline unaugmented aircraft.

Exposure to swainsonine impairs adult neurogenesis and spatial learning and memory.

PubMed

Wang, Jiutao; Song, Lingzhen; Zhang, Qi; Zhang, Wei; An, Lei; Zhang, Yamei; Tong, Dewen; Zhao, Baoyu; Chen, Shulin; Zhao, Shanting

2015-01-05

Swainsonine (SW) is an indolizidine triol plant alkaloid isolated from the species Astragalus, colloquially termed locoweed. Ingestion induces severe neurological symptoms of livestock and wildlife, including ataxia, trembling, exaggerated fright reactions. Toxicity to the central and peripheral nervous system is caused by inhibition of lysosomal a-mannosidase (AMA) and accumulation of intracellular oligosaccharide. However, the effects of SW on adult neurogenesis and cognition have remained unclear. Therefore, the present study was conducted to examine the effects of SW on adult neurogenesis and learning as well as memory performance in adult mice. SW (10μg/mL in drinking water) was administered orally to mice for 4 weeks. Our results showed that SW reduced proliferation and survival of neural progenitor cells (NPCs) in culture, and in the hippocampus of adult mice. In addition, exposure to SW led to down-regulation of doublecortin (DCX) and synaptophysin (SYP) in the hippocampus. However, caspase 3 and glial fibrillary acidic protein (GFAP) levels were significantly increased in SW-treated mice. Finally, SW-treated mice exhibited deficits in hippocampus-dependent spatial learning and memory. Our findings suggest that SW affects adult neurogenesis and cognitive function. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analysis of Flowfields over Four-Engine DC-X Rockets

NASA Technical Reports Server (NTRS)

Wang, Ten-See; Cornelison, Joni

1996-01-01

The objective of this study is to validate a computational methodology for the aerodynamic performance of an advanced conical launch vehicle configuration. The computational methodology is based on a three-dimensional, viscous flow, pressure-based computational fluid dynamics formulation. Both wind-tunnel and ascent flight-test data are used for validation. Emphasis is placed on multiple-engine power-on effects. Computational characterization of the base drag in the critical subsonic regime is the focus of the validation effort; until recently, almost no multiple-engine data existed for a conical launch vehicle configuration. Parametric studies using high-order difference schemes are performed for the cold-flow tests, whereas grid studies are conducted for the flight tests. The computed vehicle axial force coefficients, forebody, aftbody, and base surface pressures compare favorably with those of tests. The results demonstrate that with adequate grid density and proper distribution, a high-order difference scheme, finite rate afterburning kinetics to model the plume chemistry, and a suitable turbulence model to describe separated flows, plume/air mixing, and boundary layers, computational fluid dynamics is a tool that can be used to predict the low-speed aerodynamic performance for rocket design and operations.

Hepatoid Adenocarcinoma of the Stomach: A Challenging Diagnostic and Therapeutic Disease through a Case Report and Review of the Literature.

PubMed

Fakhruddin, Najla; Bahmad, Hisham F; Aridi, Tarek; Yammine, Yara; Mahfouz, Rami; Boulos, Fouad; Awada, Ahmad; Farhat, Fadi

2017-01-01

Hepatoid adenocarcinoma of the stomach (HAS) is a rare aggressive tumor with hepatocellular differentiation. HAS often produces alpha fetoprotein (AFP) and metastasizes to the lymph nodes and the liver. Molecular studies revealed Her2 amplification and overexpression, association with p53 mutations, but no association with KRAS mutations. EGFR and BRAF mutations have not yet been evaluated in hepatoid carcinoma of the stomach so far. Hereby, we present a case of a 41-year-old female patient with HAS with high AFP level and liver metastases. Molecular analysis revealed Her2 overexpression by immunohistochemistry (IHC), but no EGFR, KRAS , or BRAF mutations were detected. The patient underwent chemotherapy type DCX (docetaxel, cisplatinum, and capecitabine) every 3 weeks with partial response after two cycles, maintained for eight cycles, and then was on maintenance therapy with trastuzumab for 7 months before relapsing and dying 18 months from the day of diagnosis. Conclusively, HAS may be misdiagnosed as hepatocellular carcinoma; therefore, it should be considered in the differential diagnosis of multiple hepatic nodules with high AFP and no history of hepatitis, liver fibrosis or cirrhosis.

Time-dependent regulation of morphological changes and cartilage differentiation markers in the mouse pubic symphysis during pregnancy and postpartum recovery.

PubMed

Castelucci, Bianca Gazieri; Consonni, Sílvio Roberto; Rosa, Viviane Souza; Sensiate, Lucimara Aparecida; Delatti, Paula Cristina Rugno; Alvares, Lúcia Elvira; Joazeiro, Paulo Pinto

2018-01-01

Animal models commonly serve as a bridge between in vitro experiments and clinical applications; however, few physiological processes in adult animals are sufficient to serve as proof-of-concept models for cartilage regeneration. Intriguingly, some rodents, such as young adult mice, undergo physiological connective tissue modifications to birth canal elements such as the pubic symphysis during pregnancy; therefore, we investigated whether the differential expression of cartilage differentiation markers is associated with cartilaginous tissue morphological modifications during these changes. Our results showed that osteochondral progenitor cells expressing Runx2, Sox9, Col2a1 and Dcx at the non-pregnant pubic symphysis proliferated and differentiated throughout pregnancy, giving rise to a complex osteoligamentous junction that attached the interpubic ligament to the pubic bones until labour occurred. After delivery, the recovery of pubic symphysis cartilaginous tissues was improved by the time-dependent expression of these chondrocytic lineage markers at the osteoligamentous junction. This process potentially recapitulates embryologic chondrocytic differentiation to successfully recover hyaline cartilaginous pads at 10 days postpartum. Therefore, we propose that this physiological phenomenon represents a proof-of-concept model for investigating the mechanisms involved in cartilage restoration in adult animals.

Protein content and methyl donors in maternal diet interact to influence the proliferation rate and cell fate of neural stem cells in rat hippocampus.

PubMed

Amarger, Valérie; Lecouillard, Angèle; Ancellet, Laure; Grit, Isabelle; Castellano, Blandine; Hulin, Philippe; Parnet, Patricia

2014-10-14

Maternal diet during pregnancy and early postnatal life influences the setting up of normal physiological functions in the offspring. Epigenetic mechanisms regulate cell differentiation during embryonic development and may mediate gene/environment interactions. We showed here that high methyl donors associated with normal protein content in maternal diet increased the in vitro proliferation rate of neural stem/progenitor cells isolated from rat E19 fetuses. Gene expression on whole hippocampi at weaning confirmed this effect as evidenced by the higher expression of the Nestin and Igf2 genes, suggesting a higher amount of undifferentiated precursor cells. Additionally, protein restriction reduced the expression of the insulin receptor gene, which is essential to the action of IGFII. Inhibition of DNA methylation in neural stem/progenitor cells in vitro increased the expression of the astrocyte-specific Gfap gene and decreased the expression of the neuron-specific Dcx gene, suggesting an impact on cell differentiation. Our data suggest a complex interaction between methyl donors and protein content in maternal diet that influence the expression of major growth factors and their receptors and therefore impact the proliferation and differentiation capacities of neural stem cells, either through external hormone signals or internal genomic regulation.

Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice.

PubMed

Yang, Yuan; Zhang, Meikui; Kang, Xiaoni; Jiang, Chen; Zhang, Huan; Wang, Pei; Li, Jingjing

2015-09-26

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice. The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells. Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice. Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

PubMed Central

Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

2016-01-01

Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

Lissencephaly: expanded imaging and clinical classification

PubMed Central

Di Donato, Nataliya; Chiari, Sara; Mirzaa, Ghayda M.; Aldinger, Kimberly; Parrini, Elena; Olds, Carissa; Barkovich, A. James; Guerrini, Renzo; Dobyns, William B.

2017-01-01

Lissencephaly (“smooth brain”, LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterotopia (SBH) was developed to distinguish between the first two genetic causes of LIS – LIS1 (PAFAH1B1) and DCX. However, progress in molecular genetics has led to identification of 19 LIS-associated genes, leaving the existing classification system insufficient to distinguish the increasingly diverse patterns of LIS. To address this challenge, we reviewed clinical, imaging and molecular data on 188 patients with LIS-SBH ascertained during the last five years, and reviewed selected archival data on another ~1,400 patients. Using these data plus published reports, we constructed a new imaging based classification system with 21 recognizable patterns that reliably predict the most likely causative genes. These patterns do not correlate consistently with the clinical outcome, leading us to also develop a new scale useful for predicting clinical severity and outcome. Taken together, our work provides new tools that should prove useful for clinical management and genetic counselling of patients with LIS-SBH (imaging and severity based classifications), and guidance for prioritizing and interpreting genetic testing results (imaging based classification). PMID:28440899

Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.

PubMed

Liu, Yanqun; Tang, Guanghui; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

2014-09-05

Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (p<0.05). Immunostaining results showed that the microvessel density in the peri-focal region of metformin treated mice was greatly increased compared to the control (p<0.05). Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p<0.05). Furthermore, we demonstrated that metformin treatment activated AMPK signaling pathway and promoted eNOS phosphorylation. Thus, we concluded that metformin promoted focal angiogenesis and neurogenesis and attenuated ischemia-induced brain injury in mice after middle cerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Overview of NATO Background on Scramjet Technology. Chapter 1

NASA Technical Reports Server (NTRS)

Drummond, J. Philip; Bouchez, Marc; McClinton, Charles R.

2006-01-01

The purpose of the present overview is to summarize the current knowledge of the NATO contributors. All the topics will be addressed in this chapter, with references and some examples. This background enhances the level of knowledge of the NATO scramjet community, which will be used for writing the specific chapters of the Report. Some previous overviews have been published on scramjet technology worldwide. NASA, DOD, the U.S. industry and global community have studied scramjet-powered hypersonic vehicles for over 40 years. Within the U.S. alone, NASA, DOD (DARPA, U.S. Navy and USAF), and industry have participated in hypersonic technology development. Over this time NASA Langley Research Center continuously studied hypersonic system design, aerothermodynamics, scramjet propulsion, propulsion-airframe integration, high temperature materials and structural architectures, and associated facilities, instrumentation and test methods. These modestly funded programs were substantially augmented during the National Aero-Space Plane (X-30) Program, which spent more than $3B between 1984 and 1995, and brought the DOD and other NASA Centers, universities and industry back into hypersonics. In addition, significant progress was achieved in all technologies required for hypersonic flight, and much of that technology was transferred into other programs, such as X-33, DC-X, X-37, X-43, etc. In addition, technology transfer impacted numerous other industries, including automotive, medical, sports and aerospace.

Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment

PubMed Central

Zhao, Qiuying; Xie, Xiaofang; Fan, Yonghua; Zhang, Jinqiang; Jiang, Wei; Wu, Xiaohui; Yan, Shuo; Chen, Yubo; Peng, Cheng; You, Zili

2015-01-01

Despite the potential adverse effects of maternal sleep deprivation (MSD) on physiological and behavioral aspects of offspring, the mechanisms remain poorly understood. The present study was intended to investigate the roles of microglia on neurodevelopment and cognition in young offspring rats with prenatal sleep deprivation. Pregnant Wistar rats received 72 h sleep deprivation in the last trimester of gestation, and their prepuberty male offspring were given the intraperitoneal injection with or without minocycline. The results showed the number of Iba1+ microglia increased, that of hippocampal neurogenesis decreased, and the hippocampus-dependent spatial learning and memory were impaired in MSD offspring. The classical microglial activation markers (M1 phenotype) IL-1β, IL-6, TNF-α, CD68 and iNOS were increased, while the alternative microglial activation markers (M2 phenotype) Arg1, Ym1, IL-4, IL-10 and CD206 were reduced in hippocampus of MSD offspring. After minocycline administration, the MSD offspring showed improvement in MWM behaviors and increase in BrdU+/DCX+ cells. Minocycline reduced Iba1+ cells, suppressed the production of pro-inflammatory molecules, and reversed the reduction of M2 microglial markers in the MSD prepuberty offspring. These results indicate that dysregulation in microglial pro- and anti-inflammatory activation is involved in MSD-induced inhibition of neurogenesis and impairment of spatial learning and memory. PMID:25830666

Transcranial low-level laser therapy increases memory, learning, neuroprogenitor cells, BDNF and synaptogenesis in mice with traumatic brain injury

NASA Astrophysics Data System (ADS)

Xuan, Weijun; Huang, Liyi; Vatansever, Fatma; Agrawal, Tanupriya; Hamblin, Michael R.

2015-03-01

Increasing concern is evident over the epidemic of traumatic brain injury in both civilian and military medicine, and the lack of approved treatments. Transcranial low level laser therapy tLLLT) is a new approach in which near infrared laser is delivered to the head, penetrates the scalp and skull to reach the brain. We asked whether tLLLT at 810-nm could improve memory and learning in mice with controlled cortical impact traumatic brain injury. We investigated the mechanism of action by immunofluorescence studies in sections from brains of mice sacrificed at different times. Mice with TBI treated with 1 or 3 daily laser applications performed better on Morris Water Maze test at 28 days. Laser treated mice had increased BrdU incorporation into NeuN positive cells in the dentate gyrus and subventricular zone indicating formation of neuroprogenitor cells at 7 days and less at 28 days. Markers of neuron migration (DCX and Tuj1) were also increased, as was the neurotrophin, brain derived neurotrophic factor (BDNF) at 7 days. Markers of synaptogenesis (formation of new connections between existing neurons) were increased in the perilesional cortex at 28 days. tLLLT is proposed to be able to induce the brain to repair itself after injury. However its ability to induce neurogenesis and synaptogenesis suggests that tLLLT may have much wider applications to neurodegenerative and psychiatric disorders.

Transcranial low-level laser therapy enhances learning, memory, and neuroprogenitor cells after traumatic brain injury in mice

NASA Astrophysics Data System (ADS)

Xuan, Weijun; Vatansever, Fatma; Huang, Liyi; Hamblin, Michael R.

2014-10-01

The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 expression was lower in the lesion region at 4 days post-TBI. Double-stained BrdU-NeuN (neuroprogenitor cells) was increased in the dentate gyrus and SVZ. Increases in double-cortin (DCX) and TUJ-1 were also seen. Our study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis.

Identification of neuron-related genes for cell therapy of neurological disorders by network analysis.

PubMed

Su, Li-Ning; Song, Xiao-Qing; Wei, Hui-Ping; Yin, Hai-Feng

Bone mesenchymal stem cells (BMSCs) differentiated into neurons have been widely proposed for use in cell therapy of many neurological disorders. It is therefore important to understand the molecular mechanisms underlying this differentiation. We screened differentially expressed genes between immature neural tissues and untreated BMSCs to identify the genes responsible for neuronal differentiation from BMSCs. GSE68243 gene microarray data of rat BMSCs and GSE18860 gene microarray data of rat neurons were received from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1248 genes were up-regulated and 1273 were down-regulated in neurons compared with BMSCs. Gene Ontology functional enrichment, protein-protein interaction networks, functional modules, and hub genes were analyzed using DAVID, STRING 10, BiNGO tool, and Network Analyzer software, revealing that nine hub genes, Nrcam, Sema3a, Mapk8, Dlg4, Slit1, Creb1, Ntrk2, Cntn2, and Pax6, may play a pivotal role in neuronal differentiation from BMSCs. Seven genes, Dcx, Nrcam, sema3a, Cntn2, Slit1, Ephb1, and Pax6, were shown to be hub nodes within the neuronal development network, while six genes, Fgf2, Tgfβ1, Vegfa, Serpine1, Il6, and Stat1, appeared to play an important role in suppressing neuronal differentiation. However, additional studies are required to confirm these results.

Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats

PubMed Central

Silasi, Gergely; Klahr, Ana C; Hackett, Mark J; Auriat, Angela M; Nichol, Helen; Colbourne, Frederick

2012-01-01

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity. PMID:22434072

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

PubMed Central

Yang, Rui; Chen, Wei; Lu, Ye; Li, Yingke; Du, Hongli; Gao, Songyan; Dong, Xin; Yuan, Hongbin

2017-01-01

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation. PMID:28059131

Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling.

PubMed

Nam, Sung Min; Choi, Jung Hoon; Yoo, Dae Young; Kim, Woosuk; Jung, Hyo Young; Kim, Jong Whi; Yoo, Miyoung; Lee, Sanghee; Kim, Chul Jung; Yoon, Yeo Sung; Hwang, In Koo

2014-06-01

Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

Effects of Curcumin (Curcuma longa) on Learning and Spatial Memory as Well as Cell Proliferation and Neuroblast Differentiation in Adult and Aged Mice by Upregulating Brain-Derived Neurotrophic Factor and CREB Signaling

PubMed Central

Nam, Sung Min; Choi, Jung Hoon; Yoo, Dae Young; Kim, Woosuk; Jung, Hyo Young; Kim, Jong Whi; Yoo, Miyoung; Lee, Sanghee; Kim, Chul Jung; Yoon, Yeo Sung

2014-01-01

Abstract Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus. PMID:24712702

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate.

PubMed

Baptista, Sofia; Lasgi, Charlène; Benstaali, Caroline; Milhazes, Nuno; Borges, Fernanda; Fontes-Ribeiro, Carlos; Agasse, Fabienne; Silva, Ana Paula

2014-09-01

Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10nM) decreased DG stem cell self-renewal, while 1nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10μM). Moreover, METH (10nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers. Copyright © 2014. Published by Elsevier B.V.

Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

PubMed Central

Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

2016-01-01

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.

PubMed

Zhu, Lei; Yang, Jing-yu; Xue, Xue; Dong, Ying-xu; Liu, Yang; Miao, Feng-rong; Wang, Yong-feng; Xue, Hong; Wu, Chun-fu

2015-09-01

In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6 mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of Aβ plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+) cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1.

PubMed

Hasan, S M Mahmudul; Sheen, Ashley D; Power, Angela M; Langevin, Lisa Marie; Xiong, Jieying; Furlong, Michael; Day, Kristine; Schuurmans, Carol; Opferman, Joseph T; Vanderluit, Jacqueline L

2013-08-01

Cortical development requires the precise timing of neural precursor cell (NPC) terminal mitosis. Although cell cycle proteins regulate terminal mitosis, the factors that influence the cell cycle machinery are incompletely understood. Here we show in mice that myeloid cell leukemia 1 (Mcl1), an anti-apoptotic Bcl-2 protein required for the survival of NPCs, also regulates their terminal differentiation through the cell cycle regulator p27(Kip1). A BrdU-Ki67 cell profiling assay revealed that in utero electroporation of Mcl1 into NPCs in the embryonic neocortex increased NPC cell cycle exit (the leaving fraction). This was further supported by a decrease in proliferating NPCs (Pax6(+) radial glial cells and Tbr2(+) neural progenitors) and an increase in differentiating cells (Dcx(+) neuroblasts and Tbr1(+) neurons). Similarly, BrdU birth dating demonstrated that Mcl1 promotes premature NPC terminal mitosis giving rise to neurons of the deeper cortical layers, confirming their earlier birthdate. Changes in Mcl1 expression within NPCs caused concomitant changes in the levels of p27(Kip1) protein, a key regulator of NPC differentiation. Furthermore, in the absence of p27(Kip1), Mcl1 failed to induce NPC cell cycle exit, demonstrating that p27(Kip1) is required for Mcl1-mediated NPC terminal mitosis. In summary, we have identified a novel physiological role for anti-apoptotic Mcl1 in regulating NPC terminal differentiation.

Morphological and cellular characterization of the fetal canine (Canis lupus familiaris) subventricular zone, rostral migratory stream and olfactory bulb.

PubMed

Orechio, Dailiany; Aguiar, Bruna Andrade; Diniz, Giovanne Baroni; Bittencourt, Jackson Cioni; Haemmerle, Carlos A; Watanabe, Ii-Sei; Miglino, Maria Angelica; Castelucci, Patricia

2018-05-12

The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days-old dog fetuses. Using multiple immunohistochemical markers, we demonstrated that the SVZ in the canine fetus is remarkably similar to the adult SVZ, with glial GFAP-immunoreactive (-ir) cells, DCX-ir neuroblasts and SOX2-ir neuronal progenitors tangentially organized along the dorsal lateral ventricle. The fetal RMS has all the features of its adult counterpart and closely resembles the RMS of other mammalian species. The late-development canine MOB has most of the neurochemical features of the adult MOB, including an early-developed TH-ir population and maturing CALR-ir interneurons, but CALB-ir neurons in the granule cell layer will only appear in the post-partum period. Taken together, our results suggest that the canine fetal development of adult neurogenic niches closely resembles those of primates, and dogs may be suitable models of human adult neurogenesis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

PubMed Central

Zeke, András; Misheva, Mariya

2016-01-01

SUMMARY The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. PMID:27466283

Neurogenic Effects of Low-Dose Whole-Body HZE (Fe) Ion and Gamma Irradiation.

PubMed

Sweet, Tara B; Hurley, Sean D; Wu, Michael D; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

2016-12-01

Understanding the dose-toxicity profile of radiation is critical when evaluating potential health risks associated with natural and man-made sources in our environment. The purpose of this study was to evaluate the effects of low-dose whole-body high-energy charged (HZE) iron (Fe) ions and low-energy gamma exposure on proliferation and differentiation of adult-born neurons within the dentate gyrus of the hippocampus, cells deemed to play a critical role in memory regulation. To determine the dose-response characteristics of the brain to whole-body Fe-ion vs. gamma-radiation exposure, C57BL/6J mice were irradiated with 1 GeV/n Fe ions or a static 137 Cs source (0.662 MeV) at doses ranging from 0 to 300 cGy. The neurogenesis was analyzed at 48 h and one month postirradiation. These experiments revealed that whole-body exposure to either Fe ions or gamma radiation leads to: 1. An acute decrease in cell division within the dentate gyrus of the hippocampus, detected at doses as low as 30 and 100 cGy for Fe ions and gamma radiation, respectively; and 2. A reduction in newly differentiated neurons (DCX immunoreactivity) at one month postirradiation, with significant decreases detected at doses as low as 100 cGy for both Fe ions and gamma rays. The data presented here contribute to our understanding of brain responses to whole-body Fe ions and gamma rays and may help inform health-risk evaluations related to systemic exposure during a medical or radiologic/nuclear event or as a result of prolonged space travel.

Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death

PubMed Central

Yan, Bing Chun; Park, Joon Ha; Chen, Bai Hui; Cho, Jeong-Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae-Chul; Hwang, In Koo; Cho, Jun Hwi; Lee, Yun Lyul; Kang, Il-Jun; Won, Moo-Ho

2014-01-01

Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperitoneal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-Jade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reached the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-immunoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2′-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death. PMID:25422633

Insulin growth factor-I promotes functional recovery after a focal lesion in the dentate gyrus.

PubMed

Liquitaya-Montiel, Adhemar; Aguilar-Arredondo, Andrea; Arias, Clorinda; Zepeda, Angélica

2012-11-01

The adult brain is plastic and able to reorganize structurally and functionally after damage. Growth factors are key molecules underlying the recovery process and among trophic molecules, Insulin-Like Growth Factor-I (IGF-I) is of particular interest given that it modulates neuronal and glial responses in the hippocampus including neurogenesis, which has been proposed as a mechanism of neurorepair. In this study we analyzed the effect of intracerebroventricular chronic infusion of IGF-I on functional recovery and morphological restoration after the induction of an excitotoxic lesion in the dentate gyrus (DG) of young-adult rats. Our results show that the lesion impairs contextual fear memory which is a DG dependent task, but not cued fear memory or performance in the open field motor task, which are independent of the DG integrity. Chronic administration of IGF-I, but not vehicle, promotes functional recovery to control levels in injured subjects. Analysis in NeuN immunoprocessed tissue revealed that the lesion volume was not different between groups and that the DG was not evidently restructured in the IGF-I treated group. Glial fibrillary acidic protein (GFAP) analysis revealed an increased astrocytic response in the injured region in both groups and Doublecortin (DCX) analysis showed a similar increase in number of newly born neurons in both groups. However, a remarkable increase in young neurons dendritic arborization was observed in the IGF-I treated group. These results provide evidence for IGF-I as a molecule mediating functional and cellular plasticity during a reorganization process after damage to a neurogenic niche.

Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment.

PubMed

Feng, Shufang; Shi, Tianyao; Qiu, Jiangxia; Yang, Haihong; Wu, Yan; Zhou, Wenxia; Wang, Wei; Wu, Haitao

2017-10-01

It is well known that Notch1 signaling plays a crucial role in embryonic neural development and adult neurogenesis. The latest evidence shows that Notch1 also plays a critical role in synaptic plasticity in mature hippocampal neurons. So far, deeper insights into the function of Notch1 signaling during the different steps of adult neurogenesis are still lacking, and the mechanisms by which Notch1 dysfunction is associated with brain disorders are also poorly understood. In the current study, we found that Notch1 was highly expressed in the adult-born immature neurons in the hippocampal dentate gyrus. Using a genetic approach to selectively ablate Notch1 signaling in late immature precursors in the postnatal hippocampus by cross-breeding doublecortin (DCX) + neuron-specific proopiomelanocortin (POMC)-α Cre mice with floxed Notch1 mice, we demonstrated a previously unreported pivotal role of Notch1 signaling in survival and function of adult newborn neurons in the dentate gyrus. Moreover, behavioral and functional studies demonstrated that POMC-Notch1 -/- mutant mice showed anxiety and depressive-like behavior with impaired synaptic transmission properties in the dentate gyrus. Finally, our mechanistic study showed significantly compromised phosphorylation of cAMP response element-binding protein (CREB) in Notch1 mutants, suggesting that the dysfunction of Notch1 mutants is associated with the disrupted pCREB signaling in postnatally generated immature neurons in the dentate gyrus.-Feng, S., Shi, T., Qiu, J., Yang, H., Wu, Y., Zhou, W., Wang, W., Wu, H. Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment. © FASEB.

Caloric restriction in young rats disturbs hippocampal neurogenesis and spatial learning.

PubMed

Cardoso, Armando; Marrana, Francisco; Andrade, José P

2016-09-01

It is widely known that caloric restriction (CR) has benefits on several organic systems, including the central nervous system. However, the majority of the CR studies was performed in adult animals and the information about the consequences on young populations is limited. In this study, we analyzed the effects of young-onset CR, started at 4weeks of age, in the number of neuropeptide Y (NPY)-containing neurons and in neurogenesis of the hippocampal formation, using doublecortin (DCX) and Ki67 as markers. Knowing that CR treatment could interfere with exploratory activity, anxiety, learning and memory we have analyzed the performance of the rats in the open-field, elevated plus-maze and Morris water maze tests. Animals aged 4weeks were randomly assigned to control or CR groups. Controls were maintained in the ad libitum regimen during 2months. The adolescent CR rats were fed, during 2months, with 60% of the amount of food consumed by controls. We have found that young-onset CR treatment did not affect the total number of NPY-immunopositive neurons in dentate hilus, CA3 and CA1 hippocampal subfields and did not change the exploratory activity and anxiety levels. Interestingly, we have found that young-onset CR might affect spatial learning process since those animals showed worse performance during the acquisition phase of Morris water maze. Furthermore, young-onset CR induced alterations of neurogenesis in the dentate subgranular layer that seems to underlie the impairment of spatial learning. Our data suggest that adolescent animals are vulnerable to CR treatment and that this diet is not suitable to be applied in this age phase. Copyright © 2016 Elsevier Inc. All rights reserved.

