Sample records for maintenance deactivation alteration

  1. 78 FR 9636 - Airworthiness Directives; Cessna Aircraft Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-11

    .... We have changed paragraph (k) of the supplemental NPRM (i.e., paragraph (j) of the previous NPRM) to... Limitations, Revision 7, dated April 23, 2012, of the Cessna Model S550 Maintenance Manual. (k) Deactivation..., deactivate the A/C system as specified in paragraph (k)(1), (k)(2), or (k)(3) of this AD, as applicable. (1...

  2. PUREX/UO{sub 3} deactivation project management plan

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

    Washenfelder, D.J.

    1993-12-01

    From 1955 through 1990, the Plutonium-Uranium Extraction Plant (PUREX) provided the United States Department of Energy Hanford Site with nuclear fuel reprocessing capability. It operated in sequence with the Uranium Trioxide (UO{sub 3}) Plant, which converted the PUREX liquid uranium nitrate product to solid UO{sub 3} powder. Final UO{sub 3} Plant operation ended in 1993. In December 1992, planning was initiated for the deactivation of PUREX and UO{sub 3} Plant. The objective of deactivation planning was to identify the activities needed to establish a passively safe, environmentally secure configuration at both plants, and ensure that the configuration could be retainedmore » during the post-deactivation period. The PUREX/UO{sub 3} Deactivation Project management plan represents completion of the planning efforts. It presents the deactivation approach to be used for the two plants, and the supporting technical, cost, and schedule baselines. Deactivation activities concentrate on removal, reduction, and stabilization of the radioactive and chemical materials remaining at the plants, and the shutdown of the utilities and effluents. When deactivation is completed, the two plants will be left unoccupied and locked, pending eventual decontamination and decommissioning. Deactivation is expected to cost $233.8 million, require 5 years to complete, and yield $36 million in annual surveillance and maintenance cost savings.« less

  3. Age and Alzheimer's pathology disrupt default mode network functioning via alterations in white matter microstructure but not hyperintensities.

    PubMed

    Brown, Christopher A; Jiang, Yang; Smith, Charles D; Gold, Brian T

    2018-04-19

    The default mode network (DMN) comprises defined brain regions contributing to internally-directed thought processes. Reductions in task-induced deactivation in the DMN have been associated with increasing age and poorer executive task performance, but factors underlying these functional changes remain unclear. We investigated contributions of white matter (WM) microstructure, WM hyperintensities (WMH) and Alzheimer's pathology to age-related alterations in DMN function. Thirty-five cognitively normal older adults and 29 younger adults underwent working memory task fMRI and diffusion tensor imaging. In the older adults, we measured cerebrospinal fluid tau and Aβ 42 (markers of AD pathology), and WMH on FLAIR imaging (marker of cerebrovascular disease). We identified a set of regions showing DMN deactivation and a set of inter-connecting WM tracts (DMN-WM) common to both age groups. There were negative associations between DMN deactivation and task performance in older adults, consistent with previous studies. Decreased DMN deactivation was associated with AD pathology and WM microstructure but not with WMH volume. Mediation analyses showed that WM microstructure mediated declines in DMN deactivation associated with both aging and AD pathology. Together these results suggest that AD pathology may exert a "second-hit" on WM microstructure, over-and-above the effects of age, both contributing to diminished DMN deactivation in older adults. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Mediation Analysis of Mode Deactivation Therapy (Reanalysis and Interpretation)

    ERIC Educational Resources Information Center

    Bass, Christopher K.; Apsche, Jack A.

    2013-01-01

    A key component of Mode Deactivation Therapy (MDT) is the development of self-awareness and regulatory skills by the client with the aim of helping adolescent males with conduct disordered behaviors, including sexually inappropriate behaviors and emotional dysregulation. The goal includes altering specific behaviors to fall within socially…

  5. Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

    PubMed

    Celone, Kim A; Calhoun, Vince D; Dickerson, Bradford C; Atri, Alireza; Chua, Elizabeth F; Miller, Saul L; DePeau, Kristina; Rentz, Doreen M; Selkoe, Dennis J; Blacker, Deborah; Albert, Marilyn S; Sperling, Reisa A

    2006-10-04

    Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

  6. Work plan for the Isotopes Facilities Deactivation Project at Oak Ridge National Laboratory, Oak Ridge, Tennessee

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

    NONE

    1995-08-01

    The purpose of the Isotopes Facilities Deactivation Project (IFDP) is to place former isotopes production facilities at the Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition; suitable for an extended period of minimum surveillance and maintenance (S and M) and as quickly and economical as possible. Implementation and completion of the deactivation project will further reduce the risks to the environment and to public safety and health. Furthermore, completion of the project will result in significant S and M cost savings in future years. The IFDP work plan defines the project schedule, the cost estimate, andmore » the technical approach for the project. A companion document, the EFDP management plan, has been prepared to document the project objectives, define organizational relationships and responsibilities, and outline the management control systems to be employed in the management of the project. The project has adopted the strategy of deactivating the simple facilities first, to reduce the scope of the project and to gain experience before addressing more difficult facilities. A decision support system is being developed to identify the activities that best promote the project mission and result in the largest cost savings. This work plan will be reviewed and revised annually. Deactivation of EFDP Facilities was initiated in FY 1994 and will be completed in FY 2000. The schedule for deactivation of facilities is shown. The total cost of the project is estimated to be $51M. The costs are summarized. Upon completion of deactivation, annual S and M costs of these facilities will be reduced from the current level of $5M per year to less than $1M per year.« less

  7. Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

    PubMed

    Dunham, Lee S S; Momiji, Hiroshi; Harper, Claire V; Downton, Polly J; Hey, Kirsty; McNamara, Anne; Featherstone, Karen; Spiller, David G; Rand, David A; Finkenstädt, Bärbel; White, Michael R H; Davis, Julian R E

    2017-12-27

    Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Gemelli, Claudia, E-mail: claudia.gemelli@unimore.it; Center for Regenerative Medicine, University of Modena and Reggio Emilia, Via Gottardi 100, 41125 Modena; Martello, Andrea

    Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1 kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivationmore » experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3 – VDR – ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling. - Highlights: • ORM1 is a Vitamin D primary response gene. • VD and its receptor VDR are involved in the de-activation process mediated by human resident macrophages. • The signaling pathway VD-VDR-ORM1 plays an important role in the control of macrophage de-activation process. • ORM1 may be defined as a signaling molecule implicated in the maintenance of tissue homeostasis and remodeling.« less

  9. 75 FR 6865 - Airworthiness Directives; The Boeing Company Model 737-700 (IGW) Series Airplanes Equipped With...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-12

    ... deactivation or modification of PATS Aircraft, LLC, auxiliary fuel tanks. This proposed AD results from fuel... for fuel tank systems. As a result of those findings, we issued a regulation titled ``Transport Airplane Fuel Tank System Design Review, Flammability Reduction and Maintenance and Inspection Requirements...

  10. Distributions of Irritative Zones Are Related to Individual Alterations of Resting-State Networks in Focal Epilepsy

    PubMed Central

    Song, Yinchen; Sanganahalli, Basavaraju G.; Hyder, Fahmeed; Lin, Wei-Chiang; Riera, Jorge J.

    2015-01-01

    Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p<0.05). We were able to predict topological properties (i.e., focal/diffused, unilateral/bilateral) of the IED-evoked BOLD response network by performing hierarchical clustering analysis on major spatial features of the RSNs. All these results suggest that IEDs and disruptions in the RSNs found previously in humans may be different manifestations of the same transient events, probably reflecting altered consciousness. In our opinion, the shutdown of specific nodes of the default mode network may cause uncontrollable excitability in other functionally connected brain areas. We conclude that IED-evoked BOLD responses (i.e., activation and deactivation) and alterations of RSNs are intrinsically related, and speculate that an understanding of their interplay is necessary to discriminate focal epileptogenesis and network propagation phenomena across different brain modules via hub-based connectivity. PMID:26226628

  11. The Failure of Deactivating Intentions: Aftereffects of Completed Intentions in the Repeated Prospective Memory Cue Paradigm

    ERIC Educational Resources Information Center

    Walser, Moritz; Fischer, Rico; Goschke, Thomas

    2012-01-01

    We used a newly developed experimental paradigm to investigate aftereffects of completed intentions on subsequent performance that required the maintenance and execution of new intentions. Participants performed an ongoing number categorization task and an additional prospective memory (PM) task, which required them to respond to PM cues that…

  12. Catalyst activity maintenance study for the liquid phase dimethyl ether process

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

    Peng, X.D.; Toseland, B.A.; Underwood, R.P.

    1995-12-31

    The co-production of dimethyl ether (DME) and methanol from syngas is a process of considerable commercial attractiveness. DME coproduction can double the productivity of a LPMEOH process when using coal-derived syngas. This in itself may offer chemical producers and power companies increased flexibility and more profitable operation. DME is also known as a clean burning liquid fuel; Amoco and Haldor-Topsoe have recently announced the use of DME as an alternative diesel fuel. Moreover, DME can be an interesting intermediate in the production of chemicals such as olefins and vinyl acetate. The current APCl liquid phase dimethyl ether (LPDME) process utilizesmore » a physical mixture of a commercial methanol synthesis catalyst and a dehydration catalyst (e.g., {gamma}-alumina). While this arrangement provides a synergy that results in much higher syngas conversion per pass compared to the methanol-only process, the stability of the catalyst system suffers. The present project is aimed at reducing catalyst deactivation both by understanding the cause(s) of catalyst deactivation and by developing modified catalyst systems. This paper describes the current understanding of the deactivation mechanism.« less

  13. AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate.

    PubMed

    Partin, K M; Fleck, M W; Mayer, M L

    1996-11-01

    AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate. Point mutations from Ser to Asn, Ala, Asp, Gly, Gln, Met, Cys, Thr, Leu, Val, and Tyr were constructed in GluRAflip. The last four of these mutants were not functional; S750D was active only in the presence of cyclothiazide, and the remaining mutants exhibited altered rates of deactivation and desensitization for control responses to glutamate, and showed differential modulation by cyclothiazide and aniracetam. Results from kinetic analysis are consistent with aniracetam and cyclothiazide acting via distinct mechanisms. Our experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3-M4 extracellular loop.

  14. Reversible deactivation of higher-order posterior parietal areas. II. Alterations in response properties of neurons in areas 1 and 2

    PubMed Central

    Goldring, Adam B.; Cooke, Dylan F.; Baldwin, Mary K. L.; Recanzone, Gregg H.; Gordon, Adam G.; Pan, Tingrui; Simon, Scott I.

    2014-01-01

    The role that posterior parietal (PPC) and motor cortices play in modulating neural responses in somatosensory areas 1 and 2 was examined with reversible deactivation by transient cooling. Multiunit recordings from neurons in areas 1 and 2 were collected from six anesthetized adult monkeys (Macaca mulatta) before, during, and after reversible deactivation of areas 5L or 7b or motor cortex (M1/PM), while select locations on the hand and forelimb were stimulated. Response changes were quantified as increases and decreases to stimulus-driven activity relative to baseline and analyzed during three recording epochs: during deactivation (“cool”) and at two time points after deactivation (“rewarm 1,” “rewarm 2”). Although the type of response change observed was variable, for neurons at the recording sites tested >90% exhibited a significant change in response during cooling of 7b while cooling area 5L or M1/PM produced a change in 75% and 64% of sites, respectively. These results suggest that regions in the PPC, and to a lesser extent motor cortex, shape the response characteristics of neurons in areas 1 and 2 and that this kind of feedback modulation is necessary for normal somatosensory processing. Furthermore, this modulation appears to happen on a minute-by-minute basis and may serve as the substrate for phenomena such as somatosensory attention. PMID:25143537

  15. The unrested resting brain: sleep deprivation alters activity within the default-mode network.

    PubMed

    Gujar, Ninad; Yoo, Seung-Schik; Hu, Peter; Walker, Matthew P

    2010-08-01

    The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and the balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity, findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level.

  16. 14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Operation after maintenance, preventive...

  17. 14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Operation after maintenance, preventive...

  18. 14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Operation after maintenance, preventive...

  19. 14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Operation after maintenance, preventive...

  20. 14 CFR 91.407 - Operation after maintenance, preventive maintenance, rebuilding, or alteration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... flies the aircraft, makes an operational check of the maintenance performed or alteration made, and logs... maintenance, preventive maintenance, rebuilding, or alteration. (a) No person may operate any aircraft that... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Operation after maintenance, preventive...

  1. Emotional faces and the default mode network.

    PubMed

    Sreenivas, S; Boehm, S G; Linden, D E J

    2012-01-11

    The default-mode network (DMN) of the human brain has become a central topic of cognitive neuroscience research. Although alterations in its resting state activity and in its recruitment during tasks have been reported for several mental and neurodegenerative disorders, its role in emotion processing has received relatively little attention. We investigated brain responses to different categories of emotional faces with functional magnetic resonance imaging (fMRI) and found deactivation in ventromedial prefrontal cortex (VMPFC), posterior cingulate gyrus (PC) and cuneus. This deactivation was modulated by emotional category and was less prominent for happy than for sad faces. These deactivated areas along the midline conformed to areas of the DMN. We also observed emotion-dependent deactivation of the left middle frontal gyrus, which is not a classical component of the DMN. Conversely, several areas in a fronto-parietal network commonly linked with attention were differentially activated by emotion categories. Functional connectivity patterns, as obtained by correlation of activation levels, also varied between emotions. VMPFC, PC or cuneus served as hubs between the DMN-type areas and the fronto-parietal network. These data support recent suggestions that the DMN is not a unitary system but differentiates according to task and even type of stimulus. The emotion-specific differential pattern of DMN deactivation may be explored further in patients with mood disorder, where the quest for biological markers of emotional biases is still ongoing. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Reversible deactivation of higher-order posterior parietal areas. I. Alterations of receptive field characteristics in early stages of neocortical processing

    PubMed Central

    Cooke, Dylan F.; Goldring, Adam B.; Baldwin, Mary K. L.; Recanzone, Gregg H.; Chen, Arnold; Pan, Tingrui; Simon, Scott I.

    2014-01-01

    Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L and 7b and motor/premotor cortex (M1/PM) with microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and nonhuman primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5–22 min of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex. PMID:25143546

  3. Prefrontal responses to digit span memory phases in patients with post-traumatic stress disorder (PTSD): a functional near infrared spectroscopy study.

    PubMed

    Tian, Fenghua; Yennu, Amarnath; Smith-Osborne, Alexa; Gonzalez-Lima, F; North, Carol S; Liu, Hanli

    2014-01-01

    Neuroimaging studies of post-traumatic stress disorder (PTSD)-related memory impairments have consistently implicated abnormal activities in the frontal and parietal lobes. However, most studies have used block designs and could not dissociate the multiple phases of working memory. In this study, the involvement of the prefrontal cortex in working memory phases was assessed among veterans with PTSD and age-/gender-matched healthy controls. Multichannel functional near infrared spectroscopy (fNIRS) was utilized to measure prefrontal cortex hemodynamic activations during memory of neutral (i.e., not trauma-related) forward and backward digit span tasks. An event-related experimental design was utilized to dissociate the different phases (i.e., encoding, maintenance and retrieval) of working memory. The healthy controls showed robust hemodynamic activations during the encoding and retrieval processes. In contrast, the veterans with PTSD were found to have activations during the encoding process, but followed by distinct deactivations during the retrieval process. The PTSD participants, but not the controls, appeared to suppress prefrontal activity during memory retrieval. This deactivation was more pronounced in the right dorsolateral prefrontal cortex during the retrieval phase. These deactivations in PTSD patients might implicate an active inhibition of dorsolateral prefrontal neural activity during retrieval of working memory.

  4. Mechanistic Basis for Type 2 Long QT Syndrome Caused by KCNH2 Mutations that Disrupt Conserved Arginine Residue in the Voltage Sensor

    PubMed Central

    McBride, Christie M.; Smith, Ashley M.; Smith, Jennifer L.; Reloj, Allison R.; Velasco, Ellyn J.; Powell, Jonathan; Elayi, Claude S.; Bartos, Daniel C.; Burgess, Don E.

    2013-01-01

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (IKr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing IKr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (IKv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients’ genotypes) mostly corrected the changes in IKv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing IKr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease IKr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient. PMID:23546015

  5. Mechanistic basis for type 2 long QT syndrome caused by KCNH2 mutations that disrupt conserved arginine residues in the voltage sensor.

    PubMed

    McBride, Christie M; Smith, Ashley M; Smith, Jennifer L; Reloj, Allison R; Velasco, Ellyn J; Powell, Jonathan; Elayi, Claude S; Bartos, Daniel C; Burgess, Don E; Delisle, Brian P

    2013-05-01

    KCNH2 encodes the Kv11.1 channel, which conducts the rapidly activating delayed rectifier K+ current (I Kr) in the heart. KCNH2 mutations cause type 2 long QT syndrome (LQT2), which increases the risk for life-threatening ventricular arrhythmias. LQT2 mutations are predicted to prolong the cardiac action potential (AP) by reducing I Kr during repolarization. Kv11.1 contains several conserved basic amino acids in the fourth transmembrane segment (S4) of the voltage sensor that are important for normal channel trafficking and gating. This study sought to determine the mechanism(s) by which LQT2 mutations at conserved arginine residues in S4 (R531Q, R531W or R534L) alter Kv11.1 function. Western blot analyses of HEK293 cells transiently expressing R531Q, R531W or R534L suggested that only R534L inhibited Kv11.1 trafficking. Voltage-clamping experiments showed that R531Q or R531W dramatically altered Kv11.1 current (I Kv11.1) activation, inactivation, recovery from inactivation and deactivation. Coexpression of wild type (to mimic the patients' genotypes) mostly corrected the changes in I Kv11.1 activation and inactivation, but deactivation kinetics were still faster. Computational simulations using a human ventricular AP model showed that accelerating deactivation rates was sufficient to prolong the AP, but these effects were minimal compared to simply reducing I Kr. These are the first data to demonstrate that coexpressing wild type can correct activation and inactivation dysfunction caused by mutations at a critical voltage-sensing residue in Kv11.1. We conclude that some Kv11.1 mutations might accelerate deactivation to cause LQT2 but that the ventricular AP duration is much more sensitive to mutations that decrease I Kr. This likely explains why most LQT2 mutations are nonsense or trafficking-deficient.

  6. 14 CFR 91.1425 - CAMP: Maintenance, preventive maintenance, and alteration programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... RULES Fractional Ownership Operations Program Management § 91.1425 CAMP: Maintenance, preventive maintenance, and alteration programs. Each program manager who maintains program aircraft under a CAMP must... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false CAMP: Maintenance, preventive maintenance...

  7. Molecular basis of slow activation of the human ether-á-go-go related gene potassium channel

    PubMed Central

    Subbiah, Rajesh N; Clarke, Catherine E; Smith, David J; Zhao, JingTing; Campbell, Terence J; Vandenberg, Jamie I

    2004-01-01

    The human ether-á-go-go related gene (HERG) encodes the pore forming α-subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage-gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild-type (WT) channels in Xenopus laevis oocytes and studied them using two-electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states. PMID:15181157

  8. Age and amyloid-related alterations in default network habituation to stimulus repetition

    PubMed Central

    Vannini, Patrizia; Hedden, Trey; Becker, John A.; Sullivan, Caroline; Putcha, Deepti; Rentz, Dorene; Johnson, Keith A.; Sperling, Reisa. A.

    2011-01-01

    The neural networks supporting encoding of new information are thought to decline with age, although mnemonic techniques such as repetition may enhance performance in older individuals. Accumulation of amyloid-β, one hallmark pathology of Alzheimer’s disease (AD), may contribute to functional alterations in memory networks measured with functional magnetic resonance imaging (fMRI) prior to onset of cognitive impairment. We investigated the effects of age and amyloid burden on fMRI activity in the default network and hippocampus during repetitive encoding. Older individuals, particularly those with high amyloid burden, demonstrated decreased task-induced deactivation in the posteromedial cortices during initial stimulus presentation and failed to modulate fMRI activity in response to repeated trials, whereas young subjects demonstrated a stepwise decrease in deactivation with repetition. The hippocampus demonstrated similar patterns across the groups, showing task-induced activity that decreased in response to repetition. These findings demonstrate that age and amyloid have dissociable functional effects on specific nodes within a distributed memory network, and suggest that functional brain changes may begin far in advance of symptomatic AD. PMID:21334099

  9. Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase.

    PubMed

    Duan, Wenjuan; Zhou, Juefei; Li, Wei; Zhou, Teng; Chen, Qianqian; Yang, Fuyu; Wei, Taotao

    2013-04-01

    The activation and deactivation of Ca(2+)- and calmodulindependent neuronal nitric oxide synthase (nNOS) in the central nervous system must be tightly controlled to prevent excessive nitric oxide (NO) generation. Considering plasma membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present investigation aims to determine the key events involved in nNOS deactivation of by PMCA in living cells to maintain its cellular context. Using time-resolved Förster resonance energy transfer (FRET), we determined the occurrence of Ca(2+)-induced protein-protein interactions between plasma membrane calcium ATPase 4b (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the intracellular Ca(2+) concentrations ([Ca(2+)]i), which deactivates nNOS and slowdowns NO synthesis. Under the basal [Ca(2+)]i caused by PMCA activation, no protein-protein interactions were observed between PMCA4b and nNOS. Furthermore, both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential for the protein-protein interaction. The involvement of lipid raft microdomains on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA isoforms, PMCA4 was relatively more concentrated in the raft fractions. Disruption of lipid rafts altered the intracellular localization of PMCA4b and affected the interaction between PMCA4b and nNOS, which suggest that the unique lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for rapid nNOS deactivation.

  10. Spatial-temporal patterns of electrocorticographic spectral changes during midazolam sedation

    PubMed Central

    Nishida, Masaaki; Zestos, Maria M.; Asano, Eishi

    2015-01-01

    Objective To better understand ‘when’ and ‘where’ wideband electrophysiological signals are altered by sedation. Methods We generated animation movies showing electrocorticography (ECoG) amplitudes at eight spectral frequency bands across 1.0 to 116 Hz, every 0.1 second, on three-dimensional surface images of 10 children who underwent epilepsy surgery. We measured the onset, intensity, and variance of each band amplitude change at given nonepileptic regions separately from those at affected regions. We also determined the presence of differential ECoG changes depending on the brain anatomy. Results Within 20 seconds following injection of midazolam, beta (16–31.5 Hz) and sigma (12–15.5 Hz) activities began to be multifocally augmented with increased variance in amplitude at each site. Beta-sigma augmentation was most prominent within the association neocortex. Augmentation of low-delta activity (1.0–1.5 Hz) was relatively modest and confined to the somatosensory-motor region. Conversely, injection of midazolam induced attenuation of theta (4.0–7.5 Hz) and high-gamma (64–116 Hz) activities. Conclusions Our observations support the notion that augmentation beta-sigma and delta activities reflects cortical deactivation or inactivation, whereas theta and high-gamma activities contribute to maintenance of consciousness. The effects of midazolam on the dynamics of cortical oscillations differed across regions. Significance Sedation, at least partially, reflects a multi-local phenomenon at the cortical level rather than global brain alteration homogeneously driven by the common central control structure. PMID:26613652

  11. Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

    PubMed

    Hunt, Katharine F; Dunn, Joel T; le Roux, Carel W; Reed, Laurence J; Marsden, Paul K; Patel, Ameet G; Amiel, Stephanie A

    2016-10-01

    Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance. © 2016 by the American Diabetes Association.

  12. Altered medial prefrontal activity during dynamic face processing in schizophrenia spectrum patients.

    PubMed

    Mothersill, Omar; Morris, Derek W; Kelly, Sinead; Rose, Emma Jane; Bokde, Arun; Reilly, Richard; Gill, Michael; Corvin, Aiden P; Donohoe, Gary

    2014-08-01

    Processing the emotional content of faces is recognised as a key deficit of schizophrenia, associated with poorer functional outcomes and possibly contributing to the severity of clinical symptoms such as paranoia. At the neural level, fMRI studies have reported altered limbic activity in response to facial stimuli. However, previous studies may be limited by the use of cognitively demanding tasks and static facial stimuli. To address these issues, the current study used a face processing task involving both passive face viewing and dynamic social stimuli. Such a task may (1) lack the potentially confounding effects of high cognitive demands and (2) show higher ecological validity. Functional MRI was used to examine neural activity in 25 patients with a DSM-IV diagnosis of schizophrenia/schizoaffective disorder and 21 age- and gender-matched healthy controls while they participated in a face processing task, which involved viewing videos of angry and neutral facial expressions, and a non-biological baseline condition. While viewing faces, patients showed significantly weaker deactivation of the medial prefrontal cortex, including the anterior cingulate, and decreased activation in the left cerebellum, compared to controls. Patients also showed weaker medial prefrontal deactivation while viewing the angry faces relative to baseline. Given that the anterior cingulate plays a role in processing negative emotion, weaker deactivation of this region in patients while viewing faces may contribute to an increased perception of social threat. Future studies examining the neurobiology of social cognition in schizophrenia using fMRI may help establish targets for treatment interventions. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Altered cerebral activity associated with topiramate and its withdrawal in patients with epilepsy with language impairment: An fMRI study using the verb generation task.

    PubMed

    Tang, Yingying; Xia, Wei; Yu, Xiaofeng; Zhou, Bo; Wu, Xintong; Lui, Su; Luo, Chunyan; Huang, Xiaoqi; Ouyang, Luo; Chen, Qin; Gong, Qiyong; Zhou, Dong

    2016-06-01

    Topiramate (TPM) is well recognized for its negative effects on language in healthy volunteers and patients with epilepsy. The aim of this study was to investigate the brain activation and deactivation patterns in TPM-treated patients with epilepsy with language impairment and their dynamic alteration during TPM withdrawal using functional magnetic resonance imaging (fMRI) with the verb generation task (VGT). Twelve patients with epilepsy experiencing subjective language disfluency after TPM add-on treatment (TPM-on) and thirty sex- and age-matched healthy controls (HCs) were recruited. All subjects received a battery of neuropsychological tests and an fMRI scan with the VGT. Withdrawal of TPM was attempted in all patients. Only six patients reached complete withdrawal without seizure relapses (TPM-off), and these patients underwent a reassessment of neuropsychological and neuroimaging tests. The neuropsychological tests demonstrated objective language impairments in TPM-on patients. Compared with the HCs, the bilateral medial prefrontal cortex and the posterior midline and lateral parts of the default mode network (DMN) (including the bilateral posterior cingulate cortex (PCC), the right medial prefrontal cortex, the right angular gyrus, the right inferior temporal gyrus, and the bilateral supramarginal gyrus) in TPM-on patients failed to deactivate during the VGT. Their task-induced activation patterns were largely similar to those of the HCs. After TPM withdrawal, partial improvement of both task-induced deactivation of the DMN (the left parahippocampal gyrus and the bilateral PCC) and task-related activation of the language network (the right middle frontal gyrus and the left superior occipital gyrus) was identified along with partial improvement of neuropsychological tests. Task-induced deactivation is a more sensitive neuroimaging biomarker for the impaired language performance in patients administered TPM than task-induced activation. Disruption and reorganization of the balance between the DMN and the cortical language networks are found along with reversible TPM-related language impairment. These results may suggest an underlying brain mechanism by which TPM affects cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 14 CFR 43.17 - Maintenance, preventive maintenance, and alterations performed on U.S. aeronautical products by...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... maintenance, or alteration is performed in accordance with a Bilateral Aviation Safety Agreement between the... recorded in accordance with a Bilateral Aviation Safety Agreement between the United States and Canada and... Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE...

  15. Valence Scaling of Dynamic Facial Expressions Is Altered in High-Functioning Subjects with Autism Spectrum Disorders: An FMRI Study

    ERIC Educational Resources Information Center

    Rahko, Jukka S.; Paakki, Jyri-Johan; Starck, Tuomo H.; Nikkinen, Juha; Pauls, David L.; Katsyri, Jari V.; Jansson-Verkasalo, Eira M.; Carter, Alice S.; Hurtig, Tuula M.; Mattila, Marja-Leena; Jussila, Katja K.; Remes, Jukka J.; Kuusikko-Gauffin, Sanna A.; Sams, Mikko E.; Bolte, Sven; Ebeling, Hanna E.; Moilanen, Irma K.; Tervonen, Osmo; Kiviniemi, Vesa

    2012-01-01

    FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD…

  16. Aging and the interaction of sensory cortical function and structure.

    PubMed

    Peiffer, Ann M; Hugenschmidt, Christina E; Maldjian, Joseph A; Casanova, Ramon; Srikanth, Ryali; Hayasaka, Satoru; Burdette, Jonathan H; Kraft, Robert A; Laurienti, Paul J

    2009-01-01

    Even the healthiest older adults experience changes in cognitive and sensory function. Studies show that older adults have reduced neural responses to sensory information. However, it is well known that sensory systems do not act in isolation but function cooperatively to either enhance or suppress neural responses to individual environmental stimuli. Very little research has been dedicated to understanding how aging affects the interactions between sensory systems, especially cross-modal deactivations or the ability of one sensory system (e.g., audition) to suppress the neural responses in another sensory system cortex (e.g., vision). Such cross-modal interactions have been implicated in attentional shifts between sensory modalities and could account for increased distractibility in older adults. To assess age-related changes in cross-modal deactivations, functional MRI studies were performed in 61 adults between 18 and 80 years old during simple auditory and visual discrimination tasks. Results within visual cortex confirmed previous findings of decreased responses to visual stimuli for older adults. Age-related changes in the visual cortical response to auditory stimuli were, however, much more complex and suggested an alteration with age in the functional interactions between the senses. Ventral visual cortical regions exhibited cross-modal deactivations in younger but not older adults, whereas more dorsal aspects of visual cortex were suppressed in older but not younger adults. These differences in deactivation also remained after adjusting for age-related reductions in brain volume of sensory cortex. Thus, functional differences in cortical activity between older and younger adults cannot solely be accounted for by differences in gray matter volume. (c) 2007 Wiley-Liss, Inc.

  17. Protonated serotonin: Geometry, electronic structures and photophysical properties

    NASA Astrophysics Data System (ADS)

    Omidyan, Reza; Amanollahi, Zohreh; Azimi, Gholamhassan

    2017-07-01

    The geometry and electronic structures of protonated serotonin have been investigated by the aim of MP2 and CC2 methods. The relative stabilities, transition energies and geometry of sixteen different protonated isomers of serotonin have been presented. It has been predicted that protonation does not exhibit essential alteration on the S1 ← S0 electronic transition energy of serotonin. Instead, more complicated photophysical nature in respect to its neutral analogue is suggested for protonated system owing to radiative and non-radiative deactivation pathways. In addition to hydrogen detachment (HD), hydrogen/proton transfer (H/PT) processes from ammonium to indole ring along the NH+⋯ π hydrogen bond have been predicted as the most important photophysical consequences of SERH+ at S1 excited state. The PT processes is suggested to be responsible for fluorescence of SERH+ while the HD driving coordinate is proposed for elucidation of its nonradiative deactivation mechanism.

  18. Letterman Army Institute of Research Annual Research Progress Report, FY 1981.

    DTIC Science & Technology

    1981-10-01

    with physiology and mech- anisms of skin damage and repair. The mechanisms by which nerve agents and vesicants produce physiologic aberration and...enzyme vital for nerve function. Organophos- phates react rapidly and covalently with the enzyme to produce an in- active enzyme. Reactivation of the...warfare agents . These organic molecules may also alter the natural defense mechanism by activating or deactivating enzymes in the skin that destroy

  19. 14 CFR 43.12 - Maintenance records: Falsification, reproduction, or alteration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., reproduction, or alteration. 43.12 Section 43.12 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance records: Falsification, reproduction, or alteration. (a) No person may make or cause to be made..., kept, or used to show compliance with any requirement under this part; (2) Any reproduction, for...

  20. 14 CFR 43.12 - Maintenance records: Falsification, reproduction, or alteration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., reproduction, or alteration. 43.12 Section 43.12 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance records: Falsification, reproduction, or alteration. (a) No person may make or cause to be made..., kept, or used to show compliance with any requirement under this part; (2) Any reproduction, for...

  1. Facility Decontamination and Decommissioning Program Surveillance and Maintenance Plan, Revision 2

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

    Poderis, Reed J.; King, Rebecca A.

    This Surveillance and Maintenance (S&M) Plan describes the activities performed between deactivation and final decommissioning of the following facilities located on the Nevada National Security Site, as documented in the Federal Facility Agreement and Consent Order under the Industrial Sites program as decontamination and decommissioning sites: ? Engine Maintenance, Assembly, and Disassembly (EMAD) Facility: o EMAD Building (Building 25-3900) o Locomotive Storage Shed (Building 25-3901) ? Test Cell C (TCC) Facility: o Equipment Building (Building 25-3220) o Motor Drive Building (Building 25-3230) o Pump Shop (Building 25-3231) o Cryogenic Lab (Building 25-3232) o Ancillary Structures (e.g., dewars, water tower, piping,more » tanks) These facilities have been declared excess and are in various stages of deactivation (low-risk, long-term stewardship disposition state). This S&M Plan establishes and implements a solid, cost-effective, and balanced S&M program consistent with federal, state, and regulatory requirements. A graded approach is used to plan and conduct S&M activities. The goal is to maintain the facilities in a safe condition in a cost-effective manner until their final end state is achieved. This plan accomplishes the following: ? Establishes S&M objectives and framework ? Identifies programmatic guidance for S&M activities to be conducted by National Security Technologies, LLC, for the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) ? Provides present facility condition information and identifies hazards ? Identifies facility-specific S&M activities to be performed and their frequency ? Identifies regulatory drivers, NNSA/NFO policies and procedures, and best management practices that necessitate implementation of S&M activities ? Provides criteria and frequencies for revisions and updates ? Establishes the process for identifying and dispositioning a condition that has not been previously identified or documented ? Provides instructions for implementing annual S&M inspections and activities The following facilities that were included in Revision 1 of this plan have reached final disposition and are no longer in the S&M program: ? Reactor Maintenance, Assembly, and Disassembly Facility, Building 25-3110 ? Test Cell A Facility, Building 25-3113 ? TCC Facility, Building 25-3210 ? Pluto Disassembly Facility, Building 26-2201 ? Super Kukla Facility, Building 27-5400« less

  2. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... certificate holder has written procedures available to the pilot to evaluate the accomplishment of the task... alterations as provided in part 121 or 135. (g) Except for holders of a sport pilot certificate, the holder of a pilot certificate issued under part 61 may perform preventive maintenance on any aircraft owned or...

  3. Effect of Steam Deactivation Severity of ZSM-5 Additives on LPG Olefins Production in the FCC Process.

    PubMed

    Gusev, Andrey A; Psarras, Antonios C; Triantafyllidis, Konstantinos S; Lappas, Angelos A; Diddams, Paul A

    2017-10-21

    ZSM-5-containing catalytic additives are widely used in oil refineries to boost light olefin production and improve gasoline octanes in the Fluid Catalytic Cracking (FCC) process. Under the hydrothermal conditions present in the FCC regenerator (typically >700 °C and >8% steam), FCC catalysts and additives are subject to deactivation. Zeolites (e.g., Rare Earth USY in the base catalyst and ZSM-5 in Olefins boosting additives) are prone to dealumination and partial structural collapse, thereby losing activity, micropore surface area, and undergoing changes in selectivity. Fresh catalyst and additives are added at appropriate respective levels to the FCC unit on a daily basis to maintain overall targeted steady-state (equilibrated) activity and selectivity. To mimic this process under accelerated laboratory conditions, a commercial P/ZSM-5 additive was hydrothermally equilibrated via a steaming process at two temperatures: 788 °C and 815 °C to simulate moderate and more severe equilibration industrial conditions, respectively. n -Dodecane was used as probe molecule and feed for micro-activity cracking testing at 560 °C to determine the activity and product selectivity of fresh and equilibrated P-doped ZSM-5 additives. The fresh/calcined P/ZSM-5 additive was very active in C 12 cracking while steaming limited its activity, i.e., at catalyst-to-feed (C/F) ratio of 1, about 70% and 30% conversion was obtained with the fresh and steamed additives, respectively. A greater activity drop was observed upon increasing the hydrothermal deactivation severity due to gradual decrease of total acidity and microporosity of the additives. However, this change in severity did not result in any selectivity changes for the LPG (liquefied petroleum gas) olefins as the nature (Brønsted-to-Lewis ratio) of the acid/active sites was not significantly altered upon steaming. Steam deactivation of ZSM-5 had also no significant effect on aromatics formation which was enhanced at higher conversion levels. Coke remained low with both fresh and steam-deactivated P/ZSM-5 additives.

  4. The maintenance of elevated active chlorine levels in the Antarctic lower stratosphere through HCl null cycles

    NASA Astrophysics Data System (ADS)

    Müller, Rolf; Grooß, Jens-Uwe; Mannan Zafar, Abdul; Robrecht, Sabine; Lehmann, Ralph

    2018-03-01

    The Antarctic ozone hole arises from ozone destruction driven by elevated levels of ozone destroying (active) chlorine in Antarctic spring. These elevated levels of active chlorine have to be formed first and then maintained throughout the period of ozone destruction. It is a matter of debate how this maintenance of active chlorine is brought about in Antarctic spring, when the rate of formation of HCl (considered to be the main chlorine deactivation mechanism in Antarctica) is extremely high. Here we show that in the heart of the ozone hole (16-18 km or 85-55 hPa, in the core of the vortex), high levels of active chlorine are maintained by effective chemical cycles (referred to as HCl null cycles hereafter). In these cycles, the formation of HCl is balanced by immediate reactivation, i.e. by immediate reformation of active chlorine. Under these conditions, polar stratospheric clouds sequester HNO3 and thereby cause NO2 concentrations to be low. These HCl null cycles allow active chlorine levels to be maintained in the Antarctic lower stratosphere and thus rapid ozone destruction to occur. For the observed almost complete activation of stratospheric chlorine in the lower stratosphere, the heterogeneous reaction HCl + HOCl is essential; the production of HOCl occurs via HO2 + ClO, with the HO2 resulting from CH2O photolysis. These results are important for assessing the impact of changes of the future stratospheric composition on the recovery of the ozone hole. Our simulations indicate that, in the lower stratosphere, future increased methane concentrations will not lead to enhanced chlorine deactivation (through the reaction CH4 + Cl → HCl + CH3) and that extreme ozone destruction to levels below ≈ 0.1 ppm will occur until mid-century.

  5. Task-Related Deactivation and Functional Connectivity of the Subgenual Cingulate Cortex in Major Depressive Disorder

    PubMed Central

    Davey, Christopher G.; Yücel, Murat; Allen, Nicholas B.; Harrison, Ben J.

    2012-01-01

    Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. Methods: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. Conclusion: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive–attentional processes. PMID:22403553

  6. Task deactivation reductions and atrophy within parietal default mode regions are overlapping but only weakly correlated in mild cognitive impairment

    PubMed Central

    Threlkeld, Zachary D.; Jicha, Greg A.; Smith, Charles D.; Gold, Brian T.

    2012-01-01

    Reduced task deactivation within regions of the default mode network (DMN) has been frequently reported in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). As task deactivations reductions become increasingly used in the study of early AD states, it is important to understand their relationship to atrophy. To address this issue, the present study compared task deactivation reductions during a lexical decision task and atrophy in aMCI, using a series of parallel voxel-wise and region-wise analyses of fMRI and structural data. Our results identified multiple regions within parietal cortex as convergence areas of task deactivation and atrophy in aMCI. Relationships between parietal regions showing overlapping task deactivation reductions and atrophy in aMCI were then explored. Regression analyses demonstrated minimal correlation between task deactivation reductions and either local or global atrophy in aMCI. In addition, a logistic regression model which combined task deactivation reductions and atrophy in parietal DMN regions showed higher classificatory accuracy of aMCI than separate task deactivation or atrophy models. Results suggest that task deactivation reductions and atrophy in parietal regions provide complementary rather than redundant information in aMCI. Future longitudinal studies will be required to assess the utility of combining task deactivation reductions and atrophy in the detection of early AD. PMID:21860094

  7. A Kappa Opioid Model of Atypical Altered Consciousness and Psychosis: U50488, DOI, AC90179 Effects on Prepulse Inhibition and Locomotion in Mice.

    PubMed

    Ruderman, Michael A; Powell, Susan B; Geyer, Mark A

    2009-07-01

    Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system - the serotonin sub-type associated with classical psychedelics - were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.

  8. Carrying the past to the future: Distinct brain networks underlie individual differences in human spatial working memory capacity.

    PubMed

    Liu, Siwei; Poh, Jia-Hou; Koh, Hui Li; Ng, Kwun Kei; Loke, Yng Miin; Lim, Joseph Kai Wei; Chong, Joanna Su Xian; Zhou, Juan

    2018-08-01

    Spatial working memory (SWM) relies on the interplay of anatomically separated and interconnected large-scale brain networks. EEG studies often observe load-associated sustained negative activity during SWM retention. Yet, whether and how such sustained negative activity in retention relates to network-specific functional activation/deactivation and relates to individual differences in SWM capacity remain to be elucidated. To cover these gaps, we recorded concurrent EEG-fMRI data in 70 healthy young adults during the Sternberg delayed-match-to-sample SWM task with three memory load levels. To a subset of participants (N = 28) that performed the task properly and had artefact-free fMRI and EEG data, we employed a novel temporo-spatial principal component analysis to derive load-dependent negative slow wave (NSW) from retention-related event-related potentials. The associations between NSW responses with SWM capacity were divergent in the higher (N = 14) and lower (N = 14) SWM capacity groups. Specifically, larger load-related increase in NSW amplitude was associated with greater SWM capacity for the higher capacity group but lower SWM capacity for the lower capacity group. Furthermore, for the higher capacity group, larger NSW amplitude was related to greater activation in bilateral parietal areas of the fronto-parietal network (FPN) and greater deactivation in medial frontal gyrus and posterior mid-cingulate cortex of the default mode network (DMN) during retention. In contrast, the lower capacity group did not show similar pattern. Instead, greater NSW was linked to higher deactivation in right posterior middle temporal gyrus. Our findings shed light on the possible differential EEG-informed neural network mechanism during memory maintenance underlying individual differences in SWM capacity. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Specialization in the default mode: Task-induced brain deactivations dissociate between visual working memory and attention.

    PubMed

    Mayer, Jutta S; Roebroeck, Alard; Maurer, Konrad; Linden, David E J

    2010-01-01

    The idea of an organized mode of brain function that is present as default state and suspended during goal-directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task-induced deactivations across a wide range of cognitive tasks. In this event-related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task-induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention-selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM-selective deactivations were found predominantly in the right hemisphere including the medial-parietal, the lateral temporo-parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task-specific functional connectivity. These findings demonstrate that task-induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand ("the core DMN") and a part whose deactivation depends on the specific task. 2009 Wiley-Liss, Inc.

  10. Attention supports verbal short-term memory via competition between dorsal and ventral attention networks.

    PubMed

    Majerus, Steve; Attout, Lucie; D'Argembeau, Arnaud; Degueldre, Christian; Fias, Wim; Maquet, Pierre; Martinez Perez, Trecy; Stawarczyk, David; Salmon, Eric; Van der Linden, Martial; Phillips, Christophe; Balteau, Evelyne

    2012-05-01

    Interactions between the neural correlates of short-term memory (STM) and attention have been actively studied in the visual STM domain but much less in the verbal STM domain. Here we show that the same attention mechanisms that have been shown to shape the neural networks of visual STM also shape those of verbal STM. Based on previous research in visual STM, we contrasted the involvement of a dorsal attention network centered on the intraparietal sulcus supporting task-related attention and a ventral attention network centered on the temporoparietal junction supporting stimulus-related attention. We observed that, with increasing STM load, the dorsal attention network was activated while the ventral attention network was deactivated, especially during early maintenance. Importantly, activation in the ventral attention network increased in response to task-irrelevant stimuli briefly presented during the maintenance phase of the STM trials but only during low-load STM conditions, which were associated with the lowest levels of activity in the dorsal attention network during encoding and early maintenance. By demonstrating a trade-off between task-related and stimulus-related attention networks during verbal STM, this study highlights the dynamics of attentional processes involved in verbal STM.

  11. INACTIVATION OF E. COLI PYRUVATE FORMATE-LYASE: ROLE OF AdhE AND SMALL MOLECULES

    PubMed Central

    Nnyepi, Mbako R.; Peng, Yi; Broderick, Joan B.

    2007-01-01

    E. coli AdhE has been reported to harbor three distinct enzymatic activities: alcohol dehydrogenase, acetaldehyde-CoA dehydrogenase, and pyruvate formate-lyase (PFL) deactivase. Herein we report on the cloning, expression, and purification of E. coli AdhE, and the re-investigation of its purported enzymatic activities. While both the alcohol dehydrogenase and acetaldehyde-CoA dehydrogenase activities were readily detectible, we were unable to obtain any evidence for catalytic deactivation of PFL by AdhE, regardless of whether the reported cofactors for deactivation (Fe(II), NAD, and CoA) were present. Our results demonstrate that AdhE is not a PFL deactivating enzyme. We have also examined the potential for deactivation of active PFL by small-molecule thiols. Both β-mercaptoethanol and dithiothreitol deactivate PFL efficiently, with the former providing quite rapid deactivation. PFL deactivated by these thiols can be reactivated, suggesting that this deactivation is non-destructive transfer of an H atom equivalent to quench the glycyl radical. PMID:17280641

  12. 49 CFR 192.727 - Abandonment or deactivation of facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Abandonment or deactivation of facilities. 192.727... Abandonment or deactivation of facilities. (a) Each operator shall conduct abandonment or deactivation of... pipeline facility or each abandoned onshore pipeline facility that crosses over, under or through a...

  13. 14 CFR 121.374 - Continuous airworthiness maintenance program (CAMP) for two-engine ETOPS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Continuous airworthiness maintenance...: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.374 Continuous airworthiness maintenance program (CAMP) for two...

  14. 14 CFR 121.374 - Continuous airworthiness maintenance program (CAMP) for two-engine ETOPS.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Continuous airworthiness maintenance...: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.374 Continuous airworthiness maintenance program (CAMP) for two...

  15. 14 CFR 121.374 - Continuous airworthiness maintenance program (CAMP) for two-engine ETOPS.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Continuous airworthiness maintenance...: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.374 Continuous airworthiness maintenance program (CAMP) for two...

  16. 14 CFR 121.374 - Continuous airworthiness maintenance program (CAMP) for two-engine ETOPS.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Continuous airworthiness maintenance...: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.374 Continuous airworthiness maintenance program (CAMP) for two...

  17. 14 CFR 121.374 - Continuous airworthiness maintenance program (CAMP) for two-engine ETOPS.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Continuous airworthiness maintenance...: CERTIFICATION AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Maintenance, Preventive Maintenance, and Alterations § 121.374 Continuous airworthiness maintenance program (CAMP) for two...

  18. Family Mode Deactivation Therapy Results and Implications

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.

    2006-01-01

    This article highlights the inclusion of Mode Deactivation Therapy as a treatment modality for families in crisis. As an empirically validated treatment, Mode Deactivation Therapy has been effective in treating a wide variety of psychological issues. Mode Deactivation Therapy, (MDT) was developed to treat adolescents with disorders of conduct…

  19. Changes in default mode network as automaticity develops in a categorization task.

    PubMed

    Shamloo, Farzin; Helie, Sebastien

    2016-10-15

    The default mode network (DMN) is a set of brain regions in which blood oxygen level dependent signal is suppressed during attentional focus on the external environment. Because automatic task processing requires less attention, development of automaticity in a rule-based categorization task may result in less deactivation and altered functional connectivity of the DMN when compared to the initial learning stage. We tested this hypothesis by re-analyzing functional magnetic resonance imaging data of participants trained in rule-based categorization for over 10,000 trials (Helie et al., 2010) [12,13]. The results show that some DMN regions are deactivated in initial training but not after automaticity has developed. There is also a significant decrease in DMN deactivation after extensive practice. Seed-based functional connectivity analyses with the precuneus, medial prefrontal cortex (two important DMN regions) and Brodmann area 6 (an important region in automatic categorization) were also performed. The results show increased functional connectivity with both DMN and non-DMN regions after the development of automaticity, and a decrease in functional connectivity between the medial prefrontal cortex and ventromedial orbitofrontal cortex. Together, these results further support the hypothesis of a strategy shift in automatic categorization and bridge the cognitive and neuroscientific conceptions of automaticity in showing that the reduced need for cognitive resources in automatic processing is accompanied by a disinhibition of the DMN and stronger functional connectivity between DMN and task-related brain regions. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Brain activation during working memory is altered in patients with type 1 diabetes during hypoglycemia.

    PubMed

    Bolo, Nicolas R; Musen, Gail; Jacobson, Alan M; Weinger, Katie; McCartney, Richard L; Flores, Veronica; Renshaw, Perry F; Simonson, Donald C

    2011-12-01

    To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA(1c) was associated with lower activation in the right parahippocampal gyrus and amygdala (R(2) = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes.

  1. Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.

    PubMed

    Tan, Peter S; Perry, Matthew D; Ng, Chai Ann; Vandenberg, Jamie I; Hill, Adam P

    2012-09-01

    Human ether-a-go-go-related gene (hERG) potassium channels exhibit unique gating kinetics characterized by unusually slow activation and deactivation. The N terminus of the channel, which contains an amphipathic helix and an unstructured tail, has been shown to be involved in regulation of this slow deactivation. However, the mechanism of how this occurs and the connection between voltage-sensing domain (VSD) return and closing of the gate are unclear. To examine this relationship, we have used voltage-clamp fluorometry to simultaneously measure VSD motion and gate closure in N-terminally truncated constructs. We report that mode shifting of the hERG VSD results in a corresponding shift in the voltage-dependent equilibrium of channel closing and that at negative potentials, coupling of the mode-shifted VSD to the gate defines the rate of channel closure. Deletion of the first 25 aa from the N terminus of hERG does not alter mode shifting of the VSD but uncouples the shift from closure of the cytoplasmic gate. Based on these observations, we propose the N-terminal tail as an adaptor that couples voltage sensor return to gate closure to define slow deactivation gating in hERG channels. Furthermore, because the mode shift occurs on a time scale relevant to the cardiac action potential, we suggest a physiological role for this phenomenon in maximizing current flow through hERG channels during repolarization.

  2. Identification and root cause analysis of cell culture media precipitates in the viral deactivation treatment with high-temperature/short-time method.

    PubMed

    Cao, Xiaolin; Stimpfl, Gregory; Wen, Zai-Qing; Frank, Gregory; Hunter, Glenn

    2013-01-01

    High-temperature/short-time (HTST) treatment of cell culture media is one of the proven techniques used in the biopharmaceutical manufacturing industry for the prevention and mitigation of media viral contamination. With the HTST method, the formulated media is pasteurized (virus-deactivated) by heating and pumping the media continuously through the preset high-temperature holding tubes to achieve a specified period of time at a specific temperature. Recently, during the evaluation and implementation of HTST method in multiple Amgen, Inc. manufacturing facilities, media precipitates were observed in the tests of HTST treatments. The media precipitates may have adverse consequences such as clogging the HTST system, altering operating conditions and compromising the efficacy of viral deactivation, and ultimately affecting the media composition and cell growth. In this study, we report the identification of the composition of media precipitates from multiple media HTST runs using combined microspectroscopic methods including Raman, Fourier transform infrared spectroscopy, and scanning electron microscopy with energy-dispersive X-ray spectroscopy. The major composition in the precipitates was determined to be metal phosphates, including calcium phosphate, magnesium phosphate, and iron (III) phosphate. Based on the composition, stoichiometry, and root-cause study of media precipitations, methods were implemented for the mitigation and prevention of the occurrence of the media precipitation. Viral contamination in cell culture media is an important issue in the biopharmaceutical manufacturing industry and may have serious consequences on product quality, efficacy, and safety. High-temperature/short-time (HTST) treatment of cell culture media is one of the proven techniques used in the industry for the prevention and mitigation of media viral contamination. With the HTST method, the formulated media is pasteurized (virus-deactivated) by heating at preset conditions. This paper provides the identification and root-cause study of the media precipitates that adversely affected the HTST process and discusses the possible solutions to mitigate the precipitation problem.

  3. 14 CFR 91.421 - Rebuilt engine maintenance records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Rebuilt engine maintenance records. 91.421..., Preventive Maintenance, and Alterations § 91.421 Rebuilt engine maintenance records. (a) The owner or operator may use a new maintenance record, without previous operating history, for an aircraft engine...

  4. 14 CFR 91.421 - Rebuilt engine maintenance records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Rebuilt engine maintenance records. 91.421..., Preventive Maintenance, and Alterations § 91.421 Rebuilt engine maintenance records. (a) The owner or operator may use a new maintenance record, without previous operating history, for an aircraft engine...

  5. 1995 solid waste 30-year characteristics volume summary

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

    Templeton, K.J.; DeForest, T.J.; Rice, G.I.

    1995-10-01

    The Hanford Site has been designated by the US Department of Energy (DOE) to store, treat, and dispose of solid waste received from both onsite and offsite generators. This waste is currently or planned to be generated from ongoing operations, maintenance and deactivation activities, decontamination and decommissioning (D&D) of facilities, and environmental restoration (ER) activities. This document, prepared by Pacific Northwest Laboratory (PNL) under the direction of Westinghouse Hanford Company (WHC), describes the characteristics of the waste to be shipped to Hanford`s SWOC. The physical waste forms and hazardous constituents are described for the low-level mixed waste (LLMW) and themore » transuranic - transuranic mixed waste (TW{underscore}TRUM).« less

  6. Attention Network Dysfunction in Bulimia Nervosa - An fMRI Study

    PubMed Central

    Dahmen, Brigitte; Schulte-Rüther, Martin; Legenbauer, Tanja; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2016-01-01

    Objective Recent evidence has suggested an increased rate of comorbid ADHD and subclinical attentional impairments in bulimia nervosa (BN) patients. However, little is known regarding the underlying neural mechanisms of attentional functions in BN. Method Twenty BN patients and twenty age- and weight-matched healthy controls (HC) were investigated using a modified version of the Attention Network Task (ANT) in an fMRI study. This design enabled an investigation of the neural mechanisms associated with the three attention networks involved in alerting, reorienting and executive attention. Results The BN patients showed hyperactivation in parieto-occipital regions and reduced deactivation of default-mode-network (DMN) areas during alerting compared with HCs. Posterior cingulate activation during alerting correlated with the severity of eating-disorder symptoms within the patient group. Conversely, BN patients showed hypoactivation during reorienting and executive attention in anterior cingulate regions, the temporo-parietal junction (TPJ) and parahippocampus compared with HCs, which was negatively associated with global ADHD symptoms and impulsivity, respectively. Discussion Our findings demonstrate altered brain mechanisms in BN associated with all three attentional networks. Failure to deactivate the DMN and increased parieto-occipital activation required for alerting might be associated with a constant preoccupation with food or body image-related thoughts. Hypoactivation of executive control networks and TPJ might increase the likelihood of inattentive and impulsive behaviors and poor emotion regulation. Thus, dysfunction in the attentional network in BN goes beyond an altered executive attentional domain and needs to be considered in the diagnosis and treatment of BN. PMID:27607439

  7. SA54. The Structure of Embodied Emotions in Schizophrenia

    PubMed Central

    Hong, Seok Jin; Snodgress, Matthew A.; Nichols, Heathman S.; Nummenmaa, Lauri; Glerean, Enrico; Park, Sohee

    2017-01-01

    Abstract Background: Past research suggests a disconnection between experienced emotions and bodily sensations in individuals with schizophrenia (SZ), but mechanisms underlying abnormal embodiment of emotions in SZ are unknown. There might be an overall reduction in emotion-related bodily sensations, but it is also possible that the spatial distribution of bodily sensations associated with emotions may be altered in SZ. We hypothesized the presence of a more coherent underlying structure giving rise to embodied emotions in healthy controls (HC) compared to SZ. Methods: Fifteen SZ and 15 demographically matched HC (bootstrapped from a possible 300 HC) were asked to complete the emBODY task (Nummenmaa et al., 2014). In the emBODY task, participants were asked to shade in where they felt sensations (activation and deactivation) on the outline of a human body when presented with an emotion word. Fourteen emotion words were presented sequentially. From activation and deactivation data, body maps of emotions were generated and 2 separate principal components analyses (PCA) were conducted, one for each group to determine the multivariate structure of embodied emotions. Results: The pattern of principal components for HC differed significantly from that of the SZ group. SZ showed more diffuse components with lesser magnitude than the HC. Moreover, the variance that accounts for these dimensions was significantly reduced for SZ. This suggests anomalous embodied emotion in SZ. In this PCA framework, a particular set of innate constructs is thought to yield the activation and deactivation maps of emotions on the body. Our results imply that the complexity of this set in SZ is highly deviant from that of the HC. Conclusion: Quantitative modeling of the underlying structure of self-reported embodied emotion provided novel insight into altered emotional experience in SZ. Our findings illustrate radically different bodily maps of emotions in SZ compared to HC. Bodily sensations are not only different in intensity but also in where they are felt in SZ. While an important first step, our analysis was exploratory and limited by the small sample size. Future direction includes probing the specific contents of the underlying dimensions that give rise to embodied emotions.

  8. Comparison of Methodologies of Activation Barrier Measurements for Reactions with Deactivation

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

    Xie, Zhenhua; Yan, Binhang; Zhang, Li

    In this work, methodologies of activation barrier measurements for reactions with deactivation were theoretically analyzed. Reforming of ethane with CO 2 was introduced as an example for reactions with deactivation to experimentally evaluate these methodologies. Both the theoretical and experimental results showed that due to catalyst deactivation, the conventional method would inevitably lead to a much lower activation barrier, compared to the intrinsic value, even though heat and mass transport limitations were excluded. In this work, an optimal method was identified in order to provide a reliable and efficient activation barrier measurement for reactions with deactivation.

  9. Comparison of Methodologies of Activation Barrier Measurements for Reactions with Deactivation

    DOE PAGES

    Xie, Zhenhua; Yan, Binhang; Zhang, Li; ...

    2017-01-25

    In this work, methodologies of activation barrier measurements for reactions with deactivation were theoretically analyzed. Reforming of ethane with CO 2 was introduced as an example for reactions with deactivation to experimentally evaluate these methodologies. Both the theoretical and experimental results showed that due to catalyst deactivation, the conventional method would inevitably lead to a much lower activation barrier, compared to the intrinsic value, even though heat and mass transport limitations were excluded. In this work, an optimal method was identified in order to provide a reliable and efficient activation barrier measurement for reactions with deactivation.

  10. A thorough investigation of the progressive reset dynamics in HfO{sub 2}-based resistive switching structures

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

    Lorenzi, P., E-mail: lorenzi@die.uniroma1.it; Rao, R.; Irrera, F.

    2015-09-14

    According to previous reports, filamentary electron transport in resistive switching HfO{sub 2}-based metal-insulator-metal structures can be modeled using a diode-like conduction mechanism with a series resistance. Taking the appropriate limits, the model allows simulating the high (HRS) and low (LRS) resistance states of the devices in terms of exponential and linear current-voltage relationships, respectively. In this letter, we show that this simple equivalent circuit approach can be extended to represent the progressive reset transition between the LRS and HRS if a generalized logistic growth model for the pre-exponential diode current factor is considered. In this regard, it is demonstrated heremore » that a Verhulst logistic model does not provide accurate results. The reset dynamics is interpreted as the sequential deactivation of multiple conduction channels spanning the dielectric film. Fitting results for the current-voltage characteristics indicate that the voltage sweep rate only affects the deactivation rate of the filaments without altering the main features of the switching dynamics.« less

  11. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... provisions of paragraph (g) of this section, the Administrator may approve a certificate holder under Part... Administrator; and (3) Perform any inspection required by part 91 or part 125 of this chapter on aircraft it..., and alterations. (k) Updates of databases in installed avionics meeting the conditions of this...

  12. PUREX/UO3 Facilities deactivation lessons learned history

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

    Gerber, M.S.

    1996-09-19

    Disconnecting the criticality alarm permanently in June 1996 signified that the hazards in the PUREX (plutonium-uranium extraction) plant had been so removed and reduced that criticality was no longer a credible event. Turning off the PUREX criticality alarm also marked a salient point in a historic deactivation project, 1 year before its anticipated conclusion. The PUREX/UO3 Deactivation Project began in October 1993 as a 5-year, $222.5- million project. As a result of innovations implemented during 1994 and 1995, the project schedule was shortened by over a year, with concomitant savings. In 1994, the innovations included arranging to send contaminated nitricmore » acid from the PUREX Plant to British Nuclear Fuels, Limited (BNFL) for reuse and sending metal solutions containing plutonium and uranium from PUREX to the Hanford Site tank farms. These two steps saved the project $36.9- million. In 1995, reductions in overhead rate, work scope, and budget, along with curtailed capital equipment expenditures, reduced the cost another $25.6 million. These savings were achieved by using activity-based cost estimating and applying technical schedule enhancements. In 1996, a series of changes brought about under the general concept of ``reengineering`` reduced the cost approximately another $15 million, and moved the completion date to May 1997. With the total savings projected at about $75 million, or 33.7 percent of the originally projected cost, understanding how the changes came about, what decisions were made, and why they were made becomes important. At the same time sweeping changes in the cultural of the Hanford Site were taking place. These changes included shifting employee relations and work structures, introducing new philosophies and methods in maintaining safety and complying with regulations, using electronic technology to manage information, and, adopting new methods and bases for evaluating progress. Because these changes helped generate cost savings and were accompanied by and were an integral part of sweeping ``culture changes,`` the story of the lessons learned during the PUREX Deactivation Project are worth recounting. Foremost among the lessons is recognizing the benefits of ``right to left`` project planning. A deactivation project must start by identifying its end points, then make every task, budget, and organizational decision based on reaching those end points. Along with this key lesson is the knowledge that project planning and scheduling should be tied directly to costing, and the project status should be checked often (more often than needed to meet mandated reporting requirements) to reflect real-time work. People working on a successful project should never be guessing about its schedule or living with a paper schedule that does not represent the actual state of work. Other salient lessons were learned in the PUREX/UO3 Deactivation Project that support these guiding principles. They include recognizing the value of independent review, teamwork, and reengineering concepts; the need and value of cooperation between the DOE, its contractors, regulators, and stakeholders; and the essential nature of early and ongoing communication. Managing a successful project also requires being willing to take a fresh look at safety requirements and to apply them in a streamlined and sensible manner to deactivating facilities; draw on the enormous value of resident knowledge acquired by people over years and sometimes decades of working in old plants; and recognize the value of bringing in outside expertise for certain specialized tasks.This approach makes possible discovering the savings that can come when many creative options are pursued persistently and the wisdom of leaving some decisions to the future. The essential job of a deactivation project is to place a facility in a safe, stable, low-maintenance mode, for an interim period. Specific end points are identified to recognize and document this state. Keeping the limited objectives of the project in mind can guide decisions that reduce risks with minimal manipulation of physical materials, minimal waste generation, streamline regulations and safety requirements where possible, and separate the facility from ongoing entanglements with operating systems. Thus, the ``parked car`` state is achieved quickly and directly. The PUREX Deactivation Lessons Learned History was first issued in January 1995. Since then, several key changes have occurred in the project, making it advisable to revise and update the document. This document is organized with the significant lessons learned captured at the end of each section, and then recounted in Section 11.0, ``Lessons Consolidated.`` It is hoped and believed that the lessons learned on the PUREX Deactivation Project will have value to other facilities both inside and outside the DOE complex.« less

  13. 14 CFR 145.209 - Repair station manual contents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...; (g) Procedures for maintenance, preventive maintenance, or alterations performed under § 145.205; (h)Procedures for— (1) Maintaining and revising the contract maintenance information required by § 145.217(a)(2...) Maintaining and revising the contract maintenance information required by § 145.217(a)(2)(ii) and notifying...

  14. Automated Activation and Deactivation of a System Under Test

    NASA Technical Reports Server (NTRS)

    Poff, Mark A.