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships.

PubMed

Zeke, András; Misheva, Mariya; Reményi, Attila; Bogoyevitch, Marie A

2016-09-01

The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The geomagnetic jerk of 2003.5-characterisation with regional observatory secular variation data

NASA Astrophysics Data System (ADS)

Feng, Yan; Holme, Richard; Cox, Grace Alexandra; Jiang, Yi

2018-05-01

The 2003.5 geomagnetic jerk was identified in geomagnetic records from satellite data, and a matching feature reported in variations in length-of-day (ΔLOD), but detailed study has been hampered by lack of geomagnetic observatory data where it appears strongest. Here we examine secular variation (annual differences of monthly means) based on a new resource of 43 Chinese observatory records for 1998 until the present, focusing on 10 series of particularly high quality and consistency. To obtain a clean series, we calculate the covariance matrix of residuals between measurements and a state-of-the-art field model, CHAOS-6, and use eigenvalue analysis to remove noisy contributions from the uncorrected data. The magnitude of the most significant eigenvector correlates well with Dcx (corrected, extended Dst), suggesting the noise originates from unmodelled external magnetic field. Removal of this noise eliminates much coherent misfit around 2003-2005; nevertheless, the 2003.5 jerk is seen clearly in the first time derivative of the East component in Chinese data, and is also seen in the first time derivative of the vertical component in European data. Estimates of the jerk time are centred on 2003.5, but with some spatial variation; this variation can be eliminated if we allow a discontinuity in the secular variation as well as its temporal gradient. Both regions also provide evidence for a jerk around 2014, although less clearly than 2003.5. We create a new field model based on new data and CHAOS-6 to further examine the regional signals. The new model is close to CHAOS-6, but better fits Chinese data, although modelling also identifies some data features as unphysical.

Low-level light emitting diode therapy promotes long-term functional recovery after experimental stroke in mice.

PubMed

Lee, Hae In; Lee, Sae-Won; Kim, Nam Gyun; Park, Kyoung-Jun; Choi, Byung Tae; Shin, Yong-Il; Shin, Hwa Kyoung

2017-12-01

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU + ) in the ischemic brain, and significant increases in BrdU + /GFAP + , BrdU + /DCX + , BrdU + /NeuN + , and CD31 + cells in the subacute LED-T group. However, the BrdU + /Iba-1 + cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rescue of IL-1β-induced reduction of human neurogenesis by omega-3 fatty acids and antidepressants.

PubMed

Borsini, Alessandra; Alboni, Silvia; Horowitz, Mark A; Tojo, Luis M; Cannazza, Giuseppe; Su, Kuan-Pin; Pariante, Carmine M; Zunszain, Patricia A

2017-10-01

Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway. We allowed neural cells to proliferate for 3days and further differentiate for 7days in the presence of IL-1β (10ng/ml) and either the selective serotonin reuptake inhibitor sertraline (1µM), the serotonin and norepinephrine reuptake inhibitor venlafaxine (1µM), or the ω-3 fatty acids eicosapentaenoic acid (EPA, 10µM) or docosahexaenoic acid (DHA, 10µM). Co-incubation with each of these compounds reversed the IL-1β-induced reduction in neurogenesis (DCX- and MAP2-positive neurons), indicative of a protective effect. Moreover, EPA and DHA also reversed the IL-1β-induced increase in kynurenine, as well as mRNA levels of indolamine-2,3-dioxygenase (IDO); while DHA and sertraline reverted the IL-1β-induced increase in quinolinic acid and mRNA levels of kynurenine 3-monooxygenase (KMO). Our results show common effects of monoaminergic antidepressants and ω-3 fatty acids on the reduction of neurogenesis caused by IL-1β, but acting through both common and different kynurenine pathway-related mechanisms. Further characterization of their individual properties will be of benefit towards improving a future personalized medicine approach. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Development of the terminal nerve system in the shark Scyliorhinus canicula.

PubMed

Quintana-Urzainqui, Idoia; Anadón, Ramón; Candal, Eva; Rodríguez-Moldes, Isabel

2014-01-01

The nervus terminalis (or terminal nerve) system was discovered in an elasmobranch species more than a century ago. Over the past century, it has also been recognized in other vertebrate groups, from agnathans to mammals. However, its origin, functions or relationship with the olfactory system are still under debate. Despite the abundant literature about the nervus terminalis system in adult elasmobranchs, its development has been overlooked. Studies in other vertebrates have reported newly differentiated neurons of the terminal nerve system migrating from the olfactory epithelium to the telencephalon as part of a 'migratory mass' of cells associated with the olfactory nerve. Whether the same occurs in developing elasmobranchs (adults showing anatomically separated nervus terminalis and olfactory systems) has not yet been determined. In this work we characterized for the first time the development of the terminal nerve and ganglia in an elasmobranch, the lesser spotted dogfish (Scyliorhinus canicula), by means of tract-tracing techniques combined with immunohistochemical markers for the terminal nerve (such as FMRF-amide peptide), for the developing components of the olfactory system (Gα0 protein, GFAP, Pax6), and markers for early postmitotic neurons (HuC/D) and migrating immature neurons (DCX). We discriminated between embryonic olfactory and terminal nerve systems and determined that both components may share a common origin in the migratory mass. We also localized the exact point where they split off near the olfactory nerve-olfactory bulb junction. The study of the development of the terminal nerve system in a basal gnathostome contributes to the knowledge of the ancestral features of this system in vertebrates, shedding light on its evolution and highlighting the importance of elasmobranchs for developmental and evolutionary studies. © 2014 S. Karger AG, Basel.

Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis.

PubMed

Hill, Jeremy D; Zuluaga-Ramirez, Viviana; Gajghate, Sachin; Winfield, Malika; Persidsky, Yuri

2018-06-11

The cannabinoid system exerts functional regulation of neural stem cell (NSC) proliferation and adult neurogenesis, yet not all effects of cannabinoid-like compounds seen can be attributed to the cannabinoid 1 receptor (CB 1 R) or cannabinoid 2 receptor (CB 2 R). The recently de-orphaned GPR55 has been shown to be activated by numerous cannabinoid ligands suggesting that GPR55 is a third cannabinoid receptor. Here we examined the role of GPR55 activation in NSC proliferation and early adult neurogenesis. The effects of GPR55 agonists (LPI, O-1602, ML184) on human NSC proliferation in vitro were assessed by flow cytometry. hNSC differentiation was determined by flow cytometry, qPCR, and immunohistochemistry. Immature neuron formation in the hippocampus of C57BL/6 and GPR55 -/- mice was evaluated by immunohistochemistry. Activation of GPR55 significantly increased proliferation rates of hNSCs in vitro. These effects were attenuated by ML193, a selective GPR55 antagonist. ML184 significantly promoted neuronal differentiation in vitro while ML193 reduced differentiation rates as compared to vehicle treatment. Continuous administration into the hippocampus of O-1602 via cannula connected to osmotic pump resulted in increased Ki67+ cells within the dentate gyrus. O-1602 increased immature neuron generation as assessed by DCX+ and BrdU+ cells as compared to vehicle treated animals. GPR55 -/- animals displayed reduced rates of proliferation and neurogenesis within the hippocampus while O-1602 had no effect as compared to vehicle controls. Together, these findings suggest GPR55 activation as a novel target and strategy to regulate NSC proliferation and adult neurogenesis. This article is protected by copyright. All rights reserved.

Interrelations between the mesomeric and electronegativity effects in para-substituted derivatives of phenol/phenolate and aniline/anilide H-bonded complexes: a DFT-based computational study.

PubMed

Szatyłowicz, Halina; Krygowski, Tadeusz M; Jezierska, Aneta; Panek, Jarosław J

2009-05-14

We were able to test the Bent-Walsh rule by examining geometric parameters in the vicinity of the ipso-carbon atom of H-bonded complexes of para-substituted phenol/phenolate and aniline/anilide derivatives for the three cases (i) a versus alpha, (ii) alpha versus d(CO) or d(CN), and (iii) a versus d(CO) or d(CN), where alpha is the ring valence angle at the ipso-carbon atom (C1 substituted by OH or O(-) or NH(2) or NH(-)) and a is the arithmetic mean of the two C(ipso)-C(ortho) bond lengths. The data for nonequilibrium H-bonded complexes of unsubstituted phenol/phenolate and aniline/anilide with the respective bases F(-) and CN(-) and acids HF and HCN showed the same dependence of a on d(CX) (X = O, N) as the data for equilibrium complexes of para-Y-substituted phenol/phenolate and aniline/anilide derivatives (Y = NO, NO(2), CHO, COMe, CONH(2), Cl, F, H, Me, OMe, OH) with the same bases and acids. The slope of these dependencies was negative, as expected. In the remaining cases (a versus alpha and alpha versus d(CO) or d(CN)), the slopes for simulated complexes followed the Bent-Walsh rule. Finally, for the equilibrium complexes in which the substituent effect was included, the slopes of the trend lines for the substituted systems were opposite. This is because in the a versus alpha relationships, electonegativity and the resonance effect act in the same direction, whereas for the other two cases, these effects are opposite, and the resonance effect dominates.

Early effects of a high-caloric diet and physical exercise on brain volumetry and behavior: a combined MRI and histology study in mice.

PubMed

Sack, Markus; Lenz, Jenny N; Jakovcevski, Mira; Biedermann, Sarah V; Falfán-Melgoza, Claudia; Deussing, Jan; Bielohuby, Maximilian; Bidlingmaier, Martin; Pfister, Frederik; Stalla, Günter K; Sartorius, Alexander; Gass, Peter; Weber-Fahr, Wolfgang; Fuss, Johannes; Auer, Matthias K

2017-10-01

Excessive intake of high-caloric diets as well as subsequent development of obesity and diabetes mellitus may exert a wide range of unfavorable effects on the central nervous system (CNS) in the long-term. The potentially harmful effects of such diets were suggested to be mitigated by physical exercise. Here, we conducted a study investigating early effects of a cafeteria-diet on gray and white brain matter volume by means of voxel-based morphometry (VBM) and region-of-interest (ROI) analysis. Half of the mice performed voluntary wheel running to study if regular physical exercise prevents unfavorable effects of a cafeteria-diet. In addition, histological analyses for myelination and neurogenesis were performed. As expected, wheel running resulted in a significant increase of gray matter volume in the CA1-3 areas, the dentate gyrus and stratum granulosum of the hippocampus in the VBM analysis, while a positive effect of the cafeteria-diet was shown for the whole hippocampal CA1-3 area only in the ROI analysis, indicating a regional volume effect. It was earlier found that hippocampal neurogenesis may be related to volume increases after exercise. Interestingly, while running resulted in a significant increase in neurogenesis assessed by doublecortin (DCX)-labeling, this was not true for cafeteria diet. This indicates different underlying mechanisms for gray matter increase. Moreover, animals receiving cafeteria diet only showed mild deficits in long-term memory assessed by the puzzle-box paradigm, while executive functioning and short term memory were not affected. Our data therefore highlight that high caloric diet impacts on the brain and behavior. Physical exercise seems not to interact with these mechanisms.

Measurements using orthodontic analysis software on digital models obtained by 3D scans of plaster casts : Intrarater reliability and validity.

PubMed

Czarnota, Judith; Hey, Jeremias; Fuhrmann, Robert

2016-01-01

The purpose of this work was to determine the reliability and validity of measurements performed on digital models with a desktop scanner and analysis software in comparison with measurements performed manually on conventional plaster casts. A total of 20 pairs of plaster casts reflecting the intraoral conditions of 20 fully dentate individuals were digitized using a three-dimensional scanner (D700; 3Shape). A series of defined parameters were measured both on the resultant digital models with analysis software (Ortho Analyzer; 3Shape) and on the original plaster casts with a digital caliper (Digimatic CD-15DCX; Mitutoyo). Both measurement series were repeated twice and analyzed for intrarater reliability based on intraclass correlation coefficients (ICCs). The results from the digital models were evaluated for their validity against the casts by calculating mean-value differences and associated 95 % limits of agreement (Bland-Altman method). Statistically significant differences were identified via a paired t test. Significant differences were obtained for 16 of 24 tooth-width measurements, for 2 of 5 sites of contact-point displacement in the mandibular anterior segment, for overbite, for maxillary intermolar distance, for Little's irregularity index, and for the summation indices of maxillary and mandibular incisor width. Overall, however, both the mean differences between the results obtained on the digital models versus on the plaster casts and the dispersion ranges associated with these differences suggest that the deviations incurred by the digital measuring technique are not clinically significant. Digital models are adequately reproducible and valid to be employed for routine measurements in orthodontic practice.

Habitat-specific shaping of proliferation and neuronal differentiation in adult hippocampal neurogenesis of wild rodents

PubMed Central

Cavegn, Nicole; van Dijk, R. Maarten; Menges, Dominik; Brettschneider, Helene; Phalanndwa, Mashudu; Chimimba, Christian T.; Isler, Karin; Lipp, Hans-Peter; Slomianka, Lutz; Amrein, Irmgard

2013-01-01

Daily life of wild mammals is characterized by a multitude of attractive and aversive stimuli. The hippocampus processes complex polymodal information associated with such stimuli and mediates adequate behavioral responses. How newly generated hippocampal neurons in wild animals contribute to hippocampal function is still a subject of debate. Here, we test the relationship between adult hippocampal neurogenesis (AHN) and habitat types. To this end, we compare wild Muridae species of southern Africa [Namaqua rock mouse (Micaelamys namaquensis), red veld rat (Aethomys chrysophilus), highveld gerbil (Tatera brantsii), and spiny mouse (Acomys spinosissimus)] with data from wild European Muridae [long-tailed wood mice (Apodemus sylvaticus), pygmy field mice (Apodemus microps), yellow-necked wood mice (Apodemus flavicollis), and house mice (Mus musculus domesticus)] from previous studies. The pattern of neurogenesis, expressed in normalized numbers of Ki67- and Doublecortin(DCX)-positive cells to total granule cells (GCs), is similar for the species from a southern African habitat. However, we found low proliferation, but high neuronal differentiation in rodents from the southern African habitat compared to rodents from the European environment. Within the African rodents, we observe additional regulatory and morphological traits in the hippocampus. Namaqua rock mice with previous pregnancies showed lower AHN compared to males and nulliparous females. The phylogenetically closely related species (Namaqua rock mouse and red veld rat) show a CA4, which is not usually observed in murine rodents. The specific features of the southern environment that may be associated with the high number of young neurons in African rodents still remain to be elucidated. This study provides the first evidence that a habitat can shape adult neurogenesis in rodents across phylogenetic groups. PMID:23616743

Neurogenic Effects of Low-Dose Whole-Body HZE (Fe) Ion and Gamma Irradiation

PubMed Central

Sweet, Tara B.; Hurley, Sean D.; Wu, Michael D.; Olschowka, John A.; Williams, Jacqueline P.; O’Banion, M. Kerry

2017-01-01

Understanding the dose-toxicity profile of radiation is critical when evaluating potential health risks associated with natural and man-made sources in our environment. The purpose of this study was to evaluate the effects of low-dose whole-body high-energy charged (HZE) iron (Fe) ions and low-energy gamma exposure on proliferation and differentiation of adult-born neurons within the dentate gyrus of the hippocampus, cells deemed to play a critical role in memory regulation. To determine the dose-response characteristics of the brain to whole-body Fe-ion vs. gamma-radiation exposure, C57BL/6J mice were irradiated with 1 GeV/n Fe ions or a static 137Cs source (0.662 MeV) at doses ranging from 0 to 300 cGy. The neurogenesis was analyzed at 48 h and one month postirradiation. These experiments revealed that whole-body exposure to either Fe ions or gamma radiation leads to: 1. An acute decrease in cell division within the dentate gyrus of the hippocampus, detected at doses as low as 30 and 100 cGy for Fe ions and gamma radiation, respectively; and 2. A reduction in newly differentiated neurons (DCX immunoreactivity) at one month postirradiation, with significant decreases detected at doses as low as 100 cGy for both Fe ions and gamma rays. The data presented here contribute to our understanding of brain responses to whole-body Fe ions and gamma rays and may help inform health-risk evaluations related to systemic exposure during a medical or radiologic/nuclear event or as a result of prolonged space travel. PMID:27905869

Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior

PubMed Central

Genestine, Matthieu; Lin, Lulu; Durens, Madel; Yan, Yan; Jiang, Yiqin; Prem, Smrithi; Bailoor, Kunal; Kelly, Brian; Sonsalla, Patricia K.; Matteson, Paul G.; Silverman, Jill; Crawley, Jacqueline N.; Millonig, James H.; DiCicco-Bloom, Emanuel

2015-01-01

Many genes involved in brain development have been associated with human neurodevelopmental disorders, but underlying pathophysiological mechanisms remain undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2 (EN2) contributes to neurodevelopmental disorders, especially autism spectrum disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic mid-hindbrain regions where monoamine neurons emerge. Considering their importance in neuropsychiatric disorders, we characterized monoamine systems in relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest abnormalities. While NE levels were reduced ∼35% in forebrain, they were increased 40–75% in hindbrain and cerebellum, and these patterns paralleled changes in locus coeruleus (LC) fiber innervation, respectively. Although En2 promoter was active in Embryonic day 14.5–15.5 LC neurons, expression diminished thereafter and gene deletion did not alter brainstem NE neuron numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain regions exhibited reduced growth, particularly hippocampus, where P21 dentate gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis. Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and unexpectedly, increased proliferation. Excess proliferation was restricted to early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal injections of β-adrenergic agonists reversed cell death. These studies suggest that disruption of hindbrain patterning genes can alter monoamine system development and thereby produce forebrain defects that are relevant to human neurodevelopmental disorders. PMID:26220976

Rho kinase inhibition following traumatic brain injury in mice promotes functional improvement and acute neuron survival but has little effect on neurogenesis, glial responses or neuroinflammation.

PubMed

Bye, Nicole; Christie, Kimberly J; Turbic, Alisa; Basrai, Harleen S; Turnley, Ann M

2016-05-01

Inhibition of the Rho/Rho kinase pathway has been shown to be beneficial in a variety of neural injuries and diseases. In this manuscript we investigate the role of Rho kinase inhibition in recovery from traumatic brain injury using a controlled cortical impact model in mice. Mice subjected to a moderately severe TBI were treated for 1 or 4 weeks with the Rho kinase inhibitor Y27632, and functional outcomes and neuronal and glial cell responses were analysed at 1, 7 and 35 days post-injury. We hypothesised that Y27632-treated mice would show functional improvement, with augmented recruitment of neuroblasts from the SVZ and enhanced survival of newborn neurons in the pericontusional cortex, with protection against neuronal degeneration, neuroinflammation and modulation of astrocyte reactivity and blood-brain-barrier permeability. While Rho kinase inhibition enhanced recovery of motor function after trauma, there were no substantial increases in the recruitment of DCX(+) neuroblasts or the number of BrdU(+) or EdU(+) labelled newborn neurons in the pericontusional cortex of Y27632-treated mice. Inhibition of Rho kinase significantly reduced the number of degenerating cortical neurons at 1day post-injury compared to saline controls but had no longer term effect on neuronal degeneration, with only modest effects on astrocytic reactivity and macrophage/microglial responses. Overall, this study showed that Rho kinase contributes to acute neurodegenerative processes in the injured cortex but does not play a significant role in SVZ neural precursor cell-derived adult neurogenesis, glial responses or blood-brain barrier permeability following a moderately severe brain injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Phostine PST3.1a Targets MGAT5 and Inhibits Glioblastoma-Initiating Cell Invasiveness and Proliferation.

PubMed

Hassani, Zahra; Saleh, Ali; Turpault, Soumaya; Khiati, Salim; Morelle, Willy; Vignon, Jacques; Hugnot, Jean-Philippe; Uro-Coste, Emmanuelle; Legrand, Philippe; Delaforge, Marcel; Loiseau, Séverine; Clarion, Ludovic; Lecouvey, Marc; Volle, Jean-Noël; Virieux, David; Pirat, Jean-Luc; Duffau, Hugues; Bakalara, Norbert

2017-10-01

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and accounts for a significant proportion of all primary brain tumors. Median survival after treatment is around 15 months. Remodeling of N-glycans by the N-acetylglucosamine glycosyltransferase (MGAT5) regulates tumoral development. Here, perturbation of MGAT5 enzymatic activity by the small-molecule inhibitor 3-hydroxy-4,5-bis-benzyloxy-6-benzyloxymethyl-2-phenyl2-oxo-2λ5-[1,2]oxaphosphinane (PST3.1a) restrains GBM growth. In cell-based assays, it is demonstrated that PST3.1a alters the β1,6-GlcNAc N-glycans of GBM-initiating cells (GIC) by inhibiting MGAT5 enzymatic activity, resulting in the inhibition of TGFβR and FAK signaling associated with doublecortin (DCX) upregulation and increase oligodendrocyte lineage transcription factor 2 (OLIG2) expression. PST3.1a thus affects microtubule and microfilament integrity of GBM stem cells, leading to the inhibition of GIC proliferation, migration, invasiveness, and clonogenic capacities. Orthotopic graft models of GIC revealed that PST3.1a treatment leads to a drastic reduction of invasive and proliferative capacity and to an increase in overall survival relative to standard temozolomide therapy. Finally, bioinformatics analyses exposed that PST3.1a cytotoxic activity is positively correlated with the expression of genes of the epithelial-mesenchymal transition (EMT), while the expression of mitochondrial genes correlated negatively with cell sensitivity to the compound. These data demonstrate the relevance of targeting MGAT5, with a novel anti-invasive chemotherapy, to limit glioblastoma stem cell invasion. Mol Cancer Res; 15(10); 1376-87. ©2017 AACR . ©2017 American Association for Cancer Research.

Nitric Oxide Donor Upregulation of SDF1/CXCR4 and Ang1/Tie2 Promotes Neuroblast Cell Migration After Stroke

PubMed Central

Cui, Xu; Chen, Jieli; Zacharek, Alex; Roberts, Cynthia; Yang, Yuping; Chopp, Michael

2008-01-01

We tested the hypothesis that a nitric oxide donor, DETA-NONOate upregulates Stromal cell-Derived Factor-1 (SDF1) and Angiopoietin 1 (Ang1) in the ischemic brain and their, respective, receptors chemokine CXC motif receptor 4 (CXCR4) and Tie2 in the subventricular zone (SVZ) and thereby promote SVZ neuroblast cell migration after stroke. C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAo) and 24 hours later DETA-NONOate (0.4 mg/kg) or phosphate buffered solution were intravenously administered. Mice were sacrificed at 14 days for histological assessment or sacrificed at 3 days for analysis real-time polymerase chain reaction and migration after MCAo. To elucidate whether SDF1/CXCR4 and Ang1/Tie2 pathways mediate DETA-NONOate induced SVZ migration after stroke, SDF1α, Ang1 peptide and a specific antagonist of CXCR4 (AMD3100) and a neutralizing antibody of Tie2 (anti-Tie2) were used in vitro. DETA-NONOate significantly increased the percent area of doublecortin (a marker of migrating neuroblasts) immunoreactive-cells in the SVZ and ischemic boundary zone. DETA-NONOate significantly increased the expression of SDF1 and Ang1 in the ischemic border and upregulated CXCR4 and Tie2 in the SVZ compared with MCAo control. DCX-positive cell migration from SVZ explants was significantly increased in the DETA-NONOate treatment group compared with MCAo alone animals. In vitro, SDF1α and Ang1 significantly increased SVZ explants cell migration. In addition, inhibition of CXCR4 or Tie2 significantly attenuated DETA-NONOate induced SVZ cell migration. Our data indicated that treatment of stroke with a nitric oxide donor upregulates SDF1/CXCR4 and Ang1/Tie2 pathways and thereby likely increases SVZ neuroblast cell migration. PMID:18711749

Transcriptomic profile analysis of mouse neural tube development by RNA-Seq.

PubMed

Yu, Juan; Mu, Jianbing; Guo, Qian; Yang, Lihong; Zhang, Juan; Liu, Zhizhen; Yu, Baofeng; Zhang, Ting; Xie, Jun

2017-09-01

The neural tube is the primordium of the central nervous system (CNS) in which its development is not entirely clear. Understanding the cellular and molecular basis of neural tube development could, therefore, provide vital clues to the mechanism of neural tube defects (NTDs). Here, we investigated the gene expression profiles of three different time points (embryonic day (E) 8.5, 9.5 and 10.5) of mouse neural tube by using RNA-seq approach. About 391 differentially expressed genes (DEGs) were screened during mouse neural tube development, including 45 DEGs involved in CNS development, among which Bmp2, Ascl1, Olig2, Lhx1, Wnt7b and Eomes might play the important roles. Of 45 DEGs, Foxp2, Eomes, Hoxb3, Gpr56, Hap1, Nkx2-1, Sez6l2, Wnt7b, Tbx20, Nfib, Cntn1 and Dcx had different isoforms, and the opposite expression pattern of different isoforms was observed for Gpr56, Nkx2-1 and Sez6l2. In addition, alternative splicing, such as mutually exclusive exon, retained intron, skipped exon and alternative 3' splice site was identified in 10 neural related differentially splicing genes, including Ngrn, Ddr1, Dctn1, Dnmt3b, Ect2, Map2, Mbnl1, Meis2, Vcan and App. Moreover, seven neural splicing factors, such as Nova1/2, nSR100/Srrm4, Elavl3/4, Celf3 and Rbfox1 were differentially expressed during mouse neural tube development. Interestingly, nine DEGs identified above were dysregulated in retinoic acid-induced NTDs model, indicating the possible important role of these genes in NTDs. Taken together, our study provides more comprehensive information on mouse neural tube development, which might provide new insights on NTDs occurrence. © 2017 IUBMB Life, 69(9):706-719, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

PubMed Central

Stevenson, Jennie R; Schroeder, Jason P; Nixon, Kimberly; Besheer, Joyce; Crews, Fulton T; Hodge, Clyde W

2010-01-01

Alcoholism and depression show high degrees of comorbidity. Clinical evidence also indicates that depression that emerges during abstinence from chronic alcohol use has a greater negative impact on relapse than pre-existing depression. Although no single neurobiological mechanism can account for the behavioral pathologies associated with these devastating disorders, converging evidence suggests that aspects of both alcoholism and depression are linked to reductions in hippocampal neurogenesis. Here, we report results from a novel preclinical behavioral model showing that abstinence from voluntary alcohol drinking leads to the emergence of depression-like behavior and reductions in neurogenesis. C57BL/6J mice were allowed to self-administer ethanol (10% v/v) vs H2O in the home cage for 28 days. Alcohol was then removed for 1 or 14 days, and mice were tested in the forced swim test to measure depression-like behavior. After 14 days, but not 1 day of abstinence from alcohol drinking, mice showed a significant increase in depression-like behavior. The significant increase in depression-like behavior during abstinence was associated with a reduction in proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus indicating that both the number of proliferating neural progenitor cells (NPC) and immature neurons were reduced, respectively. The number of NPCs that were labeled with bromo-deoxyuridine (BrdU) at the beginning of alcohol exposure was not altered indicating that survival of NPCs is not linked to abstinence-induced depression. Chronic treatment (14 days) with the antidepressant desipramine during abstinence prevented both the emergence of depression-like behavior and the reduction in hippocampal neurogenesis indicating that abstinence-induced depression is associated with structural plasticity in the hippocampus. Overall, the results of this study support the conclusion that profound functional (ie behavioral) and structural changes occur during abstinence from alcohol use and suggest that antidepressant treatment may alleviate some of these pathological neurobehavioral adaptations. PMID:18563059

Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury.