    2006-01-01

    The MPLM Automated Activation/Deactivation application (MPLM means Multi-Purpose Logistic Module) was created with a three-fold purpose in mind: 1. To reduce the possibility of human error in issuing commands to, or interpreting telemetry from, the MPLM power, computer, and environmental control systems; 2. To reduce the amount of test time required for the repetitive activation/deactivation processes; and 3. To reduce the number of on-console personnel required for activation/ deactivation. All of these have been demonstrated with the release of the software. While some degree of automated end-item commanding had previously been performed for space-station hardware in the test environment, none approached the functionality and flexibility of this application. For MPLM activation, it provides mouse-click selection of the hardware complement to be activated, activates the desired hardware and verifies proper feedbacks, and alerts the user when telemetry indicates an error condition or manual intervention is required. For MPLM deactivation, the product senses which end items are active and deactivates them in the proper sequence. For historical purposes, an on-line log is maintained of commands issued and telemetry points monitored. The benefits of the MPLM Automated Activation/ Deactivation application were demonstrated with its first use in December 2002, when it flawlessly performed MPLM activation in 8 minutes (versus as much as 2.4 hours for previous manual activations), and performed MPLM deactivation in 3 minutes (versus 66 minutes for previous manual deactivations). The number of test team members required has dropped from eight to four, and in actuality the software can be operated by a sole (knowledgeable) system engineer.

  15. Reproduction alters oxidative status when it is traded-off against longevity.

    PubMed

    Beaulieu, Michaël; Geiger, Rina E; Reim, Elisabeth; Zielke, Luisa; Fischer, Klaus

    2015-07-01

    Oxidative stress has been proposed to mediate one of the most important aspects of life-history evolution: the trade-off between reproduction and self-maintenance. However, empirical studies have cast doubt on the generality of this intriguing notion. Here, we hypothesize that reproduction alters oxidative status only when a trade-off between reproduction and self-maintenance occurs. Accordingly, in female Bicyclus anynana butterflies, we found that reproduction affected oxidative markers only under challenging thermal conditions that made the trade-off between reproduction and longevity emerge. Interestingly, under such conditions, butterflies favored longevity over reproduction, suggesting that self-maintenance mechanisms were activated. Accordingly, butterflies reproducing under challenging thermal conditions exhibited enhanced antioxidant defenses and stable oxidative damage. Altogether, our results indicate that a trade-off between reproduction and self-maintenance is indeed a necessary condition for reproduction to alter oxidative status, and that the effects of such a trade-off on oxidative status depend on whether priority is given to self-maintenance or reproduction. Assessing the existence of the trade-off between self-maintenance and reproduction, and whether self-maintenance is prioritized relative to reproduction is therefore crucial for understanding variation in oxidative status in reproducing animals, which may clarify the general implication of oxidative stress in the resolution of life-history trade-offs. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  16. Serum resistance to singlet oxygen in patients with diabetes mellitus in comparison to healthy donors.

    PubMed

    Lhommeau, Isabelle; Douillard, Samuel; Bigot, Edith; Benoit, Isabelle; Krempf, Michel; Patrice, Thierry

    2011-09-01

    Diabetes mellitus causes endothelial injury through oxidative stress involving reactive oxygen species and peroxides as well as inflammation, both of which consume antioxidant defenses. Singlet oxygen ((1)O(2)) is produced by leukocytes during inflammatory and biochemical reactions and deactivated by producing reactive oxygen species and peroxides. To determine whether serum was capable of deactivating (1)O(2), we triggered a photo reaction in sera from 53 healthy donors and 52 diabetic patients. Immediately after light delivery, dichlorofluorescein was added and then its fluorescence was recorded. The mean capacity of (1)O(2) or secondary oxidant deactivation was reduced in patients with diabetes mellitus. Hemolysis reduced deactivation of (1)O(2)-induced secondary oxidants in both healthy and diabetic patients. Body mass index, age, platelet counts, and blood cell numbers exerted a nonlinear influence. High levels of glycated hemoglobin were associated with an increased deactivation of oxidative species, whereas high-density lipoprotein cholesterol, total cholesterol, and the total cholesterol to high-density lipoprotein cholesterol ratio decreased the serum deactivation capacity. Oral antidiabetics bore no influence on deactivation, which was restored by insulin in women. Deactivation capacity was lower in women, who had half the complications found in men, suggesting that, with more severe diabetes mellitus, protection was maintained against complications. Resistance to (1)O(2) should be considered during the monitoring of diabetes mellitus. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... maintenance are a result of a known or suspected mechanical difficulty or malfunction that occurred en route... is authorized in writing by the certificate holder for each item of preventive maintenance that the... satisfactorily completed an approved training program and is authorized in writing by the certificate holder to...

  18. Deactivation of cellulases by phenols

    USDA-ARS?s Scientific Manuscript database

    Pretreatment of lignocellulosic materials may result in the release of inhibitors and deactivators of cellulose enzyme hydrolysis. We report the identification of phenols with major inhibition and/or deactivation effect on enzymes used for conversion of cellulose to ethanol. The inhibition effects w...

  19. Deactivation of implantable cardioverter defibrillators in terminal illness and end of life care.

    PubMed

    Kirkpatrick, James N; Gottlieb, Maia; Sehgal, Priya; Patel, Rutuke; Verdino, Ralph J

    2012-01-01

    Cardiology professional societies have recommended that patients with cardiovascular implantable electronic devices complete advance directives (ADs). However, physicians rarely discuss end of life handling of implantable cardioverter defibrillators (ICDs), and standard AD forms do not address the presence of ICDs. We conducted a telephone survey of 278 patients with an ICD from a large, academic hospital. The average period since implantation was 5.15 years. More than 1/3 (38%) had been shocked, with a mean of 4.69 shocks. More than 1/2 had executed an AD, but only 3 had included a plan for their ICD. Most subjects (86%) had never considered what to do with their ICD if they had a serious illness and were unlikely to survive. When asked about ICD deactivation in an end of life situation, 42% said it would depend, 28% favored deactivation, and 11% would not deactivate. One quarter (26%) thought ICD deactivation was a form of assisted suicide, 22% thought a do not resuscitate order did not mean that the ICD should be deactivated, and 46% responded that the ICD should not be automatically deactivated in hospice. The answers did not correlate with any demographic factors. Almost all (95%) agreed that patients should have the opportunity to execute an AD that directs handing of an ICD. When asked who should be responsible for discussing this device for an AD, 31% said electrophysiologists, 45% said general cardiologists, and 14% said primary care physicians. In conclusion, the results of the present study highlight the lack of consensus among patients with an ICD on the issue of deactivation at the end of a patient's life. These findings suggest cardiologists should discuss end of life care and device deactivation with their patients with an ICD. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Neural correlates of reward processing in healthy siblings of patients with schizophrenia

    PubMed Central

    Hanssen, Esther; van der Velde, Jorien; Gromann, Paula M.; Shergill, Sukhi S.; de Haan, Lieuwe; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André; van Atteveldt, Nienke

    2015-01-01

    Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning. PMID:26441601

  1. Dynamic range in BOLD modulation: lifespan aging trajectories and association with performance.

    PubMed

    Kennedy, Kristen M; Boylan, Maria A; Rieck, Jenny R; Foster, Chris M; Rodrigue, Karen M

    2017-12-01

    Alteration of dynamic range of modulation to cognitive difficulty has been proposed as a salient predictor of cognitive aging. Here, we examine in 171 adults (aged 20-94 years) the effects of age on dynamic modulation of blood oxygenation-level dependent activation to difficulty in parametrically increasing working memory (WM) load (0-, 2-, 3-, and 4-back conditions). First, we examined parametric increases and decreases in activation to increasing WM load (positive modulation effect and negative modulation effect). Second, we examined the effect of age on modulation to difficulty (WM load) to identify regions that differed with age as difficulty increased (age-related positive and negative modulation effects). Weakened modulation to difficulty with age was found in both the positive modulation (middle frontal, superior/inferior parietal) and negative modulation effect (deactivated) regions (insula, cingulate, medial superior frontal, fusiform, and parahippocampal gyri, hippocampus, and lateral occipital cortex). Age-related alterations to positive modulation emerged later in the lifespan than negative modulation. Furthermore, these effects were significantly coupled in that greater upmodulation was associated with lesser downmodulation. Importantly, greater fronto-parietal upmodulation to difficulty and greater downmodulation of deactivated regions were associated with better task accuracy and upmodulation with better WM span measured outside the scanner. These findings suggest that greater dynamic range of modulation of activation to cognitive challenge is in service of current task performance, as well as generalizing to cognitive ability beyond the scanner task, lending support to its utility as a marker of successful cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A Longitudinal Mapping Study on Cortical Plasticity of Peripheral Nerve Injury Treated by Direct Anastomosis and Electroacupuncture in Rats.

    PubMed

    Wu, Jia-Jia; Lu, Ye-Chen; Hua, Xu-Yun; Ma, Shu-Jie; Xu, Jian-Guang

    2018-06-01

    We used functional magnetic resonance imaging to provide a longitudinal description of cortical plasticity caused by electroacupuncture (EA) of sciatic nerve transection and direct anastomosis in rats. Sixteen rats in a sciatic nerve transection and direct anastomosis model were randomly divided into intervention and control groups. EA intervention in the position of ST-36, GB-30 was conducted continuously for 4 months in the intervention group. Functional magnetic resonance imaging and gait assessment were performed every month after intervention. The somatosensory area was more activated in the first 2 months and then deactivated in the rest 2 months when EA was applied. The pain-related areas had the same activation pattern as the somatosensory area. The limbic/paralimbic areas fluctuated more during the EA intervention, which was not constantly activated or deactivated as previous studies reported. We attributed such changes in somatosensory and pain-related areas to the gradual reduction of sensory afferentation. The alterations in limbic/paralimbic system might be associated with the confrontation between the upregulating effect of paresthesia or pain and the downregulating effect of EA intervention through the autonomic nerve system. The gait analysis showed significantly higher maximum contact mean intensity in the intervention group. The alterations in the brain brought about by the long-term therapeutic effect of EA could be described as a synchronized activation pattern in the somatosensory and pain-related areas and a fluctuating pattern in the limbic/paralimbic system. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    NONE

    The High Ranking Facilities Deactivation Project (HRFDP), commissioned by the US Department of Energy Nuclear Materials and Facility Stabilization Program, is to place four primary high-risk surplus facilities with 28 associated ancillary facilities at Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition as rapidly and economically as possible. The facilities will be deactivated and left in a condition suitable for an extended period of minimized surveillance and maintenance (S and M) prior to decontaminating and decommissioning (D and D). These four facilities include two reactor facilities containing spent fuel. One of these reactor facilities also containsmore » 55 tons of sodium with approximately 34 tons containing activated sodium-22, 2.5 tons of lithium hydride, approximately 100 tons of potentially contaminated lead, and several other hazardous materials as well as bulk quantities of contaminated scrap metals. The other two facilities to be transferred include a facility with a bank of hot cells containing high levels of transferable contamination and also a facility containing significant quantities of uranyl nitrate and quantities of transferable contamination. This work plan documents the objectives, technical requirements, and detailed work plans--including preliminary schedules, milestones, and conceptual FY 1996 cost estimates--for the Oak Ridge National Laboratory (ORNL). This plan has been developed by the Environmental Restoration (ER) Program of Lockheed Martin Energy Systems (Energy Systems) for the US Department of Energy (DOE) Oak Ridge Operations Office (ORO).« less

  4. Structure of the Deactive State of Mammalian Respiratory Complex I.

    PubMed

    Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

    2018-02-06

    Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Combined abuse of clonidine and amitriptyline in a patient on buprenorphine maintenance treatment.

    PubMed

    Seale, J Paul; Dittmer, Trent; Sigman, Erika J; Clemons, Holly; Johnson, J Aaron

    2014-01-01

    Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed.

  6. 49 CFR 195.59 - Abandonment or deactivation of facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Abandonment or deactivation of facilities. 195.59... Abandonment or deactivation of facilities. For each abandoned offshore pipeline facility or each abandoned onshore pipeline facility that crosses over, under or through a commercially navigable waterway, the last...

  7. Plasma flux-dependent lipid A deactivation

    NASA Astrophysics Data System (ADS)

    Chang, Hung-Wen; Hsu, Cheng-Che; Ahmed, Musahid; Liu, Suet Yi; Fang, Yigang; Seog, Joonil; Oehrlein, Gottlieb S.; Graves, David B.

    2014-06-01

    This paper reports the influence of gas plasma flux on endotoxin lipid A film deactivation. To study the effect of the flux magnitude of reactive species, a modified low-pressure inductively coupled plasma (ICP) with O radical flux ˜1016 cm-2 s-1 was used. After ICP exposures, it was observed that while the Fourier transform infrared absorbance of fatty chains responsible for the toxicity drops by 80% through the film, no obvious film endotoxin deactivation is seen. This is in contrast to that previously observed under low flux exposure conducted in a vacuum beam system: near-surface only loss of fatty chains led to significant film deactivation. Secondary ion mass spectrometry characterization of changes at the film surface did not appear to correlate with the degree of deactivation. Lipid A films need to be nearly completely removed in order to detect significant deactivation under high flux conditions. Additional high reactive species flux experiments were conducted using an atmospheric pressure helium plasma jet and a UV/ozone device. Exposure of lipid A films to reactive species with these devices showed similar deactivation behaviour. The causes for the difference between low and high flux exposures may be due to the nature of near-surface structural modifications as a function of the rate of film removal.

  8. Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

    NASA Technical Reports Server (NTRS)

    Fadel, P. J.; Stromstad, M.; Hansen, J.; Sander, M.; Horn, K.; Ogoh, S.; Smith, M. L.; Secher, N. H.; Raven, P. B.

    2001-01-01

    We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

  9. Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness.

    PubMed

    Fadel, P J; Stromstad, M; Hansen, J; Sander, M; Horn, K; Ogoh, S; Smith, M L; Secher, N H; Raven, P B

    2001-06-01

    We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

  10. Role of basic and acidic centers of MgO and modified MgO in catalytic transfer hydrogenation of ketones studied by infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Szöllösi, György; Bartók, Mihály

    1999-05-01

    In this study our aim was to identify the active sites and the surface species responsible for deactivation of MgO during catalytic transfer hydrogenations (CTH) of ketones using alcohols as hydrogen donors. Our previous studies showed that deactivation of MgO could be prevented by previous treatment with chloromethanes. Therefore the surface species formed during the reaction were studied before and after treatment with chloroform or chloroform- d by in situ infrared spectroscopy (IR). As a result, it was concluded that the reaction requires the presence of surface basic and acidic centers. The presence of Lewis acid centers was not necessary, the reaction could proceed on weakly acidic surface Brönsted sites, as the alterations in intensity and position of the ν(OH) bands indicated. Modification with chloroform resulted also in the generation of surface OH groups with a proper acidity for the reaction. The shift in carbonyl vibrations led us to the conclusion that Lewis acid and base centers were responsible for the catalyst poisoning, so covering these acid sites by Cl - led to a stable catalyst.

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

    Tomasi, D.; Fowler, J.; Tomasi, D.

    Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [{sup 11}C]cocaine used as DAT radiotracer)more » and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.« less

  12. Selective inhibition of deactivated mitochondrial complex I by biguanides.

    PubMed

    Matsuzaki, Satoshi; Humphries, Kenneth M

    2015-03-24

    Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate-limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates but is rapidly and fully reversed to the active state in the presence of NADH. The objective of this study was to determine the relative sensitivity of active/de-active complex I to biguanide-mediated inhibition and resulting superoxide radical (O₂(•⁻)) production. Using isolated rat heart mitochondria, we show that deactivation of complex I sensitizes it to metformin and phenformin (4- and 3-fold, respectively), but not to other known complex I inhibitors, such as rotenone. Mitochondrial O₂(•⁻) production by deactivated complex I was measured fluorescently by NADH-dependent 2-hydroxyethidium formation at alkaline pH to impede reactivation. Superoxide production was 260.4% higher than in active complex I at pH 9.4. However, phenformin treatment of de-active complex I decreased O₂(•⁻) production by 14.9%, while rotenone increased production by 42.9%. Mitochondria isolated from rat hearts subjected to cardiac ischemia, a condition known to induce complex I deactivation, were sensitized to phenformin-mediated complex I inhibition. This supports the idea that the effects of biguanides are likely to be influenced by the complex I state in vivo. These results demonstrate that the complex I active and de-active states are a determinant in biguanide-mediated inhibition.

  13. 77 FR 41895 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-17

    ... bushing with a new bushing and deactivation pin, and installing a new or serviceable stowage bracket for... installation of a new bracket for stowing the deactivation pin. We are issuing this AD to prevent failure of... installing a new or serviceable stowage bracket for the deactivation pins on all airplanes powered by Pratt...

  14. 75 FR 906 - Airworthiness Directives; The Boeing Company Model 747-400, -400D, and -400F Series Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-07

    ... aircraft for which a manufacturer's maintenance manual or instructions for continued airworthiness has been... maintenance program by incorporating new airworthiness limitations (AWLs) for fuel tank systems to satisfy... latent failures, alterations, repairs, or maintenance actions, which, in combination with flammable fuel...

  15. Attention-Induced Deactivations in Very Low Frequency EEG Oscillations: Differential Localisation According to ADHD Symptom Status

    PubMed Central

    Broyd, Samantha J.; Helps, Suzannah K.; Sonuga-Barke, Edmund J. S.

    2011-01-01

    Background The default-mode network (DMN) is characterised by coherent very low frequency (VLF) brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD) signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings. Methodology/Principal Findings DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz) for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes. Conclusions/Significance Attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of VLF EEG power in temporal lobes. PMID:21408092

  16. Role of N-terminal domain and accessory subunits in controlling deactivation-inactivation coupling of Kv4.2 channels.

    PubMed

    Barghaan, Jan; Tozakidou, Magdalini; Ehmke, Heimo; Bähring, Robert

    2008-02-15

    We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2 Delta 2-10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2 Delta 2-10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs.

  17. Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment

    PubMed Central

    Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

    2014-01-01

    Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

  18. Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

  19. Rank-dependent deactivation in network evolution.

    PubMed

    Xu, Xin-Jian; Zhou, Ming-Chen

    2009-12-01

    A rank-dependent deactivation mechanism is introduced to network evolution. The growth dynamics of the network is based on a finite memory of individuals, which is implemented by deactivating one site at each time step. The model shows striking features of a wide range of real-world networks: power-law degree distribution, high clustering coefficient, and disassortative degree correlation.

  20. Patients' perception of implantable cardioverter defibrillator deactivation at the end of life.

    PubMed

    Hill, Loreena; McIlfatrick, Sonja; Taylor, Brian; Dixon, Lana; Harbinson, Mark; Fitzsimons, Donna

    2015-04-01

    Individualised care at the end of life requires professional understanding of the patient's perception of implantable cardioverter defibrillator deactivation. The aim was to evaluate the evidence on patients' perception of implantable cardioverter defibrillator deactivation at end of life. Systematic narrative review of empirical studies was published during 2008-2014. Data were collected from six databases, citations from relevant articles and expert recommendations. In all, 18 studies included with collective population of n = 5810. Concept mapping highlighted three themes: (1) Diverse preferences regarding discussion and deactivation. Deactivation was rarely discussed pre-implantation, with some studies demonstrating patients' reluctance to discuss implantable cardioverter defibrillator deactivation at any stage. Two studies found the majority of patients valued such discussions. Diversity was reflected in patients' willingness to deactivate, ranging from 12% (n = 9) in Irish cohort to 79% (n = 195) in Dutch study. (2) Ethical and legal considerations were predominant in Canadian and American literature as patients wanted to contribute but felt the decision should be a doctor's responsibility. Advance directives were uncommon in Europe, and where they existed the implantable cardioverter defibrillator was not mentioned. (3) 'Living in the now' was evident as despite deteriorating symptoms many patients maintained a positive outlook and anticipated surviving more than 10 years. Several studies asserted living longer was more important than quality of life. Patients regard the implantable cardioverter defibrillator as a complex and solely beneficial device, with little insight regarding its potential impact on a peaceful death. This review confirms the need for professionals to discuss with patients and families implantable cardioverter defibrillator functionality and deactivation at appropriate opportunities. © The Author(s) 2014.

  1. Activated Carbon-Based System for the Disposal of Psychoactive Medications

    PubMed Central

    Song, Yang; Manian, Mahima; Fowler, William; Korey, Andrew; Kumar Banga, Ajay

    2016-01-01

    The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications. PMID:27827989

  2. Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields

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

    Lerchl, A.; Nonaka, K.O.; Stokkan, K.A.

    Adult AMES mice and male Sprague Dawley rats were exposed to an artificial magnetic field, generated by Helmholtz coils. 3.5 hours after the onset of darkness the coils were activated for one hour resulting in an inversion of the horizontal component of the earth's magnetic field. The coils were activated and deactivated at 5 min intervals during the 1 hour exposure period. In both mice and rats, the levels of serotonin in the pineal were markedly increased by the exposure. In rats, an increase of pineal 5-hydroxyindole acetic acid and a decrease of the activity of the pineal enzyme serotonin-N-acetyltransferasemore » also was observed. However, pineal and serum melatonin levels were not altered. The results indicate that the metabolism of serotonin in the pineal is quickly affected by the exposure of animals to a magnetic field.« less

  3. Functional Consequences of Complementarity-determining Region Deactivation in a Multifunctional Anti-nucleic Acid Antibody*

    PubMed Central

    Lee, Jiyeon; Kim, Hye-Jin; Roh, Jooho; Seo, Youngsil; Kim, Minjae; Jun, Hye-Ryeong; Pham, Chuong D.; Kwon, Myung-Hee

    2013-01-01

    Many murine monoclonal anti-DNA antibodies (Abs) derived from mice models for systemic lupus erythematosus have additional cell-penetration and/or nucleic acid-hydrolysis properties. Here, we examined the influence of deactivating each complementarity-determining region (CDR) within a multifunctional anti-nucleic acid antibody (Ab) that possesses these activities, the catalytic 3D8 single chain variable fragment (scFv). CDR-deactivated 3D8 scFv variants were generated by replacing all of the amino acids within each CDR with Gly/Ser residues. The structure of 3D8 scFv accommodated single complete CDR deactivations. Different functional activities of 3D8 scFv were affected differently depending on which CDR was deactivated. The only exception was CDR1, located within the light chain (LCDR1); deactivation of LCDR1 abolished all of the functional activities of 3D8 scFv. A hybrid Ab, HW6/3D8L1, in which the LCDR1 from an unrelated Ab (HW6) was replaced with the LCDR1 from 3D8, acquired all activities associated with the 3D8 scFv. These results suggest that the activity of a multifunctional 3D8 scFv Ab can be modulated by single complete CDR deactivation and that the LCDR1 plays a crucial role in maintaining Ab properties. This study presents a new approach for determining the role of individual CDRs in multifunctional Abs with important implications for the future of Ab engineering. PMID:24155236

  4. Characterization of Deactivated Bio-oil Hydrotreating Catalysts

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

    Wang, Huamin; Wang, Yong

    Deactivation of bio-oil hydrotreating catalysts remains a significant challenge because of the poor quality of pyrolysis bio-oil input for hydrotreating and understanding their deactivation mode is critical to developing improved catalysts and processes. In this research, we developed an understanding of the deactivation of two-step bio-oil hydrotreating catalysts (sulfided Ru/C and sulfided CoMo/C) through detailed characterization of the catalysts using various complimentary analytical techniques. Severe fouling of both catalysts by carbonaceous species was the major form of deactivation, which is consistent with the significant loss of surface area and pore volume of both deactivated catalysts and the significant increase ofmore » the bulk density. Further analysis of the carbonaceous species by thermogravimetric analysis and x-ray photoelectron spectroscopy indicated that the carbonaceous species was formed by condensation reaction of active species such as sugars and sugar derivatives (aldehydes and ketones) in bio-oil feedstock during bio-oil hydrotreating under the conditions and catalysts used. Microscopy results did not show metal sintering of the Ru/C catalyst. However, X-ray diffraction indicated a probable transformation of the highly-active CoMoS phase in the sulfided CoMo/C catalyst to Co8S9 and MoS2 phase with low activity. Loss of the active site by transport of inorganic elements from the bio-oil and the reactor construction material onto the catalyst surface also might be a cause of deactivation as indicated by elemental analysis of spent catalysts.« less

  5. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

    PubMed

    Tang, Cheng; Zhou, Xi; Nguyen, Phuong Tran; Zhang, Yunxiao; Hu, Zhaotun; Zhang, Changxin; Yarov-Yarovoy, Vladimir; DeCaen, Paul G; Liang, Songping; Liu, Zhonghua

    2017-07-01

    Voltage-gated sodium channels (Na V s) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na V s have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na V s. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic Na V s Ns V Ba (nonselective voltage-gated Bacillus alcalophilus ) and NaChBac (bacterial sodium channel from Bacillus halodurans ) (IC 50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns V Ba, whereas the local anesthetic drug lidocaine was shown to antagonize Ns V Ba without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns V Ba, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of Ns V Ba in one of the deactivated states. In mammalian Na V s, JZTx-27 preferably inhibited the inactivation of Na V 1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na V s. More important, we proposed that JZTx-27 stabilized the Ns V Ba VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na V s.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. © FASEB.

  6. Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance.

    PubMed

    Heinsen, Femke-Anouska; Fangmann, Daniela; Müller, Nike; Schulte, Dominik M; Rühlemann, Malte C; Türk, Kathrin; Settgast, Ute; Lieb, Wolfgang; Baines, John F; Schreiber, Stefan; Franke, Andre; Laudes, Matthias

    2016-01-01

    In the present study, we examined the effect of a very low-calorie diet(VLCD)-based obesity program on human gut microbiome diversity and metabolism during weight loss and weight maintenance. Obese subjects underwent 3 months of VLCD followed by 3 months of weight maintenance. A lean and an obese control group were included. The microbiome was characterized by performing high-throughput dual-indexed 16S rDNA amplicon sequencing. At baseline, a significant difference in the Firmicutes/Bacteroidetes ratio between the lean and obese individuals was observed (p = 0.047). The VLCD resulted in significant alterations in gut microbiome diversity from baseline to 3 months (p = 0.0053). Acinetobacter represented an indicator species for the observed effect (indicator value = 0.998, p = 0.006). Metabolic analyses revealed alterations of the bacterial riboflavin pathway from baseline to 3 months (pnom = 0.0078). These changes in diversity and bacterial metabolism induced by VLCD diminished during the weight maintenance phase, despite sustained reductions in body weight and sustained improvements of insulin sensitivity. The present data show that a VLCD is able to beneficially alter both gut microbiome diversity and metabolism in obese humans, but that these changes are not sustained during weight maintenance. This finding might suggest that the microbiome should be targeted during obesity programs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

  7. Boron deactivation in heavily boron-doped Czochralski silicon during rapid thermal anneal: Atomic level understanding

    NASA Astrophysics Data System (ADS)

    Gao, Chao; Lu, Yunhao; Dong, Peng; Yi, Jun; Ma, Xiangyang; Yang, Deren

    2014-01-01

    The changes in hole concentration of heavily boron (B)-doped Czochralski silicon subjected to high temperature rapid thermal anneal (RTA) and following conventional furnace anneal (CFA) have been investigated. It is found that decrease in hole concentration, namely, B deactivation, is observed starting from 1050 °C and increases with RTA temperature. The following CFA at 300-500 °C leads to further B deactivation, while that at 600-800 °C results in B reactivation. It is supposed that the interaction between B atoms and silicon interstitials (I) thus forming BI pairs leads to the B deactivation during the high temperature RTA, and, moreover, the formation of extended B2I complexes results in further B deactivation in the following CFA at 300-500 °C. On the contrary, the dissociation of BI pairs during the following CFA at 600-800 °C enables the B reactivation. Importantly, the first-principles calculation results can soundly account for the above-mentioned supposition.

  8. Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance.

    PubMed

    Šmehilová, Mária; Dobrůšková, Jana; Novák, Ondřej; Takáč, Tomáš; Galuszka, Petr

    2016-01-01

    Plant hormones cytokinins (CKs) are one of the major mediators of physiological responses throughout plant life span. Therefore, a proper homeostasis is maintained by regulation of their active levels. Besides degradation, CKs are deactivated by uridine diphosphate glycosyltransferases (UGTs). Physiologically, CKs active levels decline in senescing organs, providing a signal to nutrients that a shift to reproductive tissues has begun. In this work, we show CK glucosides distribution in Arabidopsis leaves during major developmental transition phases. Besides continuous accumulation of N-glucosides we detected sharp maximum of the glucosides in senescence. This is caused prevalently by N7-glucosides followed by N9-glucosides and specifically also by trans-zeatin-O-glucoside (tZOG). Interestingly, we observed a similar trend in response to exogenously applied CK. In Arabidopsis, only three UGTs deactivate CKs in vivo: UGT76C1, UGT76C2 and UGT85A1. We thereby show that UGT85A1 is specifically expressed in senescent leaves whereas UGT76C2 is activated rapidly in response to exogenously applied CK. To shed more light on the UGTs physiological roles, we performed a comparative study on UGTs loss-of-function mutants, characterizing a true ugt85a1-1 loss-of-function mutant for the first time. Although no altered phenotype was detected under standard condition we observed reduced chlorophyll degradation with increased anthocyanin accumulation in our experiment on detached leaves accompanied by senescence and stress related genes modulated expression. Among the mutants, ugt76c2 possessed extremely diminished CK N-glucosides levels whereas ugt76c1 showed some specificity toward cis-zeatin (cZ). Besides tZOG, a broader range of CK glucosides was decreased in ugt85a1-1. Performing CK metabolism gene expression profiling, we revealed that activation of CK degradation pathway serves as a general regulatory mechanism of disturbed CK homeostasis followed by decreased CK signaling in all UGT mutants. In contrast, a specific regulation of CKX7, CKX1 and CKX2 was observed for each individual UGT mutant isoform after exogenous CK uptake. Employing an in silico prediction we proposed cytosolic localization of UGT76C1 and UGT76C2, that we further confirmed by GFP tagging of UGT76C2. Integrating all the results, we therefore hypothesize that UGTs possess different physiological roles in Arabidopsis and serve as a fine-tuning mechanism of active CK levels in cytosol.

  9. Top-down deactivation of interference from irrelevant spatial or verbal stimulus features.

    PubMed

    Frings, Christian; Wühr, Peter

    2014-11-01

    The selective-attention model of Houghton and Tipper (1994) assumes top-down deactivation of (conflicting) distractor representations as a mechanism of visual attention. Deactivation should produce an inverted-U-shaped activation function for distractor representations. In a recent study, Frings, Wentura, and Wühr (2012) tested this prediction in a variant of the flanker task in which a cue sometimes required participants to respond to the distractors rather than to the target. When reaction times and error rates were plotted as a function of the target-cue stimulus onset asynchrony, a quadratic trend emerged, consistent with the notion of distractor deactivation. However, in the flanker task, an alternative explanation for the quadratic trend in terms of attentional zooming is possible. The present experiments tested the deactivation account against the attentional-zooming account with the Stroop and the Simon task, in which attentional zooming should have minimal effects on distractor processing, because the target and distractor are presented at the same spatial location. Both experiments replicated the quadratic trend in the performance functions for responses to incongruent distractors, and additionally showed linear trends in the performance functions for responses to congruent distractors. These results provide additional support for the notion of top-down deactivation of distractor representations as a mechanism of visual selective attention.

  10. Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus.

    PubMed

    Lomber, Stephen G; Payne, Bertram R; Hilgetag, Claus C; Rushmore, JarrettR

    2002-02-01

    A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent area 7 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither area 7 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits.

  11. FROM CONCEPT TO REALITY, IN-SITU DECOMMISSIONING OF THE P AND R REACTORS AT THE SAVANNAH RIVER SITE

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

    Musall, J.; Blankenship, J.; Griffin, W.

    2012-01-09

    SRS recently completed an approximately three year effort to decommission two SRS reactors: P-Reactor (Building 105-P) and R-Reactor (Building 105-R). Completed in December 2011, the concurrent decommissionings marked the completion of two relatively complex and difficult facility disposition projects at the SRS. Buildings 105-P and 105-R began operating as production reactors in the early 1950s with the mission of producing weapons material (e.g., tritium and plutonium-239). The 'P' Reactor and was shutdown in 1991 while the 'R' Reactor and was shutdown in 1964. In the intervening period between shutdown and deactivation & decommissioning (D&D), Buildings 105-P and 105-R saw limitedmore » use (e.g., storage of excess heavy water and depleted uranium oxide). For Building 105-P, deactivation was initiated in April 2007 and was essentially complete by June 2010. For Building 105-R, deactivation was initiated in August 2008 and was essentially complete by September 2010. For both buildings, the primary objective of deactivation was to remove/mitigate hazards associated with the remaining hazardous materials, and thus prepare the buildings for in-situ decommissioning. Deactivation removed the following hazardous materials to the extent practical: combustibles/flammables, residual heavy water, acids, friable asbestos (as needed to protect workers performing deactivation and decommissioning), miscellaneous chemicals, lead/brass components, Freon(reg sign), oils, mercury/PCB containing components, mold and some radiologically-contaminated equipment. In addition to the removal of hazardous materials, deactivation included the removal of hazardous energy, exterior metallic components (representing an immediate fall hazard), and historical artifacts along with the evaporation of water from the two Disassembly Basins. Finally, so as to facilitate occupancy during the subsequent in-situ decommissioning, deactivation implemented repairs to the buildings and provided temporary power.« less

  12. Salience of working-memory maintenance and manipulation deficits in schizophrenia

    PubMed Central

    Hill, S. K.; Griffin, G. B.; Miura, T. Kazuto; Herbener, E. S.; Sweeney, J. A.

    2011-01-01

    Background Encoding and maintenance of information in working memory, followed by internal manipulation of that information for planning adaptive behavior, are two key components of working-memory systems. Both processes have been reported to be impaired in schizophrenia, but few studies have directly compared the relative severity of these abnormalities, or the degree to which manipulation deficits might be secondary to alterations in maintenance processes. Method Clinically stable schizophrenia patients (n=25) and a demographically similar healthy comparison group (n=24) were administered a verbal span task with three levels of working-memory load. Maintenance was assessed using sequential position questions. Manipulation processes were assessed by requiring comparison of the relative sequential position of test items, which entailed simultaneous serial search strategies regarding item order. Results Both groups showed reduced accuracy and increased reaction time for manipulation compared with maintenance processing. There were significant patient impairments across working-memory loads. There was no differential deficit in manipulation processing, and effect sizes of relative deficit in the patient group were higher for maintenance than manipulation processing. Conclusions The strong correlation for maintenance and manipulation deficits suggest that impairments in the ability to internally manipulate information stored in working-memory systems are not greater than alterations in the encoding and maintaining of information in working memory and that disturbances in maintenance processing may contribute to deficits in higher-order working-memory operations. PMID:20214839

  13. 49 CFR 230.37 - Steam test following repairs or alterations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam test following repairs or alterations. 230... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Pressure Testing of Boilers § 230.37 Steam test following repairs or alterations...

  14. A focus on extracellular Ca2+ entry into skeletal muscle

    PubMed Central

    Cho, Chung-Hyun; Woo, Jin Seok; Perez, Claudio F; Lee, Eun Hui

    2017-01-01

    The main task of skeletal muscle is contraction and relaxation for body movement and posture maintenance. During contraction and relaxation, Ca2+ in the cytosol has a critical role in activating and deactivating a series of contractile proteins. In skeletal muscle, the cytosolic Ca2+ level is mainly determined by Ca2+ movements between the cytosol and the sarcoplasmic reticulum. The importance of Ca2+ entry from extracellular spaces to the cytosol has gained significant attention over the past decade. Store-operated Ca2+ entry with a low amplitude and relatively slow kinetics is a main extracellular Ca2+ entryway into skeletal muscle. Herein, recent studies on extracellular Ca2+ entry into skeletal muscle are reviewed along with descriptions of the proteins that are related to extracellular Ca2+ entry and their influences on skeletal muscle function and disease. PMID:28912570

  15. Deactivating stimulation sites based on low-rate thresholds improves spectral ripple and speech reception thresholds in cochlear implant users.

    PubMed

    Zhou, Ning

    2017-03-01

    The study examined whether the benefit of deactivating stimulation sites estimated to have broad neural excitation was attributed to improved spectral resolution in cochlear implant users. The subjects' spatial neural excitation pattern was estimated by measuring low-rate detection thresholds across the array [see Zhou (2016). PLoS One 11, e0165476]. Spectral resolution, as assessed by spectral-ripple discrimination thresholds, significantly improved after deactivation of five high-threshold sites. The magnitude of improvement in spectral-ripple discrimination thresholds predicted the magnitude of improvement in speech reception thresholds after deactivation. Results suggested that a smaller number of relatively independent channels provide a better outcome than using all channels that might interact.

  16. Deactivation of Zeolite Catalyst H-ZSM-5 during Conversion of Methanol to Gasoline: Operando Time- and Space-Resolved X-ray Diffraction.

    PubMed

    Rojo-Gama, Daniel; Mentel, Lukasz; Kalantzopoulos, Georgios N; Pappas, Dimitrios K; Dovgaliuk, Iurii; Olsbye, Unni; Lillerud, Karl Petter; Beato, Pablo; Lundegaard, Lars F; Wragg, David S; Svelle, Stian

    2018-03-15

    The deactivation of zeolite catalyst H-ZSM-5 by coking during the conversion of methanol to hydrocarbons was monitored by high-energy space- and time-resolved operando X-ray diffraction (XRD) . Space resolution was achieved by continuous scanning along the axial length of a capillary fixed bed reactor with a time resolution of 10 s per scan. Using real structural parameters obtained from XRD, we can track the development of coke at different points in the reactor and link this to a kinetic model to correlate catalyst deactivation with structural changes occurring in the material. The "burning cigar" model of catalyst bed deactivation is directly observed in real time.

  17. Functional decline at the aging neuromuscular junction is associated with altered laminin-α4 expression.

    PubMed

    Lee, Kah Meng; Chand, Kirat K; Hammond, Luke A; Lavidis, Nickolas A; Noakes, Peter G

    2017-03-14

    Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice ( lama 4 -/- ). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing. Results showed maintained perturbed transmission properties at lama 4 -/- NMJs from adult (3 months) through to aged (18-22 months). Hind-limb grip force demonstrated similar trends as transmission properties, with maintained weaker grip force across age groups in lama 4 -/- . Interestingly, both transmission properties and hind-limb grip force in aged wild-types resembled those observed in adult lama 4 -/- . Most significantly, altered expression of laminin-α4 was noted at the wild-type NMJs prior to the observed decline in transmission properties, suggesting that altered laminin-α4 expression precedes the decline of neurotransmission in aging wild-types. These findings significantly support the role of laminin-α4 in maintenance of the NMJ during aging.

  18. 14 CFR 145.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Applicability. 145.1 Section 145.1 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SCHOOLS AND... follow related to its performance of maintenance, preventive maintenance, or alterations of an aircraft...

  19. 14 CFR 135.413 - Responsibility for airworthiness.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... engines, propellers, rotors, appliances, and parts, and shall have its aircraft maintained under this... maintenance, preventive maintenance, and alteration of its aircraft, including airframe, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under its manual and this chapter; or (2) Make...

  20. 14 CFR 135.413 - Responsibility for airworthiness.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... engines, propellers, rotors, appliances, and parts, and shall have its aircraft maintained under this... maintenance, preventive maintenance, and alteration of its aircraft, including airframe, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under its manual and this chapter; or (2) Make...

  1. 14 CFR 135.413 - Responsibility for airworthiness.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... engines, propellers, rotors, appliances, and parts, and shall have its aircraft maintained under this... maintenance, preventive maintenance, and alteration of its aircraft, including airframe, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under its manual and this chapter; or (2) Make...

  2. 14 CFR 135.413 - Responsibility for airworthiness.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... engines, propellers, rotors, appliances, and parts, and shall have its aircraft maintained under this... maintenance, preventive maintenance, and alteration of its aircraft, including airframe, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under its manual and this chapter; or (2) Make...

  3. 14 CFR 135.413 - Responsibility for airworthiness.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... engines, propellers, rotors, appliances, and parts, and shall have its aircraft maintained under this... maintenance, preventive maintenance, and alteration of its aircraft, including airframe, aircraft engines, propellers, rotors, appliances, emergency equipment and parts, under its manual and this chapter; or (2) Make...

  4. 14 CFR Appendix C to Part 43 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false [Reserved] C Appendix C to Part 43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION Appendix C to Part 43 [Reserved] ...

  5. 14 CFR Appendix C to Part 43 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false [Reserved] C Appendix C to Part 43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION Appendix C to Part 43 [Reserved] ...

  6. 14 CFR Appendix C to Part 43 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false [Reserved] C Appendix C to Part 43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION Appendix C to Part 43 [Reserved] ...

  7. Mechanistic Insight into Human ether-à-go-go-related Gene (hERG) K+ Channel Deactivation Gating from the Solution Structure of the EAG Domain

    PubMed Central

    Muskett, Frederick W.; Thouta, Samrat; Thomson, Steven J.; Bowen, Alexander; Stansfeld, Phillip J.; Mitcheson, John S.

    2011-01-01

    Human ether-à-go-go-related gene (hERG) K+ channels have a critical role in cardiac repolarization. hERG channels close (deactivate) very slowly, and this is vital for regulating the time course and amplitude of repolarizing current during the cardiac action potential. Accelerated deactivation is one mechanism by which inherited mutations cause long QT syndrome and potentially lethal arrhythmias. hERG deactivation is highly dependent upon an intact EAG domain (the first 135 amino acids of the N terminus). Importantly, deletion of residues 2–26 accelerates deactivation to a similar extent as removing the entire EAG domain. These and other experiments suggest the first 26 residues (NT1–26) contain structural elements required to slow deactivation by stabilizing the open conformation of the pore. Residues 26–135 form a Per-Arnt-Sim domain, but a structure for NT1–26 has not been forthcoming, and little is known about its site of interaction on the channel. In this study, we present an NMR structure for the entire EAG domain, which reveals that NT1–26 is structurally independent from the Per-Arnt-Sim domain and contains a stable amphipathic helix with one face being positively charged. Mutagenesis and electrophysiological studies indicate that neutralizing basic residues and breaking the amphipathic helix dramatically accelerate deactivation. Furthermore, scanning mutagenesis and molecular modeling studies of the cyclic nucleotide binding domain suggest that negatively charged patches on its cytoplasmic surface form an interface with the NT1–26 domain. We propose a model in which NT1–26 obstructs gating motions of the cyclic nucleotide binding domain to allosterically stabilize the open conformation of the pore. PMID:21135103

  8. Selective Inhibition of Deactivated Mitochondrial Complex I by Biguanides †

    PubMed Central

    Matsuzaki, Satoshi; Humphries, Kenneth M.

    2015-01-01

    Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates, but is rapidly and fully reversed to the active state in the presence of NADH. The objective of this study was to determine the relative sensitivity of active/de-active complex I to biguanide-mediated inhibition and resulting superoxide radical (O2•−) production. Using isolated rat heart mitochondria, we show that deactivation of complex I sensitizes it to metformin and phenformin (4- and 3-fold, respectively), but not to other known complex I inhibitors, such as rotenone. Mitochondrial O2•− production by deactivated complex I was measured fluorescently by the NADH-dependent 2-hydroxyethidium formation at alkaline pH to impede reactivation. Superoxide production was 260.4% higher than in active complex I at pH 9.4. However, phenformin treatment of de-active complex I decreased O2•− production by 14.9% while rotenone increased production by 42.9%. Mitochondria isolated from rat hearts subjected to cardiac ischemia, a condition known to induce complex I deactivation, were sensitized to phenformin:mediated complex I inhibition. This supports that the effects of biguanides are likely to be influenced by the complex I state in vivo. These results demonstrate that the complex I active/de-active states are a determinant in biguanide-mediated inhibition. PMID:25719498

  9. Spread of activation and deactivation in the brain: does age matter?

    PubMed Central

    Gordon, Brian A.; Tse, Chun-Yu; Gratton, Gabriele; Fabiani, Monica

    2014-01-01

    Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses. PMID:25360115

  10. The N–Terminal Tail of hERG Contains an Amphipathic α–Helix That Regulates Channel Deactivation

    PubMed Central

    Mobli, Mehdi; Ke, Ying; Kuchel, Philip W.; King, Glenn F.; Stock, Daniela; Vandenberg, Jamie I.

    2011-01-01

    The cytoplasmic N–terminal domain of the human ether–a–go–go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N–terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N–terminal 135 residues of hERG contains a previously described Per–Arnt–Sim (PAS) domain (residues 26–135) as well as an amphipathic α–helix (residues 13–23) and an initial unstructured segment (residues 2–9). Deletion of residues 2–25, only the unstructured segment (residues 2–9) or replacement of the α–helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α–helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N–terminal α–helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel. PMID:21249148

  11. Boron deactivation in heavily boron-doped Czochralski silicon during rapid thermal anneal: Atomic level understanding

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

    Gao, Chao; Dong, Peng; Yi, Jun

    The changes in hole concentration of heavily boron (B)-doped Czochralski silicon subjected to high temperature rapid thermal anneal (RTA) and following conventional furnace anneal (CFA) have been investigated. It is found that decrease in hole concentration, namely, B deactivation, is observed starting from 1050 °C and increases with RTA temperature. The following CFA at 300–500 °C leads to further B deactivation, while that at 600–800 °C results in B reactivation. It is supposed that the interaction between B atoms and silicon interstitials (I) thus forming BI pairs leads to the B deactivation during the high temperature RTA, and, moreover, the formation of extendedmore » B{sub 2}I complexes results in further B deactivation in the following CFA at 300–500 °C. On the contrary, the dissociation of BI pairs during the following CFA at 600–800 °C enables the B reactivation. Importantly, the first-principles calculation results can soundly account for the above-mentioned supposition.« less

  12. Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.

    PubMed

    Ng, Chai-Ann; Gravel, Andrée E; Perry, Matthew D; Arnold, Alexandre A; Marcotte, Isabelle; Vandenberg, Jamie I

    2016-08-12

    Slow deactivation of Kv11.1 channels is critical for its function in the heart. The S4-S5 linker, which joins the voltage sensor and pore domains, plays a critical role in this slow deactivation gating. Here, we use NMR spectroscopy to identify the membrane-bound surface of the S4S5 linker, and we show that two highly conserved tyrosine residues within the KCNH subfamily of channels are membrane-associated. Site-directed mutagenesis and electrophysiological analysis indicates that Tyr-542 interacts with both the pore domain and voltage sensor residues to stabilize activated conformations of the channel, whereas Tyr-545 contributes to the slow kinetics of deactivation by primarily stabilizing the transition state between the activated and closed states. Thus, the two tyrosine residues in the Kv11.1 S4S5 linker play critical but distinct roles in the slow deactivation phenotype, which is a hallmark of Kv11.1 channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Two Small Molecules Restore Stability to a Subpopulation of the Cystic Fibrosis Transmembrane Conductance Regulator with the Predominant Disease-causing Mutation.

    PubMed

    Meng, Xin; Wang, Yiting; Wang, Xiaomeng; Wrennall, Joe A; Rimington, Tracy L; Li, Hongyu; Cai, Zhiwei; Ford, Robert C; Sheppard, David N

    2017-03-03

    Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl - channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopic CFTR Cl - currents. At 37 °C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wild-type CFTR, the full-length F508del-CFTR was about 10 °C less thermostable. Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl - channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl - currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl - channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. 14 CFR 135.417 - Mechanical interruption summary report.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.417 Mechanical interruption summary report. Each... report of the following occurrences in multiengine aircraft for the preceding month to the certificate...

  15. 14 CFR 135.417 - Mechanical interruption summary report.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.417 Mechanical interruption summary report. Each... report of the following occurrences in multiengine aircraft for the preceding month to the certificate...

  16. 14 CFR 135.417 - Mechanical interruption summary report.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.417 Mechanical interruption summary report. Each... report of the following occurrences in multiengine aircraft for the preceding month to the certificate...

  17. 14 CFR 135.417 - Mechanical interruption summary report.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.417 Mechanical interruption summary report. Each... report of the following occurrences in multiengine aircraft for the preceding month to the certificate...

  18. 78 FR 6247 - Airworthiness Directives; the Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-30

    ... Company Model 757 airplanes. The existing AD currently requires revising the maintenance program by... for ignition sources inside fuel tanks caused by latent failures, alterations, repairs, or maintenance... CONTACT: Kevin Nguyen, Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, Seattle Aircraft...

  19. 76 FR 19710 - Airworthiness Directives; The Boeing Company Model 757 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ...: No person may operate an aircraft for which a manufacturer's maintenance manual or instructions for... by latent failures, alterations, repairs, or maintenance actions, which, in combination with... CONTACT: Tak Kobayashi, Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, Seattle Aircraft...

  20. Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

    PubMed Central

    Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

    2010-01-01

    Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

  1. Deactivation of 6-Aminocoumarin Intramolecular Charge Transfer Excited State through Hydrogen Bonding

    PubMed Central

    Krystkowiak, Ewa; Dobek, Krzysztof; Maciejewski, Andrzej

    2014-01-01

    This paper presents results of the spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in various aprotic hydrogen-bond forming solvents. It was established that solvent polarity as well as hydrogen-bonding ability influence solute properties. The hydrogen-bonding interactions between S1-electronic excited solute and solvent molecules were found to facilitate the nonradiative deactivation processes. The energy-gap dependence on radiationless deactivation in aprotic solvents was found to be similar to that in protic solvents. PMID:25244014

  2. Frequency-dependent actions of benzodiazepines on GABAA receptors in cultured murine cerebellar granule cells.

    PubMed Central

    Mellor, J R; Randall, A D

    1997-01-01

    1. Miniature IPSCs recorded from cultured murine cerebellar granule cells increased in half-width and amplitude following application of the benzodiazepine (BDZ) Flunitrazepam (Flu, 1 microM). The increase in the half-width was much greater than that in the amplitude. 2. Five-millisecond applications of 1 mM GABA to nucleated outside-out patches elicited rapidly rising biexponentially decaying responses that resembled IPSCs. Flu had no effect on the amplitude of such responses, but consistently slowed their deactivation by approximately 50%. This effect was reversed by Flu washout or application of the BDZ antagonist Ro15-1788. The partial inverse agonist. Ro15-4513 speeded deactivation and depressed peak current amplitude by 23 +/- 12%. 3. The EC50 for GABA was between 45 and 50 microM. At submaximally effective agonist concentrations, Flu increased response amplitude and slowed response deactivation. Both effects were present in all cells taken from young cultures (4-7 days in vitro) but the latter was absent in 55% of the neurones obtained from older cultures (14-27 days in vitro). 4. With 120 ms applications of 20 microM GABA, responses activated monoexponentially (time constant, 39.8 +/- 2.8 ms) and deactivated biexponentially (time constants, 40.4 +/- 2.1 and 251 +/- 15 ms). Application of Flu slowed both activation and deactivation. The latter effect arose from an increased contribution of the slower component of decay. 5. Desensitization of responses to 1 mM GABA was biexponential, with time constants of 47 +/- 11 and 479 +/- 49 ms. Flu speeded desensitization by decreasing both fast and slow time constants. GABAA receptor desensitization consistently slowed subsequent deactivation. No significant relationship between the level of desensitization and the amount of slowing of deactivation produced by Flu was found. 6. Responses to paired 5 ms applications of 1 mM GABA indicated that the slowing of deactivation and the speeding of desensitization produced by Flu combine to generate a marked frequency dependence in the actions of this BDZ. Thus when compared with control responses, GABA-induced charge transfer was only enhanced by Flu during the first of two successive agonist applications. PMID:9306278

  3. 14 CFR Appendix A to Part 43 - Major Alterations, Major Repairs, and Preventive Maintenance

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... alterations: (i) Changes in blade design. (ii) Changes in hub design. (iii) Changes in the governor or control... alterations: (i) Wings. (ii) Tail surfaces. (iii) Fuselage. (iv) Engine mounts. (v) Control system. (vi... the basic design of the fuel, oil, cooling, heating, cabin pressurization, electrical, hydraulic, de...

  4. 14 CFR Appendix A to Part 43 - Major Alterations, Major Repairs, and Preventive Maintenance

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... alterations: (i) Changes in blade design. (ii) Changes in hub design. (iii) Changes in the governor or control... alterations: (i) Wings. (ii) Tail surfaces. (iii) Fuselage. (iv) Engine mounts. (v) Control system. (vi... the basic design of the fuel, oil, cooling, heating, cabin pressurization, electrical, hydraulic, de...

  5. 14 CFR Appendix A to Part 43 - Major Alterations, Major Repairs, and Preventive Maintenance

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... alterations: (i) Changes in blade design. (ii) Changes in hub design. (iii) Changes in the governor or control... alterations: (i) Wings. (ii) Tail surfaces. (iii) Fuselage. (iv) Engine mounts. (v) Control system. (vi... the basic design of the fuel, oil, cooling, heating, cabin pressurization, electrical, hydraulic, de...

  6. 14 CFR Appendix A to Part 43 - Major Alterations, Major Repairs, and Preventive Maintenance

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... alterations: (i) Changes in blade design. (ii) Changes in hub design. (iii) Changes in the governor or control... alterations: (i) Wings. (ii) Tail surfaces. (iii) Fuselage. (iv) Engine mounts. (v) Control system. (vi... the basic design of the fuel, oil, cooling, heating, cabin pressurization, electrical, hydraulic, de...

  7. 14 CFR 135.419 - Approved aircraft inspection program.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.419 Approved aircraft inspection program. (a... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Approved aircraft inspection program. 135...

  8. 14 CFR 135.419 - Approved aircraft inspection program.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.419 Approved aircraft inspection program. (a... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Approved aircraft inspection program. 135...

  9. 14 CFR 135.419 - Approved aircraft inspection program.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.419 Approved aircraft inspection program. (a... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Approved aircraft inspection program. 135...

  10. 14 CFR 135.419 - Approved aircraft inspection program.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.419 Approved aircraft inspection program. (a... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Approved aircraft inspection program. 135...

  11. 14 CFR 135.419 - Approved aircraft inspection program.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OPERATING REQUIREMENTS: COMMUTER AND ON DEMAND OPERATIONS AND RULES GOVERNING PERSONS ON BOARD SUCH AIRCRAFT Maintenance, Preventive Maintenance, and Alterations § 135.419 Approved aircraft inspection program. (a... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Approved aircraft inspection program. 135...

  12. 14 CFR 135.417 - Mechanical interruption summary report.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Mechanical interruption summary report. 135... Maintenance, Preventive Maintenance, and Alterations § 135.417 Mechanical interruption summary report. Each... unscheduled stop or diversion from a route, caused by known or suspected mechanical difficulties or...

  13. 41 CFR 102-74.35 - What building services must Executive agencies provide?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 74... grounds maintenance, tenant alterations, minor repairs, building maintenance, integrated pest management... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What building services...

  14. 41 CFR 102-74.35 - What building services must Executive agencies provide?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 74... grounds maintenance, tenant alterations, minor repairs, building maintenance, integrated pest management... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What building services...

  15. 41 CFR 102-74.35 - What building services must Executive agencies provide?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 74... grounds maintenance, tenant alterations, minor repairs, building maintenance, integrated pest management... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What building services...

  16. 41 CFR 102-74.35 - What building services must Executive agencies provide?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 74... grounds maintenance, tenant alterations, minor repairs, building maintenance, integrated pest management... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What building services...

  17. 14 CFR 135.427 - Manual requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... overall responsibility for the management of both the required inspection functions and the other maintenance, preventive maintenance, and alterations functions. (9) Procedures to ensure that required... retrievable in the English language. [Doc. No. 16097, 43 FR 46783, Oct. 10, 1978, as amended by Amdt. 135-66...

  18. 40 CFR 92.115 - Calibrations; frequency and overview.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... any maintenance which could alter calibration, calibrate the engine dynamometer flywheel torque and speed measurement transducers, as specified in § 92.116. (d) At least monthly or after any maintenance... (if used) shaft torque feedback signal at steady-state conditions by comparing: (1) Shaft torque...

  19. 40 CFR 92.115 - Calibrations; frequency and overview.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... any maintenance which could alter calibration, calibrate the engine dynamometer flywheel torque and speed measurement transducers, as specified in § 92.116. (d) At least monthly or after any maintenance... (if used) shaft torque feedback signal at steady-state conditions by comparing: (1) Shaft torque...

  20. 40 CFR 92.115 - Calibrations; frequency and overview.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... any maintenance which could alter calibration, calibrate the engine dynamometer flywheel torque and speed measurement transducers, as specified in § 92.116. (d) At least monthly or after any maintenance... (if used) shaft torque feedback signal at steady-state conditions by comparing: (1) Shaft torque...

  1. 40 CFR 92.115 - Calibrations; frequency and overview.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... any maintenance which could alter calibration, calibrate the engine dynamometer flywheel torque and speed measurement transducers, as specified in § 92.116. (d) At least monthly or after any maintenance... (if used) shaft torque feedback signal at steady-state conditions by comparing: (1) Shaft torque...

  2. Diaphragmatic Myopotential Oversensing Caused by Change in Implantable Cardioverter Defibrillator Sensing Bandpass Filter.

    PubMed

    Ploux, Sylvain; Swerdlow, Charles D; Eschalier, Romain; Monteil, Benjamin; Ouali, Sana; Haïssaguerre, Michel; Bordachar, Pierre

    2016-07-01

    Diaphragmatic myopotential oversensing (DMO) causes inhibition of pacing and inappropriate detection of ventricular fibrillation in implantable cardioverter defibrillators (ICDs). It occurs almost exclusively with integrated bipolar leads and is extremely rare with dedicated bipolar leads. If DMO cannot be corrected by reducing programmed sensitivity, ventricular lead revision is often required. The new Low Frequency Attenuation (LFA) filter in St. Jude Medical ICDs (St. Jude Medical, Sylmar, CA, USA) alters the sensing bandpass to reduce T-wave oversensing. This paper aims to present the LFA filter as a reversible cause of DMO. Unnecessary lead revision can be avoided by the simple programming solution of deactivating this LFA filter. ©2016 Wiley Periodicals, Inc.

  3. Insight into the role of the promoters Pt, Ru and B in inhibiting the deactivation of Co catalysts in Fischer-Tropsch synthesis

    NASA Astrophysics Data System (ADS)

    Zhang, Riguang; Liu, Hongxia; Li, Qiaohong; Wang, Baojun; Ling, Lixia; Li, Debao

    2018-09-01

    In order to probe into the roles of the promoters Pt, Ru and B in inhibiting the deactivation of Co catalysts in FTS reactions, the adsorption ability of neighboring surface C and subsurface C atom around the promoters (Pt, Ru and B), and the mechanisms of surface C diffusion, accumulation, hydrogenation and penetration are examined by density functional theory calculations over the promoters Pt, Ru and B-modified Co catalysts, as well as the pure Co catalysts. Our results clearly show that compared to Co catalysts, both PtCo and RuCo bimetallic catalysts promote surface C hydrogenation, and inhibit surface C diffusion, accumulation and penetration, and therefore the ability of resistance toward deactivation and the stability of Co-based catalysts are enhanced; the promoter B cannot effectively improve the ability of resistance toward deactivation. Thus, the sequence for resistance toward deactivation of Co-based catalyst is BCo < Co < PtCo < RuCo. Moreover, the activation free energy of surface C accumulation to C2 species increases with the increasing of surface C adsorption free energy, namely, the adsorption characteristic of surface C species well represent the surface carbon deposition. Our results not only give an explanation for reported experiment that the Pt, Ru and B-modified Co catalysts exhibit ability of resistance toward deactivation in FTS at a molecular level, but also provide a clue for the design of efficient Co-based catalysts in FTS reactions.

  4. Using lean methodology to improve efficiency of electronic order set maintenance in the hospital.

    PubMed

    Idemoto, Lori; Williams, Barbara; Blackmore, Craig

    2016-01-01

    Order sets, a series of orders focused around a diagnosis, condition, or treatment, can reinforce best practice, help eliminate outdated practice, and provide clinical guidance. However, order sets require regular updates as evidence and care processes change. We undertook a quality improvement intervention applying lean methodology to create a systematic process for order set review and maintenance. Root cause analysis revealed challenges with unclear prioritization of requests, lack of coordination between teams, and lack of communication between producers and requestors of order sets. In March of 2014, we implemented a systematic, cyclical order set review process, with a set schedule, defined responsibilities for various stakeholders, formal meetings and communication between stakeholders, and transparency of the process. We first identified and deactivated 89 order sets which were infrequently used. Between March and August 2014, 142 order sets went through the new review process. Processing time for the build duration of order sets decreased from a mean of 79.6 to 43.2 days (p<.001, CI=22.1, 50.7). Applying Lean production principles to the order set review process resulted in significant improvement in processing time and increased quality of orders. As use of order sets and other forms of clinical decision support increase, regular evidence and process updates become more critical.

  5. 14 CFR 43.15 - Additional performance rules for inspections.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.15 Additional..., or 135 of this chapter, shall— (1) Perform the inspection so as to determine whether the aircraft, or... accordance with the instructions and procedures set forth in the inspection program for the aircraft being...

  6. 14 CFR 43.15 - Additional performance rules for inspections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.15 Additional..., or 135 of this chapter, shall— (1) Perform the inspection so as to determine whether the aircraft, or... accordance with the instructions and procedures set forth in the inspection program for the aircraft being...

  7. 14 CFR 43.15 - Additional performance rules for inspections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.15 Additional..., or 135 of this chapter, shall— (1) Perform the inspection so as to determine whether the aircraft, or... accordance with the instructions and procedures set forth in the inspection program for the aircraft being...

  8. 14 CFR 43.15 - Additional performance rules for inspections.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.15 Additional..., or 135 of this chapter, shall— (1) Perform the inspection so as to determine whether the aircraft, or... accordance with the instructions and procedures set forth in the inspection program for the aircraft being...

  9. 14 CFR 43.15 - Additional performance rules for inspections.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION § 43.15 Additional..., or 135 of this chapter, shall— (1) Perform the inspection so as to determine whether the aircraft, or... accordance with the instructions and procedures set forth in the inspection program for the aircraft being...

  10. 75 FR 52803 - Agency Information Collection Activities: Requests for Comments; Clearance of Renewed Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... Activities: Requests for Comments; Clearance of Renewed Approval of Information Collection: Maintenance, Preventative Maintenance, Rebuilding and Alteration AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... invites public comments about our intention to request the Office of Management and Budget (OMB) approval...

  11. 14 CFR 135.431 - Continuing analysis and surveillance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Continuing analysis and surveillance. 135... Maintenance, Preventive Maintenance, and Alterations § 135.431 Continuing analysis and surveillance. (a) Each certificate holder shall establish and maintain a system for the continuing analysis and surveillance of the...

  12. 14 CFR 135.431 - Continuing analysis and surveillance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Continuing analysis and surveillance. 135... Maintenance, Preventive Maintenance, and Alterations § 135.431 Continuing analysis and surveillance. (a) Each certificate holder shall establish and maintain a system for the continuing analysis and surveillance of the...

  13. 14 CFR 135.431 - Continuing analysis and surveillance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Continuing analysis and surveillance. 135... Maintenance, Preventive Maintenance, and Alterations § 135.431 Continuing analysis and surveillance. (a) Each certificate holder shall establish and maintain a system for the continuing analysis and surveillance of the...

  14. 14 CFR 135.431 - Continuing analysis and surveillance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Continuing analysis and surveillance. 135... Maintenance, Preventive Maintenance, and Alterations § 135.431 Continuing analysis and surveillance. (a) Each certificate holder shall establish and maintain a system for the continuing analysis and surveillance of the...

  15. 14 CFR 135.431 - Continuing analysis and surveillance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Continuing analysis and surveillance. 135... Maintenance, Preventive Maintenance, and Alterations § 135.431 Continuing analysis and surveillance. (a) Each certificate holder shall establish and maintain a system for the continuing analysis and surveillance of the...