PubMed

Ghazale, Hussein; Ramadan, Naify; Mantash, Sara; Zibara, Kazem; El-Sitt, Sally; Darwish, Hala; Chamaa, Farah; Boustany, Rose Mary; Mondello, Stefania; Abou-Kheir, Wassim; Soueid, Jihane; Kobeissy, Firas

2018-03-15

Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior treatment with DHA may be a desirable strategy to improve the therapeutic efficacy of NSC transplantation in TBI. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term omega-3 supplementation modulates behavior, hippocampal fatty acid concentration, neuronal progenitor proliferation and central TNF-α expression in 7 month old unchallenged mice

PubMed Central

Grundy, Trent; Toben, Catherine; Jaehne, Emily J.; Corrigan, Frances; Baune, Bernhard T.

2014-01-01

Dietary polyunsaturated fatty acid (PUFA) manipulation is being investigated as a potential therapeutic supplement to reduce the risk of developing age-related cognitive decline (ARCD). Animal studies suggest that high omega (Ω)-3 and low Ω-6 dietary content reduces cognitive decline by decreasing central nervous system (CNS) inflammation and modifying neuroimmune activity. However, no previous studies have investigated the long term effects of Ω-3 and Ω-6 dietary levels in healthy aging mice leaving the important question about the preventive effects of Ω-3 and Ω-6 on behavior and underlying molecular pathways unaddressed. We aimed to investigate the efficacy of long-term Ω-3 and Ω-6 PUFA dietary supplementation in mature adult C57BL/6 mice. We measured the effect of low, medium, and high Ω-3:Ω-6 dietary ratio, given from the age of 3–7 months, on anxiety and cognition-like behavior, hippocampal tissue expression of TNF-α, markers of neuronal progenitor proliferation and gliogenesis and serum cytokine concentration. Our results show that a higher Ω-3:Ω-6 PUFA diet ratio increased hippocampal PUFA, increased anxiety, improved hippocampal dependent spatial memory and reduced hippocampal TNF-α levels compared to a low Ω-3:Ω-6 diet. Furthermore, serum TNF-α concentration was reduced in the higher Ω-3:Ω-6 PUFA ratio supplementation group while expression of the neuronal progenitor proliferation markers KI67 and doublecortin (DCX) was increased in the dentate gyrus as opposed to the low Ω-3:Ω-6 group. Conversely, Ω-3:Ω-6 dietary PUFA ratio had no significant effect on astrocyte or microglia number or cell death in the dentate gyrus. These results suggest that supplementation of PUFAs may delay aging effects on cognitive function in unchallenged mature adult C57BL/6 mice. This effect is possibly induced by increasing neuronal progenitor proliferation and reducing TNF-α. PMID:25484856

Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors.

PubMed

Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

2016-01-01

The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine's inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3-28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1.

Influence of Post-Traumatic Stress Disorder on Neuroinflammation and Cell Proliferation in a Rat Model of Traumatic Brain Injury

PubMed Central

Diamond, David M.; Shinozuka, Kazutaka; Ishikawa, Hiroto; Hernandez, Diana G.; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesar V.

2013-01-01

Long-term consequences of traumatic brain injury (TBI) are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD), yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long-term inflammation and suppressed cell proliferation may evolve into more severe neurodegenerative diseases and psychiatric disorders currently being recognized in traumatized TBI patients. PMID:24349091

On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry.

PubMed

Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Lorenzo, Maria Luisa Sánchez; Ramchandani, Avinash; Martínez, Elena Asensio; Custodio, Ana; Garrido, Marcelo; Echavarría, Isabel; Cano, Juana María; Barreto, Jose Enrique Lorenzo; García, Teresa García; Manceñido, Felipe Álvarez; Lacalle, Alejandra; Cardona, Marta Ferrer; Mangas, Monserrat; Visa, Laura; Buxó, Elvira; Azkarate, Aitor; Díaz-Serrano, Asunción; Montes, Ana Fernández; Rivera, Fernando

2016-11-01

There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72-0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60-12.68) versus 9.60 months (95% CI, 8.44-10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64-0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60-1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63-0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity. Copyright © 2016 by the National Comprehensive Cancer Network.

Chronic exposure to WIN55,212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis.

PubMed

Abboussi, Oualid; Tazi, Abdelouahhab; Paizanis, Eleni; El Ganouni, Soumaya

2014-05-01

Several epidemiological studies show an increase in cannabis use among adolescents, especially in Morocco for being one of the major producers in the world. The neurobiological consequences of chronic cannabis use are still poorly understood. In addition, brain plasticity linked to ontogeny portrays adolescence as a period of vulnerability to the deleterious effects of drugs. The aim of this study was to investigate the behavioral neurogenic effects of chronic exposure to the cannabinoid agonist WIN55,212-2 during adolescence, by evaluating the emotional and cognitive performances, and the consequences on neurogenesis along the dorso-ventral axis of the hippocampus in adult rats. WIN55,212 was administered intraperitoneally (i.p.) once daily for 20 days to adolescent (27-30 PND) and adult Wistar rats (54-57 PND) at the dose of 1mg/kg. Following a 20 day washout period, emotional and cognitive functions were assessed by the Morris water maze test and the two-way active avoidance test. Twelve hours after, brains were removed and hippocampal neurogenesis was assessed using the doublecortin (DCX) as a marker for cell proliferation. Our results showed that chronic WIN55,212-2 treatment significantly increased thigmotaxis early in the training process whatever the age of treatment, induced spatial learning and memory deficits in adolescent but not adult rats in the Morris water maze test, while it had no significant effect in the active avoidance test during multitrial training in the shuttle box. In addition, the cognitive deficits assessed in adolescent rats were positively correlated to a decrease in the number of newly generated neurons in dorsal hippocampus. These data suggest that long term exposure to cannabinoids may affect more potently spatial learning and memory in adolescent compared to adult rats via a negative action on hippocampal plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.

Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

PubMed

Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

2015-05-10

Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in the cortical peri-infarct area. Thus, our results highlight the importance of using aged animals for translation to clinical studies.

Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.

PubMed

Bermudez-Hernandez, Keria; Lu, Yi-Ling; Moretto, Jillian; Jain, Swati; LaFrancois, John J; Duffy, Aine M; Scharfman, Helen E

2017-09-01

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.

Fatty Acid Binding Protein 5 Modulates Docosahexaenoic Acid-Induced Recovery in Rats Undergoing Spinal Cord Injury

PubMed Central

Figueroa, Johnny D.; Serrano-Illan, Miguel; Licero, Jenniffer; Cordero, Kathia; Miranda, Jorge D.

2016-01-01

Abstract Omega-3 polyunsaturated fatty acids (n-3 PUFAs) promote functional recovery in rats undergoing spinal cord injury (SCI). However, the precise molecular mechanism coupling n-3 PUFAs to neurorestorative responses is not well understood. The aim of the present study was to determine the spatiotemporal expression of fatty acid binding protein 5 (FABP5) after contusive SCI and to investigate whether this protein plays a role in n-3 PUFA–mediated functional recovery post-SCI. We found that SCI resulted in a robust spinal cord up-regulation in FABP5 mRNA levels (556 ± 187%) and protein expression (518 ± 195%), when compared to sham-operated rats, at 7 days post-injury (dpi). This upregulation coincided with significant alterations in the metabolism of fatty acids in the injured spinal cord, as revealed by metabolomics-based lipid analyses. In particular, we found increased levels of the n-3 series PUFAs, particularly docosahexaenoic acid (DHA; 22:6 n-3) and eicosapentaenoic acid (EPA; 20:5 n-3) at 7 dpi. Animals consuming a diet rich in DHA and EPA exhibited a significant upregulation in FABP5 mRNA levels at 7 dpi. Immunofluorescence showed low basal FABP5 immunoreactivity in spinal cord ventral gray matter NeuN+ neurons of sham-operated rats. SCI resulted in a robust induction of FABP5 in glial (GFAP+, APC+, and NG2+) and precursor cells (DCX+, nestin+). We found that continuous intrathecal administration of FABP5 silencing with small interfering RNA (2 μg) impaired spontaneous open-field locomotion post-SCI. Further, FABP5 siRNA administration hindered the beneficial effects of DHA to ameliorate functional recovery at 7 dpi. Altogether, our findings suggest that FABP5 may be an important player in the promotion of cellular uptake, transport, and/or metabolism of DHA post-SCI. Given the beneficial roles of n-3 PUFAs in ameliorating functional recovery, we propose that FABP5 is an important contributor to basic repair mechanisms in the injured spinal cord. PMID:26715431

Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium.

PubMed

Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

2016-01-01

The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a . Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a , whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b . Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b . Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and revealed differences in its cytoarchitecture when compared to canine OE. Equine OE type a closely resembles rat OE. Whether the observed differences contribute to species-specific susceptibility to intranasal insults such as virus infections has to be further investigated.

Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

PubMed Central

Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

2016-01-01

The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and revealed differences in its cytoarchitecture when compared to canine OE. Equine OE type a closely resembles rat OE. Whether the observed differences contribute to species-specific susceptibility to intranasal insults such as virus infections has to be further investigated. PMID:27790096

Future X Pathfinder: Quick, Low Cost Flight Testing for Tomorrow's Launch Vehicles

NASA Technical Reports Server (NTRS)

London, John, III; Sumrall, Phil

1999-01-01

The DC-X and DC-XA Single Stage Technology flight program demonstrated the value of low cost rapid prototyping and flight testing of launch vehicle technology testbeds. NASA is continuing this important legacy through a program referred to as Future-X Pathfinder. This program is designed to field flight vehicle projects that cost around $100M each, with a new vehicle flying about every two years. Each vehicle project will develop and extensively flight test a launch vehicle technology testbed that will advance the state of the art in technologies directly relevant to future space transportation systems. There are currently two experimental, or "X" vehicle projects in the Pathfinder program, with additional projects expected to follow in the near future. The first Pathfinder project is X-34. X-34 is a suborbital rocket plane capable of flights to Mach 8 and 75 kilometers altitude. There are a number of reusable launch vehicle technologies embedded in the X-34 vehicle design, such as composite structures and propellant tanks, and advanced reusable thermal protection systems. In addition, X-34 is designed to carry experiments applicable to both the launch vehicle and hypersonic aeronautics community. X-34 is scheduled to fly later this year. The second Pathfinder project is the X-37. X-37 is an orbital space plane that is carried into orbit either by the Space Shuttle or by an expendable launch vehicle. X-37 provides NASA access to the orbital and orbital reentry flight regimes with an experimental testbed vehicle. The vehicle will expose embedded and carry-on advanced space transportation technologies to the extreme environments of orbit and reentry. Early atmospheric approach and landing tests of an unpowered version of the X-37 will begin next year, with orbital flights beginning in late 2001. Future-X Pathfinder is charting a course for the future with its growing fleet of low-cost X- vehicles. X-34 and X-37 are leading the assault on high launch costs and enabling the flight testing of technologies that will lead to affordable access to space.

Semiconductor-based, large-area, flexible, electronic devices

DOEpatents

Goyal, Amit [Knoxville, TN

2011-03-15

Novel articles and methods to fabricate the same resulting in flexible, large-area, triaxially textured, single-crystal or single-crystal-like, semiconductor-based, electronic devices are disclosed. Potential applications of resulting articles are in areas of photovoltaic devices, flat-panel displays, thermophotovoltaic devices, ferroelectric devices, light emitting diode devices, computer hard disc drive devices, magnetoresistance based devices, photoluminescence based devices, non-volatile memory devices, dielectric devices, thermoelectric devices and quantum dot laser devices.

Semiconductor-based, large-area, flexible, electronic devices on {110}<100> oriented substrates

DOEpatents

Goyal, Amit

2014-08-05

Novel articles and methods to fabricate the same resulting in flexible, oriented, semiconductor-based, electronic devices on {110}<100> textured substrates are disclosed. Potential applications of resulting articles are in areas of photovoltaic devices, flat-panel displays, thermophotovoltaic devices, ferroelectric devices, light emitting diode devices, computer hard disc drive devices, magnetoresistance based devices, photoluminescence based devices, non-volatile memory devices, dielectric devices, thermoelectric devices and quantum dot laser devices.

[100] or [110] aligned, semiconductor-based, large-area, flexible, electronic devices

DOEpatents

Goyal, Amit

2015-03-24

Novel articles and methods to fabricate the same resulting in flexible, large-area, [100] or [110] textured, semiconductor-based, electronic devices are disclosed. Potential applications of resulting articles are in areas of photovoltaic devices, flat-panel displays, thermophotovoltaic devices, ferroelectric devices, light emitting diode devices, computer hard disc drive devices, magnetoresistance based devices, photoluminescence based devices, non-volatile memory devices, dielectric devices, thermoelectric devices and quantum dot laser devices.

{100}<100> or 45.degree.-rotated {100}<100>, semiconductor-based, large-area, flexible, electronic devices

DOEpatents

Goyal, Amit [Knoxville, TN

2012-05-15

Novel articles and methods to fabricate the same resulting in flexible, {100}<100> or 45.degree.-rotated {100}<100> oriented, semiconductor-based, electronic devices are disclosed. Potential applications of resulting articles are in areas of photovoltaic devices, flat-panel displays, thermophotovoltaic devices, ferroelectric devices, light emitting diode devices, computer hard disc drive devices, magnetoresistance based devices, photoluminescence based devices, non-volatile memory devices, dielectric devices, thermoelectric devices and quantum dot laser devices.

76 FR 45860 - In the Matter of Certain Electronic Devices, Including Wireless Communication Devices, Portable...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-01

..., Including Wireless Communication Devices, Portable Music and Data Processing Devices, and Tablet Computers... electronic devices, including wireless communication devices, portable music and data processing devices, and... electronic devices, including wireless communication devices, portable music and data processing devices, and...

Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis.

PubMed

Marachelian, Araz; Villablanca, Judith G; Liu, Cathy W; Liu, Betty; Goodarzian, Fariba; Lai, Hollie A; Shimada, Hiroyuki; Tran, Hung C; Parra, Jaime A; Gallego, Richard; Bedrossian, Nora; Young, Sabrina; Czarnecki, Scarlett; Kennedy, Rebekah; Weiss, Brian D; Goldsmith, Kelly; Granger, Meaghan; Matthay, Katherine K; Groshen, Susan; Asgharzadeh, Shahab; Sposto, Richard; Seeger, Robert C

2017-09-15

Purpose: We determined whether quantifying neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory neuroblastoma. Experimental Design: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in bone marrow and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold, Δ C t , for the geometric mean of genes from the TaqMan Low Density Array NB5 assay) and morphologically defined tumor cell percentage in bone marrow, 123 I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between Δ C t and progression-free survival (PFS). Results: NB-mRNA was detectable in 83% of bone marrow (185/223) and 63% (89/142) of blood specimens, and their Δ C t values were correlated (Spearman r = 0.67, P < 0.0001), although bone marrow C t was 7.9 ± 0.5 C t stronger than blood C t When bone marrow morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of bone marrow samples. When all three were negative, NB-mRNA was detected in 55% (11/20) of bone marrow samples. Bone marrow NB-mRNA correlated with bone marrow morphology or MIBG positivity ( P < 0.0001 and P = 0.007). Bone marrow and blood Δ C t values correlated with PFS ( P < 0.001; P = 0.001) even when bone marrow was morphologically negative ( P = 0.001; P = 0.014). Multivariate analysis showed that bone marrow and blood Δ C t values were associated with PFS independently of clinical disease and MYCN gene status ( P < 0.001; P = 0.055). Conclusions: This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory neuroblastoma. Clin Cancer Res; 23(18); 5374-83. ©2017 AACR . ©2017 American Association for Cancer Research.

Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice.

PubMed

Zhang, Kuo; Wang, Fang; Yang, Jing-yu; Wang, Li-juan; Pang, Huan-huan; Su, Guang-yue; Ma, Jie; Song, Shao-jiang; Xiong, Zhi-li; Wu, Chun-fu

2015-12-04

Xiaochaihutang (XCHT), a famous Chinese herbal formula which consists of seven Chinese herbs, has been used clinically in depressive disorders in China. Our previous studies have demonstrated that XCHT improved depressive-like behavior in several animal models of depression. However, therapeutic basis of XCHT on depression are challenging, due to the complex active constituents of XCHT and the unclear pharmacological mechanism of action. To provide further insights into therapeutic basis of XCHT, the core in compatibility of XCHT on antidepressant therapy was assessed by the method of orthogonal array design. The comparative evaluations on antidepressant effects of XCHT and its core in compatibility were executed by tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSFT), reserpine-induced hypothermia and palpebral ptosis. Moreover, the potential mechanism was explored by investigating levels of monoamine neurotransmitters in hypothalamus and striatum and neurogenesis in hippocampus. Chemical profile of active constituents in plasma after oral administration of the core in compatibility of XCHT was revealed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results of orthogonal array design experiment showed that Huangqin (Radix scutellariae), Renshen (Ginseng) and Gancao (Radix glycyrrhizae), defined as HRG, might be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, oral administration of HRG for 15 days significantly reduced immobility duration in TST and FST without affecting locomotor activity. Both HRG and XCHT increased immobility latency in FST, decreased the latency in NSFT, reversed reserpine-induced hypothermia and palpebral ptosis. Moreover, both HRG and XCHT significantly increased levels of 5-HT and DA in hypothalamus. In addition, HRG could remarkably increase Ki-67 and doublecortin (DCX) positive cells in hippocampus. A total 25 active constituents in plasma, including 14 prototype components and 11 metabolites, were identified by UPLC-MS/MS after oral administration of HRG. The present results reveal that HRG is supposed to be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, HRG exerts significant antidepressant-like effects, which are likely attributed to regulating serotonergic and dopaminergic systems and increasing hippocampal neurogenesis. The constituents identified in plasma after oral administration of HRG may be the potential active ingredients for the treatment of depression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The effects of a standardized Acanthopanax koreanum extract on stress-induced behavioral alterations in mice.

PubMed

Jung, Jun Man; Park, Se Jin; Lee, Young Woo; Lee, Hyung Eun; Hong, Sung In; Lew, Jae Hwan; Hong, Eunyoung; Shim, Jae Seok; Cheong, Jae Hoon; Ryu, Jong Hoon

2013-07-30

The roots and stem bark of Acanthopanax koreanum Nakai (Araliaceae), a well-known herbal medicine in Jeju Island, Korea, has been used as a tonic agent in treating stress-related states. Despite its popular application, the anti-anxiety or anti-depressive action of Acanthopanax koreanum is not yet known. This study aimed to determine the effects of Acanthopanax koreanum on stress-induced behavioral alterations such as anxiety and depression. Mice in the acute stress group were exposed to immobilization stress for 2h followed by electric foot shocks (0.5 mA in 1 s duration with a 10 s inter-shock interval) for 2 min, while sub-chronically stressed mice were exposed to these stresses for 2 weeks, once per day. 70% ethanolic extract of Acanthopanax koreanum (EEAK) (25, 50, 100, or 200 mg/kg) was administered once or sub-chronically (for 2 weeks) 1h prior to stress induction. Anxiety- or depression-like behavioral changes were evaluated using the elevated plus-maze (EPM) test and the forced swimming test (FST) a day after the final stress induction. Corticosterone levels and spleen weight were measured after conducting all the behavioral assays. The numbers of BrdU- or DCX-immunopositive cells in the hippocampal region of sub-chronically stressed mice were measured 2 days after EEAK treatment. The percentage of time spent in the open arms was decreased in both the acutely and chronically stressed mice. In the FST, the immobility time was increased by only chronic stress, but not by acute stress. Acute or sub-chronic administration of EEAK significantly prevented the anxiety- or depression-like behavioral changes caused by stress. EEAK also attenuated stress-induced decrease and increase of spleen weight and corticosterone levels, respectively. Furthermore, the sub-chronic administration of EEAK (100 or 200 mg/kg, for 2 weeks) increased the number of BrdU-, doublecortin-, and neuropeptide Y-positive cells in the hippocampal region of the sub-chronically stressed mice. EEAK attenuated the behavioral and biochemical changes in acute or sub-chronic stressed mice. These results suggest the therapeutic potential of Acanthopanax koreanum for the treatment of stress-related neuropsychiatric disorders including anxiety disorders or major depressive disorder. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Wireless device monitoring methods, wireless device monitoring systems, and articles of manufacture

DOEpatents

McCown, Steven H [Rigby, ID; Derr, Kurt W [Idaho Falls, ID; Rohde, Kenneth W [Idaho Falls, ID

2012-05-08

Wireless device monitoring methods, wireless device monitoring systems, and articles of manufacture are described. According to one embodiment, a wireless device monitoring method includes accessing device configuration information of a wireless device present at a secure area, wherein the device configuration information comprises information regarding a configuration of the wireless device, accessing stored information corresponding to the wireless device, wherein the stored information comprises information regarding the configuration of the wireless device, comparing the device configuration information with the stored information, and indicating the wireless device as one of authorized and unauthorized for presence at the secure area using the comparing.

16 CFR § 1507.9 - Toy smoke devices and flitter devices.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Toy smoke devices and flitter devices. Â... SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES § 1507.9 Toy smoke devices and flitter devices. (a) Toy smoke... fuse and firstfire upon ignition) during normal operation. (b) Toy smoke devices and flitter devices...

16 CFR 1507.9 - Toy smoke devices and flitter devices.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Toy smoke devices and flitter devices. 1507... SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES § 1507.9 Toy smoke devices and flitter devices. (a) Toy smoke... fuse and firstfire upon ignition) during normal operation. (b) Toy smoke devices and flitter devices...

16 CFR 1507.9 - Toy smoke devices and flitter devices.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Toy smoke devices and flitter devices. 1507... SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES § 1507.9 Toy smoke devices and flitter devices. (a) Toy smoke... fuse and firstfire upon ignition) during normal operation. (b) Toy smoke devices and flitter devices...

16 CFR 1507.9 - Toy smoke devices and flitter devices.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Toy smoke devices and flitter devices. 1507... SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES § 1507.9 Toy smoke devices and flitter devices. (a) Toy smoke... fuse and firstfire upon ignition) during normal operation. (b) Toy smoke devices and flitter devices...

77 FR 58576 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-21

... Devices, Portable Music and Data Processing Devices, Computers, and Components Thereof; Institution of... communication devices, portable music and data processing devices, computers, and components thereof by reason... certain wireless communication devices, portable music and data processing devices, computers, and...

78 FR 34669 - Certain Electronic Devices, Including Wireless Communication Devices, Portable Music and Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-10

..., Including Wireless Communication Devices, Portable Music and Data Processing Devices, and Tablet Computers... importing wireless communication devices, portable music and data processing devices, and tablet computers... certain electronic devices, including wireless communication devices, portable music and data processing...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 882.1560 - Skin potential measurement device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Skin potential measurement device. 882.1560... (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1560 Skin potential measurement device. (a) Identification. A skin potential measurement device is a general diagnostic device...

21 CFR 872.2060 - Jaw tracking device.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2060 Jaw tracking device. (a) Jaw tracking device... Controls Guidance Document: Dental Sonography and Jaw Tracking Devices.” [68 FR 67367, Dec. 2, 2003] ...

21 CFR 872.2050 - Dental sonography device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental sonography device. 872.2050 Section 872...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2050 Dental sonography device. (a) Dental sonography device for monitoring—(1) Identification. A dental sonography device for monitoring is an...

21 CFR 872.2050 - Dental sonography device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental sonography device. 872.2050 Section 872...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2050 Dental sonography device. (a) Dental sonography device for monitoring—(1) Identification. A dental sonography device for monitoring is an...

21 CFR 872.2050 - Dental sonography device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental sonography device. 872.2050 Section 872...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2050 Dental sonography device. (a) Dental sonography device for monitoring—(1) Identification. A dental sonography device for monitoring is an...

21 CFR 872.2050 - Dental sonography device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental sonography device. 872.2050 Section 872...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2050 Dental sonography device. (a) Dental sonography device for monitoring—(1) Identification. A dental sonography device for monitoring is an...

21 CFR 872.2050 - Dental sonography device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental sonography device. 872.2050 Section 872...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2050 Dental sonography device. (a) Dental sonography device for monitoring—(1) Identification. A dental sonography device for monitoring is an...

21 CFR 872.6010 - Abrasive device and accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

21 CFR 872.6010 - Abrasive device and accessories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

21 CFR 872.6010 - Abrasive device and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

21 CFR 872.6010 - Abrasive device and accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

21 CFR 872.6010 - Abrasive device and accessories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6010 Abrasive device and accessories... crowns. The device is attached to a shank that is held by a handpiece. The device includes the abrasive...

Processes for multi-layer devices utilizing layer transfer

DOEpatents

Nielson, Gregory N; Sanchez, Carlos Anthony; Tauke-Pedretti, Anna; Kim, Bongsang; Cederberg, Jeffrey; Okandan, Murat; Cruz-Campa, Jose Luis; Resnick, Paul J

2015-02-03

A method includes forming a release layer over a donor substrate. A plurality of devices made of a first semiconductor material are formed over the release layer. A first dielectric layer is formed over the plurality of devices such that all exposed surfaces of the plurality of devices are covered by the first dielectric layer. The plurality of devices are chemically attached to a receiving device made of a second semiconductor material different than the first semiconductor material, the receiving device having a receiving substrate attached to a surface of the receiving device opposite the plurality of devices. The release layer is etched to release the donor substrate from the plurality of devices. A second dielectric layer is applied over the plurality of devices and the receiving device to mechanically attach the plurality of devices to the receiving device.

21 CFR 872.1740 - Caries detection device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Caries detection device. 872.1740 Section 872.1740...) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1740 Caries detection device. (a) Identification. The caries detection device is a device intended to show the existence of decay in a patient's tooth...