  16. THE SYMPATHETIC NERVOUS SYSTEM ALTERATIONS IN HUMAN HYPERTENSION

    PubMed Central

    Grassi, Guido; Mark, Allyn; Esler, Murray

    2015-01-01

    A number of articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as “promoters” and “amplifiers” of human hypertension. We expand on the role of the sympathetic nervous system in two increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves. PMID:25767284

  17. Relationship among tobacco habits, human papilloma virus (HPV) infection, p53 polymorphism/mutation and the risk of oral squamous cell carcinoma.

    PubMed

    Chakrobarty, Bidyut; Roy, Jay Gopal; Majumdar, Sumit; Uppala, Divya

    2014-05-01

    The prevalence of oral squamous cell carcinoma (OSCC) has significantly increased over decades in several countries and human papilloma virus (HPV) has been indicated as one of the underlying causes. This suggests that HPV plays a role in the early stages of carcinogenesis but is not a requisite for the maintenance and progression of malignant state. p53 is a tumor suppressor gene that checks the cell and promotes apoptosis and cell repair that can be deactivated by mutations and a viral interaction leading to cancer and individuals with particular polymorphic variant of p53 is more susceptible to HPV-induced carcinogenesis. The present study has been carried out to detect and correlate p53 polymorphism/mutation, HPV DNA in the biopsy samples of oral cancer patients who had tobacco habits.

  18. Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

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

    Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina

    Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

  19. Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder

    PubMed Central

    Gonçalves, Óscar F.; Soares, José Miguel; Carvalho, Sandra; Leite, Jorge; Ganho-Ávila, Ana; Fernandes-Gonçalves, Ana; Pocinho, Fernando; Carracedo, Angel; Sampaio, Adriana

    2017-01-01

    The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content. PMID:28287615

  20. Deactivation of Legionella Pneumophila in municipal wastewater by ozone generated in arrays of microchannel plasmas

    NASA Astrophysics Data System (ADS)

    Dong, Shengkun; Li, Jun; Kim, Min-Hwan; Cho, Jinhoon; Park, Sung-Jin; Nguyen, Thanh H.; Eden, J. Gary

    2018-06-01

    A greater than four log10 reduction in the concentration of Legionella pneumophila in municipal wastewater has been achieved in 1 min with ozone produced by a microchannel plasma reactor. Requiring less than 22 W of electrical power, and ambient air as the feedstock gas, the microplasma ozone generator is robust and a promising alternative to conventional corona and dielectric barrier discharge (DBD) technologies. Contrary to previous studies, the Ct model for pathogen deactivation (i.e. rate proportional to the product of the available disinfectant concentration and the exposure duration) is found to be valid for L. pneumophila. Accordingly, wastewater-specific Ct equations have been developed to predict the deactivation of L. pneumophila in the secondary wastewater environment. Inactivation of this pathogen was found to be dependent on temperature only in the absence of wastewater organic matter (WOM). In the presence of WOM, pathogen deactivation is controlled by the disinfection contact time, initial ozone concentration (varied between 15 and 281 µg l‑1), and initial WOM loading. The data reported here will assist in the implementation of plasma ozone generators for L. pneumophila deactivation in cooling towers, point-of-use systems, and wastewater reclamation facilities.

  1. Catalytic cracking of model compounds of bio-oil over HZSM-5 and the catalyst deactivation.

    PubMed

    Chen, Guanyi; Zhang, Ruixue; Ma, Wenchao; Liu, Bin; Li, Xiangping; Yan, Beibei; Cheng, Zhanjun; Wang, Tiejun

    2018-08-01

    The catalytic cracking upgrading reactions over HZSM-5 of different model compounds of bio-oil have been studied with a self-designed fluid catalytic cracking (FCC) equipment. Typical bio-oil model compounds, such as acetic acid, guaiacol, n-heptane, acetol and ethyl acetate, were chosen to study the products distribution, reaction pathway and deactivation of catalysts. The results showed: C 6 -C 8 aromatic hydrocarbons, C 2 -C 4 olefins, C 1 -C 5 alkanes, CO and CO 2 were the main products, and the selectivity of olefins was: ethylene>propylene>butylene. Catalyst characterization methods, such as FI-IR, TG-TPO and Raman, were used to study the deactivation mechanism of catalysts. According to the catalyst characterization results, a catalyst deactivation mechanism was proposed as follows: Firstly, the precursor which consisted of a large number of long chain saturated aliphatic hydrocarbons and a small amount CC of aromatics formed on the catalyst surface. Then the active sites of catalysts had been covered, the coke type changed from thermal coke to catalytic coke and gradually blocked the channels of the molecular sieve, which accelerated the deactivation of catalyst. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

    DOE PAGES

    Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina; ...

    2017-05-02

    Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

  3. Quenching-induced deactivation of photosensitizer by nanoencapsulation to improve phototherapy of cancer.

    PubMed

    Zeisser-Labouèbe, Magali; Mattiuzzo, Marc; Lange, Norbert; Gurny, Robert; Delie, Florence

    2009-09-01

    Photodynamic therapy has emerged as a promising alternative to current cancer treatment. However, conventional photosensitizers have several limitations due to their unsuitable pharmaceutical formulations and lack of selectivity. Our strategy was to exploit the advantages of nanoparticles and the quenching-induced deactivation of the model photosensitizer hypericin to produce "activatable" drug delivery systems. Efficient fluorescence and activity quenching were achieved by increasing the drug-loading rate of nanoparticles. In vitro assays confirmed the reversibility of hypericin deactivation, as the hypericin fluorescence and photodynamic activity were recovered upon cell internalization.

  4. Exposure to smoking cues during an emotion recognition task can modulate limbic fMRI activation in cigarette smokers.

    PubMed

    Artiges, Eric; Ricalens, Emmanuel; Berthoz, Sylvie; Krebs, Marie-Odile; Penttilä, Jani; Trichard, Christian; Martinot, Jean-Luc

    2009-09-01

    Smoking cues (SCs) refer to smoking-associated environmental stimuli that may trigger craving and withdrawal symptoms, and predispose to relapse in smokers. Although previous brain imaging studies have explored neural responses to SCs, no study has characterized the effects of SCs on cerebral activity in smokers engaged in an attention-demanding cognitive task that is unrelated to smoking. Thirteen tobacco smokers and a demographically matched group of 13 healthy non-smokers participated in a fast event-related functional magnetic resonance imaging (fMRI) study that involved a visual task integrating SCs and neutral cues (NCs) during emotion recognition trials requiring a high level of attention. No significant SC-induced alterations were detected in smokers' behavioural performance. fMRI results show that non-smokers exhibited no difference between SC and NC trials; in contrast, smokers showed SC-induced widespread deactivations in a limbic, paralimbic and striatal network classically involved in addiction, and activation in the right dorsolateral prefrontal cortex. In addition, a correlation between deactivation of the right insula and the severity of smoking dependence (Fagerström test) was detected in smokers. These results suggest that the neural reactivity of smokers to SCs can be modified in the context of a cognitive challenge. This could reflect smokers' ability to inhibit cue-induced craving and may help in smoking cessation.

  5. Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

    PubMed

    Yu, Yang; Yu, Xiaohui; Fan, Chenling; Wang, Hong; Wang, Renee; Feng, Chen; Guan, Haixia

    2018-06-25

    Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT 2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer. PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

  6. Structural stability of E. coli transketolase to temperature and pH denaturation.

    PubMed

    Jahromi, Raha R F; Morris, Phattaraporn; Martinez-Torres, Ruben J; Dalby, Paul A

    2011-09-10

    We have previously shown that the denaturation of TK with urea follows a non-aggregating though irreversible denaturation pathway in which the cofactor binding appears to become altered but without dissociating, then followed at higher urea by partial denaturation of the homodimer prior to any further unfolding or dissociation of the two monomers. Urea is not typically present during biocatalysis, whereas access to TK enzymes that retain activity at increased temperature and extreme pH would be useful for operation under conditions that increase substrate and product stability or solubility. To provide further insight into the underlying causes of its deactivation in process conditions, we have characterised the effects of temperature and pH on the structure, stability, aggregation and activity of Escherichia coli transketolase. The activity of TK was initially found to progressively improve after pre-incubation at increasing temperatures. Loss of activity at higher temperature and low pH resulted primarily from protein denaturation and subsequent irreversible aggregation. By contrast, high pH resulted in the formation of a native-like state that was only partially inactive. The apo-TK enzyme structure content also increased at pH 9 to converge on that of the holo-TK. While cofactor dissociation was previously proposed for high pH deactivation, the observed structural changes in apo-TK but not holo-TK indicate a more complex mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Inhibition of recombinant Ca(v)3.1 (alpha(1G)) T-type calcium channels by the antipsychotic drug clozapine.

    PubMed

    Choi, Kee-Hyun; Rhim, Hyewhon

    2010-01-25

    Low voltage-activated T-type calcium channels are involved in the regulation of the neuronal excitability, and could be subject to many antipsychotic drugs. The effects of clozapine, an atypical antipsychotic drug, on recombinant Ca(v)3.1 T-type calcium channels heterologously expressed in human embryonic kidney 293 cells were examined using whole-cell patch-clamp recordings. At a standard holding potential of -100 mV, clozapine inhibited Ca(v)3.1 currents with an IC(50) value of 23.7+/-1.3 microM in a use-dependent manner. However, 10 microM clozapine inhibited more than 50% of the Ca(v)3.1 currents in recordings at a more physiologically relevant holding potential of -75 mV. Clozapine caused a significant hyperpolarizing shift in the steady-state inactivation curve of the Ca(v)3.1 channels, which is presumably the main mechanism accounting for the inhibition of the Ca(v)3.1 currents. In addition, clozapine slowed Ca(v)3.1 deactivation and inactivation kinetics but not activation kinetics. Clozapine-induced changes in deactivation and inactivation rates of the Ca(v)3.1 channel gating would likely facilitate calcium influx via Ca(v)3.1 T-type calcium channels. Thus, clozapine may exert its therapeutic and/or side effects by altering cell's excitability and firing properties through actions on T-type calcium channels.

  8. 46 CFR 131.545 - Maintenance in general.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... points with the recommended lubricants. (5) A list of replaceable parts. (6) A list of sources of spare parts. (7) A log for records of inspections, maintenance, and repair. (b) The master shall ensure that... test in subchapter Q of this chapter. (g) The master shall report each emergency repair or alteration...

  9. 14 CFR Appendix E to Part 43 - Altimeter System Test and Inspection

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Altimeter System Test and Inspection E Appendix E to Part 43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT MAINTENANCE, PREVENTIVE MAINTENANCE, REBUILDING, AND ALTERATION Pt. 43, App. E Appendix E to Part...

  10. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... category. (h) Notwithstanding the provisions of paragraph (g) of this section, the Administrator may... Product and Process Specification issued by the Administrator; and (3) Perform any inspection required by... manufactures under a production certificate. (k) Updates of databases in installed avionics meeting the...

  11. 42 CFR 460.200 - Maintenance of records and reporting of data.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., or inappropriate alteration. (e) Confidentiality of health information. A PACE organization must..., and other participant health information. (f) Retention of records. (1) A PACE organization must... 42 Public Health 4 2014-10-01 2014-10-01 false Maintenance of records and reporting of data. 460...

  12. 42 CFR 460.200 - Maintenance of records and reporting of data.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., or inappropriate alteration. (e) Confidentiality of health information. A PACE organization must..., and other participant health information. (f) Retention of records. (1) A PACE organization must... 42 Public Health 4 2012-10-01 2012-10-01 false Maintenance of records and reporting of data. 460...

  13. 30 CFR 75.800-4 - Testing, examination, and maintenance of circuit breakers; record.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... mine. (b) Record security. These records shall be made in a secure book that is not susceptible to alteration or electronically in a computer system so as to be secure and not susceptible to alteration. (c...

  14. 30 CFR 75.800-4 - Testing, examination, and maintenance of circuit breakers; record.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... mine. (b) Record security. These records shall be made in a secure book that is not susceptible to alteration or electronically in a computer system so as to be secure and not susceptible to alteration. (c...

  15. 30 CFR 75.800-4 - Testing, examination, and maintenance of circuit breakers; record.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... mine. (b) Record security. These records shall be made in a secure book that is not susceptible to alteration or electronically in a computer system so as to be secure and not susceptible to alteration. (c...

  16. 30 CFR 75.800-4 - Testing, examination, and maintenance of circuit breakers; record.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... mine. (b) Record security. These records shall be made in a secure book that is not susceptible to alteration or electronically in a computer system so as to be secure and not susceptible to alteration. (c...

  17. 75 FR 17987 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... time on an intraday basis at its discretion if it determined that volatility warranted deactivation. Members would be notified of intraday OPP deactivation due to volatility and any subsequent intraday...

  18. N Reactor Deactivation Program Plan. Revision 4

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

    Walsh, J.L.

    1993-12-01

    This N Reactor Deactivation Program Plan is structured to provide the basic methodology required to place N Reactor and supporting facilities {center_dot} in a radiologically and environmentally safe condition such that they can be decommissioned at a later date. Deactivation will be in accordance with facility transfer criteria specified in Department of Energy (DOE) and Westinghouse Hanford Company (WHC) guidance. Transition activities primarily involve shutdown and isolation of operational systems and buildings, radiological/hazardous waste cleanup, N Fuel Basin stabilization and environmental stabilization of the facilities. The N Reactor Deactivation Program covers the period FY 1992 through FY 1997. The directivemore » to cease N Reactor preservation and prepare for decommissioning was issued by DOE to WHC on September 20, 1991. The work year and budget data supporting the Work Breakdown Structure in this document are found in the Activity Data Sheets (ADS) and the Environmental Restoration Program Baseline, that are prepared annually.« less

  19. Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

    DOE PAGES

    Cheng, Shouyun; Wei, Lin; Zhao, Xianhui; ...

    2016-12-07

    The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction,more » and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.« less

  20. Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

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

    Cheng, Shouyun; Wei, Lin; Zhao, Xianhui

    The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction,more » and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.« less

  1. Deactivation of TEM-1 β-Lactamase Investigated by Isothermal Batch and Non-Isothermal Continuous Enzyme Membrane Reactor Methods

    PubMed Central

    Rogers, Thomas A.

    2011-01-01

    The thermal deactivation of TEM-1 β-lactamase was examined using two experimental techniques: a series of isothermal batch assays and a single, continuous, non-isothermal assay in an enzyme membrane reactor (EMR). The isothermal batch-mode technique was coupled with the three-state “Equilibrium Model” of enzyme deactivation, while the results of the EMR experiment were fitted to a four-state “molten globule model”. The two methods both led to the conclusions that the thermal deactivation of TEM-1 β-lactamase does not follow the Lumry-Eyring model and that the Teq of the enzyme (the point at which active and inactive states are present in equal amounts due to thermodynamic equilibrium) is at least 10 °C from the Tm (melting temperature), contrary to the idea that the true temperature optimum of a biocatalyst is necessarily close to the melting temperature. PMID:22039393

  2. The ethics of deactivating a pacemaker in a pacing-dependent patient: reflections on a case study.

    PubMed

    Malpas, Phillipa J; Cooper, Lisa

    2012-11-01

    The decision to deactivate a pacemaker in a pacing-dependent patient is troubling for some health professionals who may regard such interventions as hastening death and therefore ethically impermissible. This may be especially concerning in situations where a patient is unable to clearly state what their preferences may be and the decision--were it to be made--will almost certainly result in the patient's immediate death. In this discussion, we reflect on some of the ethical aspects that arise when JP, a 75-year-old woman who is pacing dependent, suffers a significant brain injury, and the family request that her pacemaker be deactivated. Taking into account the clinical reality of her situation, the united wishes and loving concern of her husband and family, and their substituted judgment regarding her likely preferences, we claim that the decision to deactivate her pacemaker was ethically sound.

  3. Highly controlled nest homeostasis of honey bees helps deactivate phenolics in nectar

    NASA Astrophysics Data System (ADS)

    Liu, Fanglin; He, Jianzhong; Fu, Wenjun

    2005-06-01

    Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35°C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.

  4. Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition.

    PubMed

    Devery Iii, James J; Douglas, James J; Nguyen, John D; Cole, Kevin P; Flowers Ii, Robert A; Stephenson, Corey R J

    2015-01-01

    Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac -Ir(ppy) 3 in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac -Ir(ppy) 3 under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.

  5. On the CCN (de)activation nonlinearities

    NASA Astrophysics Data System (ADS)

    Arabas, Sylwester; Shima, Shin-ichiro

    2017-09-01

    We take into consideration the evolution of particle size in a monodisperse aerosol population during activation and deactivation of cloud condensation nuclei (CCN). Our analysis reveals that the system undergoes a saddle-node bifurcation and a cusp catastrophe. The control parameters chosen for the analysis are the relative humidity and the particle concentration. An analytical estimate of the activation timescale is derived through estimation of the time spent in the saddle-node bifurcation bottleneck. Numerical integration of the system coupled with a simple air-parcel cloud model portrays two types of activation/deactivation hystereses: one associated with the kinetic limitations on droplet growth when the system is far from equilibrium, and one occurring close to equilibrium and associated with the cusp catastrophe. We discuss the presented analyses in context of the development of particle-based models of aerosol-cloud interactions in which activation and deactivation impose stringent time-resolution constraints on numerical integration.

  6. Conflict anticipation in alcohol dependence - A model-based fMRI study of stop signal task.

    PubMed

    Hu, Sien; Ide, Jaime S; Zhang, Sheng; Sinha, Rajita; Li, Chiang-Shan R

    2015-01-01

    Our previous work characterized altered cerebral activations during cognitive control in individuals with alcohol dependence (AD). A hallmark of cognitive control is the ability to anticipate changes and adjust behavior accordingly. Here, we employed a Bayesian model to describe trial-by-trial anticipation of the stop signal and modeled fMRI signals of conflict anticipation in a stop signal task. Our goal is to characterize the neural correlates of conflict anticipation and its relationship to response inhibition and alcohol consumption in AD. Twenty-four AD and 70 age and gender matched healthy control individuals (HC) participated in the study. fMRI data were pre-processed and modeled with SPM8. We modeled fMRI signals at trial onset with individual events parametrically modulated by estimated probability of the stop signal, p(Stop), and compared regional responses to conflict anticipation between AD and HC. To address the link to response inhibition, we regressed whole-brain responses to conflict anticipation against the stop signal reaction time (SSRT). Compared to HC (54/70), fewer AD (11/24) showed a significant sequential effect - a correlation between p(Stop) and RT during go trials - and the magnitude of sequential effect is diminished, suggesting a deficit in proactive control. Parametric analyses showed decreased learning rate and over-estimated prior mean of the stop signal in AD. In fMRI, both HC and AD responded to p(Stop) in bilateral inferior parietal cortex and anterior pre-supplementary motor area, although the magnitude of response increased in AD. In contrast, HC but not AD showed deactivation of the perigenual anterior cingulate cortex (pgACC). Furthermore, deactivation of the pgACC to increasing p(Stop) is positively correlated with the SSRT in HC but not AD. Recent alcohol consumption is correlated with increased activation of the thalamus and cerebellum in AD during conflict anticipation. The current results highlight altered proactive control that may serve as an additional behavioral and neural marker of alcohol dependence.

  7. ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

    PubMed Central

    Babot, Marion; Labarbuta, Paola; Birch, Amanda; Kee, Sara; Fuszard, Matthew; Botting, Catherine H.; Wittig, Ilka; Heide, Heinrich; Galkin, Alexander

    2014-01-01

    An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III2 + IV (S1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover. PMID:24560811

  8. Oral Bacterial Deactivation Using a Low-Temperature Atmospheric Argon Plasma Brush

    PubMed Central

    Yang, Bo; Chen, Jierong; Yu, Qingsong; Li, Hao; Lin, Mengshi; Mustapha, Azlin; Hong, Liang; Wang, Yong

    2010-01-01

    Summary Objectives To study the plasma treatment effects on deactivation effectiveness of oral bacteria. Methods A low temperature atmospheric argon plasma brush were used to study the oral bacterial deactivation effects in terms of plasma conditions, plasma exposure time, and bacterial supporting media. Oral bacteria of Streptococcus mutans and Lactobacillus acidophilus with an initial bacterial population density between 1.0 × 108 and 5.0 × 108 cfu/ml were seeded on various media and their survivability with plasma exposure was examined. Scanning electron microscopy was used to examine the morphological changes of the plasma treated bacteria. Optical absorption was used to determine the leakage of intracellular proteins and DNAs of the plasma treated bacteria. Results The experimental data indicated that the argon atmospheric plasma brush was very effective in deactivating oral bacteria. The plasma exposure time for a 99.9999% cell reduction was less than 15 seconds for S. mutans and within 5 minutes for L. acidophilus. It was found that the plasma deactivation efficiency was also dependent on the bacterial supporting media. With plasma exposure, significant damages to bacterial cell structures were observed with both bacterium species. Leakage of intracellular proteins and DNAs after plasma exposure was observed through monitoring the absorbance peaks at wavelengths of 280nm and 260nm, respectively. Conclusion The experimental results from this study indicated that low temperature atmospheric plasma treatment was very effective in deactivation of oral bacteria and could be a promising technique in various dental clinical applications such as bacterial disinfection and caries early prevention, etc. PMID:20951184

  9. Developing an energy efficient steam reforming process to produce hydrogen from sulfur-containing fuels

    NASA Astrophysics Data System (ADS)

    Simson, Amanda

    Hydrogen powered fuel cells have the potential to produce electricity with higher efficiency and lower emissions than conventional combustion technology. In order to realize the benefits of a hydrogen fuel cell an efficient method to produce hydrogen is needed. Currently, over 90% of hydrogen is produced from the steam reforming of natural gas. However, for many applications including fuel cell vehicles, the use of a liquid fuel rather than natural gas is desirable. This work investigates the feasibility of producing hydrogen efficiently by steam reforming E85 (85% ethanol/15% gasoline), a commercially available sulfur-containing transportation fuel. A Rh-Pt/SiO2-ZrO2 catalyst has demonstrated good activity for the E85 steam reforming reaction. An industrial steam reforming process is often run less efficiently, with more water and at higher temperatures, in order to prevent catalyst deactivation. Therefore, it is desirable to develop a process that can operate without catalyst deactivation at more energy efficient conditions. In this study, the steam reforming of a sulfur-containing fuel (E85) was studied at near stoichiometric steam/carbon ratios and at 650C, conditions at which catalyst deactivation is normally measured. At these conditions the catalyst was found to be stable steam reforming a sulfur-free E85. However, the addition of low concentrations of sulfur significantly deactivated the catalyst. The presence of sulfur in the fuel caused catalyst deactivation by promoting ethylene which generates surface carbon species (coke) that mask catalytic sites. The amount of coke increased during time on stream and became increasingly graphitic. However, the deactivation due to both sulfur adsorption and coke formation was reversible with air treatment at 650°C. However, regenerations were found to reduce the catalyst life. Air regenerations produce exotherms on the catalyst surface that cause structural changes to the catalyst. During regenerations the accessibility of the precious metal particles is reduced which causes the catalyst to deactivate more rapidly during subsequent steam reforming cycles. Changes to the carrier morphology also occur at these conditions. Regenerating the catalyst before significant deactivation is measured can improve the stability of the catalyst. Thus a process with preemptive controlled air regenerations is proposed in order to run a steam reforming process with sulfur containing fuels.

  10. 76 FR 23351 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... Exchange would also be able to temporarily deactivate OPP from time to time on an intraday basis at its... intraday OPP deactivation due to volatility and any subsequent intraday reactivation by the Exchange...

  11. Systems and methods for deactivating a matrix converter

    DOEpatents

    Ransom, Ray M.

    2013-04-02

    Systems and methods are provided for deactivating a matrix conversion module. An electrical system comprises an alternating current (AC) interface, a matrix conversion module coupled to the AC interface, an inductive element coupled between the AC interface and the matrix conversion module, and a control module. The control module is coupled to the matrix conversion module, and in response to a shutdown condition, the control module is configured to operate the matrix conversion module to deactivate the first conversion module when a magnitude of a current through the inductive element is less than a threshold value.

  12. Nanotube-assisted protein deactivation

    NASA Astrophysics Data System (ADS)

    Joshi, Amit; Punyani, Supriya; Bale, Shyam Sundhar; Yang, Hoichang; Borca-Tasciuc, Theodorian; Kane, Ravi S.

    2008-01-01

    Conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. However, remotely controlling the activity of proteins in these conjugates has never been demonstrated. Here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. We designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can self-clean following either visible or near-infrared irradiation. Nanotube-assisted protein deactivation may be broadly applicable to the selective destruction of pathogens and cells, and will have applications ranging from antifouling coatings to functional proteomics.

  13. Regional brain activation/deactivation during word generation in schizophrenia: fMRI study.

    PubMed

    John, John P; Halahalli, Harsha N; Vasudev, Mandapati K; Jayakumar, Peruvumba N; Jain, Sanjeev

    2011-03-01

    Examination of the brain regions that show aberrant activations and/or deactivations during semantic word generation could pave the way for a better understanding of the neurobiology of cognitive dysfunction in schizophrenia. To examine the pattern of functional magnetic resonance imaging blood oxygen level dependent activations and deactivations during semantic word generation in schizophrenia. Functional magnetic resonance imaging was performed on 24 participants with schizophrenia and 24 matched healthy controls during an overt, paced, 'semantic category word generation' condition and a baseline 'word repetition' condition that modelled all the lead-in/associated processes involved in the performance of the generation task. The brain regions activated during word generation in healthy individuals were replicated with minimal redundancies in participants with schizophrenia. The individuals with schizophrenia showed additional activations of temporo-parieto-occipital cortical regions as well as subcortical regions, despite significantly poorer behavioural performance than the healthy participants. Importantly, the extensive deactivations in other brain regions during word generation in healthy individuals could not be replicated in those with schizophrenia. More widespread activations and deficient deactivations in the poorly performing participants with schizophrenia may reflect an inability to inhibit competing cognitive processes, which in turn could constitute the core information-processing deficit underlying impaired word generation in schizophrenia.

  14. Multiple Interactions between Cytoplasmic Domains Regulate Slow Deactivation of Kv11.1 Channels*

    PubMed Central

    Ng, Chai Ann; Phan, Kevin; Hill, Adam P.; Vandenberg, Jamie I.; Perry, Matthew D.

    2014-01-01

    The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg56 of the PAS domain and Asp803 of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels. PMID:25074935

  15. Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

    PubMed Central

    Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

    2013-01-01

    The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

  16. Brain activation and deactivation during location and color working memory tasks in 11-13-year-old children.

    PubMed

    Vuontela, Virve; Steenari, Maija-Riikka; Aronen, Eeva T; Korvenoja, Antti; Aronen, Hannu J; Carlson, Synnöve

    2009-02-01

    Using functional magnetic resonance imaging (fMRI) and n-back tasks we investigated whether, in 11-13-year-old children, spatial (location) and nonspatial (color) information is differentially processed during visual attention (0-back) and working memory (WM) (2-back) tasks and whether such cognitive task performance, compared to a resting state, results in regional deactivation. The location 0-back task, compared to the color 0-back task, activated segregated areas in the frontal, parietal and occipital cortices whereas no differentially activated voxels were obtained when location and color 2-back tasks were directly contrasted. Several midline cortical areas were less active during 0- and 2-back task performance than resting state. The task-induced deactivation increased with task difficulty as demonstrated by larger deactivation during 2-back than 0-back tasks. The results suggest that, in 11-13-year-old children, the visual attentional network is differently recruited by spatial and nonspatial information processing, but the functional organization of cortical activation in WM in this age group is not based on the type of information processed. Furthermore, 11-13-year-old children exhibited a similar pattern of cortical deactivation that has been reported in adults during cognitive task performance compared to a resting state.

  17. 75 FR 9095 - Production and Airworthiness Approval, Part Marking, and Miscellaneous Amendments; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... first paragraph of section 6, Location of or Change to Manufacturing Facilities, remove the words ``or physical changes'' from the first sentence, and remove the word ``only'' from the last sentence. 3. On page... Maintenance, Preventive Maintenance, Rebuilding, and Alterations, remove the word ``only'' from the last...

  18. Distinctive Spectral Features of Exciton and Excimer States in the Ultrafast Electronic Deactivation of the Adenine Dinucleotide

    NASA Astrophysics Data System (ADS)

    Stuhldreier, Mayra C.; Röttger, Katharina; Temps, Friedrich

    We report the observation by transient absorption spectroscopy of distinctive spectro-temporal signatures of delocalized exciton versus relaxed, weakly bound excimer states in the ultrafast electronic deactivation after UV photoexcitation of the adenine dinucleotide.

  19. Sources of deactivation during glycerol conversion on Ni/γ-Al 2 O 3

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

    Chimentão, R. J.; Miranda, B. C.; Szanyi, J.

    Hydrogenolysis of glycerol was studied using a diluted aqueous solution of glycerol in gas phase and atmospheric pressure on Ni/γ-Al2O3 catalyst. The catalytic transformation of glycerol generates products derived from dehydration, dehydrogenation, hydrogenolysis and condensation reactions. Deep hydrogenolysis route to produce CH4 prevails in the first few hours of reaction. As the reaction time progress, dehydration-dehydrogenation products start to appear. Here, a description of the deactivation sources and its effects on the catalytic performance of Ni catalyst was proposed. The catalyst was characterized before and after the catalytic reaction by high-resolution transmission electron microscopy (HRTEM) and by employing Fourier transformedmore » infrared spectroscopy (FTIR) of adsorbed CO. A source of deactivation was due to carbonaceous deposition. FTIR at low CO dosing pressure reveal bands assignments species essentially due to linear and bridge carbonyls, whereas high pressure CO dosing produces a complex spectra due to polycarbonyls. X-ray absorption near edge structure (XANES) analysis was employed to reveal the initial degree of reduction of the fresh catalyst. The oxidation of metallic Ni in the course of reaction may also be considered as a source of deactivation. Ni oxide species promote dehydration routes. Alumina support facilitates nickel species to be more active toward interacting with glycerol. Dehydration, which takes place on the acid sites, is the mainly route related to the generation of carbon deposition and to the observed catalyst deactivation. Another source of deactivation was due to carbiding of Ni to form Ni3C. The regeneration of used Ni catalyst was achieved by oxidation-reduction steps at 723 K.« less

  20. Implantable cardioverter defibrillator knowledge and end-of-life device deactivation: A cross-sectional survey.

    PubMed

    McEvedy, Samantha M; Cameron, Jan; Lugg, Eugene; Miller, Jennifer; Haedtke, Chris; Hammash, Muna; Biddle, Martha J; Lee, Kyoung Suk; Mariani, Justin A; Ski, Chantal F; Thompson, David R; Chung, Misook Lee; Moser, Debra K

    2018-01-01

    End-of-life implantable cardioverter defibrillator deactivation discussions should commence before device implantation and be ongoing, yet many implantable cardioverter defibrillators remain active in patients' last days. To examine associations among implantable cardioverter defibrillator knowledge, patient characteristics and attitudes to implantable cardioverter defibrillator deactivation. Cross-sectional survey using the Experiences, Attitudes and Knowledge of End-of-Life Issues in Implantable Cardioverter Defibrillator Patients Questionnaire. Participants were classified as insufficient or sufficient implantable cardioverter defibrillator knowledge and the two groups were compared. Implantable cardioverter defibrillator recipients ( n = 270, mean age 61 ± 14 years; 73% male) were recruited from cardiology and implantable cardioverter defibrillator clinics attached to two tertiary hospitals in Melbourne, Australia, and two in Kentucky, the United States. Participants with insufficient implantable cardioverter defibrillator knowledge ( n = 77, 29%) were significantly older (mean age 66 vs 60 years, p = 0.001), less likely to be Caucasian (77% vs 87%, p  = 0.047), less likely to have received implantable cardioverter defibrillator shocks (26% vs 40%, p = 0.031), and more likely to have indications of mild cognitive impairment (Montreal Cognitive Assessment score <24: 44% vs 16%, p < 0.001). Insufficient implantable cardioverter defibrillator knowledge was associated with attitudes suggesting unwillingness to discuss implantable cardioverter defibrillator deactivation, even during the last days towards end of life ( p < 0.05). Implantable cardioverter defibrillator recipients, especially those who are older or have mild cognitive impairment, often have limited knowledge about implantable cardioverter defibrillator deactivation. This study identified several potential teachable moments throughout the patients' treatment trajectory. An interdisciplinary approach is required to ensure that discussions about implantable cardioverter defibrillator deactivation issues are initiated at appropriate time points, with family members ideally also included.