21 CFR 892.2010 - Medical image storage device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical image storage device. 892.2010 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2010 Medical image storage device. (a) Identification. A medical image storage device is a device that provides electronic storage and retrieval...

21 CFR 892.2010 - Medical image storage device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical image storage device. 892.2010 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2010 Medical image storage device. (a) Identification. A medical image storage device is a device that provides electronic storage and retrieval...

21 CFR 892.2010 - Medical image storage device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical image storage device. 892.2010 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2010 Medical image storage device. (a) Identification. A medical image storage device is a device that provides electronic storage and retrieval...

21 CFR 892.2010 - Medical image storage device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical image storage device. 892.2010 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2010 Medical image storage device. (a) Identification. A medical image storage device is a device that provides electronic storage and retrieval...

21 CFR 886.1450 - Corneal radius measuring device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal radius measuring device. 886.1450 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1450 Corneal radius measuring device. (a) Identification. A corneal radius measuring device is an AC-powered device intended to measure...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 886.4360 - Ocular surgery irrigation device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ocular surgery irrigation device. 886.4360 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4360 Ocular surgery irrigation device. (a) Identification. An ocular surgery irrigation device is a device intended to be suspended over the...

21 CFR 892.2010 - Medical image storage device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical image storage device. 892.2010 Section 892...) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2010 Medical image storage device. (a) Identification. A medical image storage device is a device that provides electronic storage and retrieval...

21 CFR 872.1820 - Dental x-ray exposure alignment device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental x-ray exposure alignment device. 872.1820... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1820 Dental x-ray exposure alignment device. (a) Identification. A dental x-ray exposure alignment device is a device intended to position x...

21 CFR 872.1840 - Dental x-ray position indicating device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Dental x-ray position indicating device. 872.1840... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1840 Dental x-ray position indicating device. (a) Identification. A dental x-ray position indicating device is a device, such as a collimator...

21 CFR 872.1840 - Dental x-ray position indicating device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental x-ray position indicating device. 872.1840... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1840 Dental x-ray position indicating device. (a) Identification. A dental x-ray position indicating device is a device, such as a collimator...

21 CFR 872.1820 - Dental x-ray exposure alignment device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental x-ray exposure alignment device. 872.1820... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1820 Dental x-ray exposure alignment device. (a) Identification. A dental x-ray exposure alignment device is a device intended to position x...

21 CFR 872.1820 - Dental x-ray exposure alignment device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental x-ray exposure alignment device. 872.1820... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1820 Dental x-ray exposure alignment device. (a) Identification. A dental x-ray exposure alignment device is a device intended to position x...

21 CFR 872.1820 - Dental x-ray exposure alignment device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental x-ray exposure alignment device. 872.1820... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1820 Dental x-ray exposure alignment device. (a) Identification. A dental x-ray exposure alignment device is a device intended to position x...

21 CFR 872.1840 - Dental x-ray position indicating device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Dental x-ray position indicating device. 872.1840... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1840 Dental x-ray position indicating device. (a) Identification. A dental x-ray position indicating device is a device, such as a collimator...

21 CFR 872.1840 - Dental x-ray position indicating device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Dental x-ray position indicating device. 872.1840... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1840 Dental x-ray position indicating device. (a) Identification. A dental x-ray position indicating device is a device, such as a collimator...

21 CFR 872.1820 - Dental x-ray exposure alignment device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Dental x-ray exposure alignment device. 872.1820... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1820 Dental x-ray exposure alignment device. (a) Identification. A dental x-ray exposure alignment device is a device intended to position x...

21 CFR 872.1840 - Dental x-ray position indicating device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Dental x-ray position indicating device. 872.1840... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1840 Dental x-ray position indicating device. (a) Identification. A dental x-ray position indicating device is a device, such as a collimator...

21 CFR 892.2040 - Medical image hardcopy device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical image hardcopy device. 892.2040 Section... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2040 Medical image hardcopy device. (a) Identification. A medical image hardcopy device is a device that produces a visible printed record of a medical...

21 CFR 892.2040 - Medical image hardcopy device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical image hardcopy device. 892.2040 Section... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2040 Medical image hardcopy device. (a) Identification. A medical image hardcopy device is a device that produces a visible printed record of a medical...

21 CFR 892.2040 - Medical image hardcopy device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical image hardcopy device. 892.2040 Section... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2040 Medical image hardcopy device. (a) Identification. A medical image hardcopy device is a device that produces a visible printed record of a medical...

21 CFR 892.2040 - Medical image hardcopy device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical image hardcopy device. 892.2040 Section... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2040 Medical image hardcopy device. (a) Identification. A medical image hardcopy device is a device that produces a visible printed record of a medical...

21 CFR 892.1610 - Diagnostic x-ray beam-limiting device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Diagnostic x-ray beam-limiting device. 892.1610... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1610 Diagnostic x-ray beam-limiting device. (a) Identification. A diagnostic x-ray beam-limiting device is a device such as a collimator, a...

21 CFR 892.1610 - Diagnostic x-ray beam-limiting device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Diagnostic x-ray beam-limiting device. 892.1610... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1610 Diagnostic x-ray beam-limiting device. (a) Identification. A diagnostic x-ray beam-limiting device is a device such as a collimator, a...

21 CFR 892.1610 - Diagnostic x-ray beam-limiting device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Diagnostic x-ray beam-limiting device. 892.1610... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1610 Diagnostic x-ray beam-limiting device. (a) Identification. A diagnostic x-ray beam-limiting device is a device such as a collimator, a...

21 CFR 892.1610 - Diagnostic x-ray beam-limiting device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Diagnostic x-ray beam-limiting device. 892.1610... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1610 Diagnostic x-ray beam-limiting device. (a) Identification. A diagnostic x-ray beam-limiting device is a device such as a collimator, a...

21 CFR 892.1610 - Diagnostic x-ray beam-limiting device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Diagnostic x-ray beam-limiting device. 892.1610... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1610 Diagnostic x-ray beam-limiting device. (a) Identification. A diagnostic x-ray beam-limiting device is a device such as a collimator, a...

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood mixing devices and blood weighing devices... Manufacture Blood and Blood Products § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. A blood mixing device is a device intended for medical purposes that is used to mix blood or...

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Blood mixing devices and blood weighing devices... Manufacture Blood and Blood Products § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. A blood mixing device is a device intended for medical purposes that is used to mix blood or...

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Blood mixing devices and blood weighing devices... Manufacture Blood and Blood Products § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. A blood mixing device is a device intended for medical purposes that is used to mix blood or...

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Blood mixing devices and blood weighing devices... Manufacture Blood and Blood Products § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. A blood mixing device is a device intended for medical purposes that is used to mix blood or...

21 CFR 864.9195 - Blood mixing devices and blood weighing devices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Blood mixing devices and blood weighing devices... Manufacture Blood and Blood Products § 864.9195 Blood mixing devices and blood weighing devices. (a) Identification. A blood mixing device is a device intended for medical purposes that is used to mix blood or...

78 FR 16865 - Certain Electronic Devices, Including Wireless Communication Devices, Portable Music and Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-794] Certain Electronic Devices, Including Wireless Communication Devices, Portable Music and Data Processing Devices, and Tablet Computers... certain electronic devices, including wireless communication devices, portable music and data processing...

Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study.

PubMed

Phillips, Sharon J; Hofler, Lisa G; Modest, Anna M; Harvey, Lara F B; Wu, Lily H; Hacker, Michele R

2017-07-01

Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intrauterine device, and whether women who continue using intrauterine devices differ from those who discontinue. We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ 2 tests and calculated hazard ratios using a multivariable Cox model. Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P < .01), and at 5 years continuation rates were 28.1% for levonorgestrel intrauterine device and 23.8% for copper intrauterine device (P = .33). Black race, primiparity, and age were positively associated with discontinuation; education was not. The hazard ratio for discontinuation of levonorgestrel intrauterine device compared with copper intrauterine device >4 years was 0.71 (95% confidence interval, 0.55-0.93) and >5 years was 0.82 (95% confidence interval, 0.64-1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper intrauterine device vs 4.9% levonorgestrel intrauterine device, P < .01) over the study period and to become pregnant in the first year of use (1.6% copper intrauterine device vs 0.1% levonorgestrel intrauterine device, P < .01). We found a difference in continuation rates between levonorgestrel and copper intrauterine device users at 4 years but not at 5 years. Copper intrauterine device users were more likely to experience expulsion and pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Continuation of copper and levonorgestrel intrauterine devices: a retrospective cohort study

PubMed Central

Phillips, Sharon J.; Hofler, Lisa G.; Modest, Anna M.; Harvey, Lara F. B.; Wu, Lily H.; Hacker, Michele R.

2018-01-01

Background Studies conflict on whether the duration of use of the copper intrauterine device is longer than that of the levonorgestrel intra-uterine device, and whether women who continue using intrauterine devices differ from those who discontinue. Objective We sought to assess continuation rates and performance of levonorgestrel intrauterine devices compared with copper intrauterine devices over a 5-year period. Study Design We performed a retrospective cohort study of 1164 individuals who underwent intrauterine device placement at an urban academic medical center. The analysis focused on a comparison of continuation rates between those using levonorgestrel intrauterine device and copper intrauterine device, factors associated with discontinuation, and intrauterine device performance. We assessed the differences in continuation at discrete time points, pregnancy, and expulsion rates using χ2 tests and calculated hazard ratios using a multivariable Cox model. Results Of 1164 women who underwent contraceptive intrauterine device insertion, 956 had follow-up data available. At 2 years, 64.9% of levonorgestrel intrauterine device users continued their device, compared with 57.7% of copper intrauterine device users (P = .11). At 4 years, continuation rates were 45.1% for levonorgestrel intrauterine device and 32.6% for copper intrauterine device (P < .01), and at 5 years continuation rates were 28.1% for levonorgestrel intrauterine device and 23.8% for copper intrauterine device (P = .33). Black race, primiparity, and age were positively associated with discontinuation; education was not. The hazard ratio for discontinuation of levonorgestrel intrauterine device compared with copper intrauterine device >4 years was 0.71 (95% confidence interval, 0.55–0.93) and >5 years was 0.82 (95% confidence interval, 0.64–1.05) after adjusting for race, age, parity, and education. Copper intrauterine device users were more likely to experience expulsion (10.2% copper intrauterine device vs 4.9% levonorgestrel intrauterine device, P < .01) over the study period and to become pregnant in the first year of use (1.6% copper intrauterine device vs 0.1% levonorgestrel intrauterine device, P < .01). Conclusion We found a difference in continuation rates between levonorgestrel and copper intrauterine device users at 4 years but not at 5 years. Copper intrauterine device users were more likely to experience expulsion and pregnancy. PMID:28315664

Evaluation of tissue interactions with mechanical elements of a transscleral drug delivery device.

PubMed

Cohen, Sarah J; Chan, Robison V Paul; Keegan, Mark; Andreoli, Christopher M; Borenstein, Jeffrey T; Miller, Joan W; Gragoudas, Evangelos S

2012-03-12

The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device-one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.

77 FR 60720 - Certain Electronic Devices, Including Wireless Commmunication Devices, Portable Music and Data...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-794] Certain Electronic Devices, Including Wireless Commmunication Devices, Portable Music and Data Processing Devices, and Tablet Computers... communication devices, portable music and data processing devices, and tablet computers, imported by Apple Inc...

21 CFR 892.2020 - Medical image communications device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical image communications device. 892.2020... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2020 Medical image communications device. (a) Identification. A medical image communications device provides electronic transfer of medical...

21 CFR 892.2020 - Medical image communications device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical image communications device. 892.2020... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2020 Medical image communications device. (a) Identification. A medical image communications device provides electronic transfer of medical...

21 CFR 892.2020 - Medical image communications device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical image communications device. 892.2020... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2020 Medical image communications device. (a) Identification. A medical image communications device provides electronic transfer of medical...

21 CFR 892.2020 - Medical image communications device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical image communications device. 892.2020... (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.2020 Medical image communications device. (a) Identification. A medical image communications device provides electronic transfer of medical...

Release strategies for making transferable semiconductor structures, devices and device components

DOEpatents

Rogers, John A; Nuzzo, Ralph G; Meitl, Matthew; Ko, Heung Cho; Yoon, Jongseung; Menard, Etienne; Baca, Alfred J

2014-11-25

Provided are methods for making a device or device component by providing a multilayer structure having a plurality of functional layers and a plurality of release layers and releasing the functional layers from the multilayer structure by separating one or more of the release layers to generate a plurality of transferable structures. The transferable structures are printed onto a device substrate or device component supported by a device substrate. The methods and systems provide means for making high-quality and low-cost photovoltaic devices, transferable semiconductor structures, (opto-)electronic devices and device components.

Release strategies for making transferable semiconductor structures, devices and device components

DOEpatents

Rogers, John A [Champaign, IL; Nuzzo, Ralph G [Champaign, IL; Meitl, Matthew [Raleigh, NC; Ko, Heung Cho [Urbana, IL; Yoon, Jongseung [Urbana, IL; Menard, Etienne [Durham, NC; Baca, Alfred J [Urbana, IL

2011-04-26

Provided are methods for making a device or device component by providing a multilayer structure having a plurality of functional layers and a plurality of release layers and releasing the functional layers from the multilayer structure by separating one or more of the release layers to generate a plurality of transferable structures. The transferable structures are printed onto a device substrate or device component supported by a device substrate. The methods and systems provide means for making high-quality and low-cost photovoltaic devices, transferable semiconductor structures, (opto-)electronic devices and device components.

Release strategies for making transferable semiconductor structures, devices and device components

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

Rogers, John A.; Nuzzo, Ralph G.; Meitl, Matthew

2016-05-24

Provided are methods for making a device or device component by providing a multi layer structure having a plurality of functional layers and a plurality of release layers and releasing the functional layers from the multilayer structure by separating one or more of the release layers to generate a plurality of transferable structures. The transferable structures are printed onto a device substrate or device component supported by a device substrate. The methods and systems provide means for making high-quality and low-cost photovoltaic devices, transferable semiconductor structures, (opto-)electronic devices and device components.

21 CFR 872.1745 - Laser fluorescence caries detection device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Laser fluorescence caries detection device. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1745 Laser fluorescence caries detection device. (a) Identification. A laser fluorescence caries detection device is a laser, a...

Extending Wi-Fi Direct for Automated Operations

DTIC Science & Technology

2015-03-01

functionalities. These added functionalities include: automatic device discovery, a mutual awareness of capabilities between devices (inter-device capability ...functionalities include: automatic device discove1y, a mutual awareness of capabilities between devices (inter-device capability awareness...Figure 7. P2P Device GO Negotiation Request (The P2P IE includes P2P Capability , P2P Device Info, Group Owner Intent, Configuration Timeout, Listen

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 884.5360 - Contraceptive intrauterine device (IUD) and introducer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive intrauterine device (IUD) and... Gynecological Therapeutic Devices § 884.5360 Contraceptive intrauterine device (IUD) and introducer. (a) Identification. A contraceptive intrauterine device (IUD) is a device used to prevent pregnancy. The device is...

21 CFR 872.2060 - Jaw tracking device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Jaw tracking device. 872.2060 Section 872.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2060 Jaw tracking device. (a) Jaw tracking device...

21 CFR 872.2060 - Jaw tracking device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Jaw tracking device. 872.2060 Section 872.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2060 Jaw tracking device. (a) Jaw tracking device...

21 CFR 872.2060 - Jaw tracking device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Jaw tracking device. 872.2060 Section 872.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2060 Jaw tracking device. (a) Jaw tracking device...

21 CFR 872.2060 - Jaw tracking device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Jaw tracking device. 872.2060 Section 872.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.2060 Jaw tracking device. (a) Jaw tracking device...

21 CFR 801.437 - User labeling for devices that contain natural rubber.

Code of Federal Regulations, 2014 CFR

2014-04-01

... User labeling for devices that contain natural rubber. (a) Data in the Medical Device Reporting System... of the device packaging, the outside package, container or wrapper, and the immediate device package... panel of the device packaging, the outside package, container or wrapper, and the immediate device...

21 CFR 801.437 - User labeling for devices that contain natural rubber.

Code of Federal Regulations, 2011 CFR

2011-04-01

... User labeling for devices that contain natural rubber. (a) Data in the Medical Device Reporting System... of the device packaging, the outside package, container or wrapper, and the immediate device package... panel of the device packaging, the outside package, container or wrapper, and the immediate device...

21 CFR 801.437 - User labeling for devices that contain natural rubber.

Code of Federal Regulations, 2013 CFR

2013-04-01

... User labeling for devices that contain natural rubber. (a) Data in the Medical Device Reporting System... of the device packaging, the outside package, container or wrapper, and the immediate device package... panel of the device packaging, the outside package, container or wrapper, and the immediate device...

21 CFR 801.437 - User labeling for devices that contain natural rubber.

Code of Federal Regulations, 2012 CFR

2012-04-01

... User labeling for devices that contain natural rubber. (a) Data in the Medical Device Reporting System... of the device packaging, the outside package, container or wrapper, and the immediate device package... panel of the device packaging, the outside package, container or wrapper, and the immediate device...

21 CFR 801.437 - User labeling for devices that contain natural rubber.

Code of Federal Regulations, 2010 CFR

2010-04-01

... User labeling for devices that contain natural rubber. (a) Data in the Medical Device Reporting System... of the device packaging, the outside package, container or wrapper, and the immediate device package... panel of the device packaging, the outside package, container or wrapper, and the immediate device...

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

Bolenbaugh, Jonathan M.; Naqi, Syed

A method to operate a clutch device in an electro-mechanical transmission mechanically-operatively coupled to an internal combustion engine and at least one electric machine includes, in response to a failure condition detected within a flow control device configured to facilitate flow of hydraulic fluid for operating the clutch device, selectively preventing the flow of hydraulic fluid from entering the flow control device and feeding the clutch device. Synchronization of the clutch device is initiated when the clutch device is intended for activation, and only if the clutch device is synchronized, the flow of hydraulic fluid is selectively permitted to entermore » the flow control device to activate the clutch device.« less

Evaluation of an investigational wearable injector in healthy human volunteers.

PubMed

Torjman, Marc C; Machnicki, Robert; Lessin, Jennifer; Loeum, Channy; Steinberger, Douglas; Mycroft, Sarah; Joseph, Jeffrey I

2017-01-01

Introduction of a wearable device for subcutaneous delivery of larger volume bolus injections would encourage patient compliance and reduce the burden on healthcare services. With one such wearable device commercially available, this study examined the safety and functionality of an investigational device in volunteers. Four devices were applied to the subject's abdomen: 1) Investigational Device, 2) Investigational Device: subject movement, 3) Control Device: FDA-cleared syringe driver with FDA-cleared infusion set, 4) Control Device: FDA-cleared syringe driver attached to investigational device. Three milliliters of saline were infused through the four devices over 3 minutes. 84 devices were applied to 21 subjects. Three milliliters of saline were safely delivered subcutaneously from the investigational and control devices. Two control devices had occlusions and in each case the pump reached its high pressure limit of 12 psi. VAS pain measurements showed minimal pain for all subjects. Pain scores were significantly (p < 0.001) higher than baseline at the end of injection: mean pain level ranged from 2.0-22.0 mm. The investigational device performed as intended with minimal pain during needle insertion and infusion, and no leaking of fluid at the skin puncture site. Two occlusions occurred with the control devices.

77 FR 18829 - Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

...] Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY... public. Name of Committee: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory... and 11, 2012, the committee will discuss general issues related to medical devices intended for obese...

78 FR 77688 - Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

...] Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Ophthalmic Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To... Swink, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave...

21 CFR 880.6310 - Medical device data system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... medical device data; (ii) The electronic storage of medical device data; (iii) The electronic conversion... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Medical device data system. 880.6310 Section 880... Devices § 880.6310 Medical device data system. (a) Identification. (1) A medical device data system (MDDS...

21 CFR 880.6310 - Medical device data system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... medical device data; (ii) The electronic storage of medical device data; (iii) The electronic conversion... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Medical device data system. 880.6310 Section 880... Devices § 880.6310 Medical device data system. (a) Identification. (1) A medical device data system (MDDS...

21 CFR 880.6310 - Medical device data system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... medical device data; (ii) The electronic storage of medical device data; (iii) The electronic conversion... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Medical device data system. 880.6310 Section 880... Devices § 880.6310 Medical device data system. (a) Identification. (1) A medical device data system (MDDS...

21 CFR 880.6310 - Medical device data system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... medical device data; (ii) The electronic storage of medical device data; (iii) The electronic conversion... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Medical device data system. 880.6310 Section 880... Devices § 880.6310 Medical device data system. (a) Identification. (1) A medical device data system (MDDS...

76 FR 29006 - In the Matter of Certain Motion-Sensitive Sound Effects Devices and Image Display Devices and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... Effects Devices and Image Display Devices and Components and Products Containing Same; Notice of... United States after importation of certain motion-sensitive sound effects devices and image display... devices and image display devices and components and products containing same that infringe one or more of...

CONTROL LIMITER DEVICE

DOEpatents

DeShong, J.A.

1960-03-01

A control-limiting device for monltoring a control system is described. The system comprises a conditionsensing device, a condition-varying device exerting a control over the condition, and a control means to actuate the condition-varying device. A control-limiting device integrates the total movement or other change of the condition-varying device over any interval of time during a continuum of overlapping periods of time, and if the tothl movement or change of the condition-varying device exceeds a preset value, the control- limiting device will switch the control of the operated apparatus from automatic to manual control.

Eager protocol on a cache pipeline dataflow

DOEpatents

Ohmacht, Martin; Sugavanam, Krishnan

2012-11-13

A master device sends a request to communicate with a slave device to a switch. The master device waits for a period of cycles the switch takes to decide whether the master device can communicate with the slave device, and the master device sends data associated with the request to communicate at least after the period of cycles has passed since the master device sent the request to communicate to the switch without waiting to receive an acknowledgment from the switch that the master device can communicate with the slave device.

Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices.

PubMed

Sezdi, Mana

2016-01-01

A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices.

Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices

PubMed Central

Sezdi, Mana

2016-01-01

A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices. PMID:27195666

Radiology of cardiac devices and their complications

PubMed Central

Dipoce, J; Spindola-Franco, H

2015-01-01

This article familiarizes the reader with several different cardiac devices including pacemakers and implantable cardioverter defibrillators, intra-aortic balloon pumps, ventricular assist devices, valve replacements and repairs, shunt-occluding devices and passive constraint devices. Many cardiac devices are routinely encountered in clinical practice. Other devices are in the early stages of development, but circumstances suggest that they too will become commonly found. The radiologist must be familiar with these devices and their complications. PMID:25411826

Wireless device monitoring systems and monitoring devices, and associated methods

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

McCown, Steven H; Derr, Kurt W; Rohde, Kenneth W

Wireless device monitoring systems and monitoring devices include a communications module for receiving wireless communications of a wireless device. Processing circuitry is coupled with the communications module and configured to process the wireless communications to determine whether the wireless device is authorized or unauthorized to be present at the monitored area based on identification information of the wireless device. Methods of monitoring for the presence and identity of wireless devices are also provided.

Localized electrical fine tuning of passive microwave and radio frequency devices

DOEpatents

Findikoglu, Alp T.

2001-04-10

A method and apparatus for the localized electrical fine tuning of passive multiple element microwave or RF devices in which a nonlinear dielectric material is deposited onto predetermined areas of a substrate containing the device. An appropriate electrically conductive material is deposited over predetermined areas of the nonlinear dielectric and the signal line of the device for providing electrical contact with the nonlinear dielectric. Individual, adjustable bias voltages are applied to the electrically conductive material allowing localized electrical fine tuning of the devices. The method of the present invention can be applied to manufactured devices, or can be incorporated into the design of the devices so that it is applied at the time the devices are manufactured. The invention can be configured to provide localized fine tuning for devices including but not limited to coplanar waveguides, slotline devices, stripline devices, and microstrip devices.

Processing module operating methods, processing modules, and communications systems

DOEpatents

McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

2014-09-09

A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

Wafer bonded epitaxial templates for silicon heterostructures

DOEpatents

Atwater, Jr., Harry A.; Zahler, James M [Pasadena, CA; Morral, Anna Fontcubera I [Paris, FR

2008-03-11

A heterostructure device layer is epitaxially grown on a virtual substrate, such as an InP/InGaAs/InP double heterostructure. A device substrate and a handle substrate form the virtual substrate. The device substrate is bonded to the handle substrate and is composed of a material suitable for fabrication of optoelectronic devices. The handle substrate is composed of a material suitable for providing mechanical support. The mechanical strength of the device and handle substrates is improved and the device substrate is thinned to leave a single-crystal film on the virtual substrate such as by exfoliation of a device film from the device substrate. An upper portion of the device film exfoliated from the device substrate is removed to provide a smoother and less defect prone surface for an optoelectronic device. A heterostructure is epitaxially grown on the smoothed surface in which an optoelectronic device may be fabricated.

Photoelectrochemically driven self-assembly method

DOEpatents

Nielson, Gregory N.; Okandan, Murat

2017-01-17

Various technologies described herein pertain to assembling electronic devices into a microsystem. The electronic devices are disposed in a solution. Light can be applied to the electronic devices in the solution. The electronic devices can generate currents responsive to the light applied to the electronic devices in the solution, and the currents can cause electrochemical reactions that functionalize regions on surfaces of the electronic devices. Additionally or alternatively, the light applied to the electronic devices in the solution can cause the electronic devices to generate electric fields, which can orient the electronic devices and/or induce movement of the electronic devices with respect to a receiving substrate. Further, electrodes on a receiving substrate can be biased to attract and form connections with the electronic devices having the functionalized regions on the surfaces. The microsystem can include the receiving substrate and the electronic devices connected to the receiving substrate.

Wafer bonded epitaxial templates for silicon heterostructures

NASA Technical Reports Server (NTRS)

Atwater, Harry A., Jr. (Inventor); Zahler, James M. (Inventor); Morral, Anna Fontcubera I (Inventor)

2008-01-01

A heterostructure device layer is epitaxially grown on a virtual substrate, such as an InP/InGaAs/InP double heterostructure. A device substrate and a handle substrate form the virtual substrate. The device substrate is bonded to the handle substrate and is composed of a material suitable for fabrication of optoelectronic devices. The handle substrate is composed of a material suitable for providing mechanical support. The mechanical strength of the device and handle substrates is improved and the device substrate is thinned to leave a single-crystal film on the virtual substrate such as by exfoliation of a device film from the device substrate. An upper portion of the device film exfoliated from the device substrate is removed to provide a smoother and less defect prone surface for an optoelectronic device. A heterostructure is epitaxially grown on the smoothed surface in which an optoelectronic device may be fabricated.