  1. Negative BOLD in sensory cortices during verbal memory: a component in generating internal representations?

    PubMed

    Azulay, Haim; Striem, Ella; Amedi, Amir

    2009-05-01

    People tend to close their eyes when trying to retrieve an event or a visual image from memory. However the brain mechanisms behind this phenomenon remain poorly understood. Recently, we showed that during visual mental imagery, auditory areas show a much more robust deactivation than during visual perception. Here we ask whether this is a special case of a more general phenomenon involving retrieval of intrinsic, internally stored information, which would result in crossmodal deactivations in other sensory cortices which are irrelevant to the task at hand. To test this hypothesis, a group of 9 sighted individuals were scanned while performing a memory retrieval task for highly abstract words (i.e., with low imaginability scores). We also scanned a group of 10 congenitally blind, which by definition do not have any visual imagery per se. In sighted subjects, both auditory and visual areas were robustly deactivated during memory retrieval, whereas in the blind the auditory cortex was deactivated while visual areas, shown previously to be relevant for this task, presented a positive BOLD signal. These results suggest that deactivation may be most prominent in task-irrelevant sensory cortices whenever there is a need for retrieval or manipulation of internally stored representations. Thus, there is a task-dependent balance of activation and deactivation that might allow maximization of resources and filtering out of non relevant information to enable allocation of attention to the required task. Furthermore, these results suggest that the balance between positive and negative BOLD might be crucial to our understanding of a large variety of intrinsic and extrinsic tasks including high-level cognitive functions, sensory processing and multisensory integration.

  2. Fuel Efficiency Mapping of a 2014 6-Cylinder GM EcoTec 4.3L Engine with Cylinder Deactivation (SAE 2016-01-0662)

    EPA Science Inventory

    This paper describes the method and test results of the engine dyno portion of the benchmarking test results including engine fuel consumption maps showing the effects of cylinder deactivation engine technology.

  3. Mathematics anxiety reduces default mode network deactivation in response to numerical tasks.

    PubMed

    Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H

    2015-01-01

    Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval.

  4. Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

    PubMed

    Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

    2017-02-01

    Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

  5. Mathematics anxiety reduces default mode network deactivation in response to numerical tasks

    PubMed Central

    Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H.

    2015-01-01

    Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval. PMID:25954179

  6. Low temperature deactivation of Ge heavily n-type doped by ion implantation and laser thermal annealing

    NASA Astrophysics Data System (ADS)

    Milazzo, R.; Impellizzeri, G.; Piccinotti, D.; De Salvador, D.; Portavoce, A.; La Magna, A.; Fortunato, G.; Mangelinck, D.; Privitera, V.; Carnera, A.; Napolitani, E.

    2017-01-01

    Heavy doping of Ge is crucial for several advanced micro- and optoelectronic applications, but, at the same time, it still remains extremely challenging. Ge heavily n-type doped at a concentration of 1 × 1020 cm-3 by As ion implantation and melting laser thermal annealing (LTA) is shown here to be highly metastable. Upon post-LTA conventional thermal annealing As electrically deactivates already at 350 °C reaching an active concentration of ˜4 × 1019 cm-3. No significant As diffusion is detected up to 450 °C, where the As activation decreases further to ˜3 × 1019 cm-3. The reason for the observed detrimental deactivation was investigated by Atom Probe Tomography and in situ High Resolution X-Ray Diffraction measurements. In general, the thermal stability of heavily doped Ge layers needs to be carefully evaluated because, as shown here, deactivation might occur at very low temperatures, close to those required for low resistivity Ohmic contacting of n-type Ge.

  7. Solvent effects on the ultrafast nonradiative deactivation mechanisms of thymine in aqueous solution: Excited-state QM/MM molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Nakayama, Akira; Arai, Gaku; Yamazaki, Shohei; Taketsugu, Tetsuya

    2013-12-01

    On-the-fly excited-state quantum mechanics/molecular mechanics molecular dynamics (QM/MM-MD) simulations of thymine in aqueous solution are performed to investigate the role of solvent water molecules on the nonradiative deactivation process. The complete active space second-order perturbation theory (CASPT2) method is employed for a thymine molecule as the QM part in order to provide a reliable description of the excited-state potential energies. It is found that, in addition to the previously reported deactivation pathway involving the twisting of the C-C double bond in the pyrimidine ring, another efficient deactivation pathway leading to conical intersections that accompanies the out-of-plane displacement of the carbonyl group is observed in aqueous solution. Decay through this pathway is not observed in the gas phase simulations, and our analysis indicates that the hydrogen bonds with solvent water molecules play a key role in stabilizing the potential energies of thymine in this additional decay pathway.

  8. Immobilized glucose oxidase--catalase and their deactivation in a differential-bed loop reactor.

    PubMed

    Prenosil, J E

    1979-01-01

    Glucose oxidase containing catalase was immobilized with a copolymer of phenylenediamine and glutaraldehyde on pumice and titania carrier to study the enzymatic oxidation of glucose in a differential-bed loop reactor. The reaction rate was found to be first order with respect to the concentration of limiting oxygen substrate, suggesting a strong external mass-transfer resistance for all the flow rates used. The partial pressure of oxygen was varied from 21.3 up to 202.6 kPa. The use of a differential-bed loop reactor for the determination of the active enzyme concentration in the catalyst with negligible internal pore diffusion resistance is shown. Catalyst deactivation was studied, especially with respect to the presence of catalase. It is believed that the hydrogen peroxide formed in the oxidation reaction deactivates catalase first; if an excess of catalase is present, the deactivation of glucose oxidase remains small. The mathematical model subsequently developed adequately describes the experimental results.

  9. Deactivation Mechanisms of Pt/Pd-based Diesel Oxidation Catalysts

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

    Wiebenga, Michelle H.; Kim, Chang H.; Schmieg, Steven J.

    2012-04-30

    Currently precious metal-based diesel oxidation catalysts (DOC) containing platinum (Pt) and palladium (Pd) are most commonly used for the oxidation of hydrocarbon and NO in diesel exhaust hydrocarbon oxidation. The present work has been carried out to investigate the deactivation mechanisms of the DOC from its real-world vehicle operation by coupling its catalytic activity measurements with surface characterization including x-ray diffraction, transmission electron microscopy, and x-ray photoelectron spectroscopy. A production Pt-Pd DOC was obtained after being aged on a vehicle driven for 135,000 miles in order to study its deactivation behavior. The performance of the vehicle-aged part was correlated withmore » that of the simulated hydrothermal lab aged sample assuming that Pt-Pd sintering plays a major role in irreversible catalyst deactivation. In addition to the hydrothermal sintering, the deterioration of hydrocarbon and NO oxidation performance was caused by surface poisoning. The role of the various aging factors in determining long-term performance in mobile applications will be discussed.« less

  10. The Role of Phosphorus and Soot on the Deactivation of Diesel Oxidation Catalysts

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

    Eaton, Scott J; Nguyen, Ke; Bunting, Bruce G

    The deactivation of diesel oxidation catalysts (DOCs) by soot contamination and lube-oil derived phosphorus poisoning is investigated. Pt/CeO2/-Al2O3 DOCs aged using three different protocols developed by the authors and six high mileage field-returned DOCs of similar formulation are evaluated for THC and CO oxidation performance using a bench-flow reactor. Collectively, these catalysts exhibit a variety of phosphorus and soot morphologies contributing to performance deactivation. To isolate and examine the contribution of each deactivation mechanism, performance evaluations are carried out for each DOC ''as received'' and after removal of surface carbon in a high-temperature oxidizing environment. In such a manner themore » deactivation contribution of soot contamination is de-convoluted from that of phosphorus poisoning. It will be shown that this is accomplished while preserving phosphorus (and to a lesser degree sulfur, calcium and zinc) chemistries and concentrations within the washcoat. Washcoat contaminant information and materials changes are characterized using electron-probe microanalysis (EPMA), X-ray diffraction (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), BET surface area, oxygen storage capacity (OSC), X-ray fluorescence (XRF) and inductively coupled plasma (ICP) analysis, from which the relative severity of each mechanism can be quantified. Results show that soot contamination from diesel exhaust severely degrades THC and CO oxidation performance by acting as a catalyst surface diffusion barrier. This results in a considerable increase of light-off temperatures. In contrast, phosphorus poisoning, which is considered a significant deactivation mechanism in three-way catalysts, is shown to have minimal effect on DOC oxidation performance for the conditions studied here. Material changes include the formation of both Ce(III-IV) and aluminum phosphates which do not significantly hinder the THC and CO oxidation in lean exhaust. In addition, thermal aging and sulfur poisoning are shown to produce minimal contributions to the overall deactivation. Consequently, performance of aged DOCs after soot removal is observed to be comparable to that of a fresh catalyst under our testing conditions.« less

  11. 14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 135. (g) Except for holders of a sport pilot certificate, the holder of a pilot certificate issued... is not used under part 121, 129, or 135 of this chapter. The holder of a sport pilot certificate may... airworthiness certificate in the light-sport category. (h) Notwithstanding the provisions of paragraph (g) of...

  12. Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

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

    Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

    The stability of palladium supported on ceria (Pd/CeO 2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

  13. Psychophysiological changes following auditory subliminal suggestions for activation and deactivation.

    PubMed

    Borgeat, F; Goulet, J

    1983-06-01

    This study was to measure eventual psychophysiological changes resulting from auditory subliminal activation or deactivation suggestions. 18 subjects were alternately exposed to a control situation and to 25-dB activating and deactivating suggestions masked by a 40-dB white noise. Physiological measures (EMG, heart rate, skin-conductance levels and responses, and skin temperature) were recorded while subjects listened passively to the suggestions, during a stressing task that followed and after that task. Multivariate analysis of variance showed a significant effect of the activation subliminal suggestions during and following the stressing task. This result is discussed as indicating effects of consciously unrecognized perceptions on psychophysiological responses.

  14. Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

    DOE PAGES

    Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

    2016-11-21

    The stability of palladium supported on ceria (Pd/CeO 2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

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

    Miller, Daniel P.; Tymińska, Nina; Zurek, Eva, E-mail: ezurek@buffalo.edu

    Dispersion corrected Density Functional Theory calculations were employed to study the adsorption of benzenes derivatized with functional groups encompassing a large region of the activated/deactivated spectrum to the Ag(111) surface. Benzenes substituted with weak activating or deactivating groups, such as methyl and fluoro, do not have a strong preference for adsorbing to a particular site on the substrate, with the corrugations in the potential energy surface being similar to those of benzene. Strong activating (N(CH{sub 3}){sub 2}) and deactivating (NO{sub 2}) groups, on the other hand, possess a distinct site preference. The nitrogen in the former prefers to lie abovemore » a silver atom (top site), but in the latter a hollow hexagonal-closed-packed (H{sub hcp}) site of the Ag(111) surface is favored instead. Benzenes derivatized with classic activating groups donate electron density from their highest occupied molecular orbital to the surface, and those functionalized with deactivating groups withdraw electron density from the surface into orbitals that are unoccupied in the gas phase. For benzenes functionalized with two substituents, the groups that are strongly activating or deactivating control the site preference and the other groups assume sites that are, to a large degree, dictated by their positions on the benzene ring. The relative stabilities of the ortho, meta, and para positional isomers of disubstituted benzenes can, in some cases, be modified by adsorption to the surface.« less

  16. The β1 Subunit Enhances Oxidative Regulation of Large-Conductance Calcium-activated K+ Channels

    PubMed Central

    Santarelli, Lindsey Ciali; Chen, Jianguo; Heinemann, Stefan H.; Hoshi, Toshinori

    2004-01-01

    Oxidative stress may alter the functions of many proteins including the Slo1 large conductance calcium-activated potassium channel (BKCa). Previous results demonstrated that in the virtual absence of Ca2+, the oxidant chloramine-T (Ch-T), without the involvement of cysteine oxidation, increases the open probability and slows the deactivation of BKCa channels formed by human Slo1 (hSlo1) α subunits alone. Because native BKCa channel complexes may include the auxiliary subunit β1, we investigated whether β1 influences the oxidative regulation of hSlo1. Oxidation by Ch-T with β1 present shifted the half-activation voltage much further in the hyperpolarizing direction (−75 mV) as compared with that with α alone (−30 mV). This shift was eliminated in the presence of high [Ca2+]i, but the increase in open probability in the virtual absence of Ca2+ remained significant at physiologically relevant voltages. Furthermore, the slowing of channel deactivation after oxidation was even more dramatic in the presence of β1. Oxidation of cysteine and methionine residues within β1 was not involved in these potentiated effects because expression of mutant β1 subunits lacking cysteine or methionine residues produced results similar to those with wild-type β1. Unlike the results with α alone, oxidation by Ch-T caused a significant acceleration of channel activation only when β1 was present. The β1 M177 mutation disrupted normal channel activation and prevented the Ch-T–induced acceleration of activation. Overall, the functional effects of oxidation of the hSlo1 pore-forming α subunit are greatly amplified by the presence of β1, which leads to the additional increase in channel open probability and the slowing of deactivation. Furthermore, M177 within β1 is a critical structural determinant of channel activation and oxidative sensitivity. Together, the oxidized BKCa channel complex with β1 has a considerable chance of being open within the physiological voltage range even at low [Ca2+]i. PMID:15452197

  17. RTEMS Centre - Support and Maintenance Centre to RTEMS Operating System

    NASA Astrophysics Data System (ADS)

    Silva, H.; Constantino, A.; Freitas, D.; Coutinho, M.; Faustino, S.; Mota, M.; Colaço, P.; Sousa, J.; Dias, L.; Damjanovic, B.; Zulianello, M.; Rufino, J.

    2009-05-01

    RTEMS CENTRE - Support and Maintenance Centre to RTEMS Operating System is a joint ESA/Portuguese Task Force initiative to develop a support and maintenance centre to the Real-Time Executive for Multiprocessor Systems (RTEMS). This paper gives a high level visibility of the progress, the results obtained and the future work in the RTEMS CENTRE [6] and in the RTEMS Improvement [7] projects. RTEMS CENTRE started officially in November 2006, with the RTEMS 4.6.99.2 version. A full analysis of RTEMS operating system was produced. The architecture was analysed in terms of conceptual, organizational and operational concepts. The original objectives [1] of the centre were primarily to create and maintain technical expertise and competences in this RTOS, to develop a website to provide the European Space Community an entry point for obtaining support (http://rtemscentre.edisoft.pt), to design, develop, maintain and integrate some RTEMS support tools (Timeline Tool, Configuration and Management Tools), to maintain flight libraries and Board Support Packages, to develop a strong relationship with the World RTEMS Community and finally to produce some considerations in ARINC-653, DO-178B and ECSS E-40 standards. RTEMS Improvement is the continuation of the RTEMS CENTRE. Currently the RTEMS, version 4.8.0, is being facilitated for a future qualification. In this work, the validation material is being produced following the Galileo Software Standards Development Assurance Level B [5]. RTEMS is being completely tested, errors analysed, dead and deactivated code removed and tests produced to achieve 100% statement and decision coverage of source code [2]. The SW to exploit the LEON Memory Management Unit (MMU) hardware will be also added. A brief description of the expected implementations will be given.

  18. Using Spatial Multiple Regression to Identify Intrinsic Connectivity Networks Involved in Working Memory Performance

    PubMed Central

    Gordon, Evan M.; Stollstorff, Melanie; Vaidya, Chandan J.

    2012-01-01

    Many researchers have noted that the functional architecture of the human brain is relatively invariant during task performance and the resting state. Indeed, intrinsic connectivity networks (ICNs) revealed by resting-state functional connectivity analyses are spatially similar to regions activated during cognitive tasks. This suggests that patterns of task-related activation in individual subjects may result from the engagement of one or more of these ICNs; however, this has not been tested. We used a novel analysis, spatial multiple regression, to test whether the patterns of activation during an N-back working memory task could be well described by a linear combination of ICNs delineated using Independent Components Analysis at rest. We found that across subjects, the cingulo-opercular Set Maintenance ICN, as well as right and left Frontoparietal Control ICNs, were reliably activated during working memory, while Default Mode and Visual ICNs were reliably deactivated. Further, involvement of Set Maintenance, Frontoparietal Control, and Dorsal Attention ICNs was sensitive to varying working memory load. Finally, the degree of left Frontoparietal Control network activation predicted response speed, while activation in both left Frontoparietal Control and Dorsal Attention networks predicted task accuracy. These results suggest that a close relationship between resting-state networks and task-evoked activation is functionally relevant for behavior, and that spatial multiple regression analysis is a suitable method for revealing that relationship. PMID:21761505

  19. Deactivating the Writing Program.

    ERIC Educational Resources Information Center

    Strickland, James

    A written language learner must be given an environment that enables or fosters writing development. Unfortunately, the typical system of education and the learning strategies that are taught are at times the very things that deactivate, frustrate, and even pervert the writing program. In fact, some of the rules that student writers respond to are…

  20. Cerebral processing of auditory stimuli in patients with irritable bowel syndrome

    PubMed Central

    Andresen, Viola; Poellinger, Alexander; Tsrouya, Chedwa; Bach, Dominik; Stroh, Albrecht; Foerschler, Annette; Georgiewa, Petra; Schmidtmann, Marco; van der Voort, Ivo R; Kobelt, Peter; Zimmer, Claus; Wiedenmann, Bertram; Klapp, Burghard F; Monnikes, Hubert

    2006-01-01

    AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found in IBS patients. PMID:16586541

  1. Alterations in post-movement beta event related synchronization throughout the migraine cycle: A controlled, longitudinal study.

    PubMed

    Mykland, Martin Syvertsen; Bjørk, Marte Helene; Stjern, Marit; Sand, Trond

    2018-04-01

    Background The migraine brain is believed to have altered cortical excitability compared to controls and between migraine cycle phases. Our aim was to evaluate post-activation excitability through post-movement beta event related synchronization (PMBS) in sensorimotor cortices with and without sensory discrimination. Subjects and methods We recorded EEG of 41 migraine patients and 31 healthy controls on three different days with classification of days in relation to migraine phases. During each recording, subjects performed one motor and one sensorimotor task with the right wrist. Controls and migraine patients in the interictal phase were compared with repeated measures (R-) ANOVA and two sample Student's t-test. Migraine phases were compared to the interictal phase with R-ANOVA and paired Student's t-test. Results The difference between PMBS at the contralateral and ipsilateral sensorimotor cortex was altered throughout the migraine cycle. Compared to the interictal phase, we found decreased PMBS at the ipsilateral sensorimotor cortex in the ictal phase and increased PMBS in the preictal phase. Lower ictal PMBS was found in bilateral sensorimotor cortices in patients with right side headache predominance. Conclusion The cyclic changes of PMBS in migraine patients may indicate that a dysfunction in deactivation and interhemispheric inhibition of the sensorimotor cortex is involved in the migraine attack cascade.

  2. High-Fructose Consumption Impairs the Redox System and Protein Quality Control in the Brain of Syrian Hamsters: Therapeutic Effects of Melatonin.

    PubMed

    Bermejo-Millo, Juan Carlos; Guimarães, Marcela Rodrigues Moreira; de Luxán-Delgado, Beatriz; Potes, Yaiza; Pérez-Martínez, Zulema; Díaz-Luis, Andrea; Caballero, Beatriz; Solano, Juan José; Vega-Naredo, Ignacio; Coto-Montes, Ana

    2018-02-28

    Although numerous studies have demonstrated the harmful effect of excessive fructose consumption at the systemic level, there is little information on its effects in the central nervous system. The purpose of the present work was to study the cellular alterations related to oxidative stress and protein quality control systems induced by a high-fructose diet in the brain of Syrian hamsters and their possible attenuation by exogenous melatonin. High-fructose intake induced type II diabetes together with oxidative damage, led to alterations of the unfolded protein response by activating the eIF2α branch, and impaired the macroautophagic machinery in the brain, favoring the accumulation of aggregates labeled for selective degradation and neurodegeneration markers such as β-amyloid (1-42), tau-p-S199, and tau-p-S404. Melatonin attenuated the manifestation of type II diabetes and reduced oxidative stress, deactivated eIF2α, and decreased tau-p-S404 levels in the brain of animals fed a high-fructose diet.

  3. Threat-Detection and Attentional Bias to Threat in Women Recovered from Anorexia Nervosa: Neural Alterations in Extrastriate and Medial Prefrontal Cortices.

    PubMed

    Bang, Lasse; Rø, Øyvind; Endestad, Tor

    2017-03-01

    Behavioral studies have shown that anorexia nervosa (AN) is associated with attentional bias to general threat cues. The neurobiological underpinnings of attentional bias to threat in AN are unknown. This study investigated the neural responses associated with threat-detection and attentional bias to threat in AN. We measured neural responses to a dot-probe task, involving pairs of angry and neutral face stimuli, in 22 adult women recovered from AN and 21 comparison women. Recovered AN women did not exhibit a behavioral attentional bias to threat. In response to angry faces, recovered women showed significant hypoactivation in the extrastriate cortex. During attentional bias to angry faces, recovered women showed significant hyperactivation in the medial prefrontal cortex. This was because of significant deactivation in comparison women, which was absent in recovered AN women. Women recovered from AN are characterized by altered neural responses to threat cues. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  4. Silica supported palladium nanoparticles for the decarboxylation of high-acid feedstocks: Design, deactivation and regeneration

    NASA Astrophysics Data System (ADS)

    Ping, Eric Wayne

    2011-12-01

    The major goals of this thesis were to (1) design and synthesize a supported catalyst with well-defined monodisperse palladium nanoparticles evenly distributed throughout an inorganic oxide substrate with tunable porosity characteristics, (2) demonstrate the catalytic activity of this material in the decarboxylation of long chain fatty acids and their derivatives to make diesel-length hydrocarbons, (3) elucidate the deactivation mechanism of supported palladium catalysts under decarboxylation conditions via post mortem catalyst characterization and develop a regeneration methodology thereupon, and (4) apply this catalytic system to a real low-value biofeedstock. Initial catalyst designs were based on the SBA-15 silica support, but in an effort to maximize loading and minimize mass transfer limitations, silica MCF was synthesized as catalyst support. Functionalization with various silane ligands yielded a surface that facilitated even distribution of palladium precursor salts throughout the catalyst particle, and, after reduction, monodisperse palladium nanoparticles approximately 2 nm in diameter. Complete characterization was performed on this Pd-MCF catalyst. The Pd-MCF catalyst showed high one-time activity in the decarboxylation of fatty acids to hydrocarbons in dodecane at 300°C. Hydrogen was found to be an unnecessary reactant in the absence of unsaturations, but was required in their presence---full hydrogenation of the double bonds occurs before any decarboxylation can take place. The Pd-MCF also exhibited good activity for alkyl esters and glycerol, providing a nice hypothetical description of a stepwise reaction pathway for catalytic decarboxylation of acids and their derivatives. As expected, the Pd-MCF catalyst experienced severe deactivation after only one use. Substantial effort was put into elucidating the nature of this deactivation via post mortem catalyst characterization. H2 chemisorption confirmed a loss of active surface area, but TEM and EXAFS ruled out morphological alterations in the supported nanoparticles. Significant decreases in pore volume and surface area via N2 physisorption put deposition under suspicion and TGA confirmed the presence of organic species in the material. Initial attempts to remove the deposits via calcination were successful, but at the expense of severe nanoparticle growth. GC-MS, NMR and FT-IR helped speciate the deposition, mainly confirming the presence of residual reactant acid. A regeneration scheme was developed to remove these compounds, and subsequent catalyst reuses exhibited high decarboxylation activity. Finally, the Pd-MCF catalyst was applied to a real feedstock: a wastewater-derived brown grease from a poultry rendering facility. Attempts at decarboxylating the raw material failed, so efforts to polish the material via dewaxing and degumming were undertaken. The treatments were able to optimize a three-phase separation, and the resultant polished brown grease was successfully decarboxylated to diesel-length hydrocarbons with high conversions and selectivities.

  5. Characterization of coke, or carbonaceous matter, formed on CoMo catalysts used in hydrodesulfurization unit in oil refinery

    NASA Astrophysics Data System (ADS)

    Kimura, Nobuharu; Iwanami, Yoshimu; Koide, Ryutaro; Kudo, Reiko

    2017-06-01

    When a mixture of light gas oil (LGO) and light cycle oil is fed into an oil refinery’s hydrodesulfurization (HDS) unit to produce diesel fuel, the catalyst in the HDS unit is rapidly deactivated. By contrast, when the feed is LGO mixed with residue desulfurization gas oil, the catalyst is deactivated slowly. Hoping to understand why, the authors focused on the coke formed on the catalysts during the HDS reaction. The result of a comprehensive analysis of the coke suggested that the ways coke formed and grew on the catalysts may differ depending on the feeds used, which in turn could affect the deactivation behaviors of the catalysts.

  6. Decommissioning of the 247-F Fuel Manufacturing Facility at the Savannah River Site (SRS)

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

    Santos, Joseph K.; Chostner, Stephen M.

    Building 247-F at SRS was a roughly 110,000 ft{sup 2} two-story facility designed and constructed during the height of the cold war naval buildup to provide additional naval nuclear fuel manufacturing capacity in early 1980's. The manufacturing process employed a wide variety of acids, bases, and other hazardous materials. As the need for naval fuel declined, the facility was shut down and underwent initial deactivation, which was completed in 1990. All process systems were flushed with water and drained using the existing process drain valves. However, since these drains were not always installed at the lowest point in piping andmore » equipment systems, a significant volume of liquid remained after initial deactivation. After initial deactivation, a non-destructive assay of the process area identified approximately 17 ({+-}100%) kg of uranium held up in equipment and piping. The facility was placed in Surveillance and Maintenance mode until 2003, when the decision was made to perform final deactivation, and then decommission the facility. The following lessons were learned as a result of the D and D of building 247-F. Successful D and D of a major radiochemical process building requires significant up-front planning by a team of knowledgeable personnel led by a strong project manager. The level of uncertainty and resultant risk to timely, cost effective project execution was found to be high. Examples of the types of problems encountered which had high potential to adversely impact cost and schedule performance are described below. Low level and sanitary waste acceptance criteria do not allow free liquids in waste containers. These liquids, which are often corrosive, must be safely removed from the equipment before it is loaded to waste containers. Drained liquids must be properly managed, often as hazardous or mixed waste. Tapping and draining of process lines is a dangerous operation, which must be performed carefully. The temptation to become complacent when breaking into lines is great. Incidents of personnel exposure to liquids during draining are likely. Records from the initial 1990 deactivation led early work planners to assume the facility was cold, dark and dry. This turned out to be a poor assumption. Work instructions had to be modified to require that engineers evaluate each of several hundred process lines to identify the low point, where a tap and drain system could be installed to allow positive verification that the line was empty before the line was cut for removal. During the period between facility shut down in 1990 and the start of final deactivation in 2003, roof leaks had developed, allowing rain water to enter building 247-F, which provided an environment for mold growth. Sampling confirmed the presence of Stachybotrys chartarum, a toxic indoor mold that grows on wet cellulosic material, such as drywall paper. D and D workers in areas where this hazard was identified were required to where proper personal protective equipment, which complicated work execution. Discovery of the potential presence of uniquely hazardous chemicals such as shock sensitive compounds and toxic uranium hexafluoride became issues which required investigation and special handling strategies. Team access to subject matter experts, who could quickly provide the required guidance for safe material handling, was critical to keeping the project on schedule. In old legacy facilities, it is possible that the D and D workers will be exposed to undocumented energy sources such as energized electrical conductors and pipes containing hazardous materials that originate outside the boundaries of the facility. Significant effort must be expended on adequate mechanical and electrical isolation. Subdividing the facility into well defined zones for which detailed zone-specific end points could be developed proved to be a highly effective project management strategy. Waste management must be carefully planned. The rate of waste generation as the facility is converted from a structure to waste can frequently exceed the D and D team's resources to characterize, package, store and transport the waste to a disposal facility in a timely manner. This can lead to schedule delays and/or increased project cost.« less

  7. Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

    PubMed Central

    Wachholtz, Amy; Gonzalez, Gerardo

    2014-01-01

    Introduction Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. Method 120 individuals with chronic pain were recruited in 4 groups (n=30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M=121 weeks; SD=23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. Results A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (Log rank=15.50; p<.001) and tolerance (Log rank=20.11; p<.001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p’s<.01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p<.05), with the highest tolerance found among opioid naïve control group participants (p’s<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R=.37; p<.05); but duration of abstinence did not alter sensitivity (ns). Conclusion Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. PMID:25456326

  8. Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain.

    PubMed

    Wachholtz, Amy; Gonzalez, Gerardo

    2014-12-01

    Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation. 120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses. A Kaplan-Meier-Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's < .001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns). Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Maintenance of forest ecosystem health and vitality

    Treesearch

    Ryan D. DeSantis; W. Keith Moser

    2016-01-01

    Forest health will likely be threatened by a number of factors - including fragmentation, fire regime alteration, and a variety of diseases, insects, and invasive plants - along with global climate change (Krist et al. 2007, Tkacz et al. 2008). By itself, global climate change could dramatically and rapidly alter forest composition and structure (Allen and Breshears...

  10. CATALYTIC STEAM REFORMING OF CHLOROCARBONS: CATALYST DEACTIVATION. (R826694C633)

    EPA Science Inventory

    Deactivation of 0.5 wt.% Pt/small gamma, Greek-Al2O3 catalysts during trichloroethylene (TCE)–steam reforming was studied with experiments at 700°C, H

  11. A Literature Review and Analysis of Mode Deactivation Therapy

    ERIC Educational Resources Information Center

    Apsche, Jack A.

    2010-01-01

    This article is a review of articles, chapters and current research examining Mode Deactivation Therapy. Current applications of MDT suggest that mindfulness is a core component of MDT, as well as acceptance, defusion and validation, clarification and redirection of the functional alternative beliefs. These components are the core of MDT and a…

  12. 77 FR 10406 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... powered by Pratt & Whitney JT9D series engines require installation of a new bracket for stowing the... serviceable stowage bracket for the deactivation pins on all airplanes powered by Pratt & Whitney JT9D series... Pratt & Whitney JT9D series engines require installation of a new bracket for stowing the deactivation...

  13. Mode Deactivation Therapy (MDT) Family Therapy: A Theoretical Case Analysis

    ERIC Educational Resources Information Center

    Apsche, J. A.; Ward Bailey, S. R.

    2004-01-01

    This case study presents a theoretical analysis of implementing mode deactivation therapy (MDT) (Apsche & Ward Bailey, 2003) family therapy with a 13 year old Caucasian male. MDT is a form of cognitive behavioral therapy (CBT) that combines the balance of dialectical behavior therapy (DBT) (Linehan, 1993), the importance of perception from…

  14. Mode Deactivation Therapy (MDT): A Theoretical Case Analysis on a Suicidal Adolescent

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Siv, Alexander M.

    2005-01-01

    This case study presents a case study of the effectiveness of Mode deactivation therapy (MDT) (Apsche, Bass, Jennings, Murphy, Hunter, and Siv, 2005) with an adolescent male, with reactive conduct disorder, PTSD and 8 lethal suicide attempts. The youngster was hospitalized four times for suicide attempts, three previous placements in residential…

  15. The Approach of Emotional Deactivation of Prejudice

    ERIC Educational Resources Information Center

    Boucher, Jean-Nil

    2011-01-01

    The aim of the approach of emotional deactivation is to help students reduce the prejudice they may feel towards diverse social groups. Be those groups homosexuals, people living with a disability or immigrants, the victims of prejudice are invited to come into classrooms and to confront the preconceptions that students have in their respect.…

  16. Subject specific finite element modeling of periprosthetic femoral fracture using element deactivation to simulate bone failure.

    PubMed

    Miles, Brad; Kolos, Elizabeth; Walter, William L; Appleyard, Richard; Shi, Angela; Li, Qing; Ruys, Andrew J

    2015-06-01

    Subject-specific finite element (FE) modeling methodology could predict peri-prosthetic femoral fracture (PFF) for cementless hip arthoplasty in the early postoperative period. This study develops methodology for subject-specific finite element modeling by using the element deactivation technique to simulate bone failure and validate with experimental testing, thereby predicting peri-prosthetic femoral fracture in the early postoperative period. Material assignments for biphasic and triphasic models were undertaken. Failure modeling with the element deactivation feature available in ABAQUS 6.9 was used to simulate a crack initiation and propagation in the bony tissue based upon a threshold of fracture strain. The crack mode for the biphasic models was very similar to the experimental testing crack mode, with a similar shape and path of the crack. The fracture load is sensitive to the friction coefficient at the implant-bony interface. The development of a novel technique to simulate bone failure by element deactivation of subject-specific finite element models could aid prediction of fracture load in addition to fracture risk characterization for PFF. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

  17. Effect of pH on subunit association and heat protection of soybean alpha-galactosidase

    NASA Technical Reports Server (NTRS)

    Porter, J. E.; Sarikaya, A.; Herrmann, K. M.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

    1992-01-01

    Soybeans contain the enzyme alpha-galactosidase, which hydrolyzes alpha-1, 6 linkages in stachyose and raffinose to give sucrose and galactose. We have found that galactose, a competitive product inhibitor of alpha-galactosidase, strongly promotes the heat stability of the tetrameric form of the enzyme at pH 4.0 and at temperatures of up to 70 degrees C for 60 min. Stachyose and raffinose also protect alpha-galactosidase from denaturation at pH 4.0 although to a lesser extent. Glucose and mannose have little effect. At pH 7.0 the enzyme is a monomer, and galactose has no effect on the heat stability of the enzyme. In the absence of heat protection of the enzyme by added sugars, a series deactivation mechanism was found to describe the deactivation data. In comparison, a unimolecular, non-first order deactivation model applies at pH 4.0, where heat protection effects were observed. At a temperature above 60 degrees C, simple deactivation is a suitable model. The results suggest that alpha-galactosidase conformation and heat stability are directly related.

  18. Lignocellulosic hydrolysate inhibitors selectively inhibit/deactivate cellulase performance.

    PubMed

    Mhlongo, Sizwe I; den Haan, Riaan; Viljoen-Bloom, Marinda; van Zyl, Willem H

    2015-12-01

    In this study, we monitored the inhibition and deactivation effects of various compounds associated with lignocellulosic hydrolysates on individual and combinations of cellulases. Tannic acid representing polymeric lignin residues strongly inhibited cellobiohydrolase 1 (CBH1) and β-glucosidase 1 (BGL1), but had a moderate inhibitory effect on endoglucanase 2 (EG2). Individual monomeric lignin residues had little or no inhibitory effect on hydrolytic enzymes. However, coniferyl aldehyde and syringaldehyde substantially decreased the activity of CBH1 and deactivated BGL1. Acetic and formic acids also showed strong inhibition of BGL1 but not CBH1 and EG2, whereas tannic, acetic and formic acid strongly inhibited a combination of CBH1 and EG2 during Avicel hydrolysis. Diminishing enzymatic hydrolysis is largely a function of inhibitor concentration and the enzyme-inhibitor relationship, rather than contact time during the hydrolysis process (i.e. deactivation). This suggests that decreased rates of hydrolysis during the enzymatic depolymerisation of lignocellulosic hydrolysates may be imparted by other factors related to substrate crystallinity and accessibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump.

    PubMed

    Bennekou, P; Kristensen, B I; Christophersen, P

    2003-09-01

    The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow ( t(1/2) about 30 s), whereas the deactivation was fast ( t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl(-) concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca(2+) influx via the cation channel and ensuing efflux via the Ca(2+) pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca(2+) pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

  20. Learning and recall of form discriminations during reversible cooling deactivation of ventral-posterior suprasylvian cortex in the cat.

    PubMed Central

    Lomber, S G; Payne, B R; Cornwell, P

    1996-01-01

    Extrastriate visual cortex of the ventral-posterior suprasylvian gyrus (vPS cortex) of freely behaving cats was reversibly deactivated with cooling to determine its role in performance on a battery of simple or masked two-dimensional pattern discriminations, and three-dimensional object discriminations. Deactivation of vPS cortex by cooling profoundly impaired the ability of the cats to recall the difference between all previously learned pattern and object discriminations. However, the cats' ability to learn or relearn pattern and object discriminations while vPS was deactivated depended upon the nature of the pattern or object and the cats' prior level of exposure to them. During cooling of vPS cortex, the cats could neither learn the novel object discriminations nor relearn a highly familiar masked or partially occluded pattern discrimination, although they could relearn both the highly familiar object and simple pattern discriminations. These cooling-induced deficits resemble those induced by cooling of the topologically equivalent inferotemporal cortex of monkeys and provides evidence that the equivalent regions contribute to visual processing in similar ways. Images Fig. 1 Fig. 3 PMID:8643686

  1. Free-energy studies reveal a possible mechanism for oxidation-dependent inhibition of MGL

    PubMed Central

    Scalvini, Laura; Vacondio, Federica; Bassi, Michele; Pala, Daniele; Lodola, Alessio; Rivara, Silvia; Jung, Kwang-Mook; Piomelli, Daniele; Mor, Marco

    2016-01-01

    The function of monoacylglycerol lipase (MGL), a key actor in the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2AG), is tightly controlled by the cell’s redox state: oxidative signals such as hydrogen peroxide suppress MGL activity in a reversible manner through sulfenylation of the peroxidatic cysteines, C201 and C208. Here, using as a starting point the crystal structures of human MGL (hMGL), we present evidence from molecular dynamics and metadynamics simulations along with high-resolution mass spectrometry studies indicating that sulfenylation of C201 and C208 alters the conformational equilibrium of the membrane-associated lid domain of MGL to favour closed conformations of the enzyme that do not permit the entry of substrate into the active site. PMID:27499063

  2. High-intensity erotic visual stimuli de-activate the primary visual cortex in women.

    PubMed

    Huynh, Hieu K; Beers, Caroline; Willemsen, Antoon; Lont, Erna; Laan, Ellen; Dierckx, Rudi; Jansen, Monique; Sand, Michael; Weijmar Schultz, Willibrord; Holstege, Gert

    2012-06-01

    The primary visual cortex, Brodmann's area (BA 17), plays a vital role in basic survival mechanisms in humans. In most neuro-imaging studies in which the volunteers have to watch pictures or movies, the primary visual cortex is similarly activated independent of the content of the pictures or movies. However, in case the volunteers perform demanding non-visual tasks, the primary visual cortex becomes de-activated, although the amount of incoming visual sensory information is the same. Do low- and high-intensity erotic movies, compared to neutral movies, produce similar de-activation of the primary visual cortex? Brain activation/de-activation was studied by Positron Emission Tomography scanning of the brains of 12 healthy heterosexual premenopausal women, aged 18-47, who watched neutral, low- and high-intensity erotic film segments. We measured differences in regional cerebral blood flow (rCBF) in the primary visual cortex during watching neutral, low-intensity erotic, and high-intensity erotic film segments. Watching high-intensity erotic, but not low-intensity erotic movies, compared to neutral movies resulted in strong de-activation of the primary (BA 17) and adjoining parts of the secondary visual cortex. The strong de-activation during watching high-intensity erotic film might represent compensation for the increased blood supply in the brain regions involved in sexual arousal, also because high-intensity erotic movies do not require precise scanning of the visual field, because the impact is clear to the observer. © 2012 International Society for Sexual Medicine.

  3. A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides

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

    Du Yuzhe; Song Weizhong; Groome, James R.

    2010-08-15

    Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivation. Recent studies have begun to reveal sodium channel residues important for pyrethroid binding. However, how pyrethroid binding leads to inhibition of sodium channel deactivation and inactivation remains elusive. In this study, we show that a negatively charged aspartic acid residue at position 802 (D802) located in the extracellular end of transmembrane segment 1 of domain II (IIS1) is critical for both the action ofmore » pyrethroids and the voltage dependence of channel activation. Charge-reversing or -neutralizing substitutions (K, G, or A) of D802 shifted the voltage dependence of activation in the depolarizing direction and reduced channel sensitivity to deltamethrin, a pyrethroid insecticide. The charge-reversing mutation D802K also accelerated open-state deactivation, which may have counteracted the inhibition of sodium channel deactivation by deltamethrin. In contrast, the D802G substitution slowed open-state deactivation, suggesting an additional mechanism for neutralizing the action of deltamethrin. Importantly, Schild analysis showed that D802 is not involved in pyrethroid binding. Thus, we have identified a sodium channel residue that is critical for regulating the action of pyrethroids on the sodium channel without affecting the receptor site of pyrethroids.« less

  4. Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity

    PubMed Central

    Samu, Dávid; Campbell, Karen L.; Tsvetanov, Kamen A.; Shafto, Meredith A.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Henson, Richard N.; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Mustafa, Abdur; Price, Darren; Taylor, Jason R.; Treder, Matthias; van Belle, Janna; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Henriques, Rafael; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Tyler, Lorraine K.

    2017-01-01

    Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23–87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains. PMID:28480894

  5. Tailoring the Employment of Offshore Wind Turbine Support Structure Load Mitigation Controllers

    NASA Astrophysics Data System (ADS)

    Shrestha, Binita; Kühn, Martin

    2016-09-01

    The currently available control concepts to mitigate aerodynamic and hydrodynamic induced support structure loads reduce either fore-aft or side-to-side damage under certain operational conditions. The load reduction is achieved together with an increase in loads in other components of the turbine e.g. pitch actuators or drive train, increasing the risk of unscheduled maintenance. The main objective of this paper is to demonstrate a methodology for reduction of support structure damage equivalent loads (DEL) in fore-aft and side-to-side directions using already available control concepts. A multi-objective optimization problem is formulated to minimize the DELs, while limiting the collateral effects of the control algorithms for load reduction. The optimization gives trigger values of sea state condition for the activation or deactivation of certain control concepts. As a result, by accepting the consumption of a small fraction of the load reserve in the design load envelope of other turbine components, a considerable reduction of the support structure loads is facilitated.

  6. Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity.

    PubMed

    Samu, Dávid; Campbell, Karen L; Tsvetanov, Kamen A; Shafto, Meredith A; Tyler, Lorraine K

    2017-05-08

    Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23-87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains.

  7. 30 CFR 75.1721 - Opening of new underground coal mines, or reopening and reactivating of abandoned or deactivated...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Opening of new underground coal mines, or reopening and reactivating of abandoned or deactivated coal mines, notification by the operator... LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75...

  8. A One Year Study of Mode Deactivation Therapy: Adolescent Residential Patients with Conduct and Personality Disorders

    ERIC Educational Resources Information Center

    Murphy, Christopher J.; Siv, Alexander M.

    2011-01-01

    This case study is to evaluate the effectiveness of Mode Deactivation Therapy (MDT) implementation in a child and adolescent residential treatment unit and provide preliminary effectiveness data on MDT versus treatment as usual (TAU). This case study compared the efficacy of two treatment methodologies for adolescent males in residential treatment…

  9. Family Mode Deactivation Therapy in a Residential Setting: Treating Adolescents with Conduct Disorder and Multi-Axial Diagnosis

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Zeiter, J. Scott; Houston, Marsha Ann

    2008-01-01

    Mode Deactivation Therapy (MDT) has been shown to be an effective treatment for a variety of adolescent disorders including emotional dysregulation, behavioral dysregulation, physical aggression, sexual aggression, and many harmful symptoms of anxiety and traumatic stress. MDT Family Therapy has been effective in reducing family disharmony in case…

  10. 40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

  11. 40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

  12. 40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

  13. 40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

  14. The presence of isolated hydrogen donors in heavily carbon-doped GaAs

    NASA Astrophysics Data System (ADS)

    Fushimi, Hiroshi; Wada, Kazumi

    1994-12-01

    The deactivation mechanism of carbon acceptors in GaAs has systematically been studied by measuring the annealing behavior and depth profiles of the carrier concentration. It is found that hydrogen impurities dominate carbon deactivation. Their deactivation undergoes two different ways: Hydrogen donors isolated from carbon acceptors compensate carbon and hydrogen impurities neutralize the carbon by forming neutral carbon-hydrogen complexes. The compensating hydrogen donors diffuse out extremely fast at relatively low temperatures. This is, to the best of our knowledge, the first report on the presence of isolated hydrogen donors in heavily carbon-doped GaAs. The dissociation of carbon-hydrogen complexes is much slower than reported. The mechanism is discussed in terms of a hydrogen retrapping effect by carbon.

  15. Age-related differences in brain network activation and co-activation during multiple object tracking.

    PubMed

    Dørum, Erlend S; Alnæs, Dag; Kaufmann, Tobias; Richard, Geneviève; Lund, Martina J; Tønnesen, Siren; Sneve, Markus H; Mathiesen, Nina C; Rustan, Øyvind G; Gjertsen, Øivind; Vatn, Sigurd; Fure, Brynjar; Andreassen, Ole A; Nordvik, Jan Egil; Westlye, Lars T

    2016-11-01

    Multiple object tracking (MOT) is a powerful paradigm for measuring sustained attention. Although previous fMRI studies have delineated the brain activation patterns associated with tracking and documented reduced tracking performance in aging, age-related effects on brain activation during MOT have not been characterized. In particular, it is unclear if the task-related activation of different brain networks is correlated, and also if this coordination between activations within brain networks shows differential effects of age. We obtained fMRI data during MOT at two load conditions from a group of younger ( n  = 25, mean age = 24.4 ± 5.1 years) and older ( n  = 21, mean age = 64.7 ± 7.4 years) healthy adults. Using a combination of voxel-wise and independent component analysis, we investigated age-related differences in the brain network activation. In order to explore to which degree activation of the various brain networks reflect unique and common mechanisms, we assessed the correlations between the brain networks' activations. Behavioral performance revealed an age-related reduction in MOT accuracy. Voxel and brain network level analyses converged on decreased load-dependent activations of the dorsal attention network (DAN) and decreased load-dependent deactivations of the default mode networks (DMN) in the old group. Lastly, we found stronger correlations in the task-related activations within DAN and within DMN components for younger adults, and stronger correlations between DAN and DMN components for older adults. Using MOT as means for measuring attentional performance, we have demonstrated an age-related attentional decline. Network-level analysis revealed age-related alterations in network recruitment consisting of diminished activations of DAN and diminished deactivations of DMN in older relative to younger adults. We found stronger correlations within DMN and within DAN components for younger adults and stronger correlations between DAN and DMN components for older adults, indicating age-related alterations in the coordinated network-level activation during attentional processing.

  16. Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

    PubMed

    Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

    2009-09-01

    Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

  17. Defibrillator patients should not be denied a peaceful death.

    PubMed

    Westerdahl, Annika Kinch; Sutton, Richard; Frykman, Viveka

    2015-03-01

    Implantable defibrillators (ICDs) prevent sudden cardiac death. With declining health, ICD therapy may prolong death and expose the patient to unnecessary pain and anxiety. Few studies have addressed end of life care in ICD patients. The objective of this study was to investigate end of life in ICD patients, with respect to location of death; duration between do-not-resuscitate (DNR)-orders and deactivation of ICD therapy or DNR and time of death. A descriptive analysis of 65 deceased ICD patients, all whom had a written DNR-order before death, is presented. The majority (86%) was treated in hospitals, mainly (63%) university hospitals, and many (33%) in cardiology wards. Despite DNR-order, ICD shock therapy was active in 51% of all patients. In those with therapy deactivated at death, therapy deactivation was carried out two days or more after DNR-order in more than a third (38%). The time from DNR decision to death in patients with therapy active had a median of four days (IQR 1-38). During the last 24h of life, 24% of the patients experienced shock treatment. The majority of ICD patients with a DNR-order were treated in university hospitals. More than half still had shock treatment active at time of death with a median of four days or more between DNR decision and death. Patients with therapy deactivated, two days or more elapsed in more than a third from DNR decision to deactivation of therapy, exposing patients to a high risk of painful shocks before death. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.

    PubMed

    MacLean, David M; Jayaraman, Vasanthi

    2017-03-21

    Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients, both recombinant and native ASICs show extremely rapid deactivation in outside-out patches when jumping from a pH 5 stimulus to a single resting pH of 8. Given that the resting pH of the synaptic cleft is highly dynamic and depends on recent synaptic activity, we explored the kinetics of ASIC1a and 1a/2a heteromers to such brief pH transients over a wider [H + ] range to approximate neuronal conditions better. Surprisingly, the deactivation of ASICs was steeply dependent on the pH, spanning nearly three orders of magnitude from extremely fast (<1 ms) at pH 8 to very slow (>300 ms) at pH 7. This study provides an example of a ligand-gated ion channel whose deactivation is sensitive to agonist concentrations that do not directly activate the receptor. Kinetic simulations and further mutagenesis provide evidence that ASICs show such steeply agonist-dependent deactivation because of strong cooperativity in proton binding. This capacity to signal across such a large synaptically relevant bandwidth enhances the response to small-amplitude acidifications likely to occur at the cleft and may provide ASICs with the ability to shape activity in response to the recent history of the synapse.

  19. Biodegradation at Dynamic Plume Fringes: Mixing Versus Reaction Control

    NASA Astrophysics Data System (ADS)

    Cirpka, O. A.; Eckert, D.; Griebler, C.; Haberer, C.; Kürzinger, P.; Bauer, R.; Mellage, A.

    2014-12-01

    Biodegradation of continuously emitted plumes is known to be most pronounced at the plume fringe, where mixing of contaminated water and ambient groundwater, containing dissolved electron acceptors, stimulates microbial activity. Under steady-state conditions, physical mixing of contaminant and electron acceptor by transverse dispersion was shown to be the major bottleneck for biodegradation, with plume lengths scaling inversely with the bulk transverse dispersivity in quasi two-dimensional settings. Under these conditions, the presence of suitable microbes is essential but the biokinetic parameters do not play an important role. When the location of the plume shifts (caused, e.g., by a fluctuating groundwater table), however, the bacteria are no more situated at the plume fringe and biomass growth, decay, activation and deactivation determine the time lag until the fringe-controlled steady state is approached again. During this time lag, degradation is incomplete. The objective of the presented study was to analyze to which extent flow and transport dynamics diminish effectiveness of fringe-controlled biodegradation and which microbial processes and related biokinetic parameters determine the system response in overall degradation to hydraulic fluctuations. We performed experiments in quasi-two-dimensional flow through microcosms on aerobic toluene degradation by Pseudomonas putida F1. Plume dynamics were simulated by vertical alteration of the toluene plume position and experimental results were analyzed by reactive-transport modeling. We found that, even after disappearance of the toluene plume for two weeks, the majority of microorganisms stayed attached to the sediment and regained their full biodegradation potential within two days after reappearance of the toluene plume. Our results underline that besides microbial growth and maintenance (often subsumed as "biomass decay") microbial dormancy (that is, change into a metabolically inactive state) and endogeneous respiration are important to understand the dynamic behavior of electron-acceptor and -donor fluxes under transient environmental conditions and therefore deserve increased consideration in future reactive-transport modeling.

  20. Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

    PubMed

    Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

    2015-01-01

    Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help researchers and clinicians to better understand the underlying modulation mechanisms of orofacial neuropathic pain and indicate a novel mechanism of ERK inhibitor-induced analgesia.

  1. A Review and Empirical Comparison of Two Treatments for Adolescent Males with Conduct and Personality Disorder: Mode Deactivation Therapy and Cognitive Behavior Therapy

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Siv, Alexander M.

    2005-01-01

    This research study compared the efficacy of two treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  2. Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

    2005-01-01

    This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  3. Brief and Rare Mental "Breaks" Keep You Focused: Deactivation and Reactivation of Task Goals Preempt Vigilance Decrements

    ERIC Educational Resources Information Center

    Ariga, Atsunori; Lleras, Alejandro

    2011-01-01

    We newly propose that the vigilance decrement occurs because the cognitive control system fails to maintain active the goal of the vigilance task over prolonged periods of time (goal habituation). Further, we hypothesized that momentarily deactivating this goal (via a switch in tasks) would prevent the activation level of the vigilance goal from…

  4. Holographic monitoring of spatial distributions of singlet oxygen in water

    NASA Astrophysics Data System (ADS)

    Belashov, A. V.; Bel'tyukova, D. M.; Vasyutinskii, O. S.; Petrov, N. V.; Semenova, I. V.; Chupov, A. S.

    2014-12-01

    A method for monitoring spatial distributions of singlet oxygen in biological media has been developed. Singlet oxygen was generated using Radachlorin® photosensitizer, while thermal disturbances caused by nonradiative deactivation of singlet oxygen were detected by the holographic interferometry technique. Processing of interferograms yields temperature maps that characterize the deactivation process and show the distribution of singlet oxygen species.

  5. Gamification of Learning Deactivates the Default Mode Network

    PubMed Central

    Howard-Jones, Paul A.; Jay, Tim; Mason, Alice; Jones, Harvey

    2016-01-01

    We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated. PMID:26779054

  6. Ligand-specific Deactivation Time Course of GluN1/GluN2D NMDA Receptors

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

    K Vance; N Simorowski; S Traynelis

    2011-12-31

    N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors that mediate a majority of excitatory synaptic transmission. One unique property of GluN1/GluN2D NMDA receptors is an unusually prolonged deactivation time course following the removal of L-glutamate. Here we show, using x-ray crystallography and electrophysiology, that the deactivation time course of GluN1/GluN2D receptors is influenced by the conformational variability of the ligand-binding domain (LBD) as well as the structure of the activating ligand. L-glutamate and L-CCG-IV induce significantly slower deactivation time courses compared with other agonists. Crystal structures of the isolated GluN2D LBD in complex with various ligands revealmore » that the binding of L-glutamate induces a unique conformation at the backside of the ligand-binding site in proximity to the region at which the transmembrane domain would be located in the intact receptors. These data suggest that the activity of the GluN1/GluN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate.« less

  7. Gamification of Learning Deactivates the Default Mode Network.

    PubMed

    Howard-Jones, Paul A; Jay, Tim; Mason, Alice; Jones, Harvey

    2015-01-01

    We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated.

  8. Availability of the basal planes of graphene oxide determines whether it is antibacterial.

    PubMed

    Hui, Liwei; Piao, Ji-Gang; Auletta, Jeffrey; Hu, Kan; Zhu, Yanwu; Meyer, Tara; Liu, Haitao; Yang, Lihua

    2014-08-13

    There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of <1% at 200 μg/mL. Supplementing saline with ≤10% Luria-Bertani (LB) broth, however, progressively deactivated its bactericidal activity depending on LB-supplementation ratio. Supplementation of 10% LB made GO completely inactive; instead, ∼100-fold bacterial growth was observed. Atomic force microscopy images showed that certain LB components were adsorbed on GO basal planes. Using bovine serum albumin and tryptophan as well-defined model adsorbates, we found that noncovalent adsorption on GO basal planes may account for the deactivation of GO's bactericidal activity. Moreover, this deactivation mechanism was shown to be extrapolatable to GO's cytotoxicity against mammalian cells. Taken together, our observations suggest that bare GO intrinsically kills both bacteria and mammalian cells and noncovalent adsorption on its basal planes may be a global deactivation mechanism for GO's cytotoxicity.

  9. Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV

    PubMed Central

    Rubin, Leah H.; Wu, Minjie; Sundermann, Erin E.; Meyer, Vanessa J.; Smith, Rachael; Weber, Kathleen M.; Cohen, Mardge H.; Little, Deborah M.; Maki, Pauline M.

    2016-01-01

    HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p’s<0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher versus lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p’s<0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p=0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory. PMID:27094924

  10. Caffeine impact on working memory-related network activation patterns in early stages of cognitive decline.

    PubMed

    Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Giannakopoulos, Panteleimon

    2017-04-01

    Recent evidence indicates that caffeine may have a beneficial effect on cognitive decline and dementia. The current investigation assessed the effect of acute caffeine administration on working memory during the earliest stage of cognitive decline in elderly participants. The study includes consecutive 45 elderly controls and 18 individuals with mild cognitive impairment (MCI, 71.6 ± 4.7 years, 7 females). During neuropsychological follow-up at 18 months, 24 controls remained stable (sCON, 70.0 ± 4.3 years, 11 women), while the remaining 21 showed subtle cognitive deterioration (dCON, 73.4 ± 5.9 years, 14 women). All participants underwent an established 2-back working task in a crossover design of 200 mg caffeine versus placebo. Data analysis included task-related general linear model and functional connectivity tensorial independent component analysis. Working memory behavioral performances did not differ between sCON and dCON, while MCI was slower and less accurate than both control groups (p < 0.05). The dCON group had a less pronounced effect of acute caffeine administration essentially restricted to the right hemisphere (p < 0.05 corrected) and reduced default mode network (DMN) deactivation compared to sCON (p < 0.01 corrected). dCON cases are characterized by decreased sensitivity to caffeine effects on brain activation and DMN deactivation. These complex fMRI patterns possibly reflect the instable status of these cases with intact behavioral performances despite already existing functional alterations in neocortical circuits.

  11. Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV.

    PubMed

    Rubin, Leah H; Wu, Minjie; Sundermann, Erin E; Meyer, Vanessa J; Smith, Rachael; Weber, Kathleen M; Cohen, Mardge H; Little, Deborah M; Maki, Pauline M

    2016-12-01

    HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

  12. Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

    PubMed Central

    Vercammen, Ans; Morris, Richard; Green, Melissa J.; Lenroot, Rhoshel; Kulkarni, Jayashri; Carr, Vaughan J.; Weickert, Cynthia Shannon; Weickert, Thomas W.

    2012-01-01

    Background Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia. Methods Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. Results We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. Limitations Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables. Conclusion Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life. PMID:22617625

  13. Abnormal brain activation in neurofibromatosis type 1: a link between visual processing and the default mode network.

    PubMed

    Violante, Inês R; Ribeiro, Maria J; Cunha, Gil; Bernardino, Inês; Duarte, João V; Ramos, Fabiana; Saraiva, Jorge; Silva, Eduardo; Castelo-Branco, Miguel

    2012-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified.

  14. Oxidative degradation of silica-supported polyethylenimine for CO2 adsorption: insights into the nature of deactivated species.

    PubMed

    Ahmadalinezhad, Asieh; Sayari, Abdelhamid

    2014-01-28

    The oxidative degradation of polyethylenimine-impregnated mesoporous SBA-15 silica for CO2 capture was investigated at the molecular level. The adsorbents were exposed to flowing air at different temperatures, and their degree of deactivation was evaluated through the measurement of CO2 adsorption capacity prior and subsequent to air exposure. A solvent-extraction method was employed to isolate the deactivated species from the silica support. The extracted species were investigated by a variety of 1D and 2D NMR techniques such as (13)C, (1)H, (1)H-(15)N HMBC, (1)H-(13)C HMQC, and (1)H-(13)C HMBC. This in-depth investigation showed that they contain predominantly fragments involving imine and carbonyl groups. Several structural units were conclusively established.

  15. KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia.

    PubMed

    Carr, Gregory V; Chen, Jingshan; Yang, Feng; Ren, Ming; Yuan, Peixiong; Tian, Qingjun; Bebensee, Audrey; Zhang, Grace Y; Du, Jing; Glineburg, Paul; Xun, Randy; Akhile, Omoye; Akuma, Daniel; Pickel, James; Barrow, James C; Papaleo, Francesco; Weinberger, Daniel R

    2016-11-01

    Overexpression in humans of KCNH2-3.1, which encodes a primate-specific and brain-selective isoform of the human ether-a-go-go-related potassium channel, is associated with impaired cognition, inefficient neural processing and schizophrenia. Here, we describe a new mouse model that incorporates the KCNH2-3.1 molecular phenotype. KCNH2-3.1 transgenic mice are viable and display normal sensorimotor behaviors. However, they show alterations in neuronal structure and microcircuit function in the hippocampus and prefrontal cortex, areas affected in schizophrenia. Specifically, in slice preparations from the CA1 region of the hippocampus, KCNH2-3.1 transgenic mice have fewer mature dendrites and impaired theta burst stimulation long-term potentiation. Abnormal neuronal firing patterns characteristic of the fast deactivation kinetics of the KCNH2-3.1 isoform were also observed in prefrontal cortex. Transgenic mice showed significant deficits in a hippocampal-dependent object location task and a prefrontal cortex-dependent T-maze working memory task. Interestingly, the hippocampal-dependent alterations were not present in juvenile transgenic mice, suggesting a developmental trajectory to the phenotype. Suppressing KCNH2-3.1 expression in adult mice rescues both the behavioral and physiological phenotypes. These data provide insight into the mechanism of association of KCNH2-3.1 with variation in human cognition and neuronal physiology and may explain its role in schizophrenia.

  16. Lipid Raft: A Floating Island Of Death or Survival

    PubMed Central

    George, Kimberly S.; Wu, Shiyong

    2012-01-01

    Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid rafts microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid rafts disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity. PMID:22289360

  17. A Review and Empirical Comparison of Three Treatments for Adolescent Males with Conduct and Personality Disorder: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.

    2006-01-01

    This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  18. Plasma Deactivation of Oral Bacteria Seeded on Hydroxyapatite Disks as Tooth Enamel Analogue

    PubMed Central

    Blumhagen, Adam; Singh, Prashant; Mustapha, Azlin; Chen, Meng; Wang, Yong; Yu, Qingsong

    2014-01-01

    Purpose To study the plasma treatment effects on deactivation of oral bacteria seeded on a tooth enamel analogue. Methods A non-thermal atmospheric pressure argon plasma brush was used to treat two different Gram-positive oral bacteria including Lactobacillus acidophilus (L. acidophilus) and Streptococcus mutans (S. mutans). The bacteria were seeded on hydroxyapatite (HA) disks used as tooth enamel analogue with three initial bacterial seeding concentrations: a low inoculum concentration between 2.1×108 and 2.4×108 cfu/mL, a medium inoculum concentration between 9.8×108 and 2.4×109 cfu/mL, and a high inoculum concentration between 1.7×1010 and 3.5×1010 cfu/mL. The bacterial survivability upon plasma exposure was examined in terms of plasma exposure time and oxygen addition into the plasmas. SEM was performed to examine bacterial morphological changes after plasma exposure. Results The experimental data indicated that 13 second plasma exposure time completely killed all the bacteria when initial bacterial seeding density on HA surfaces were less than 6.9×106 cfu/cm2 for L. acidophilus and 1.7×107 cfu/cm2 for S. mutans, which were resulted from low initial seeding inoculum concentration between 2.1×108 and 2.4×108 cfu/mL. Plasma exposure of the bacteria at higher initial bacterial seeding density obtained with high initial seeding inoculum concentration, however, only resulted in ~ 1.5 to 2 log reduction and ~ 2 to 2.5 log reduction for L. acidophilus and S. mutans, respectively. It was also noted that oxygen addition into the argon plasma brush did not affect the plasma deactivation effectiveness. SEM images showed that plasma deactivation mainly occurred with the top layer bacteria, while shadowing effects from the resulting bacterial debris reduced the plasma deactivation of the underlying bacteria. Clinical Significance The experimental results indicate that, with direct contact, nonthermal atmospheric pressure argon plasmas could rapidly and effectively deactivate oral bacteria seeded on HA surfaces and thus could be a promising technique in various dental clinical applications. PMID:25000666

  19. Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution.

    PubMed

    Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

    2011-01-01

    The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.