Event-recording devices with identification codes

NASA Technical Reports Server (NTRS)

Watters, David G. (Inventor); Huestis, David L. (Inventor); Bahr, Alfred J. (Inventor); Vidmar, Robert J. (Inventor)

2003-01-01

A recording device allows wireless interrogation to determine its identity and its state. The state indicates whether one or more physical or chemical events have taken place. In effect, the one or more physical or chemical events are recorded by the device. The identity of the device allows it to be distinguished from a number of similar devices. The recording device may be used in an array of devices that allows wireless probing by an interrogation unit. When probed, each device tells the interrogator who it is and what state it is in. The devices allow multiple use and the interrogator may use a logical reset to determine the state of each device. The interrogator can thus easily identify particular items in an array that have reached a particular condition. The device may record the status of each device in a database to maintain a history for each.

Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device

PubMed Central

Cohen, Sarah J.; Chan, Robison V. Paul; Keegan, Mark; Andreoli, Christopher M.; Borenstein, Jeffrey T.; Miller, Joan W.; Gragoudas, Evangelos S.

2012-01-01

The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation. PMID:24300189

What people know about electronic devices: A descriptive study

NASA Astrophysics Data System (ADS)

Kieras, D. E.

1982-10-01

Informal descriptive results on the nature of people's natural knowledge of electronic devices are presented. Expert and nonexpert subjects were given an electronic device to examine and describe orally. The devices ranged from familiar everyday devices, to those familiar only to the expert, to unusual devices unfamiliar even to an expert. College students were asked to describe everyday devices from memory. The results suggest that device knowledge consists of the major categories of what the device is for, how it is used, its structure in terms of subdevices, its physical layout, how it works, and its behavior. A preliminary theoretical framework for device knowledge is that it consists of a hierarchy of schemas, corresponding to a hierarchial decomposition of the device into subdevices, with each level containing the major categories of information.

75 FR 35495 - Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...] Ophthalmic Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Ophthalmic Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To... Glaukos iStent Trabecular Micro-Bypass Stent, Model GTS-100 L/R, sponsored by Glaukos Corp. The device is...

76 FR 50485 - Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee; Amendment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

...] Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee; Amendment of Notice AGENCY... an amendment to the notice of meeting of the Obstetrics and Gynecology Devices Panel of the Medical... Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee would be held on September...

75 FR 61507 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Amendment of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

...] General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Amendment of Notice... announcing an amendment to the notice of meeting of the General and Plastic Surgery Devices Panel of the..., FDA announced that a meeting of the General and Plastic Surgery Devices Panel of the Medical Devices...

Hardware device binding and mutual authentication

DOEpatents

Hamlet, Jason R; Pierson, Lyndon G

2014-03-04

Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

78 FR 1247 - Certain Electronic Devices, Including Wireless Communication Devices, Tablet Computers, Media...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

... Wireless Communication Devices, Tablet Computers, Media Players, and Televisions, and Components Thereof... devices, including wireless communication devices, tablet computers, media players, and televisions, and... wireless communication devices, tablet computers, media players, and televisions, and components thereof...

Tracking down a solution: exploring the acceptability and value of wearable GPS devices for older persons, individuals with a disability and their support persons.

PubMed

Williamson, Brittany; Aplin, Tammy; de Jonge, Desleigh; Goyne, Matthew

2017-11-01

To explore the acceptability and value of three wearable GPS devices for older persons and individuals with a disability and safety concerns when accessing the community. This pilot study explored six wearers' and their support persons' experience of using three different wearable GPS devices (a pendant, watch, and mini GPS phone), each for a two-week period. Participants identified safety as the main value of using a wearable GPS device. The acceptability and value of these devices was strongly influenced by device features, ease of use, cost, appearance, the reliability of the GPS coordinates, the wearer's health condition and the users familiarity with technology. Overall, participants indicated that they preferred the pendant. Wearable GPS devices are potentially useful in providing individuals who have safety concerns with reassurance and access to assistance as required. To ensure successful utilization, future device design and device selection should consider the user's familiarity with technology and their health condition. This study also revealed that not all wearable GPS devices provide continuous location tracking. It is therefore critical to ensure that the device's location tracking functions address the wearer's requirements and reason for using the device. Implications for Rehabilitation The acceptability and usability of wearable GPS devices is strongly influenced by the device features, ease of use, cost, appearance, the reliability of the device to provide accurate and timely GPS coordinates, as well as the health condition of the wearer and their familiarity with technology. Wearable GPS devices need to be simple to use and support and training is essential to ensure they are successfully utilized. Not all wearable GPS devices provide continuous location tracking and accuracy of location is impacted by line of sight to satellites. Therefore, care needs to be taken when choosing a suitable device, to ensure that the device's location tracking features are based on the wearer's requirements and value behind using the device.

Techniques for trans-catheter retrieval of embolized Nit-Occlud® PDA-R and ASD-R devices.

PubMed

Sinha, Sanjay; Levi, Daniel; Peirone, Alejandro; Pedra, Carlos

2018-02-15

Nit-Occlud ® (atrial septal defect) ASD-R and (patent ductus arteriosus) PDA-R devices are used outside the United States for percutaneous closure of the patent ductus arteriosus and atrial septal defects. When embolization occurs, these devices have been difficult to retrieve. Bench simulations of retrieval of PDA-R and ASD-R devices were performed in a vascular model. Retrieval of each device was attempted using snare techniques or with bioptome forceps with a range of devices. The same devices were then intentionally embolized in an animal model. Retrieval methods were systematically tested in a range of sheath sizes, and graded in terms of difficulty and retrieval time. Devices that were grasped by the bioptome in the center of the proximal part of the devices were easily retrieved in both models. Bench studies determined the minimum sheath sizes needed for retrieval of each device with this method. In general sheathes two french sizes greater than the delivery sheath were successful with this technique. Three out of the four PDA-R devices were successfully retrieved in vivo. Two were retrieved by grasping the middle of the PA end of the PDA-R device with a Maslanka bioptome and one small PDA-R device was retrieved using a 10 mm Snare. Four of the five ASD-R devices were retrieved successfully grasping the right atrial ASD-R disc or by passing a wire through the device and snaring this loop. For ASD-R 28 and 30 mm devices, a double bioptome technique was needed to retrieve the device. ASD-R and PDA-R devices can be successfully retrieved in the catheterization lab. It is critical to grab the center portion of the right atrial disc of the ASD-R device or pulmonary portion of the PDA-R device and to use adequately sized sheathes. © 2018 Wiley Periodicals, Inc.

Applications and Methods of Operating a Three-dimensional Nano-electro-mechanical Resonator and Related Devices

NASA Technical Reports Server (NTRS)

Kaul, Anupama B. (Inventor); Epp, Larry W. (Inventor); Bagge, Leif (Inventor)

2013-01-01

Carbon nanofiber resonator devices, methods for use, and applications of said devices are disclosed. Carbon nanofiber resonator devices can be utilized in or as high Q resonators. Resonant frequency of these devices is a function of configuration of various conducting components within these devices. Such devices can find use, for example, in filtering and chemical detection.

Current state of medical device nomenclature and taxonomy systems in the UK: spotlight on GMDN and SNOMED CT

PubMed Central

White, Judith; Carolan-Rees, Grace

2013-01-01

A standardised terminology for describing medical devices can enable safe and unambiguous exchange of information. Proposed changes to EU-wide medical devices regulations mandate the use of such a system. This article reviews two important classification systems for medical devices in the UK. The Global Medical Device Nomenclature (GMDN) provides a classification system specifically for medical devices and diagnostics, and facilitates data exchange between manufacturers and regulators. SNOMED CT is the terminology of choice in the NHS for communicating, sharing and storing information about patients’ healthcare episodes. Harmonisation of GMDN and SNOMED CT will encourage use of single terminology throughout the lifetime of a device; from regulatory approval through clinical use and post-marketing surveillance. Manufacturers will be required to register medical devices with a European device database (Eudamed) and to fit certain devices with a Unique Device Identifier; both are efforts to improve transparency and traceability of medical devices. Successful implementation of these elements depends on having a consistent nomenclature for medical devices. PMID:23885299

Examining the Relationship between Parental Involvement and Mobile Technology Use

NASA Astrophysics Data System (ADS)

Flowers, Toinette M.

Understanding how mobile devices can enhance parent/teacher communication is important because parents play an important part in their children's learning. Research on parents' use of mobile devices to communicate with their children's teachers is limited. The purpose of this cross-sectional correlational study was to determine the relationships between parents' (a) knowledge of using mobile devices, (b) general use of mobile devices, (c) purpose for using mobile devices, (d) perceived ease of using mobile devices, (e) perceived usefulness of mobile devices, (f) attitude toward using mobile devices, and (g) use of mobile devices to communicate with teachers. The study was informed by the technology acceptance model and used a participant pool of 73 parents of high school students attending a Title I high school in a large Midwestern city in the United States. Data were collected using an online survey and analyzed using Pearson's correlations. The study results indicate significant correlations between parents' use of mobile devices to communicate with teachers and knowledge of using mobile devices, purpose for using mobile devices, perceived ease of using mobile devices, perceived usefulness of mobile devices, and attitudes toward using mobile devices. These findings suggest that parental use of mobile devices to communicate with teachers can be enhanced by administrators and school personnel using strategies that consider parents' and the school culture. Social implication includes sharing the results of this study with district and school administrators who have the power to implement programs that encourage and support the use of mobile devices as a communication tool between parents and teachers, therefore increasing parental involvement and ultimately student academic success.

21 CFR 882.5050 - Biofeedback device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Biofeedback device. 882.5050 Section 882.5050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5050 Biofeedback device. (a...

21 CFR 872.3660 - Impression material.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3660 Impression material. (a) Identification. Impression material is a device composed of materials such as alginate or polysulfide intended to be placed... device is intended to provide models for study and for production of restorative prosthetic devices, such...

21 CFR 872.3660 - Impression material.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3660 Impression material. (a) Identification. Impression material is a device composed of materials such as alginate or polysulfide intended to be placed... device is intended to provide models for study and for production of restorative prosthetic devices, such...

78 FR 24775 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Commission Decision... importation of certain wireless communication devices, portable music and data processing devices, computers...

78 FR 12785 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Commission Decision... importation of certain wireless communication devices, portable music and data processing devices, computers...

Three fundamental devices in one: a reconfigurable multifunctional device in two-dimensional WSe2

NASA Astrophysics Data System (ADS)

Dhakras, Prathamesh; Agnihotri, Pratik; Lee, Ji Ung

2017-06-01

The three pillars of semiconductor device technologies are (1) the p-n diode, (2) the metal-oxide-semiconductor field-effect transistor and (3) the bipolar junction transistor. They have enabled the unprecedented growth in the field of information technology that we see today. Until recently, the technological revolution for better, faster and more efficient devices has been governed by scaling down the device dimensions following Moore’s Law. With the slowing of Moore’s law, there is a need for alternative materials and computing technologies that can continue the advancement in functionality. Here, we describe a single, dynamically reconfigurable device that implements these three fundamental device functions. The device uses buried gates to achieve n- and p-channels and fits into a larger effort to develop devices with enhanced functionalities, including logic functions, over device scaling. As they are all surface conducting devices, we use one material parameter, the interface trap density of states, to describe the key figure-of-merit of each device.

Content analysis of Australian direct-to-consumer websites for emerging breast cancer imaging devices.

PubMed

Vreugdenburg, Thomas D; Laurence, Caroline O; Willis, Cameron D; Mundy, Linda; Hiller, Janet E

2014-09-01

To describe the nature and frequency of information presented on direct-to-consumer websites for emerging breast cancer imaging devices. Content analysis of Australian website advertisements from 2 March 2011 to 30 March 2012, for three emerging breast cancer imaging devices: digital infrared thermal imaging, electrical impedance scanning and electronic palpation imaging. Type of imaging offered, device safety, device performance, application of device, target population, supporting evidence and comparator tests. Thirty-nine unique Australian websites promoting a direct-to-consumer breast imaging device were identified. Despite a lack of supporting evidence, 22 websites advertised devices for diagnosis, 20 advertised devices for screening, 13 advertised devices for prevention and 13 advertised devices for identifying breast cancer risk factors. Similarly, advertised ranges of diagnostic sensitivity (78%-99%) and specificity (44%-91%) were relatively high compared with published literature. Direct comparisons with conventional screening tools that favoured the new device were highly prominent (31 websites), and one-third of websites (12) explicitly promoted their device as a suitable alternative. Australian websites for emerging breast imaging devices, which are also available internationally, promote the use of such devices as safe and effective solutions for breast cancer screening and diagnosis in a range of target populations. Many of these claims are not supported by peer-reviewed evidence, raising questions about the manner in which these devices and their advertising material are regulated, particularly when they are promoted as direct alternatives to established screening interventions.

Lossless hybridization between photovoltaic and thermoelectric devices.

PubMed

Park, Kwang-Tae; Shin, Sun-Mi; Tazebay, Abdullah S; Um, Han-Don; Jung, Jin-Young; Jee, Sang-Won; Oh, Min-Wook; Park, Su-Dong; Yoo, Bongyoung; Yu, Choongho; Lee, Jung-Ho

2013-01-01

The optimal hybridization of photovoltaic (PV) and thermoelectric (TE) devices has long been considered ideal for the efficient harnessing solar energy. Our hybrid approach uses full spectrum solar energy via lossless coupling between PV and TE devices while collecting waste energy from thermalization and transmission losses from PV devices. Achieving lossless coupling makes the power output from the hybrid device equal to the sum of the maximum power outputs produced separately from individual PV and TE devices. TE devices need to have low internal resistances enough to convey photo-generated currents without sacrificing the PV fill factor. Concomitantly, a large number of p-n legs are preferred to drive a high Seebeck voltage in TE. Our simple method of attaching a TE device to a PV device has greatly improved the conversion efficiency and power output of the PV device (~30% at a 15°C temperature gradient across a TE device).

Lossless hybridization between photovoltaic and thermoelectric devices

PubMed Central

Park, Kwang-Tae; Shin, Sun-Mi; Tazebay, Abdullah S.; Um, Han-Don; Jung, Jin-Young; Jee, Sang-Won; Oh, Min-Wook; Park, Su-Dong; Yoo, Bongyoung; Yu, Choongho; Lee, Jung-Ho

2013-01-01

The optimal hybridization of photovoltaic (PV) and thermoelectric (TE) devices has long been considered ideal for the efficient harnessing solar energy. Our hybrid approach uses full spectrum solar energy via lossless coupling between PV and TE devices while collecting waste energy from thermalization and transmission losses from PV devices. Achieving lossless coupling makes the power output from the hybrid device equal to the sum of the maximum power outputs produced separately from individual PV and TE devices. TE devices need to have low internal resistances enough to convey photo-generated currents without sacrificing the PV fill factor. Concomitantly, a large number of p-n legs are preferred to drive a high Seebeck voltage in TE. Our simple method of attaching a TE device to a PV device has greatly improved the conversion efficiency and power output of the PV device (~30% at a 15°C temperature gradient across a TE device). PMID:23820973

21 CFR 882.4250 - Cryogenic surgical device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cryogenic surgical device. 882.4250 Section 882.4250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4250 Cryogenic surgical device...

21 CFR 882.4250 - Cryogenic surgical device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cryogenic surgical device. 882.4250 Section 882.4250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Surgical Devices § 882.4250 Cryogenic surgical device...

21 CFR 872.1870 - Sulfide detection device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Sulfide detection device. 872.1870 Section 872.1870 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1870 Sulfide detection device. (a) Identification...

21 CFR 872.1740 - Caries detection device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Caries detection device. 872.1740 Section 872.1740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1740 Caries detection device. (a) Identification...

21 CFR 872.1740 - Caries detection device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Caries detection device. 872.1740 Section 872.1740 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1740 Caries detection device. (a) Identification...

78 FR 68853 - International Medical Device Regulators Forum; Medical Device Single Audit Program International...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

...] International Medical Device Regulators Forum; Medical Device Single Audit Program International Coalition Pilot... Drug Administration (FDA) is announcing participation in the Medical Device Single Audit Program International Coalition Pilot Program. The Medical Device Single Audit Program (MDSAP) was designed and...

21 CFR 866.2580 - Gas-generating device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gas-generating device. 866.2580 Section 866.2580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2580 Gas-generating device...

21 CFR 866.2580 - Gas-generating device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gas-generating device. 866.2580 Section 866.2580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2580 Gas-generating device...

21 CFR 866.2580 - Gas-generating device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gas-generating device. 866.2580 Section 866.2580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2580 Gas-generating device...

21 CFR 866.2580 - Gas-generating device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gas-generating device. 866.2580 Section 866.2580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2580 Gas-generating device...

21 CFR 866.2580 - Gas-generating device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gas-generating device. 866.2580 Section 866.2580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2580 Gas-generating device...

77 FR 52759 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... INTERNATIONAL TRADE COMMISSION [Investigation No. 337-TA-745] Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers and Components Thereof; Notice of... communication devices, portable music and data processing devices, computers and components thereof by reason of...

77 FR 51571 - Certain Wireless Communication Devices, Portable Music and Data Processing Devices, Computers...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-24

... Music and Data Processing Devices, Computers, and Components Thereof; Notice of Receipt of Complaint... complaint entitled Wireless Communication Devices, Portable Music and Data Processing Devices, Computers..., portable music and data processing devices, computers, and components thereof. The complaint names as...

21 CFR 874.5840 - Antistammering device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Antistammering device. 874.5840 Section 874.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5840 Antistammering device. (a...

21 CFR 874.5840 - Antistammering device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Antistammering device. 874.5840 Section 874.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5840 Antistammering device. (a...

21 CFR 874.5840 - Antistammering device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Antistammering device. 874.5840 Section 874.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5840 Antistammering device. (a...

21 CFR 874.5840 - Antistammering device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Antistammering device. 874.5840 Section 874.5840 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5840 Antistammering device. (a...

21 CFR 810.10 - Cease distribution and notification order.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE RECALL AUTHORITY Mandatory Medical Device Recall Procedures § 810... usual name of the device; (iii) The model, catalog, or product code numbers of the device; and (iv) The... opportunity to consult with the agency, FDA finds that there is a reasonable probability that a device...

21 CFR 810.10 - Cease distribution and notification order.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE RECALL AUTHORITY Mandatory Medical Device Recall Procedures § 810... usual name of the device; (iii) The model, catalog, or product code numbers of the device; and (iv) The... opportunity to consult with the agency, FDA finds that there is a reasonable probability that a device...

21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

21 CFR 884.5380 - Contraceptive tubal occlusion device (TOD) and introducer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contraceptive tubal occlusion device (TOD) and... Gynecological Therapeutic Devices § 884.5380 Contraceptive tubal occlusion device (TOD) and introducer. (a) Identification. A contraceptive tubal occlusion device (TOD) and introducer is a device designed to close a...

Integrated device architectures for electrochromic devices

DOEpatents

Frey, Jonathan Mack; Berland, Brian Spencer

2015-04-21

This disclosure describes systems and methods for creating monolithically integrated electrochromic devices which may be a flexible electrochromic device. Monolithic integration of thin film electrochromic devices may involve the electrical interconnection of multiple individual electrochromic devices through the creation of specific structures such as conductive pathway or insulating isolation trenches.

21 CFR 892.1670 - Spot-film device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Spot-film device. 892.1670 Section 892.1670 Food... DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1670 Spot-film device. (a) Identification. A spot-film... medical purposes to position a radiographic film cassette to obtain radiographs during fluoroscopy. (b...

21 CFR 892.1670 - Spot-film device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Spot-film device. 892.1670 Section 892.1670 Food... DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1670 Spot-film device. (a) Identification. A spot-film... medical purposes to position a radiographic film cassette to obtain radiographs during fluoroscopy. (b...

21 CFR 892.1670 - Spot-film device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Spot-film device. 892.1670 Section 892.1670 Food... DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1670 Spot-film device. (a) Identification. A spot-film... medical purposes to position a radiographic film cassette to obtain radiographs during fluoroscopy. (b...

21 CFR 892.1670 - Spot-film device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Spot-film device. 892.1670 Section 892.1670 Food... DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1670 Spot-film device. (a) Identification. A spot-film... medical purposes to position a radiographic film cassette to obtain radiographs during fluoroscopy. (b...

76 FR 14028 - Center for Devices and Radiological Health 510(k) Implementation: Online Repository of Medical...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

...] Center for Devices and Radiological Health 510(k) Implementation: Online Repository of Medical Device... public meeting entitled ``510(k) Implementation: Discussion of an Online Repository of Medical Device... establish an online public repository of medical device labeling and strategies for displaying device...

76 FR 28689 - Microbiology Devices; Classification of In Vitro Diagnostic Device for Bacillus Species Detection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-18

.... FDA-2011-N-0103] Microbiology Devices; Classification of In Vitro Diagnostic Device for Bacillus... of the Microbiology Devices Advisory Panel (the Panel). In addition, the proposed rule would... in the Federal Register. 1. Transcript of the FDA Microbiology Devices Panel meeting, March 7, 2002...

21 CFR 892.1670 - Spot-film device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Spot-film device. 892.1670 Section 892.1670 Food... DEVICES RADIOLOGY DEVICES Diagnostic Devices § 892.1670 Spot-film device. (a) Identification. A spot-film... medical purposes to position a radiographic film cassette to obtain radiographs during fluoroscopy. (b...

47 CFR 2.801 - Radiofrequency device defined.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Radiofrequency device defined. 2.801 Section 2... MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.801 Radiofrequency device defined. As used in this part, a radiofrequency device is any device which in its operation is capable of...

21 CFR 886.4170 - Cryophthalmic unit.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVICES OPHTHALMIC DEVICES Surgical Devices § 886.4170 Cryophthalmic unit. (a) Identification. A cryophthalmic unit is a device that is a probe with a small tip that becomes extremely cold through the controlled use of a refrigerant or gas. The device may be AC-powered. The device is intended to remove...

21 CFR 874.5370 - Tongs antichoke device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tongs antichoke device. 874.5370 Section 874.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5370 Tongs antichoke device. (a...

21 CFR 874.5350 - Suction antichoke device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Suction antichoke device. 874.5350 Section 874.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5350 Suction antichoke device. (a...

21 CFR 874.5350 - Suction antichoke device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Suction antichoke device. 874.5350 Section 874.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5350 Suction antichoke device. (a...

21 CFR 874.5350 - Suction antichoke device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Suction antichoke device. 874.5350 Section 874.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5350 Suction antichoke device. (a...

21 CFR 874.5370 - Tongs antichoke device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tongs antichoke device. 874.5370 Section 874.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5370 Tongs antichoke device. (a...

21 CFR 874.5350 - Suction antichoke device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Suction antichoke device. 874.5350 Section 874.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5350 Suction antichoke device. (a...

21 CFR 874.5350 - Suction antichoke device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Suction antichoke device. 874.5350 Section 874.5350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5350 Suction antichoke device. (a...

21 CFR 874.5370 - Tongs antichoke device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tongs antichoke device. 874.5370 Section 874.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5370 Tongs antichoke device. (a...

21 CFR 874.5370 - Tongs antichoke device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tongs antichoke device. 874.5370 Section 874.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5370 Tongs antichoke device. (a...

21 CFR 874.5370 - Tongs antichoke device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tongs antichoke device. 874.5370 Section 874.5370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Therapeutic Devices § 874.5370 Tongs antichoke device. (a...

21 CFR 864.6100 - Bleeding time device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bleeding time device. 864.6100 Section 864.6100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6100 Bleeding time device...

21 CFR 864.6100 - Bleeding time device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bleeding time device. 864.6100 Section 864.6100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6100 Bleeding time device...

21 CFR 864.6100 - Bleeding time device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bleeding time device. 864.6100 Section 864.6100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6100 Bleeding time device...

21 CFR 864.6100 - Bleeding time device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bleeding time device. 864.6100 Section 864.6100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6100 Bleeding time device...

21 CFR 864.6100 - Bleeding time device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bleeding time device. 864.6100 Section 864.6100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6100 Bleeding time device...

21 CFR 878.4930 - Suture retention device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Suture retention device. 878.4930 Section 878.4930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4930 Suture retention device...

21 CFR 878.4930 - Suture retention device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Suture retention device. 878.4930 Section 878.4930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4930 Suture retention device...

21 CFR 878.4930 - Suture retention device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Suture retention device. 878.4930 Section 878.4930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4930 Suture retention device...

21 CFR 878.4930 - Suture retention device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Suture retention device. 878.4930 Section 878.4930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4930 Suture retention device...

21 CFR 878.4930 - Suture retention device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Suture retention device. 878.4930 Section 878.4930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4930 Suture retention device...

Methods and devices for fabricating and assembling printable semiconductor elements

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

Nuzzo, Ralph G.; Rogers, John A.; Menard, Etienne

The invention provides methods and devices for fabricating printable semiconductor elements and assembling printable semiconductor elements onto substrate surfaces. Methods, devices and device components of the present invention are capable of generating a wide range of flexible electronic and optoelectronic devices and arrays of devices on substrates comprising polymeric materials. The present invention also provides stretchable semiconductor structures and stretchable electronic devices capable of good performance in stretched configurations.

Methods and devices for fabricating and assembling printable semiconductor elements

DOEpatents

Nuzzo, Ralph G; Rogers, John A; Menard, Etienne; Lee, Keon Jae; Khang, Dahl-Young; Sun, Yugang; Meitl, Matthew; Zhu, Zhengtao

2014-03-04

The invention provides methods and devices for fabricating printable semiconductor elements and assembling printable semiconductor elements onto substrate surfaces. Methods, devices and device components of the present invention are capable of generating a wide range of flexible electronic and optoelectronic devices and arrays of devices on substrates comprising polymeric materials. The present invention also provides stretchable semiconductor structures and stretchable electronic devices capable of good performance in stretched configurations.

Medical Devices; General Hospital and Personal Use Devices; Classification of the Ultraviolet Radiation Chamber Disinfection Device. Final order.

PubMed

2015-11-20

The Food and Drug Administration (FDA or the Agency) is classifying the ultraviolet (UV) radiation chamber disinfection device into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the UV radiation chamber disinfection device classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

The Importance of State and Context in Safe Interoperable Medical Systems

PubMed Central

Jaffe, Michael B.; Robkin, Michael; Rausch, Tracy; Arney, David; Goldman, Julian M.

2016-01-01

This paper describes why “device state” and “patient context” information are necessary components of device models for safe interoperability. This paper includes a discussion of the importance of describing the roles of devices with respect to interactions (including human user workflows involving devices, and device to device communication) within a system, particularly those intended for use at the point-of-care, and how this role information is communicated. In addition, it describes the importance of clinical scenarios in creating device models for interoperable devices. PMID:27730013

Policy-based secure communication with automatic key management for industrial control and automation systems

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

Chernoguzov, Alexander; Markham, Thomas R.; Haridas, Harshal S.

A method includes generating at least one access vector associated with a specified device in an industrial process control and automation system. The specified device has one of multiple device roles. The at least one access vector is generated based on one or more communication policies defining communications between one or more pairs of devices roles in the industrial process control and automation system, where each pair of device roles includes the device role of the specified device. The method also includes providing the at least one access vector to at least one of the specified device and one ormore » more other devices in the industrial process control and automation system in order to control communications to or from the specified device.« less

Progress and Prospects in Stretchable Electroluminescent Devices

NASA Astrophysics Data System (ADS)

Wang, Jiangxin; Lee, Pooi See

2017-03-01

Stretchable electroluminescent (EL) devices are a new form of mechanically deformable electronics that are gaining increasing interests and believed to be one of the essential technologies for next generation lighting and display applications. Apart from the simple bending capability in flexible EL devices, the stretchable EL devices are required to withstand larger mechanical deformations and accommodate stretching strain beyond 10%. The excellent mechanical conformability in these devices enables their applications in rigorous mechanical conditions such as flexing, twisting, stretching, and folding.The stretchable EL devices can be conformably wrapped onto arbitrary curvilinear surface and respond seamlessly to the external or internal forces, leading to unprecedented applications that cannot be addressed with conventional technologies. For example, they are in demand for wide applications in biomedical-related devices or sensors and soft interactive display systems, including activating devices for photosensitive drug, imaging apparatus for internal tissues, electronic skins, interactive input and output devices, robotics, and volumetric displays. With increasingly stringent demand on the mechanical requirements, the fabrication of stretchable EL device is encountering many challenges that are difficult to resolve. In this review, recent progresses in the stretchable EL devices are covered with a focus on the approaches that are adopted to tackle materials and process challenges in stretchable EL devices and delineate the strategies in stretchable electronics. We first introduce the emission mechanisms that have been successfully demonstrated on stretchable EL devices. Limitations and advantages of the different mechanisms for stretchable EL devices are also discussed. Representative reports are reviewed based on different structural and material strategies. Unprecedented applications that have been enabled by the stretchable EL devices are reviewed. Finally, we summarize with our perspectives on the approaches for the stretchable EL devices and our proposals on the future development in these devices.

Multiple constraints compromise decision-making about implantable medical devices for individual patients: qualitative interviews with physicians.

PubMed

Gagliardi, Anna R; Ducey, Ariel; Lehoux, Pascale; Turgeon, Thomas; Kolbunik, Jeremy; Ross, Sue; Trbovich, Patricia; Easty, Anthony; Bell, Chaim; Urbach, David R

2017-12-22

Little research has examined how physicians choose medical devices for treating individual patients to reveal if interventions are needed to support decision-making and reduce device-associated morbidity and mortality. This study explored factors that influence choice of implantable device from among available options. A descriptive qualitative approach was used. Physicians who implant orthopedic and cardiovascular devices were identified in publicly available directories and web sites. They were asked how they decided what device to use in a given patient, sources of information they consulted, and how patients were engaged in decision-making. Sampling was concurrent with data collection and analysis to achieve thematic saturation. Data were analyzed using constant comparative technique by all members of the research team. Twenty-two physicians from five Canadian provinces (10 cardiovascular, 12 orthopedic; 8, 10 and 4 early, mid and late career, respectively) were interviewed. Responses did not differ by specialty, geographic region or career stage. Five major categories of themes emerged that all influence decision-making about a range of devices, and often compromise choice of the most suitable device for a given patient, potentially leading to sub-optimal clinical outcomes: lack of evidence on device performance, patient factors, physician factors, organizational and health system factors, and device and device market factors. In the absence of evidence from research or device registries, tacit knowledge from trusted colleagues and less-trusted industry representatives informed device choice. Patients were rarely engaged in decision-making. Physician preference for particular devices was a barrier to acquiring competency in devices potentially more suitable for patients. Access to suitable devices was further limited to the number of comparable devices on the market, local inventory and purchasing contract specifications. This study revealed that decision-making about devices is complex, cognitively challenging and constrained by several factors limiting access to and use of devices that could optimize patient outcomes. Further research is needed to assess the impact of these constraints on clinical outcomes, and develop interventions that optimize decision-making about device choice for treating given patients.

[Comparative study of device labeling regulation in U.S.A. and China].

PubMed

Li, Fei; Wei, Jing; Ma, Yanbin; Li, Zhu

2010-09-01

To provide references for the evolvement of medical devices labeling and manual administration in China, By content analysis, 10 juristic documents relevant to device labeling and manual were collected from FDA website, compared to which, the federal regulation was mainly analyzed. There are five main differences of device labeling regulation between U.S.A. and China: juristic system, administrative scope, administrative target, characteristics and practice, A set of comprehensive juristic system for device labeling has been established by FDA. from which China should draw experience, to administrate the prescription devices and the over-the-counter devices in classification, and set up device labeling guidance, thus guarantee the safety and efficacy of device.

Surface Acoustic Wave Monitor for Deposition and Analysis of Ultra-Thin Films

NASA Technical Reports Server (NTRS)

Hines, Jacqueline H. (Inventor)

2015-01-01

A surface acoustic wave (SAW) based thin film deposition monitor device and system for monitoring the deposition of ultra-thin films and nanomaterials and the analysis thereof is characterized by acoustic wave device embodiments that include differential delay line device designs, and which can optionally have integral reference devices fabricated on the same substrate as the sensing device, or on a separate device in thermal contact with the film monitoring/analysis device, in order to provide inherently temperature compensated measurements. These deposition monitor and analysis devices can include inherent temperature compensation, higher sensitivity to surface interactions than quartz crystal microbalance (QCM) devices, and the ability to operate at extreme temperatures.

21 CFR 872.1745 - Laser fluorescence caries detection device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1745 Laser fluorescence caries... fluorescence detector housed in a dental handpiece, and a control console that performs device calibration, as...

21 CFR 872.1745 - Laser fluorescence caries detection device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1745 Laser fluorescence caries... fluorescence detector housed in a dental handpiece, and a control console that performs device calibration, as...

76 FR 48871 - Immunology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Immunology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Immunology Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To...

76 FR 55398 - Immunology Devices Panel of the Medical Devices Advisory Committee: Notice of Postponement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Immunology Devices Panel of the Medical Devices Advisory Committee: Notice of Postponement of Meeting AGENCY... postponing the meeting of the Immunology Devices Panel of the Medical Devices Advisory Committee scheduled...

76 FR 6625 - Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Neurological Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To...

76 FR 12973 - Neurological Devices Panel of the Medical Devices Advisory Committee; Amendment of Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

...] Neurological Devices Panel of the Medical Devices Advisory Committee; Amendment of Notice AGENCY: Food and Drug... notice of meeting of the Neurological Devices Panel of the Medical Devices Advisory Committee. This... INFORMATION: In the Federal Register of February 7, 2011, FDA announced that a meeting of the Neurological...

76 FR 36548 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

...] Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and... of Committee: Circulatory System Devices Panel of the Medical Devices Advisory Committee. General... also comes with a sheath, introducer, loader, dilator, balloon (used to pre-dilate the native annulus...

77 FR 25183 - Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

...] Circulatory System Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and... of Committee: Circulatory System Devices Panel of the Medical Devices Advisory Committee. General..., introducer, loader, dilator, balloon (used to pre-dilate the native annulus) and a crimper. FDA intends to...

78 FR 26786 - Microbiology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Microbiology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Microbiology Devices Panel of the Medical Devices Advisory Committee. General Function of the Committee: To...

76 FR 69034 - Microbiology Devices; Classification of In Vitro Diagnostic Device for Yersinia Species Detection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... Drug Administration 21 CFR Part 866 Microbiology Devices; Classification of In Vitro Diagnostic Device... CFR Part 866 [Docket No. FDA-2011-N-0729] Microbiology Devices; Classification of In Vitro Diagnostic... of the Microbiology Devices Advisory Panel (the panel). FDA is publishing in this document the...

75 FR 57968 - Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

...] Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY... public. Name of Committee: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory... committee will discuss, make recommendations, and vote on information related to the PMA for the LAP-BAND...

76 FR 54156 - National Standards for Traffic Control Devices; the Manual on Uniform Traffic Control Devices for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-31

... traffic control device design, location, or operation that have made some existing devices in the field...-2010-0159] RIN 2125-AF43 National Standards for Traffic Control Devices; the Manual on Uniform Traffic Control Devices for Streets and Highways; Revision AGENCY: Federal Highway Administration (FHWA...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

21 CFR 868.5115 - Device to relieve acute upper airway obstruction.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Device to relieve acute upper airway obstruction. 868.5115 Section 868.5115 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5115 Device to...

14 CFR 23.373 - Speed control devices.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Speed control devices. 23.373 Section 23....373 Speed control devices. If speed control devices (such as spoilers and drag flaps) are incorporated....441 and 23.443, with the device extended at speeds up to the placard device extended speed; and (b) If...

14 CFR 23.373 - Speed control devices.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Speed control devices. 23.373 Section 23....373 Speed control devices. If speed control devices (such as spoilers and drag flaps) are incorporated....441 and 23.443, with the device extended at speeds up to the placard device extended speed; and (b) If...

75 FR 47606 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of... General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee scheduled for August...

78 FR 30928 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting... the public. Name of Committee: General and Plastic Surgery Devices Panel of the Medical Devices...

75 FR 49940 - General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting... the public. Name of Committee: General and Plastic Surgery Devices Panel of the Medical Devices...

21 CFR 830.300 - Devices subject to device identification data submission requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Devices subject to device identification data submission requirements. 830.300 Section 830.300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Identification Database § 830.300 Devices subject to device identification data submission requirements. (a) In...

21 CFR 880.6785 - Manual patient transfer device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Miscellaneous Devices § 880.6785 Manual patient transfer device. (a) Identification. A manual patient transfer device is a device consisting of a wheeled stretcher and a mechanism on which a patient can be placed so... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual patient transfer device. 880.6785 Section...

The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems.

PubMed

Weininger, Sandy; Jaffe, Michael B; Goldman, Julian M

2017-01-01

Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account these systems' perspective. In this article, we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate standards development groups, some of which focus on safety and effectiveness and others focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development.

The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems

PubMed Central

Weininger, Sandy; Jaffe, Michael B.; Goldman, Julian M

2016-01-01

Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account this systems perspective. In this article we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate standards development groups; some which focus on safety and effectiveness, and others that focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development. PMID:27584685

Regulatory science based approach in development of novel medical devices.

PubMed

Sakuma, Ichiro

2015-08-01

For development rational evaluation method for medical devices' safety and efficacy, regulatory science studies are important. Studies on regulatory affairs related to a medical device under development should be conducted as well as its technological development. Clinical performance of a medical device is influenced by performance of the device, medical doctors' skill, pathological condition of a patient, and so on. Thus it is sometimes difficult to demonstrate superiority of the device in terms of clinical outcome although its efficacy as a medical device is accepted. Setting of appropriate end points is required to evaluate a medical device appropriately. Risk assessment and risk management are the basis of medical device safety assurance. In case of medical device software, there are difficulties in identifying the risk due to its complexity of user environment and different design and manufacturing procedure compared with conventional hardware based medical devices. Recent technological advancement such as information and communication technologies (ICT) for medical devices and wireless network has raised new issue on risk management: cybersecurity. We have to watch closely the progress of safety standard development.

Implantation reduces the negative effects of bio-logging devices on birds.

PubMed

White, Craig R; Cassey, Phillip; Schimpf, Natalie G; Halsey, Lewis G; Green, Jonathan A; Portugal, Steven J

2013-02-15

Animal-borne logging or telemetry devices are widely used for measurements of physiological and movement data from free-living animals. For such measurements to be relevant, however, it is essential that the devices themselves do not affect the data of interest. A recent meta-analysis reported an overall negative effect of these devices on the birds that bear them, i.e. on nesting productivity, clutch size, nest initiation date, offspring quality, body condition, flying ability, foraging behaviours, energy expenditure and survival rate. Method of attachment (harness, collar, glue, anchor, implant, breast-mounted or tailmount) had no influence on the strength of these effects but anchored and implanted transmitters had the highest reported rates of device-induced mortality. Furthermore, external devices, but not internal devices, caused an increase in 'device-induced behaviour' (comfort behaviours such as preening, fluffing and stretching, and unrest activities including unquantifiable 'active' behaviours). These findings suggest that, with the exception of device-induced behaviour, external attachment is preferable to implantation. In the present study we undertake a meta-analysis of 183 estimates of device impact from 39 studies of 36 species of bird designed to explicitly compare the effects of externally attached and surgically implanted devices on a range of traits, including condition, energy expenditure and reproduction. In contrast to a previous study, we demonstrate that externally attached devices have a consistent detrimental effect (i.e. negative influences on body condition, reproduction, metabolism and survival), whereas implanted devices have no consistent effect. We also show that the magnitude of the negative effect of externally attached devices decreases with time. We therefore conclude that device implantation is preferable to external attachment, providing that the risk of mortality associated with the anaesthesia and surgery required for implantation can be mitigated. We recommend that studies employing external devices use devices that can be borne for long periods, and, wherever possible, deploy devices in advance of the time period of interest.

Adolescents' Use of Basic, Intermediate, and Advanced Device Types for Vaping.

PubMed

Pepper, Jessica K; MacMonegle, Anna J; Nonnemaker, James M

2017-12-23

Advanced models of electronic vaping products (EVPs) likely pose a greater risk to adolescent health than basic or intermediate models because advanced models deliver nicotine more effectively and heat e-liquid to higher temperatures, producing more harmful chemical emissions. However, little is known about adolescents' risk factors for using different device types. We used social media to recruit an online sample of 1,508 U.S. adolescents aged 15-17 who reported past 30-day use of e-cigarettes. We assessed tobacco use, beliefs and knowledge about EVPs, and EVP use behavior, including the device type participants use most frequently. We used multinomial logistic regression to examine differences between adolescents who usually use intermediate versus basic and advanced versus basic devices. Most respondents usually used modifiable advanced devices (56.8%) rather than basic "cigalike" (14.5%) or pen-style intermediate (28.7%) devices. Use of multiple device types was common, particularly among those who primarily used basic devices. Younger age and less frequent vaping were associated with mainly using basic devices. Adolescents who were older, male, personally bought their main device, and had ever mixed e-liquids were at elevated risk for usually using advanced devices. Adolescents who primarily use basic devices may be newer users who are experimenting with multiple devices. Future research should examine which adolescents are most likely to transition to advanced devices in order to develop targeted interventions. Regulators should consider strategies to reduce access to all types of EVPs, such as better enforcement of the current ban on sales to minors. This research addresses two gaps in research on adolescent electronic vaping product use: (1) characterizing use of advanced devices as distinct from intermediate devices rather than grouping them together and (2) examining factors associated with use of specific device types. This study suggests that there are distinct profiles of adolescents who use primarily basic, intermediate, or advanced devices. Adolescents who most often use basic devices may be new users experimenting with vaping, whereas adolescents who most often use advanced devices appear to be buying devices for themselves and engaging in risky behaviors such as mixing their own e-liquid. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fabrication of a microfluidic device for the compartmentalization of neuron soma and axons.

PubMed

Harris, Joseph; Lee, Hyuna; Vahidi, Behrad; Tu, Christina; Cribbs, David; Jeon, Noo Li; Cotman, Carl

2007-01-01

In this video, we demonstrate the technique of soft lithography with polydimethyl siloxane (PDMS) which we use to fabricate a microfluidic device for culturing neurons. Previously, a silicon wafer was patterned with the design for the neuron microfluidic device using SU-8 and photolithography to create a master mold, or what we simply refer to as a "master". Next, we pour the silicon polymer PDMS on top of the master which is then cured by heating the PDMS to 80 degrees C for 1 hour. The PDMS forms a negative mold of the device. The PDMS is then carefully cut and lifted away from the master. Holes are punched where the reservoirs will be and the excess PDMS trimmed away from the device. Nitrogen is used to blow away any excess debris from the device. At this point the devices are now ready for use and can either bonded to corning No. 1 cover glass with a plasma sterilizer/cleaner or can be reversibly bound to the cover glass by simply placing the device on top of the cover glass. The reversible bonding of the device to glass is covered in a separate video and requires first that the device be sterilized either with 70% ethanol or by autoclaving. Plasma treating sterilizes the devices so no further treatment is necessary. It is, however, important, when plasma-treating the devices, to add liquid to the devices within 10 minutes of the plasma treatment while the surfaces are still hydrophilic. Waiting longer than 10 minutes to add liquid to the device makes it difficult for the liquid to enter the device. The neuron devices are typically plasma-bound to cover glass and 0.5 mg/ml poly-L-lysine (PLL) in pH 8.5 borate buffer is immediately added to the device. After a minimum of 3 hours incubating with PLL, the devices are washed with dH2O water a minimum of 3 times with at least 15 minutes between each wash. Next, the water is removed and fresh media is added to the device. At this point the device is ready for use. It is important to remember at this point to never remove all the media from the device. Always leave media in the main channel.

[Industry regulation and its relationship to the rapid marketing of medical devices].

PubMed

Matsuoka, Atsuko

2012-01-01

In the market of medical devices, non-Japanese products hold a large part even in Japan. To overcome this situation, the Japanese government has been announcing policies to encourage the medical devices industry, such as the 5-year strategy for medical innovation (June 6, 2012). The Division of Medical Devices has been contributing to rapid marketing of medical devices by working out the standards for approval review and accreditation of medical devices, guidances on evaluation of medical devices with emerging technology, and test methods for biological safety evaluation of medical devices, as a part of practice in the field of regulatory science. The recent outcomes are 822 standards of accreditation for Class II medical devices, 14 guidances on safety evaluation of medical devices with emerging technology, and the revised test methods for biological safety evaluation (MHLW Notification by Director, OMDE, Yakushokuki-hatsu 0301 No. 20 "Basic Principles of Biological Safety Evaluation Required for Application for Approval to Market Medical Devices").

An Integrated Device View on Photo-Electrochemical Solar-Hydrogen Generation.

PubMed

Modestino, Miguel A; Haussener, Sophia

2015-01-01

Devices that directly capture and store solar energy have the potential to significantly increase the share of energy from intermittent renewable sources. Photo-electrochemical solar-hydrogen generators could become an important contributor, as these devices can convert solar energy into fuels that can be used throughout all sectors of energy. Rather than focusing on scientific achievement on the component level, this article reviews aspects of overall component integration in photo-electrochemical water-splitting devices that ultimately can lead to deployable devices. Throughout the article, three generalized categories of devices are considered with different levels of integration and spanning the range of complete integration by one-material photo-electrochemical approaches to complete decoupling by photovoltaics and electrolyzer devices. By using this generalized framework, we describe the physical aspects, device requirements, and practical implications involved with developing practical photo-electrochemical water-splitting devices. Aspects reviewed include macroscopic coupled multiphysics device models, physical device demonstrations, and economic and life cycle assessments, providing the grounds to draw conclusions on the overall technological outlook.

Development of reversible vas deferens occlusive device: IV. Rigid prosthetic devices.

PubMed

Drueschke, E E; Zaneveld, L J; Burns, M; Rodzen, R; Wingfield, J R; Maness, J H

1975-01-01

Different types of rigid, reversible, vas deferens occlusive devices were developed and evaluated in 14 unilaterally vasectomized dogs. All prosthetic devices had molded silicone rubber bodies, and rigid inflow and outflow tubes. Various techniques for the removal of the vas luminal epithelium, and for the preparation of porous ceramic and etched stainless steel surfaces to encourage tissue ingrowth into the prosthetic device end tubues were attempted. The devices differed in their methods of achieving occlusion. One device used a "rotary stem valve" which had a C-section rotating mechanism; the others used the "shuttle stem valve" which possessed an occlusive element that moved transverse to the axis of flow in the device, thus occluding the device when the stem was depressed. The rotarystem valve was implanted by means of a longitudinal incision. The remaining 13 shuttle stem devices were placed in the vas using either a longitudinal or a transverse implantation. Inno case was sperm transport through the prosthetic devices obtained for more than a few ejaculations.

[Status of diagnosis and treatment devices of acupuncture based on SooPAT and bibliometrics in China].

PubMed

Bai, Lin; Ren, Yulan; Guo, Taipin; Chen, Lin; Zhou, Yumei; Feng, Shuwei; Li, Ji; Liang, Fanrong

2016-11-12

To perform a bibliometrics analysis on patent literature regarding diagnosis and treatment devices of acupuncture in China, aiming to provide references for the development of diagnosis and treatment devices of acupuncture. Based on SooPAT, a patent database, the patent literature regarding diagnosis and treatment devices of acupuncture in China was collected. With bibliometrics methods, the annual distribution of type, quantity, classification and content of diagnosis and treatment devices of acupuncture were analyzed. The number of acupuncture diagnosis and treatment devices reached its peak in 2012 and 2013 in China. The A61N in patent and utility model patent were the most, which were mainly related to electrotherapy, magnetic therapy, radioactive therapy and ultrasound therapy, etc. The main content was acupuncture treatment devices and meridian treatment devices. The 24-01 in design patent was the most, involving fixation devices used by doctors, hospitals and laboratories, etc. Currently the majority of diagnosis and treatment devices of acupuncture is therapeutic apparatus, while the acupuncture diagnosis devices are needed.

Technology assessment of medical devices at the Center for Devices and Radiological Health.

PubMed

Kessler, L; Richter, K

1998-09-25

We reviewed the Food and Drug Administration's regulatory process for medical devices and described the issues that arise in assessing device safety and effectiveness during the postmarket period. The Center for Devices and Radiological Health (CDRH), an organization within the Food and Drug Administration, has the legal authority and responsibility for ensuring that medical devices marketed in the United States are both reasonably safe and effective for their intended use. This is an enormous challenge given the diversity of medical devices and the large number of different types of devices on the market. Many scientific and regulatory activities are necessary to ensure device safety and effectiveness, including technology assessment, albeit in a manner quite different from that of conventional technology assessment. The basic approach taken at the CDRH to ensure device safety and effectiveness is to develop an understanding of the way in which a medical device works and how it will perform in clinical situations.

Power spectrum analysis for defect screening in integrated circuit devices

DOEpatents

Tangyunyong, Paiboon; Cole Jr., Edward I.; Stein, David J.

2011-12-01

A device sample is screened for defects using its power spectrum in response to a dynamic stimulus. The device sample receives a time-varying electrical signal. The power spectrum of the device sample is measured at one of the pins of the device sample. A defect in the device sample can be identified based on results of comparing the power spectrum with one or more power spectra of the device that have a known defect status.

Cooling of superconducting devices by liquid storage and refrigeration unit

DOEpatents

Laskaris, Evangelos Trifon; Urbahn, John Arthur; Steinbach, Albert Eugene

2013-08-20

A system is disclosed for cooling superconducting devices. The system includes a cryogen cooling system configured to be coupled to the superconducting device and to supply cryogen to the device. The system also includes a cryogen storage system configured to supply cryogen to the device. The system further includes flow control valving configured to selectively isolate the cryogen cooling system from the device, thereby directing a flow of cryogen to the device from the cryogen storage system.

21 CFR 806.20 - Records of corrections and removals not required to be reported.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND... known, and the intended use of the device. (2) The model, catalog, or code number of the device and the...) Each device manufacturer or importer who initiates a correction or removal of a device that is not...

21 CFR 803.32 - If I am a user facility, what information must I submit in my individual adverse event reports?

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING User... device; (10) Event problem codes—patient code and device code (refer to the “MEDWATCH Medical Device... device was involved, nature of the problem, patient followup or required treatment, and any environmental...

21 CFR 803.32 - If I am a user facility, what information must I submit in my individual adverse event reports?

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING User... device; (10) Event problem codes—patient code and device code (refer to the “MEDWATCH Medical Device... device was involved, nature of the problem, patient followup or required treatment, and any environmental...

21 CFR 806.20 - Records of corrections and removals not required to be reported.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND... known, and the intended use of the device. (2) The model, catalog, or code number of the device and the...) Each device manufacturer or importer who initiates a correction or removal of a device that is not...

Pipe inspection and repair system

NASA Technical Reports Server (NTRS)

Schempf, Hagen (Inventor); Mutschler, Edward (Inventor); Chemel, Brian (Inventor); Boehmke, Scott (Inventor); Crowley, William (Inventor)

2004-01-01

A multi-module pipe inspection and repair device. The device includes a base module, a camera module, a sensor module, an MFL module, a brush module, a patch set/test module, and a marker module. Each of the modules may be interconnected to construct one of an inspection device, a preparation device, a marking device, and a repair device.

An UV photochromic memory effect in proton-based WO3 electrochromic devices

NASA Astrophysics Data System (ADS)

Zhang, Yong; Lee, S.-H.; Mascarenhas, A.; Deb, S. K.

2008-11-01

We report an UV photochromic memory effect on a standard proton-based WO3 electrochromic device. It exhibits two memory states, associated with the colored and bleached states of the device, respectively. Such an effect can be used to enhance device performance (increasing the dynamic range), re-energize commercial electrochromic devices, and develop memory devices.

78 FR 11612 - Medical Devices; Pediatric Uses of Devices; Requirement for Submission of Information on...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... information that will have been reviewed by the applicant during the course of its development of the device..., infants, children, adolescents) that suffer from the disease or condition that the device is intended to.... FDA-2009-N-0458] RIN 0910-AG29 Medical Devices; Pediatric Uses of Devices; Requirement for Submission...

Medical Devices; General Hospital and Personal Use Devices; Classification of the Image Processing Device for Estimation of External Blood Loss. Final order.

PubMed

2017-12-20

The Food and Drug Administration (FDA or we) is classifying the image processing device for estimation of external blood loss into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the image processing device for estimation of external blood loss' classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Method for triggering an action

DOEpatents

Hall, David R.; Bartholomew, David B.; Johnson, Monte L.; Moon, Justin; Koehler, Roger O.

2006-10-17

A method for triggering an action of at least one downhole device on a downhole network integrated into a downhole tool string synchronized to an event comprises determining latency, sending a latency adjusted signal, and performing the action. The latency is determined between a control device and the at least one downhole device. The latency adjusted signal for triggering an action is sent to the downhole device. The action is performed downhole synchronized to the event. A preferred method for determining latency comprises the steps: a control device sends a first signal to the downhole device; after receiving the signal, the downhole device sends a response signal to the control device; and the control device analyzes the time from sending the signal to receiving the response signal.

Radiofrequency ablation for hepatocellular carcinoma: a prospective comparison of four radiofrequency devices.

PubMed

Lin, Shi-Ming; Lin, Chen-Chun; Chen, Wei-Ting; Chen, Yi-Chen; Hsu, Chao-Wei

2007-09-01

To compare the effectiveness of ablation techniques for hepatocellular carcinoma (HCC) with the use of four radiofrequency (RF) devices. One hundred patients with 133 HCC lesions no larger than 4 cm were treated with one of four RF devices: RF 2000 (maximum power, 100 W) and RF 3000 generators (maximum power, 200 W) with LeVeen expandable electrodes with a maximum dimension of 3.5 cm or 4 cm, internally cooled single electrode with a thermal dimension of 3 cm, and a RITA RF generator with expandable electrodes with a maximum dimension of 5 cm. Numbers of RF sessions needed per HCC to achieve complete necrosis were 1.4 +/- 0.5 with the RF 2000 device and greater than 1.1 +/- 0.3 with the other three devices (P < .05). The RF 2000 device required a more interactive algorithm than the RF 3000 device. Session times per patient were 31.7 minutes +/- 13.2 in the RF 2000 group and longer than 16.6 minutes +/- 7.5 in the RF 3000 group, 28.3 minutes +/- 12 in the RITA device group, and 27.1 minutes +/- 12 with the internally cooled electrode device (P < .005 for RF 2000 vs other devices and for RF 3000 vs RITA or internally cooled electrode device). Complete necrosis and local tumor progression rates at 2 years in the RF 2000, RF 3000, RITA, and internally cooled electrode device groups were 91.1%, 97.1%, 96.7%, and 96.8% and 12%, 8%, 8.2%, and 8.3%, respectively (P = .37). Ablation with the RF 3000 device required a shorter time than the other three devices and required a less interactive algorithm than the RF 2000 device. However, complete necrosis and local tumor progression rates were similar among devices.

FDA's perspectives on cardiovascular devices.

PubMed

Chen, Eric A; Patel-Raman, Sonna M; O'Callaghan, Kathryn; Hillebrenner, Matthew G

2009-06-01

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

Materials for electrochemical device safety

DOEpatents

Vissers, Daniel R.; Amine, Khalil; Thackeray, Michael M.; Kahaian, Arthur J.; Johnson, Christopher S.

2015-04-07

An electrochemical device includes a thermally-triggered intumescent material or a gas-triggered intumescent material. Such devices prevent or minimize short circuits in a device that could lead to thermal run-away. Such devices may include batteries or supercapacitors.

Illusion thermal device based on material with constant anisotropic thermal conductivity for location camouflage

NASA Astrophysics Data System (ADS)

Hou, Quanwen; Zhao, Xiaopeng; Meng, Tong; Liu, Cunliang

2016-09-01

Thermal metamaterials and devices based on transformation thermodynamics often require materials with anisotropic and inhomogeneous thermal conductivities. In this study, still based on the concept of transformation thermodynamics, we designed a planar illusion thermal device, which can delocalize a heat source in the device such that the temperature profile outside the device appears to be produced by a virtual source at another position. This device can be constructed by only one kind of material with constant anisotropic thermal conductivity. The condition which should be satisfied by the device is provided, and the required anisotropic thermal conductivity is then deduced theoretically. This study may be useful for the designs of metamaterials or devices since materials with constant anisotropic parameters have great facility in fabrication. A prototype device has been fabricated based on a composite composed by two naturally occurring materials. The experimental results validate the effectiveness of the device.

Flexible devices: from materials, architectures to applications

NASA Astrophysics Data System (ADS)

Zou, Mingzhi; Ma, Yue; Yuan, Xin; Hu, Yi; Liu, Jie; Jin, Zhong

2018-01-01

Flexible devices, such as flexible electronic devices and flexible energy storage devices, have attracted a significant amount of attention in recent years for their potential applications in modern human lives. The development of flexible devices is moving forward rapidly, as the innovation of methods and manufacturing processes has greatly encouraged the research of flexible devices. This review focuses on advanced materials, architecture designs and abundant applications of flexible devices, and discusses the problems and challenges in current situations of flexible devices. We summarize the discovery of novel materials and the design of new architectures for improving the performance of flexible devices. Finally, we introduce the applications of flexible devices as key components in real life. Project supported by the National Key R&D Program of China (Nos. 2017YFA0208200, 2016YFB0700600, 2015CB659300), the National Natural Science Foundation of China (Nos. 21403105, 21573108), and the Fundamental Research Funds for the Central Universities (No. 020514380107).

The FDA's role in medical device clinical studies of human subjects

NASA Astrophysics Data System (ADS)

Saviola, James

2005-03-01

This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.

Method and system for reducing device performance degradation of organic devices

DOEpatents

Teague, Lucile C.

2014-09-02

Methods and systems for reducing the deleterious effects of gate bias stress on the drain current of an organic device, such as an organic thin film transistor, are provided. In a particular aspect, the organic layer of an organic device is illuminated with light having characteristics selected to reduce the gate bias voltage effects on the drain current of the organic device. For instance, the wavelength and intensity of the light are selected to provide a desired recovery of drain current of the organic device. If the characteristics of the light are appropriately matched to the organic device, recovery of the deleterious effects caused by gate bias voltage stress effects on the drain current of the organic device can be achieved. In a particular aspect, the organic device is selectively illuminated with light to operate the organic device in multiple modes of operation.

Non- contacting capacitive diagnostic device

DOEpatents

Ellison, Timothy

2005-07-12

A non-contacting capacitive diagnostic device includes a pulsed light source for producing an electric field in a semiconductor or photovoltaic device or material to be evaluated and a circuit responsive to the electric field. The circuit is not in physical contact with the device or material being evaluated and produces an electrical signal characteristic of the electric field produced in the device or material. The diagnostic device permits quality control and evaluation of semiconductor or photovoltaic device properties in continuous manufacturing processes.

Method for integrating microelectromechanical devices with electronic circuitry

DOEpatents

Montague, Stephen; Smith, James H.; Sniegowski, Jeffry J.; McWhorter, Paul J.

1998-01-01

A method for integrating one or more microelectromechanical (MEM) devices with electronic circuitry. The method comprises the steps of forming each MEM device within a cavity below a device surface of the substrate; encapsulating the MEM device prior to forming electronic circuitry on the substrate; and releasing the MEM device for operation after fabrication of the electronic circuitry. Planarization of the encapsulated MEM device prior to formation of the electronic circuitry allows the use of standard processing steps for fabrication of the electronic circuitry.

Update on Tissue Tightening

PubMed Central

2010-01-01

A variety of medical devices are described under the heading of tissue tightening devices. This article reviews the tissue tightening devices currently available in the United States and some that may receive clearance in the upcoming year. These include the various radiofrequency devices as well as the pulsed light devices that achieve similar end results. The one noticeable factor seen with this group of devices is the paucity of large, clinical, controlled trials that appear in the medical literature for this group of medical devices as a whole. PMID:20725568

Perceptions of healthcare professionals' support, shock anxiety and device acceptance among implantable cardioverter defibrillator recipients.

PubMed

Morken, Ingvild M; Norekvål, Tone M; Bru, Edvin; Larsen, Alf I; Karlsen, Bjørg

2014-09-01

To investigate the extent to which perceived support from healthcare professionals and shock anxiety is related to device acceptance among implantable cardioverter defibrillator recipients. Device acceptance can be influenced by several factors, one of which is shock anxiety associated with poor device acceptance. Reduced shock anxiety, as well as increased device acceptance, has been reported after psycho-educational programmes. As healthcare professionals appear to play a significant role in providing support and education during regular follow-up visits, they may constitute an important social support system that could be another factor influencing device acceptance. However, little is known about the relationship between perceived support from healthcare professionals and device acceptance among recipients. A cross-sectional survey design. A sample comprising implantable cardioverter defibrillator recipients completed questionnaires assessing perceived support from healthcare professionals, shock anxiety and device acceptance. Demographic and clinical data were collected by self-report and from medical records in September-October 2010. The descriptive results indicated that approximately 85% of the recipients experienced high device acceptance. Regression analysis demonstrated that constructive support from healthcare professionals was positively associated with device acceptance and moderated the negative relationship between shock anxiety and device acceptance. Non-constructive support and shock anxiety had a negative statistical association with device acceptance. Healthcare professionals may represent a valuable constructive support system that can enhance device acceptance among implantable cardioverter defibrillator recipients, partly by preventing shock anxiety from leading to poor device acceptance. Non-constructive communication on the part of healthcare professionals could hinder device acceptance. © 2014 John Wiley & Sons Ltd.

Implantable biomedical devices on bioresorbable substrates

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

Rogers, John A.; Kim, Dae-Hyeong; Omenetto, Fiorenzo

Provided herein are implantable biomedical devices and methods of administering implantable biomedical devices, making implantable biomedical devices, and using implantable biomedical devices to actuate a target tissue or sense a parameter associated with the target tissue in a biological environment.

16 CFR 1507.9 - Toy smoke devices and flitter devices.

Code of Federal Regulations, 2010 CFR

2010-01-01

... SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES § 1507.9 Toy smoke devices and flitter devices. (a) Toy smoke... shall not be of such color and configuration so as to be confused with banned fireworks such as M-80...

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

Nuzzo, Ralph G.; Rogers, John A.; Menard, Etienne

The invention provides methods and devices for fabricating printable semiconductor elements and assembling printable semiconductor elements onto substrate surfaces. Methods, devices and device components of the present invention are capable of generating a wide range of flexible electronic and optoelectronic devices and arrays of devices on substrates comprising polymeric materials. The present invention also provides stretchable semiconductor structures and stretchable electronic devices capable of good performance in stretched configurations.

Wireless event-recording device with identification codes

NASA Technical Reports Server (NTRS)

Watters, David G. (Inventor); Huestis, David L. (Inventor); Bahr, Alfred J. (Inventor)

2004-01-01

A wireless recording device can be interrogated to determine its identity and its state. The state indicates whether a particular physical or chemical event has taken place. In effect, the physical or chemical event is recorded by the device. The identity of the device allows it to be distinguished from a number of similar devices. Thus the sensor device may be used in an array of devices that can be probed by a wireless interrogation unit. The device tells the interrogator who it is and what state it is in. The interrogator can thus easily identify particular items in an array that have reached a particular condition.

Energy conversion device with support member having pore channels

DOEpatents

Routkevitch, Dmitri [Longmont, CO; Wind, Rikard A [Johnstown, CO

2014-01-07

Energy devices such as energy conversion devices and energy storage devices and methods for the manufacture of such devices. The devices include a support member having an array of pore channels having a small average pore channel diameter and having a pore channel length. Material layers that may include energy conversion materials and conductive materials are coaxially disposed within the pore channels to form material rods having a relatively small cross-section and a relatively long length. By varying the structure of the materials in the pore channels, various energy devices can be fabricated, such as photovoltaic (PV) devices, radiation detectors, capacitors, batteries and the like.

Micro devices using shape memory polymer patches for mated connections

DOEpatents

Lee, Abraham P.; Fitch, Joseph P.

2000-01-01

A method and micro device for repositioning or retrieving miniature devices located in inaccessible areas, such as medical devices (e.g., stents, embolic coils, etc.) located in a blood vessel. The micro repositioning or retrieving device and method uses shape memory polymer (SMP) patches formed into mating geometries (e.g., a hoop and a hook) for re-attachment of the deposited medical device to a catheter or guidewire. For example, SMP or other material hoops are formed on the medical device to be deposited in a blood vessel, and SMP hooks are formed on the micro device attached to a guidewire, whereby the hooks on the micro device attach to the hoops on the medical device, or vice versa, enabling deposition, movement, re-deposit, or retrieval of the medical device. By changing the temperature of the SMP hooks, the hooks can be attached to or released from the hoops located on the medical device. An exemplary method for forming the hooks and hoops involves depositing a sacrificial thin film on a substrate, patterning and processing the thin film to form openings therethrough, depositing or bonding SMP materials in the openings so as to be attached to the substrate, and removing the sacrificial thin film.

A literature review of the effects of computer input device design on biomechanical loading and musculoskeletal outcomes during computer work.

PubMed

Bruno Garza, J L; Young, J G

2015-01-01

Extended use of conventional computer input devices is associated with negative musculoskeletal outcomes. While many alternative designs have been proposed, it is unclear whether these devices reduce biomechanical loading and musculoskeletal outcomes. To review studies describing and evaluating the biomechanical loading and musculoskeletal outcomes associated with conventional and alternative input devices. Included studies evaluated biomechanical loading and/or musculoskeletal outcomes of users' distal or proximal upper extremity regions associated with the operation of alternative input devices (pointing devices, mice, other devices) that could be used in a desktop personal computing environment during typical office work. Some alternative pointing device designs (e.g. rollerbar) were consistently associated with decreased biomechanical loading while other designs had inconsistent results across studies. Most alternative keyboards evaluated in the literature reduce biomechanical loading and musculoskeletal outcomes. Studies of other input devices (e.g. touchscreen and gestural controls) were rare, however, those reported to date indicate that these devices are currently unsuitable as replacements for traditional devices. Alternative input devices that reduce biomechanical loading may make better choices for preventing or alleviating musculoskeletal outcomes during computer use, however, it is unclear whether many existing designs are effective.

The current situation and development of medical device testing institutes in China.

PubMed

Yang, Xiaofang; Mu, Ruihong; Fan, Yubo; Wang, Chunren; Li, Deyu

2017-04-01

This article analyses the current situation and development of Chinese medical device testing institutes from the perspectives of the two most important functions - testing functions and medical device standardization functions. Areas Covered: The objective of the Chinese government regulations for medical device industry is to ensure the safety and effectiveness of medical devices for Chinese patients. To support the regulation system, the Chinese government has established medical device testing institutes at different levels for example, the national, provincial, and municipal levels. These testing institutes also play an important role in technical support during medical device premarket registration and post market surveillance, they are also the vital practitioners of Chinese medical device standardization. Expert Commentary: Chinese medical device testing institutes are technical departments established by government, and serve the regulatory functions of government agency. In recent years, with the rapid development of medical device industry as well as constantly increasing international and domestic medical device market, the importance of medical device testing institute is more prominent, However, there are still some problems unsolved, such as their overall capacity remains to be improved, construction of standardization is to be strengthened, etc.

Design of a SIP device cooperation system on OSGi service platforms

NASA Astrophysics Data System (ADS)

Takayama, Youji; Koita, Takahiro; Sato, Kenya

2007-12-01

Home networks feature such various technologies as protocols, specifications, and middleware, including HTTP, UPnP, and Jini. A service platform is required to handle such technologies to enable them to cooperate with different devices. The OSGi service platform, which meets the requirements based on service-oriented architecture, is designed and standardized by OSGi Alliance and consists of two parts: one OSGi Framework and bundles. On the OSGi service platform, APIs are defined as services that can handle these technologies and are implemented in the bundle. By using the OSGi Framework with bundles, various technologies can cooperate with each other. On the other hand, in IP networks, Session Initiation Protocol (SIP) is often used in device cooperation services to resolve an IP address, control a session between two or more devices, and easily exchange the statuses of devices. However, since many existing devices do not correspond to SIP, it cannot be used for device cooperation services. A device that does not correspond to SIP is called an unSIP device. This paper proposes and implements a prototype system that enables unSIP devices to correspond to SIP. For unSIP devices, the proposed system provides device cooperation services with SIP.

Advancing medical device innovation through collaboration and coordination of structured data capture pilots: Report from the Medical Device Epidemiology Network (MDEpiNet) Specific, Measurable, Achievable, Results-Oriented, Time Bound (SMART) Think Tank.

PubMed

Reed, Terrie L; Drozda, Joseph P; Baskin, Kevin M; Tcheng, James; Conway, Karen; Wilson, Natalia; Marinac-Dabic, Danica; Heise, Theodore; Krucoff, Mitchell W

2017-12-01

The Medical Device Epidemiology Network (MDEpiNet) is a public private partnership (PPP) that provides a platform for collaboration on medical device evaluation and depth of expertise for supporting pilots to capture, exchange and use device information for improving device safety and protecting public health. The MDEpiNet SMART Think Tank, held in February, 2013, sought to engage expert stakeholders who were committed to improving the capture of device data, including Unique Device Identification (UDI), in key electronic health information. Prior to the Think Tank there was limited collaboration among stakeholders beyond a few single health care organizations engaged in electronic capture and exchange of device data. The Think Tank resulted in what has become two sustainable multi-stakeholder device data capture initiatives, BUILD and VANGUARD. These initiatives continue to mature within the MDEpiNet PPP structure and are well aligned with the goals outlined in recent FDA-initiated National Medical Device Planning Board and Medical Device Registry Task Force white papers as well as the vision for the National Evaluation System for health Technology.%. Published by Elsevier Inc.

Simulating ideal assistive devices to reduce the metabolic cost of walking with heavy loads.

PubMed

Dembia, Christopher L; Silder, Amy; Uchida, Thomas K; Hicks, Jennifer L; Delp, Scott L

2017-01-01

Wearable robotic devices can restore and enhance mobility. There is growing interest in designing devices that reduce the metabolic cost of walking; however, designers lack guidelines for which joints to assist and when to provide the assistance. To help address this problem, we used musculoskeletal simulation to predict how hypothetical devices affect muscle activity and metabolic cost when walking with heavy loads. We explored 7 massless devices, each providing unrestricted torque at one degree of freedom in one direction (hip abduction, hip flexion, hip extension, knee flexion, knee extension, ankle plantarflexion, or ankle dorsiflexion). We used the Computed Muscle Control algorithm in OpenSim to find device torque profiles that minimized the sum of squared muscle activations while tracking measured kinematics of loaded walking without assistance. We then examined the metabolic savings provided by each device, the corresponding device torque profiles, and the resulting changes in muscle activity. We found that the hip flexion, knee flexion, and hip abduction devices provided greater metabolic savings than the ankle plantarflexion device. The hip abduction device had the greatest ratio of metabolic savings to peak instantaneous positive device power, suggesting that frontal-plane hip assistance may be an efficient way to reduce metabolic cost. Overall, the device torque profiles generally differed from the corresponding net joint moment generated by muscles without assistance, and occasionally exceeded the net joint moment to reduce muscle activity at other degrees of freedom. Many devices affected the activity of muscles elsewhere in the limb; for example, the hip flexion device affected muscles that span the ankle joint. Our results may help experimentalists decide which joint motions to target when building devices and can provide intuition for how devices may interact with the musculoskeletal system. The simulations are freely available online, allowing others to reproduce and extend our work.

Simulating ideal assistive devices to reduce the metabolic cost of walking with heavy loads

PubMed Central

Silder, Amy; Uchida, Thomas K.; Hicks, Jennifer L.; Delp, Scott L.

2017-01-01

Wearable robotic devices can restore and enhance mobility. There is growing interest in designing devices that reduce the metabolic cost of walking; however, designers lack guidelines for which joints to assist and when to provide the assistance. To help address this problem, we used musculoskeletal simulation to predict how hypothetical devices affect muscle activity and metabolic cost when walking with heavy loads. We explored 7 massless devices, each providing unrestricted torque at one degree of freedom in one direction (hip abduction, hip flexion, hip extension, knee flexion, knee extension, ankle plantarflexion, or ankle dorsiflexion). We used the Computed Muscle Control algorithm in OpenSim to find device torque profiles that minimized the sum of squared muscle activations while tracking measured kinematics of loaded walking without assistance. We then examined the metabolic savings provided by each device, the corresponding device torque profiles, and the resulting changes in muscle activity. We found that the hip flexion, knee flexion, and hip abduction devices provided greater metabolic savings than the ankle plantarflexion device. The hip abduction device had the greatest ratio of metabolic savings to peak instantaneous positive device power, suggesting that frontal-plane hip assistance may be an efficient way to reduce metabolic cost. Overall, the device torque profiles generally differed from the corresponding net joint moment generated by muscles without assistance, and occasionally exceeded the net joint moment to reduce muscle activity at other degrees of freedom. Many devices affected the activity of muscles elsewhere in the limb; for example, the hip flexion device affected muscles that span the ankle joint. Our results may help experimentalists decide which joint motions to target when building devices and can provide intuition for how devices may interact with the musculoskeletal system. The simulations are freely available online, allowing others to reproduce and extend our work. PMID:28700630

A randomised control trial of prompt and feedback devices and their impact on quality of chest compressions--a simulation study.

PubMed

Yeung, Joyce; Davies, Robin; Gao, Fang; Perkins, Gavin D

2014-04-01

This study aims to compare the effect of three CPR prompt and feedback devices on quality of chest compressions amongst healthcare providers. A single blinded, randomised controlled trial compared a pressure sensor/metronome device (CPREzy), an accelerometer device (Phillips Q-CPR) and simple metronome on the quality of chest compressions on a manikin by trained rescuers. The primary outcome was compression depth. Secondary outcomes were compression rate, proportion of chest compressions with inadequate depth, incomplete release and user satisfaction. The pressure sensor device improved compression depth (37.24-43.64 mm, p=0.02), the accelerometer device decreased chest compression depth (37.38-33.19 mm, p=0.04) whilst the metronome had no effect (39.88 mm vs. 40.64 mm, p=0.802). Compression rate fell with all devices (pressure sensor device 114.68-98.84 min(-1), p=0.001, accelerometer 112.04-102.92 min(-1), p=0.072 and metronome 108.24 min(-1) vs. 99.36 min(-1), p=0.009). The pressure sensor feedback device reduced the proportion of compressions with inadequate depth (0.52 vs. 0.24, p=0.013) whilst the accelerometer device and metronome did not have a statistically significant effect. Incomplete release of compressions was common, but unaffected by the CPR feedback devices. Users preferred the accelerometer and metronome devices over the pressure sensor device. A post hoc study showed that de-activating the voice prompt on the accelerometer device prevented the deterioration in compression quality seen in the main study. CPR feedback devices vary in their ability to improve performance. In this study the pressure sensor device improved compression depth, whilst the accelerometer device reduced it and metronome had no effect. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Tulip deformity with Cera atrial septal defect devices: a report of 3 cases.

PubMed

Kohli, Vikas

2015-02-01

Device closure of secundum atrial septal defect (ASD) is the treatment of choice when anatomy is favourable. Amplatzer device has remained the gold standard for closure of ASD. Cobra deformity is a well-reported problem with devices. Recently, Tulip deformity has been reported in a single case. We report a series of cases where we noted Tulip deformity along with inability to retract the device in the sheath in Cera Lifetech devices. This resulted in prolongation of procedure, excessive fluoroscopic exposure and additional interventional procedures not usually anticipated in ASD device closure. We believe that the problem is due to the stiffness of the device resulting in its inability to be retracted into the sheath. We also report a unique way of retrieving the device.

Medical Devices; Immunology and Microbiology Devices; Classification of the Device To Detect and Identify Microbial Pathogen Nucleic Acids in Cerebrospinal Fluid. Final order.

PubMed

2017-10-20

The Food and Drug Administration (FDA or we) is classifying the device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid into class II (special controls). The special controls that will apply to the device type are identified in this order and will be part of the codified language for the device to detect and identify microbial pathogen nucleic acids in cerebrospinal fluid’s classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Wireless device connection problems and design solutions

NASA Astrophysics Data System (ADS)

Song, Ji-Won; Norman, Donald; Nam, Tek-Jin; Qin, Shengfeng

2016-09-01

Users, especially the non-expert users, commonly experience problems when connecting multiple devices with interoperability. While studies on multiple device connections are mostly concentrated on spontaneous device association techniques with a focus on security aspects, the research on user interaction for device connection is still limited. More research into understanding people is needed for designers to devise usable techniques. This research applies the Research-through-Design method and studies the non-expert users' interactions in establishing wireless connections between devices. The "Learning from Examples" concept is adopted to develop a study focus line by learning from the expert users' interaction with devices. This focus line is then used for guiding researchers to explore the non-expert users' difficulties at each stage of the focus line. Finally, the Research-through-Design approach is used to understand the users' difficulties, gain insights to design problems and suggest usable solutions. When connecting a device, the user is required to manage not only the device's functionality but also the interaction between devices. Based on learning from failures, an important insight is found that the existing design approach to improve single-device interaction issues, such as improvements to graphical user interfaces or computer guidance, cannot help users to handle problems between multiple devices. This study finally proposes a desirable user-device interaction in which images of two devices function together with a system image to provide the user with feedback on the status of the connection, which allows them to infer any required actions.

Study on intelligent processing system of man-machine interactive garment frame model

NASA Astrophysics Data System (ADS)

Chen, Shuwang; Yin, Xiaowei; Chang, Ruijiang; Pan, Peiyun; Wang, Xuedi; Shi, Shuze; Wei, Zhongqian

2018-05-01

A man-machine interactive garment frame model intelligent processing system is studied in this paper. The system consists of several sensor device, voice processing module, mechanical parts and data centralized acquisition devices. The sensor device is used to collect information on the environment changes brought by the body near the clothes frame model, the data collection device is used to collect the information of the environment change induced by the sensor device, voice processing module is used for speech recognition of nonspecific person to achieve human-machine interaction, mechanical moving parts are used to make corresponding mechanical responses to the information processed by data collection device.it is connected with data acquisition device by a means of one-way connection. There is a one-way connection between sensor device and data collection device, two-way connection between data acquisition device and voice processing module. The data collection device is one-way connection with mechanical movement parts. The intelligent processing system can judge whether it needs to interact with the customer, realize the man-machine interaction instead of the current rigid frame model.

Method for accurately positioning a device at a desired area of interest

DOEpatents

Jones, Gary D.; Houston, Jack E.; Gillen, Kenneth T.

2000-01-01

A method for positioning a first device utilizing a surface having a viewing translation stage, the surface being movable between a first position where the viewing stage is in operational alignment with a first device and a second position where the viewing stage is in operational alignment with a second device. The movable surface is placed in the first position and an image is produced with the first device of an identifiable characteristic of a calibration object on the viewing stage. The moveable surface is then placed in the second position and only the second device is moved until an image of the identifiable characteristic in the second device matches the image from the first device. The calibration object is then replaced on the stage of the surface with a test object, and the viewing translation stage is adjusted until the second device images the area of interest. The surface is then moved to the first position where the test object is scanned with the first device to image the area of interest. An alternative embodiment where the devices move is also disclosed.

Wind noise within and across behind-the-ear and miniature behind-the-ear hearing aids.

PubMed

Zakis, Justin A; Hawkins, Daniel J

2015-10-01

Previous studies investigated wind noise with Behind-The-Ear (BTE) hearing aids, but not the more common mini-BTE style of device, which typically has a smaller shell and microphones located more deeply behind the pinna. The current study investigated wind-noise levels across one BTE and two mini-BTE devices, and between the front and rear omni-directional microphones within devices. Levels were measured at two wind speeds (3 and 6 m/s) and 36 wind azimuths (10° increments). The pattern of wind-noise level versus azimuth was similar across mini-BTE devices, and differed for the BTE device. However, mean levels were markedly different across mini-BTE devices, and could be higher, lower, or similar to those of the BTE device. For within-device level differences, the pattern and mean across azimuth were similar across mini-BTE devices, and differed for the BTE device. Wind noise had the potential to slightly or severely reduce speech intelligibility at 3 or 6 m/s, respectively, across all devices.

A sampling device with a capped body and detachable handle

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

Jezek, Gerd-Rainer

1997-12-01

The present invention relates to a device for sampling radioactive waste and more particularly to a device for sampling radioactive waste which prevents contamination of a sampled material and the environment surrounding the sampled material. During vitrification of nuclear wastes, it is necessary to remove contamination from the surfaces of canisters filled with radioactive glass. After removal of contamination, a sampling device is used to test the surface of the canister. The one piece sampling device currently in use creates a potential for spreading contamination during vitrification operations. During operations, the one piece sampling device is transferred into and outmore » of the vitrification cell through a transfer drawer. Inside the cell, a remote control device handles the sampling device to wipe the surface of the canister. A one piece sampling device can be contaminated by the remote control device prior to use. Further, the sample device can also contaminate the transfer drawer producing false readings for radioactive material. The present invention overcomes this problem by enclosing the sampling pad in a cap. The removable handle is reused which reduces the amount of waste material.« less

Electro-optic component mounting device

DOEpatents

Gruchalla, M.E.

1994-09-13

A technique is provided for integrally mounting a device such as an electro-optic device in a transmission line to avoid series resonant effects. A center conductor of the transmission line has an aperture formed therein for receiving the device. The aperture splits the center conductor into two parallel sections on opposite sides of the device. For a waveguide application, the center conductor is surrounded by a conductive ground surface which is spaced apart from the center conductor with a dielectric material. One set of electrodes formed on the surface of the electro-optic device is directly connected to the center conductor and an electrode formed on the surface of the electro-optic device is directly connected to the conductive ground surface. The electrodes formed on the surface of the electro-optic device are formed on curved sections of the surface of the device to mate with correspondingly shaped electrodes on the conductor and ground surface to provide a uniform electric field across the electro-optic device. The center conductor includes a passage formed therein for passage of optical signals to an electro-optic device. 10 figs.

Medical devices; hematology and pathology devices; classification of the Factor V Leiden DNA mutation detection systems devices. Final rule.

PubMed

2004-03-16

The Food and Drug Administration (FDA) is classifying the Factor V Leiden deoxyribonucleic acid (DNA) mutation detections systems device into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), the Food and Drug Administration Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Evaluation of semiconductor devices for Electric and Hybrid Vehicle (EHV) ac-drive applications, volume 1

NASA Technical Reports Server (NTRS)

Lee, F. C.; Chen, D. Y.; Jovanovic, M.; Hopkins, D. C.

1985-01-01

The results of evaluation of power semiconductor devices for electric hybrid vehicle ac drive applications are summarized. Three types of power devices are evaluated in the effort: high power bipolar or Darlington transistors, power MOSFETs, and asymmetric silicon control rectifiers (ASCR). The Bipolar transistors, including discrete device and Darlington devices, range from 100 A to 400 A and from 400 V to 900 V. These devices are currently used as key switching elements inverters for ac motor drive applications. Power MOSFETs, on the other hand, are much smaller in current rating. For the 400 V device, the current rating is limited to 25 A. For the main drive of an electric vehicle, device paralleling is normally needed to achieve practical power level. For other electric vehicle (EV) related applications such as battery charger circuit, however, MOSFET is advantageous to other devices because of drive circuit simplicity and high frequency capability. Asymmetrical SCR is basically a SCR device and needs commutation circuit for turn off. However, the device poses several advantages, i.e., low conduction drop and low cost.

The use of medication compliance devices by district nursing services.

PubMed

McGraw, C; Drennan, V

2000-07-01

This article presents a critical review of the literature relating to medication compliance devices and the findings of a survey that examined the use of such devices by district nursing services. The UKCC (1992) does not regard the loading of compliance devices by nurses as safe practice; however, compliance devices continue to be used by district nurses. The evidence base concerning the value and use of medication compliance devices is examined and significant gaps in the literature relating to the use of such devices are identified. There is an absence of studies that focus on the effect of compliance devices on adherence among older patients and the nature and frequency of drug administration errors involving these devices. The survey findings show that nurse-loaded compliance devices are used in over one-third of the sample. Further research is necessary to assess the clinical effectiveness of, and clinical risk attached to, compliance devices for older patients in the community. It is suggested that this is an issue of serious concern for primary care groups considering the principles of clinical governance.

Spin pumping driven auto-oscillator for phase-encoded logic—device design and material requirements

NASA Astrophysics Data System (ADS)

Rakheja, S.; Kani, N.

2017-05-01

In this work, we propose a spin nano-oscillator (SNO) device where information is encoded in the phase (time-shift) of the output oscillations. The spin current required to set up the oscillations in the device is generated through spin pumping from an input nanomagnet that is precessing at RF frequencies. We discuss the operation of the SNO device, in which either the in-plane (IP) or out-of-plane (OOP) magnetization oscillations are utilized toward implementing ultra-low-power circuits. Using physical models of the nanomagnet dynamics and the spin transport through non-magnetic channels, we quantify the reliability of the SNO device using a "scaling ratio". Material requirements for the nanomagnet and the channel to ensure correct logic functionality are identified using the scaling ratio metric. SNO devices consume (2-5)× lower energy compared to CMOS devices and other spin-based devices with similar device sizes and material parameters. The analytical models presented in this work can be used to optimize the performance and scaling of SNO devices in comparison to CMOS devices at ultra-scaled technology nodes.

Gold nanostructures and methods of use

DOEpatents

Zhang, Jin Z [Santa Cruz, CA; Schwartzberg, Adam [Santa Cruz, CA; Olson, Tammy Y [Santa Cruz, CA

2012-03-20

The invention is drawn to novel nanostructures comprising hollow nanospheres and nanotubes for use as chemical sensors, conduits for fluids, and electronic conductors. The nanostructures can be used in microfluidic devices, for transporting fluids between devices and structures in analytical devices, for conducting electrical currents between devices and structure in analytical devices, and for conducting electrical currents between biological molecules and electronic devices, such as bio-microchips.

Connector device for building integrated photovoltaic device

DOEpatents

Keenihan, James R.; Langmaid, Joe A.; Eurich, Gerald K.; Lesniak, Michael J.; Mazor, Michael H.; Cleerman, Robert J.; Gaston, Ryan S.

2015-11-10

The present invention is premised upon a connector device and method that can more easily electrically connect a plurality of PV devices or photovoltaic system components and/or locate these devices/components upon a building structure. It also may optionally provide some additional sub-components (e.g. at least one bypass diode and/or an indicator means) and may enhance the serviceability of the device.

Connector device for building integrated photovoltaic device

DOEpatents

Keenihan, James R.; Langmaid, Joseph A.; Eurich, Gerald K.; Lesniak, Michael J.; Mazor, Michael H.; Cleereman, Robert J.; Gaston, Ryan S.

2014-06-03

The present invention is premised upon a connector device and method that can more easily electrically connect a plurality of PV devices or photovoltaic system components and/or locate these devices/components upon a building structure. It also may optionally provide some additional sub-components (e.g. at least one bypass diode and/or an indicator means) and may enhance the serviceability of the device.

Energy management system for a rotary machine and method therefor

DOEpatents

Bowman, Michael John; Sinha, Gautam; Sheldon, Karl Edward

2004-11-09

In energy management system is provided for a power generating device having a working fluid intake in which the energy management system comprises an electrical dissipation device coupled to the power generating device and a dissipation device cooling system configured to direct a portion of a working fluid to the electrical dissipation device so as to provide thermal control to the electrical dissipation device.

Gold nanostructures and methods of use

DOEpatents

Zhang, Jin Z.; Schwartzberg, Adam; Olson, Tammy Y.

2016-03-01

The invention is drawn to novel nanostructures comprising hollow nanospheres and nanotubes for use as chemical sensors, conduits for fluids, and electronic conductors. The nanostructures can be used in microfluidic devices, for transporting fluids between devices and structures in analytical devices, for conducting electrical currents between devices and structure in analytical devices, and for conducting electrical currents between biological molecules and electronic devices, such as bio-microchips.

Shape Memory Actuation and Release Devices.

DTIC Science & Technology

1996-10-01

shelf devices such as pyrotechnics, gas-discharge systems, paraffin wax actuators, and other electro-mechanical devices may not be able to meet...shelf devices such as pyrotechnics, gas-discharge systems, paraffin wax actuators, and other electro-mechanical devices may not be able to meet future...shard mounts. They do have wide utility as pin-pullers and single point release devices for a variety of spacecraft appendages. Parrafin based mechanisms

Smart portable rehabilitation devices.

PubMed

Mavroidis, Constantinos; Nikitczuk, Jason; Weinberg, Brian; Danaher, Gil; Jensen, Katherine; Pelletier, Philip; Prugnarola, Jennifer; Stuart, Ryan; Arango, Roberto; Leahey, Matt; Pavone, Robert; Provo, Andrew; Yasevac, Dan

2005-07-12

The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s). In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device. Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit. Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved.

Smart portable rehabilitation devices

PubMed Central

Mavroidis, Constantinos; Nikitczuk, Jason; Weinberg, Brian; Danaher, Gil; Jensen, Katherine; Pelletier, Philip; Prugnarola, Jennifer; Stuart, Ryan; Arango, Roberto; Leahey, Matt; Pavone, Robert; Provo, Andrew; Yasevac, Dan

2005-01-01

Background The majority of current portable orthotic devices and rehabilitative braces provide stability, apply precise pressure, or help maintain alignment of the joints with out the capability for real time monitoring of the patient's motions and forces and without the ability for real time adjustments of the applied forces and motions. Improved technology has allowed for advancements where these devices can be designed to apply a form of tension to resist motion of the joint. These devices induce quicker recovery and are more effective at restoring proper biomechanics and improving muscle function. However, their shortcoming is in their inability to be adjusted in real-time, which is the most ideal form of a device for rehabilitation. This introduces a second class of devices beyond passive orthotics. It is comprised of "active" or powered devices, and although more complicated in design, they are definitely the most versatile. An active or powered orthotic, usually employs some type of actuator(s). Methods In this paper we present several new advancements in the area of smart rehabilitation devices that have been developed by the Northeastern University Robotics and Mechatronics Laboratory. They are all compact, wearable and portable devices and boast re-programmable, real time computer controlled functions as the central theme behind their operation. The sensory information and computer control of the three described devices make for highly efficient and versatile systems that represent a whole new breed in wearable rehabilitation devices. Their applications range from active-assistive rehabilitation to resistance exercise and even have applications in gait training. The three devices described are: a transportable continuous passive motion elbow device, a wearable electro-rheological fluid based knee resistance device, and a wearable electrical stimulation and biofeedback knee device. Results Laboratory tests of the devices demonstrated that they were able to meet their design objectives. The prototypes of portable rehabilitation devices presented here did demonstrate that these concepts are capable of the performance their commercially available but non-portable counterparts exhibit. Conclusion Smart, portable devices with the ability for real time monitoring and adjustment open a new era in rehabilitation where the recovery process could be dramatically improved. PMID:16011801

[Innovation of characteristic medicinal cupping devices].

PubMed

Li, Jianping; Zhang, Hui; Yang, Jianmei; Xu, Xinchun; Niu, Yanxia; Cai, Jun

2015-08-01

To compare the differences in the characteristic medicinal cupping therapy between the traditional cupping device and the innovated cupping device. Fifty patients of neck and low back pain were selected. The self-comparison was adopted. The cupping therapy was applied to the acupoints located on the left or right side with the traditional cupping device and the innovated cupping device. The cupping sites were centered at bilateral Quyuan (SI 13) and Dachangshu (BL 25). The cups were retained for 10 min. The traditional cupping device was the glass with smooth border, 100mL. The innovated cupping device was the vacuum-sucking cup. The operative time, medicinal leakage, comfort and cupping marks were observed for the two different cupping devices. The operative time with the innovated medicinal cupping device was shorter obviously compared with the traditional one at Quyuan (SI 13) and Dachangshu (BL 25, both P<0. 05). The comfort with the innovated medicinal cupping device was remarkably improved as compared with the traditional one at the two acupoints (both P<0. 05). The medicinal leakage was similar between the two different devices during the cupping operation (both P>0. 05). The cupping marks with the innovated medicinal cupping device were much deeper than those with the traditional one after cupping therapy. The innovated cupping device is more convenent and comfortable in operation during the characteristic medicinal cupping therapy.

The RFET—a reconfigurable nanowire transistor and its application to novel electronic circuits and systems

NASA Astrophysics Data System (ADS)

Mikolajick, T.; Heinzig, A.; Trommer, J.; Baldauf, T.; Weber, W. M.

2017-04-01

With CMOS scaling reaching physical limits in the next decade, new approaches are required to enhance the functionality of electronic systems. Reconfigurability on the device level promises to realize more complex systems with a lower device count. In the last five years a number of interesting concepts have been proposed to realize such a device level reconfiguration. Among these the reconfigurable field effect transistor (RFET), a device that can be configured between an n-channel and p-channel behavior by applying an electrical signal, can be considered as an end-of-roadmap extension of current technology with only small modifications and even simplifications to the process flow. This article gives a review on the RFET basics and current status. In the first sections state-of-the-art of reconfigurable devices will be summarized and the RFET will be introduced together with related devices based on silicon nanowire technology. The device optimization with respect to device symmetry and performance will be discussed next. The potential of the RFET device technology will then be shown by discussing selected circuit implementations making use of the unique advantages of this device concept. The basic device concept was also extended towards applications in flexible devices and sensors, also extending the capabilities towards so-called More-than-Moore applications where new functionalities are implemented in CMOS-based processes. Finally, the prospects of RFET device technology will be discussed.

Home Use Devices: How to Prepare for and Handle Power Outages for Medical Devices That Require Electricity

MedlinePlus

... Handle Power Outages for Medical Devices that Require Electricity Center for De CDRH vices and Rad lth ... Handle Power Outages for Medical Devices that Require Electricity As a home medical device user, it is ...

21 CFR 882.1570 - Powered direct-contact temperature measurement device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Powered direct-contact temperature measurement... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1570 Powered direct-contact temperature measurement device. (a) Identification. A powered direct...

21 CFR 882.1570 - Powered direct-contact temperature measurement device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Powered direct-contact temperature measurement... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1570 Powered direct-contact temperature measurement device. (a) Identification. A powered direct...

21 CFR 882.1570 - Powered direct-contact temperature measurement device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Powered direct-contact temperature measurement... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1570 Powered direct-contact temperature measurement device. (a) Identification. A powered direct...

76 FR 7222 - Medical Device Innovation Initiative; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

...] Medical Device Innovation Initiative; Public Meeting; Request for Comments AGENCY: Food and Drug... Administration (FDA) is announcing a public meeting entitled ``CDRH's Medical Device Innovation Initiative Public... Center for Devices and Radiological Health's (CDRH) document, ``Medical Device Innovation Initiative...

47 CFR 15.303 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... measurement. (d) Isochronous devices. Devices that transmit at a regular interval, typified by time-division... Communications Service Devices § 15.303 Definitions. (a) Asynchronous devices. Devices that transmit RF energy at... with a fixed infrastructure or by disabling mechanisms to allow adequate coordination of their...

21 CFR 886.1700 - Pupillometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... eye. (b) Classification. Class I (general controls). The AC-powered device and the manual device are... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1700 Pupillometer. (a) Identification. A pupillometer is an AC...

Device characteristics of antenna-coupled metal-insulator-metal diodes (rectenna) using Al2O3, TiO2, and Cr2O3 as insulator layer for energy harvesting applications

NASA Astrophysics Data System (ADS)

Inac, Mesut; Shafique, Atia; Ozcan, Meric; Gurbuz, Yasar

2015-09-01

Antenna-coupled metal-insulator-metal devices are most potent candidate for future energy harvesting devices. The reason for that they are ultra-high speed devices that can rectify the electromagnetic radiation at high frequencies. In addition to their speed, they are also small devices that can have more number of devices in unit area. In this work, it is aimed design and develop a device which can harvest and detect IR radiation.

Medical devices; immunology and microbiology devices; classification of nucleic acid-based devices for the detection of Mycobacterium tuberculosis complex and the genetic mutations associated with antibiotic resistance. Final order.

PubMed

2014-10-22

The Food and Drug Administration (FDA) is classifying nucleic acid-based in vitro diagnostic devices for the detection of Mycobacterium tuberculosis complex (MTB-complex) and the genetic mutations associated with MTB-complex antibiotic resistance in respiratory specimens devices into class II (special controls). The Agency is classifying the device into class II (special controls) because special controls, in addition to general controls, will provide a reasonable assurance of safety and effectiveness of the device.

Method and apparatus for actively controlling a micro-scale flexural plate wave device

DOEpatents

Dohner, Jeffrey L.

2001-01-01

An actively controlled flexural plate wave device provides a micro-scale pump. A method of actively controlling a flexural plate wave device produces traveling waves in the device by coordinating the interaction of a magnetic field with actively controlled currents. An actively-controlled flexural plate wave device can be placed in a fluid channel and adapted for use as a micro-scale fluid pump to cool or drive micro-scale systems, for example, micro-chips, micro-electrical-mechanical devices, micro-fluid circuits, or micro-scale chemical analysis devices.

Communicating with residential electrical devices via a vehicle telematics unit

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

Roth, Rebecca C.; Pebbles, Paul H.

A method of communicating with residential electrical devices using a vehicle telematics unit includes receiving information identifying a residential electrical device to control; displaying in a vehicle one or more controlled features of the identified residential electrical device; receiving from a vehicle occupant a selection of the displayed controlled features of the residential electrical device; sending an instruction from the vehicle telematics unit to the residential electrical device via a wireless carrier system in response to the received selection; and controlling the residential electrical device using the sent instruction.

Technique for calibrating angular measurement devices when calibration standards are unavailable

NASA Technical Reports Server (NTRS)

Finley, Tom D.

1991-01-01

A calibration technique is proposed that will allow the calibration of certain angular measurement devices without requiring the use of absolute standard. The technique assumes that the device to be calibrated has deterministic bias errors. A comparison device must be available that meets the same requirements. The two devices are compared; one device is then rotated with respect to the other, and a second comparison is performed. If the data are reduced using the described technique, the individual errors of the two devices can be determined.

Method for integrating microelectromechanical devices with electronic circuitry

DOEpatents

Montague, S.; Smith, J.H.; Sniegowski, J.J.; McWhorter, P.J.

1998-08-25

A method is disclosed for integrating one or more microelectromechanical (MEM) devices with electronic circuitry. The method comprises the steps of forming each MEM device within a cavity below a device surface of the substrate; encapsulating the MEM device prior to forming electronic circuitry on the substrate; and releasing the MEM device for operation after fabrication of the electronic circuitry. Planarization of the encapsulated MEM device prior to formation of the electronic circuitry allows the use of standard processing steps for fabrication of the electronic circuitry. 13 figs.

All APAPs Are Not Equivalent for the Treatment of Sleep Disordered Breathing: A Bench Evaluation of Eleven Commercially Available Devices

PubMed Central

Zhu, Kaixian; Roisman, Gabriel; Aouf, Sami; Escourrou, Pierre

2015-01-01

Study Objectives: This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports. Methods: Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle. Results: In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports. Conclusion: Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study. Citation: Zhu K, Roisman G, Aouf S, Escourrou P. All APAPs are not equivalent for the treatment of sleep disordered breathing: a bench evaluation of eleven commercially available devices. J Clin Sleep Med 2015;11(7):725–734. PMID:25766708

Fabrication and testing of unileg oxide thermoelectric device

NASA Astrophysics Data System (ADS)

Sharma, Jyothi; Purohit, R. D.; Prakash, Deep; Sinha, P. K.

2017-05-01

A prototype of oxide thermoelectric unileg device was fabricated. This device was based on only n-legs made of La doped calcium manganate. The powder was synthesized, characterised and consolidated in rectangular thermoelements. A 3×3 device was fabricated by fitting 9 rectangular bars in alumina housing and connected by silver strips. The device has been tested under large temperature difference (ΔT=480°C) using an indegenous system. An open circuit voltage of 468 mV was obtained for a nine leg `unileg' device. The device exhibits a internal resistance of ˜1Ω. The maximum power output for this nine leg device reached upto 50 mW in these working condition.

Implantable biomedical devices on bioresorbable substrates

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

Rogers, John A; Kim, Dae-Hyeong; Omenetto, Fiorenzo

Provided herein are implantable biomedical devices, methods of administering implantable biomedical devices, methods of making implantable biomedical devices, and methods of using implantable biomedical devices to actuate a target tissue or sense a parameter associated with the target tissue in a biological environment. Each implantable biomedical device comprises a bioresorbable substrate, an electronic device having a plurality of inorganic semiconductor components supported by the bioresorbable substrate, and a barrier layer encapsulating at least a portion of the inorganic semiconductor components. Upon contact with a biological environment the bioresorbable substrate is at least partially resorbed, thereby establishing conformal contact between themore » implantable biomedical device and the target tissue in the biological environment.« less

A DRM based on renewable broadcast encryption

NASA Astrophysics Data System (ADS)

Ramkumar, Mahalingam; Memon, Nasir

2005-07-01

We propose an architecture for digital rights management based on a renewable, random key pre-distribution (KPD) scheme, HARPS (hashed random preloaded subsets). The proposed architecture caters for broadcast encryption by a trusted authority (TA) and by "parent" devices (devices used by vendors who manufacture compliant devices) for periodic revocation of devices. The KPD also facilitates broadcast encryption by peer devices, which permits peers to distribute content, and efficiently control access to the content encryption secret using subscription secrets. The underlying KPD also caters for broadcast authentication and mutual authentication of any two devices, irrespective of the vendors manufacturing the device, and thus provides a comprehensive solution for securing interactions between devices taking part in a DRM system.

Separating semiconductor devices from substrate by etching graded composition release layer disposed between semiconductor devices and substrate including forming protuberances that reduce stiction

DOEpatents

Tauke-Pedretti, Anna; Nielson, Gregory N; Cederberg, Jeffrey G; Cruz-Campa, Jose Luis

2015-05-12

A method includes etching a release layer that is coupled between a plurality of semiconductor devices and a substrate with an etch. The etching includes etching the release layer between the semiconductor devices and the substrate until the semiconductor devices are at least substantially released from the substrate. The etching also includes etching a protuberance in the release layer between each of the semiconductor devices and the substrate. The etch is stopped while the protuberances remain between each of the semiconductor devices and the substrate. The method also includes separating the semiconductor devices from the substrate. Other methods and apparatus are also disclosed.

System and method for evaluating wind flow fields using remote sensing devices

DOEpatents

Schroeder, John; Hirth, Brian; Guynes, Jerry

2016-12-13

The present invention provides a system and method for obtaining data to determine one or more characteristics of a wind field using a first remote sensing device and a second remote sensing device. Coordinated data is collected from the first and second remote sensing devices and analyzed to determine the one or more characteristics of the wind field. The first remote sensing device is positioned to have a portion of the wind field within a first scanning sector of the first remote sensing device. The second remote sensing device is positioned to have the portion of the wind field disposed within a second scanning sector of the second remote sensing device.

Management of Patients With Cardiovascular Implantable Electronic Devices in Dental, Oral, and Maxillofacial Surgery.

PubMed

Tom, James

2016-01-01

The prevalence of cardiovascular implantable electronic devices as life-prolonging and life-saving devices has evolved from a treatment of last resort to a first-line therapy for an increasing number of patients. As these devices become more and more popular in the general population, dental providers utilizing instruments and medications should be aware of dental equipment and medications that may affect these devices and understand the management of patients with these devices. This review article will discuss the various types and indications for pacemakers and implantable cardioverter-defibrillators, common drugs and instruments affecting these devices, and management of patients with these devices implanted for cardiac dysrhythmias.

Management of Patients With Cardiovascular Implantable Electronic Devices in Dental, Oral, and Maxillofacial Surgery

PubMed Central

Tom, James

2016-01-01

The prevalence of cardiovascular implantable electronic devices as life-prolonging and life-saving devices has evolved from a treatment of last resort to a first-line therapy for an increasing number of patients. As these devices become more and more popular in the general population, dental providers utilizing instruments and medications should be aware of dental equipment and medications that may affect these devices and understand the management of patients with these devices. This review article will discuss the various types and indications for pacemakers and implantable cardioverter-defibrillators, common drugs and instruments affecting these devices, and management of patients with these devices implanted for cardiac dysrhythmias. PMID:27269668

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.

Graphene device and method of using graphene device

DOEpatents

Bouchiat, Vincent; Girit, Caglar; Kessler, Brian; Zettl, Alexander K.

2015-08-11

An embodiment of a graphene device includes a layered structure, first and second electrodes, and a dopant island. The layered structure includes a conductive layer, an insulating layer, and a graphene layer. The electrodes are coupled to the graphene layer. The dopant island is coupled to an exposed surface of the graphene layer between the electrodes. An embodiment of a method of using a graphene device includes providing the graphene device. A voltage is applied to the conductive layer of the graphene device. Another embodiment of a method of using a graphene device includes providing the graphene device without the dopant island. A dopant island is placed on an exposed surface of the graphene layer between the electrodes. A voltage is applied to the conductive layer of the graphene device. A response of the dopant island to the voltage is observed.

Dynamic mapping of EDDL device descriptions to OPC UA

NASA Astrophysics Data System (ADS)

Atta Nsiah, Kofi; Schappacher, Manuel; Sikora, Axel

2017-07-01

OPC UA (Open Platform Communications Unified Architecture) is already a well-known concept used widely in the automation industry. In the area of factory automation, OPC UA models the underlying field devices such as sensors and actuators in an OPC UA server to allow connecting OPC UA clients to access device-specific information via a standardized information model. One of the requirements of the OPC UA server to represent field device data using its information model is to have advanced knowledge about the properties of the field devices in the form of device descriptions. The international standard IEC 61804 specifies EDDL (Electronic Device Description Language) as a generic language for describing the properties of field devices. In this paper, the authors describe a possibility to dynamically map and integrate field device descriptions based on EDDL into OPCUA.

Clocked Magnetostriction-Assisted Spintronic Device Design and Simulation

NASA Astrophysics Data System (ADS)

Mousavi Iraei, Rouhollah; Kani, Nickvash; Dutta, Sourav; Nikonov, Dmitri E.; Manipatruni, Sasikanth; Young, Ian A.; Heron, John T.; Naeemi, Azad

2018-05-01

We propose a heterostructure device comprised of magnets and piezoelectrics that significantly improves the delay and the energy dissipation of an all-spin logic (ASL) device. This paper studies and models the physics of the device, illustrates its operation, and benchmarks its performance using SPICE simulations. We show that the proposed device maintains low voltage operation, non-reciprocity, non-volatility, cascadability, and thermal reliability of the original ASL device. Moreover, by utilizing the deterministic switching of a magnet from the saddle point of the energy profile, the device is more efficient in terms of energy and delay and is robust to thermal fluctuations. The results of simulations show that compared to ASL devices, the proposed device achieves 21x shorter delay and 27x lower energy dissipation per bit for a 32-bit arithmetic-logic unit (ALU).

21 CFR 882.5235 - Aversive conditioning device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Aversive conditioning device. 882.5235 Section 882.5235 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Therapeutic Devices § 882.5235 Aversive conditioning...