  20. Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

    PubMed

    Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

    2013-12-01

    Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

  1. Mechanism of acetaldehyde-induced deactivation of microbial lipases

    PubMed Central

    2011-01-01

    Background Microbial lipases represent the most important class of biocatalysts used for a wealth of applications in organic synthesis. An often applied reaction is the lipase-catalyzed transesterification of vinyl esters and alcohols resulting in the formation of acetaldehyde which is known to deactivate microbial lipases, presumably by structural changes caused by initial Schiff-base formation at solvent accessible lysine residues. Previous studies showed that several lipases were sensitive toward acetaldehyde deactivation whereas others were insensitive; however, a general explanation of the acetaldehyde-induced inactivation mechanism is missing. Results Based on five microbial lipases from Candida rugosa, Rhizopus oryzae, Pseudomonas fluorescens and Bacillus subtilis we demonstrate that the protonation state of lysine ε-amino groups is decisive for their sensitivity toward acetaldehyde. Analysis of the diverse modification products of Bacillus subtilis lipases in the presence of acetaldehyde revealed several stable products such as α,β-unsaturated polyenals, which result from base and/or amino acid catalyzed aldol condensation of acetaldehyde. Our studies indicate that these products induce the formation of stable Michael-adducts at solvent-accessible amino acids and thus lead to enzyme deactivation. Further, our results indicate Schiff-base formation with acetaldehyde to be involved in crosslinking of lipase molecules. Conclusions Differences in stability observed with various commercially available microbial lipases most probably result from different purification procedures carried out by the respective manufacturers. We observed that the pH of the buffer used prior to lyophilization of the enzyme sample is of utmost importance. The mechanism of acetaldehyde-induced deactivation of microbial lipases involves the generation of α,β-unsaturated polyenals from acetaldehyde which subsequently form stable Michael-adducts with the enzymes. Lyophilization of the enzymes from buffer at pH 6.0 can provide an easy and effective way to stabilize lipases toward inactivation by acetaldehyde. PMID:21342514

  2. Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

    PubMed Central

    Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

    2011-01-01

    Background The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Methodology/Principal Findings Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. Conclusions/Significance The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing. PMID:21829668

  3. The S4–S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating

    PubMed Central

    Ng, Chai Ann; Perry, Matthew D.; Tan, Peter S.; Hill, Adam P.; Kuchel, Philip W.; Vandenberg, Jamie I.

    2012-01-01

    Human ether-à-go-go-related gene (hERG) K+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel. PMID:22359612

  4. Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti-fibrosis effect by inhibition of mammalian target of rapamycin.

    PubMed

    Shi, Hongbo; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

    2017-03-01

    A previous study has demonstrated that Ganshuang granule (GSG) plays an anti-fibrotic role partially by deactivation of hepatic stellate cells (HSCs). In HSCs activation, mammalian target of rapamycin (mTOR)-autophagy plays an important role. We attempted to investigate the role of mTOR-autophagy in anti-fibrotic effect of GSG. The cirrhotic mouse model was prepared to demonstrate the anti-fibrosis effect of GSG. High performance liquid chromatography (HPLC) analyses were used to identify the active component of GSG. The primary mouse HSCs were isolated and naringin was added into activated HSCs to observe its anti-fibrotic effect. 3-methyladenine (3-MA) and Insulin-like growth factor-1 (IGF-1) was added, respectively, into fully activated HSCs to explore the role of autophagy and mTOR. GSG played an anti-fibrotic role through deactivation of HSCs in cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC analyses and naringin markedly suppressed HSCs activation in vitro, which suggested that naringin was the main active component of GSG. The deactivation of HSCs caused by naringin was not because of the autophagic activation but mTOR inhibition, which was supported by the following evidence: first, naringin induced autophagic activation, but when autophagy was blocked by 3-MA, deactivation of HSCs was not attenuated or reversed. Second, naringin inhibited mTOR pathway, meanwhile when mTOR was activated by IGF-1, deactivation of HSCs was reversed. In conclusion, we have demonstrated naringin in GSG suppressed activation of HSCs for anti-fibrosis effect by inhibition of mTOR, indicating a potential therapeutic application for liver cirrhosis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  5. 17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats.

    PubMed

    Long, Nathan; Serey, Chhorvann; Sinchak, Kevin

    2014-09-01

    In female rats sexual receptivity (lordosis) can be induced with either a single large dose of estradiol benzoate (EB), or a priming dose of EB that does not induce sexual receptivity followed by 17β-estradiol (E2). Estradiol priming initially inhibits lordosis through a multi-synaptic circuit originating in the arcuate nucleus of the hypothalamus (ARH) that activates and internalizes μ-opioid receptors (MOR) in medial preoptic nucleus (MPN) neurons. Lordosis is facilitated when MPN MOR are deactivated after the initial estradiol-induced activation. We tested the hypothesis that E2 given 47.5 h post EB acts rapidly through G protein-coupled estrogen receptor 1 (GPER) in the ARH to deactivate MPN MOR and facilitate lordosis. Ovariectomized Long Evans rats implanted with a third ventricle cannula were primed with 2 μg EB. DMSO control, E2, or G1 (GPER selective agonist) was infused 47.5 h later, and rats were tested for sexual receptivity. E2 and G1 infusions significantly increased levels of sexual receptivity compared to DMSO controls and pretreatment with G15 (GPER antagonist) blocked the facilitation of sexual receptivity. Brains were processed for MPN MOR immunohistochemistry to measure MPN MOR activation levels. E2 and G1 both significantly reduced MPN MOR activation compared to DMSO controls, while pretreatment with G15 blocked MPN MOR deactivation. In another group of EB treated ovariectomized rats, GPER immunofluorescence positive staining was observed throughout the ARH. Together these data indicate that in the 2 μg EB primed rat, E2 rapidly signals through GPER in the ARH to deactivate MPN MOR and facilitate lordosis. Published by Elsevier Inc.

  6. Safe and Effective Deactivation of Metallic Sodium Filled Scrap and Cold Traps From Sodium-cooled Nuclear Reactor D and D - 12176

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

    Nester, Dean; Crocker, Ben; Smart, Bill

    2012-07-01

    As part of the Plateau Remediation Project at US Department of Energy's Hanford, Washington site, CH2M Hill Plateau Remediation Company (CHPRC) contracted with IMPACT Services, LLC to receive and deactivate approximately 28 cubic meters of sodium metal contaminated debris from two sodium-cooled research reactors (Enrico Fermi Unit 1 and the Fast Flux Test Facility) which had been stored at Hanford for over 25 years. CHPRC found an off-site team composed of IMPACT Services and Commodore Advanced Sciences, Inc., with the facilities and technological capabilities to safely and effectively perform deactivation of this sodium metal contaminated debris. IMPACT Services provided themore » licensed fixed facility and the logistical support required to receive, store, and manage the waste materials before treatment, and the characterization, manifesting, and return shipping of the cleaned material after treatment. They also provided a recycle outlet for the liquid sodium hydroxide byproduct resulting from removal of the sodium from reactor parts. Commodore Advanced Sciences, Inc. mobilized their patented AMANDA unit to the IMPACT Services site and operated the unit to perform the sodium removal process. Approximately 816 Kg of metallic sodium were removed and converted to sodium hydroxide, and the project was accomplished in 107 days, from receipt of the first shipment at the IMPACT Services facility to the last outgoing shipment of deactivated scrap metal. There were no safety incidents of any kind during the performance of this project. The AMANDA process has been demonstrated in this project to be both safe and effective for deactivation of sodium and NaK. It has also been used in other venues to treat other highly reactive alkali metals, such as lithium (Li), potassium (K), NaK and Cesium (Cs). (authors)« less

  7. Poisoning of a silica supported cobalt catalyst due to the presence of sulfur impurities in syngas during Fischer-Tropsch synthesis: Effect of chelating agent

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

    Bambal, A.S.; Gardner, T.H.; Kugler, E.L.

    2012-01-01

    Sulfur compounds that are generally found in syngas derived from coal and biomass are a poison to Fischer-Tropsch (FT) catalysts. The presence of sulfur impurities in the ppm range can limit the life of a FT catalyst to a few hours or a few days. In this study, FT synthesis was carried out in a fixed-bed reactor at 230 °C, 20 bar, and 13,500 Ncm3/h/gcat for 72 h using syngas with H2/CO = 2.0. Cobalt-based catalysts were subjected to poisoning by 10 and 50 ppm sulfur in the syngas. The performance of FT catalyst was compared in context of syngasmore » conversion, product selectivities and yields, during the poisoning as well as post-poisoning stages. At both the impurity concentrations, the sulfur was noted to cause permanent loss in the activity, possibly by adsorbing irreversibly on the surface. The sulfur poison affects the hydrogenation and the chain-propagation ability of the catalysts, and shifts the product selectivity towards short-chain hydrocarbons with higher percentages of olefins. Additional diffusion limitations caused due to sulfur poisoning are thought to alter the product selectivity. The shifts in product selectivities suggest that the sulfur decreases the ability of the catalyst to form C-C bonds to produce longer-chain hydrocarbons. The selective blocking of sulfur is thought to affect the hydrogenation ability on the catalyst, resulting in more olefins in the product after sulfur poisoning. The sulfur poisoning on the cobalt catalyst is expected to cause an increase in the number of sites responsible for WGS or to influence the Boudouard reaction, resulting in a higher CO2 selectivity. Both the sites responsible for CO adsorptions as well as the sites for chain growth are poisoned during the poisoning. Additionally, the performance of a base-case cobalt catalyst is compared with that of catalysts modified by chelating agents (CAs). The superior performance of CA-modified catalysts during sulfur poisoning is attributed to the presence of smaller crystallite sizes and higher dispersions of cobalt on the support. Finally, the sulfur deactivation data is modeled by a simple kinetic expression to determine the deactivation constant, deactivation rates and half-life of the FT catalyst.« less

  8. The Role of Actin Cytoskeleton in Dendritic Spines in the Maintenance of Long-Term Memory.

    PubMed

    Basu, Sreetama; Lamprecht, Raphael

    2018-01-01

    Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such alterations induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. This is especially intriguing as the half-life of most of the proteins that underlie such changes is usually in the range of hours to days and these proteins may change their location over time. In this review we describe studies that indicate the involvement of dendritic spines in memory formation and its maintenance. These studies show that learning leads to changes in the number and morphology of spines. Disruption in spines morphology or manipulations that lead to alteration in their number after consolidation are associated with impairment in memory maintenance. We further ask how changes in dendritic spines morphology, induced by learning and reputed to encode memory, are maintained to preserve long-term memory. We propose a mechanism, based on studies described in the review, whereby the actin cytoskeleton and its regulatory proteins involved in the initial alteration in spine morphology induced by learning are also essential for spine structural stabilization that maintains long-term memory. In this model glutamate receptors and other synaptic receptors activation during learning leads to the creation of new actin cytoskeletal scaffold leading to changes in spines morphology and memory formation. This new actin cytoskeletal scaffold is preserved beyond actin and its regulatory proteins turnover and dynamics by active stabilization of the level and activity of actin regulatory proteins within these memory spines.

  9. Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

    PubMed

    Sánchez-Moreno, M; Gómez-Contreras, F; Navarro, P; Marín, C; Ramírez-Macías, I; Rosales, M J; Campayo, L; Cano, C; Sanz, A M; Yunta, M J R

    2015-07-01

    The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.

  10. Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step.

    PubMed

    Chen, Chun-Chi; Chen, Teh-Liang; Tsai, Shau-Wei

    2006-06-05

    With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators. Copyright 2006 Wiley Periodicals, Inc.

  11. Task-evoked fMRI changes in attention networks are associated with preclinical Alzheimer's disease biomarkers.

    PubMed

    Gordon, Brian A; Zacks, Jeffrey M; Blazey, Tyler; Benzinger, Tammie L S; Morris, John C; Fagan, Anne M; Holtzman, David M; Balota, David A

    2015-05-01

    There is a growing emphasis on examining preclinical levels of Alzheimer's disease (AD)-related pathology in the absence of cognitive impairment. Previous work examining biomarkers has focused almost exclusively on memory, although there is mounting evidence that attention also declines early in disease progression. In the current experiment, 2 attentional control tasks were used to examine alterations in task-evoked functional magnetic resonance imaging data related to biomarkers of AD pathology. Seventy-one cognitively normal individuals (females = 44, mean age = 63.5 years) performed 2 attention-demanding cognitive tasks in a design that modeled both trial- and task-level functional magnetic resonance imaging changes. Biomarkers included amyloid β42, tau, and phosphorylated tau measured from cerebrospinal fluid and positron emission tomography measures of amyloid deposition. Both tasks elicited widespread patterns of activation and deactivation associated with large task-level manipulations of attention. Importantly, results from both tasks indicated that higher levels of tau and phosphorylated tau pathologies were associated with block-level overactivations of attentional control areas. This suggests early alteration in attentional control with rising levels of AD pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Kinetic deuterium isotope effects in glucocorticoid receptor activation

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

    Aranyi, P.

    1984-01-01

    Activation and deactivation of the chick thymus glucocorticoid receptor protein was studied in ordinary and heavy water by DNA-cellulose binding of the tritiated triamcinolone acetonide-receptor complex. Activation was significantly slower in heavy water if it was promoted by incubation at elevated temperature in buffers of low ionic strength. In the presence of 300 mM KC1 or after separation from the low molecular weight cytosol constituents, the complex was activated at the same rate in both solvents. Deactivation (time dependent loss of DNA-binding capacity) was much faster in ordinary than in heavy water regardless of gel filtration or the presence ofmore » KC1. A model of receptor activation-deactivation was constructed on the basis of these data that accounts for the observed kinetic deuterium isotope effects and reveals some submolecular details of the process.« less

  13. 29 CFR 4.130 - Types of covered service contracts illustrated.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... services. (8) Chemical testing and analysis. (9) Clothing alteration and repair. (10) Computer services... maintenance and operation and engineering support services. (16) Exploratory drilling (other than part of...

  14. 29 CFR 4.130 - Types of covered service contracts illustrated.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... services. (8) Chemical testing and analysis. (9) Clothing alteration and repair. (10) Computer services... maintenance and operation and engineering support services. (16) Exploratory drilling (other than part of...

  15. Photosensitized singlet oxygen luminescence from the protein matrix of Zn-substituted myoglobin.

    PubMed

    Lepeshkevich, Sergei V; Parkhats, Marina V; Stasheuski, Alexander S; Britikov, Vladimir V; Jarnikova, Ekaterina S; Usanov, Sergey A; Dzhagarov, Boris M

    2014-03-13

    A nanosecond laser near-infrared spectrometer was used to study singlet oxygen ((1)O2) emission in a protein matrix. Myoglobin in which the intact heme is substituted by Zn-protoporphyrin IX (ZnPP) was employed. Every collision of ground state molecular oxygen with ZnPP in the excited triplet state results in (1)O2 generation within the protein matrix. The quantum yield of (1)O2 generation was found to be equal to 0.9 ± 0.1. On the average, six from every 10 (1)O2 molecules succeed in escaping from the protein matrix into the solvent. A kinetic model for (1)O2 generation within the protein matrix and for a subsequent (1)O2 deactivation was introduced and discussed. Rate constants for radiative and nonradiative (1)O2 deactivation within the protein were determined. The first-order radiative rate constant for (1)O2 deactivation within the protein was found to be 8.1 ± 1.3 times larger than the one in aqueous solutions, indicating the strong influence of the protein matrix on the radiative (1)O2 deactivation. Collisions of singlet oxygen with each protein amino acid and ZnPP were assumed to contribute independently to the observed radiative as well as nonradiative rate constants.

  16. Modification of a three-way catalyst washcoat by aging: A study along the longitudinal axis

    NASA Astrophysics Data System (ADS)

    Granados, M. López; Galisteo, F. Cabello; Mariscal, R.; Alifanti, M.; Gurbani, A.; Fierro, J. L. G.; Fernández-Ruíz, R.

    2006-10-01

    This work reports the research carried out by studying aliquots extracted at different axial coordinates from Three Way Catalyst (TWC) monoliths aged under real traffic conditions. Our study focused on the catalytic properties and on several chemical and physical effects caused in the Front and Rear monolith washcoat surfaces by vehicle aging after 60,000 km. Regarding the catalytic properties, all the used aliquots showed poorer activity than their corresponding fresh counterparts. The strongest deactivation was detected for NO and hydrocarbon conversion. CO conversion was less affected and the Rear monolith was as deactivated as the Front one. The characterisation techniques (TXRF, N 2 adsorption-desorption isotherms, XRD and H 2-TPR) detected - (i) the deposition of P, Zn and Pb; (ii) the formation of CePO 4 on account of the Ce from the washcoat; (iii) thermal sintering; (iv) inhibition of the reducibility of Ce oxides - as the main effects brought about by vehicle aging conditions. The deactivation observed at the beginning of the Front monolith was the result of a combination of the former effects. When moving downstream to higher axial coordinates, Pb accumulation and the loss of specific area appeared to be the only probable sources of deactivation.

  17. Rapid localized deactivation of self-assembled monolayers by propagation-controlled laser-induced plasma and its application to self-patterning of electronics and biosensors

    NASA Astrophysics Data System (ADS)

    Kim, Jongsu; Kwon, Seung-Gab; Back, Seunghyun; Kang, Bongchul

    2018-03-01

    We present a novel laser-induced surface treatment process to rapidly control the spatial wettabilities of various functional solutions with submicron to micron resolutions. Ultrathin hydrophobic self-assembled monolayers (SAMs) that little absorb typical laser lights due to short penetration depth were selectively deactivated by instantaneous interaction with laser-induced metallic plasmas. The spatial region of the deactivated SAM, which corresponds to process resolution, is adjustable by controlling the spatial propagation of the plasma. This method leads to the parallel formation of hydrophilic functional solutions on glass substrates with a minimum resolution on the submicron scale. To show its feasibility in device engineering fields, this method was applied to the cost-effective fabrication of electronics and biosensors. Rapid self-patterning of electronic and biological functional solutions (silver nanoparticle solution and streptavidin protein solution) was successfully realized by selective deactivation of two different SAMs (tridecafluoro-1,1,2,2-tetrahydrooctyltrichlorosilane (FOTS) for electronics and the hetero-hybrid SAM (octadecyltrichlorosilane (OTS)/2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG)) for biosensors). As a result, this method can be exploited for the rapid and low-cost fabrication of various thin film devices such as electronics, biosensors, energy, displays, and photonics.

  18. Receiving and use of streams of monodisperse ice granules for cleaning and deactivation of surfaces

    NASA Astrophysics Data System (ADS)

    Boukharov, A.; Balashov, A.; Timohin, A.; Ivanov, A.; Holin, B.

    2017-11-01

    The most generally useful methods for cleaning and processing of surfaces are the sand-jets and shot blasting jets. Installations of this kind are used for cleaning of corrosion surfaces, the oil-dirt deposits, paint coatings. However the use of these installations follows to high investment and operational expenditure, larger risk of operators disease, the negative affect for a environment. These problems can be solved with the use of new cleaning method through application of mono-disperse (identical by the size and the form) ice granules of 300 - 1000 microns, accelerated by air stream in the nozzle device to the speed of 10 - 100 m/s. In view of the extreme complexity of the receiving such particles by means of cooling and the subsequent freezing of water drops are necessary additional experimental researches. For study of thermal processes of receiving mono-disperse ice granules the experimental installation was created and experiments on deactivation and cleaning of surfaces with pollution of various types are made. Experiments showed that by means of a stream of the accelerated ice granules it is rather successfully possible to delete oil-dirt deposits, outdated paint coats and rust. Besides, efficient deactivation of radioactive surfaces is possible. The coefficient deactivation of γ activity is highest.

  19. Ionic liquids as silica deactivating agents in gas chromatography for direct analysis of primary amines in water.

    PubMed

    Krzyżaniak, Agnieszka; Weggemans, Wilko; Schuur, Boelo; de Haan, André B

    2011-12-16

    Analysis of primary amines in aqueous samples remains a challenging analytical issue. The preferred approach by gas chromatography is hampered by interactions of free silanol groups with the highly reactive amine groups, resulting in inconsistent measurements. Here, we report a method for direct analysis of aliphatic amines and diamines in aqueous samples by gas chromatography (GC) with silanol deactivation using ionic liquids (ILs). ILs including trihexyl(tetradecyl)phosphonium bis 2,4,4-(trimethylpentyl)phosphinate (Cyphos IL-104), 1-methyl-3-propylimidazolium bis(trifluoromethylsulfonyl)imide [pmim][Tf(2)N] and N″-ethyl-N,N,N',N'-tetramethylguanidinium tris(pentafluoroethyl)trifluorophosphate [etmg][FAP] were tested as deactivating media for the GC liner. Solutions of these ILs in methanol were injected in the system prior to the analysis of primary amines. Butane-1,4-diamine (putrescine, BDA) was used as a reference amine. The best results were obtained using the imidazolium IL [pmim][Tf(2)N]. With this deactivator, excellent reproducibility of the analysis was achieved, and the detection limit of BDA was as low as 1mM. The applicability of the method was proven for the analysis of two different primary amines (C4-C5) and pentane-1,5-diamine. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Inter-costal Liver Ablation Under Real Time MR-Thermometry With Partial Activation Of A HIFU Phased Array Transducer

    NASA Astrophysics Data System (ADS)

    Quesson, Bruno; Merle, Mathilde; Köhler, Max; Mougenot, Charles; Roujol, Sebastien; de Senneville, Baudouin Denis; Moonen, Chrit

    2010-03-01

    HIFU ablation of tumours located inside the liver is hampered by the rib cage, which partially obstructs the beam path and may create adverse effects such as skin burns. This study presents a method for selectively deactivating the transducer elements causing undesired temperature increases near the bones. A manual segmentation of the bones visualized on 3D anatomical MR images acquired prior to sonication was performed to identify the beam obstruction. The resulting mask was projected (ray tracing starting from the focal point) on the transducer and elements with more than 50% obstruction of their active surface were deactivated. The effectiveness of the method for HIFU ablations is demonstrated ex vivo and in vivo in the liver of pigs with real-time MR thermometry, using the proton resonant frequency (PRF) method. For both ex vivo and in vivo experiments, the temperature increase near the bones was significantly reduced when the elements located in front of the ribs were deactivated. The temperature evolution at the focal point were similar, indicative of the absence of loss of heating efficacy when the elements were deactivated. This method is simple, rapid and reliable and allows to perform intercostal MRgHIFU ablation of the liver while sparing the ribs.

  1. Implications of Subliminal Classical Conditioning for Defeating the Use of Countermeasures in the Detection of Deception: Subliminal Evaluation

    DTIC Science & Technology

    1993-08-01

    presented emotional stimuli than for subliminally presented neutral stimuli. Emotional stimuli consisted of sexually charged photographs, and the neutral...behavior. In addition to research using visual stimuli, some 13 studies have been conducted using subliminal (masked by 40 dB white noise) auditory ...deactivating suggestions masked by a 40-dB white noise signal. For the deactivating subliminal auditory messages, suggestions of heaviness and warmth

  2. Highly catalytic asymmetric addition of deactivated alkyl grignard reagents to aldehydes.

    PubMed

    Da, Chao-Shan; Wang, Jun-Rui; Yin, Xiao-Gang; Fan, Xin-Yuan; Liu, Yi; Yu, Sheng-Li

    2009-12-17

    Generally used and highly reactive RMgBr reagents were effectively deactivated by bis[2-(N,N-dimethylamino)ethyl] ether and then were employed in the highly enantioselective addition of Grignard reagents to aldehydes. The reaction was catalyzed by the complex of commercially available (S)-BINOL and Ti(O(i-)Pr)(4) under mild conditions. Compared with the other observed Grignard reagents, alkyl Grignard reagents showed higher enantioselectivity and they achieved >99% ee.

  3. Boosting functionality of synthetic DNA circuits with tailored deactivation

    PubMed Central

    Montagne, Kevin; Gines, Guillaume; Fujii, Teruo; Rondelez, Yannick

    2016-01-01

    Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems. The function of molecular circuits is deeply related to their topological structure, but dynamical features (rate laws) also play a critical role. Here we introduce a mechanism to tune the nonlinearities associated with individual nodes of a synthetic network. This mechanism is based on programming deactivation laws using dedicated saturable pathways. We demonstrate this approach through the conversion of a single-node homoeostatic network into a bistable and reversible switch. Furthermore, we prove its generality by adding new functions to the library of reported man-made molecular devices: a system with three addressable bits of memory, and the first DNA-encoded excitable circuit. Specific saturable deactivation pathways thus greatly enrich the functional capability of a given circuit topology. PMID:27845324

  4. Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning.

    PubMed

    Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

    2014-01-01

    Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.

  5. Kinetic model of 1,3-specific triacylglycerols alcoholysis catalyzed by lipases.

    PubMed

    Pilarek, Maciej; Szewczyk, Krzysztof W

    2007-01-20

    A new model of enzymatic 1,3-specific alcoholysis of triacylglycerols has been developed. The irreversibility of the acyl bounds cleavage in glycerides, a reversible monoglycerides isomerization and an irreversible enzyme deactivation have been assumed. The Ping Pong Bi Bi mechanism with competitive inhibition by alcohol has been applied to describe rates of acyl bonds cleavage. The enzymatic propanolysis and iso-propanolysis of triacetin and tricaprylin catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) have been investigated to verify the model. Good agreement between experimental data and calculations has been obtained. It was shown that the rate of tricaprylin alcoholysis is higher than the triacetin alcoholysis and that the rate of iso-propanolysis reactions are higher than propanolysis. The irreversible enzyme deactivation affects the conversion of glycerides whereas the competitive alcohol inhibition may be neglected. Empirical correlations of rates for monoglycerides isomerization and enzyme deactivation have been proposed.

  6. Epidemics in Adaptive Social Networks with Temporary Link Deactivation

    NASA Astrophysics Data System (ADS)

    Tunc, Ilker; Shkarayev, Maxim S.; Shaw, Leah B.

    2013-04-01

    Disease spread in a society depends on the topology of the network of social contacts. Moreover, individuals may respond to the epidemic by adapting their contacts to reduce the risk of infection, thus changing the network structure and affecting future disease spread. We propose an adaptation mechanism where healthy individuals may choose to temporarily deactivate their contacts with sick individuals, allowing reactivation once both individuals are healthy. We develop a mean-field description of this system and find two distinct regimes: slow network dynamics, where the adaptation mechanism simply reduces the effective number of contacts per individual, and fast network dynamics, where more efficient adaptation reduces the spread of disease by targeting dangerous connections. Analysis of the bifurcation structure is supported by numerical simulations of disease spread on an adaptive network. The system displays a single parameter-dependent stable steady state and non-monotonic dependence of connectivity on link deactivation rate.

  7. Effect of phenolic compounds from pretreated sugarcane bagasse on cellulolytic and hemicellulolytic activities.

    PubMed

    Michelin, Michele; Ximenes, Eduardo; de Lourdes Teixeira de Moraes Polizeli, Maria; Ladisch, Michael R

    2016-01-01

    This work shows both cellulases and hemicellulases are inhibited and deactivated by water-soluble and acetone extracted phenolics from sugarcane bagasse pretreated at 10% (w/v) for 30 min in liquid hot water at 180 or 200°C. The dissolved phenolics in vacuum filtrate increased from 1.4 to 2.4 g/L as temperature increased from 180 to 200°C. The suppression of cellulose and hemicellulose hydrolysis by phenolics is dominated by deactivation of the β-glucosidase or β-xylosidase components of cellulase and hemicellulase enzyme by acetone extract at 0.2-0.65 mg phenolics/mg enzyme protein and deactivation of cellulases and hemicellulases by the water soluble components in vacuum filtrate at 0.05-2mg/mg. Inhibition was a function of the type of enzyme and the manner in which the phenolics were extracted from the bagasse. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Photocatalytic acceptorless alkane dehydrogenation: scope, mechanism, and conquering deactivation with carbon dioxide.

    PubMed

    Chowdhury, Abhishek Dutta; Julis, Jennifer; Grabow, Kathleen; Hannebauer, Bernd; Bentrup, Ursula; Adam, Martin; Franke, Robert; Jackstell, Ralf; Beller, Matthias

    2015-01-01

    Alkane dehydrogenation is of special interest for basic science but also offers interesting opportunities for industry. The existing dehydrogenation methodologies make use of heterogeneous catalysts, which suffer from harsh reaction conditions and a lack of selectivity, whereas homogeneous methodologies rely mostly on unsolicited waste generation from hydrogen acceptors. Conversely, acceptorless photochemical alkane dehydrogenation in the presence of trans-Rh(PMe3 )2 (CO)Cl can be regarded as a more benign and atom efficient alternative. However, this methodology suffers from catalyst deactivation over time. Herein, we provide a detailed investigation of the trans-Rh(PMe3 )2 (CO)Cl-photocatalyzed alkane dehydrogenation using spectroscopic and theoretical investigations. These studies inspired us to utilize CO2 to prevent catalyst deactivation, which leads eventually to improved catalyst turnover numbers in the dehydrogenation of alkanes that include liquid organic hydrogen carriers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. High exhaust temperature, zoned, electrically-heated particulate matter filter

    DOEpatents

    Gonze, Eugene V.; Paratore, Jr., Michael J.; Bhatia, Garima

    2015-09-22

    A system includes a particulate matter (PM) filter, an electric heater, and a control circuit. The electric heater includes multiple zones, which each correspond to longitudinal zones along a length of the PM filter. A first zone includes multiple discontinuous sub-zones. The control circuit determines whether regeneration is needed based on an estimated level of loading of the PM filter and an exhaust flow rate. In response to a determination that regeneration is needed, the control circuit: controls an operating parameter of an engine to increase an exhaust temperature to a first temperature during a first period; after the first period, activates the first zone; deactivates the first zone in response to a minimum filter face temperature being reached; subsequent to deactivating the first zone, activates a second zone; and deactivates the second zone in response to the minimum filter face temperature being reached.

  10. Using liquid desiccant as a regenerable filter for capturing and deactivating contaminants

    DOEpatents

    Slayzak, Steven J.; Anderson, Ren S.; Judkoff, Ronald D.; Blake, Daniel M.; Vinzant, Todd B.; Ryan, Joseph P.

    2007-12-11

    A method, and systems for implementing such method, for purifying and conditioning air of weaponized contaminants. The method includes wetting a filter packing media with a salt-based liquid desiccant, such as water with a high concentration of lithium chloride. Air is passed through the wetted filter packing media and the contaminants in are captured with the liquid desiccant while the liquid desiccant dehumidifies the air. The captured contaminants are then deactivated in the liquid desiccant, which may include heating the liquid desiccant. The liquid desiccant is regenerated by applying heat to the liquid desiccant and then removing moisture. The method includes repeating the wetting with the regenerated liquid desiccant which provides a regenerable filtering process that captures and deactivates contaminants on an ongoing basis while also conditioning the air. The method may include filtration effectiveness enhancement by electrostatic or inertial means.

  11. Double dissociation of 'what' and 'where' processing in auditory cortex.

    PubMed

    Lomber, Stephen G; Malhotra, Shveta

    2008-05-01

    Studies of cortical connections or neuronal function in different cerebral areas support the hypothesis that parallel cortical processing streams, similar to those identified in visual cortex, may exist in the auditory system. However, this model has not yet been behaviorally tested. We used reversible cooling deactivation to investigate whether the individual regions in cat nonprimary auditory cortex that are responsible for processing the pattern of an acoustic stimulus or localizing a sound in space could be doubly dissociated in the same animal. We found that bilateral deactivation of the posterior auditory field resulted in deficits in a sound-localization task, whereas bilateral deactivation of the anterior auditory field resulted in deficits in a pattern-discrimination task, but not vice versa. These findings support a model of cortical organization that proposes that identifying an acoustic stimulus ('what') and its spatial location ('where') are processed in separate streams in auditory cortex.

  12. Increases in brain activity during social competition predict decreases in working memory performance and later recall.

    PubMed

    DiMenichi, Brynne C; Tricomi, Elizabeth

    2017-01-01

    In our fMRI experiment, participants completed a learning task in both a noncompetitive and a socially competitive learning environment. Despite reporting a preference for completing the task while competing, participants remembered significantly more during the task and later recalled more from the noncompetitive learning environment. Furthermore, during working memory maintenance, there was performance-related deactivation in the medial prefrontal cortex (mPFC) and the precuneus/PCC. During feedback presentation, there was greater activation in the mPFC and the precuneus/PCC while competing. Differential activation in the precuneus/PCC predicted worse later recall for information learned competitively. Since previous research suggests that the mPFC is involved in social-referencing, while the precuneus/PCC is implicated in off-task thoughts, our results suggest that receiving feedback regarding competition produces more activation in brain regions implicated in social interaction, as well as task distraction. While competition may make a task more enjoyable, the goal of winning may distract from maximizing performance. Hum Brain Mapp 38:457-471, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Evaluation of the mechanical properties and surface topography of as-received, immersed and as-retrieved orthodontic archwires

    PubMed Central

    POP, SILVIA IZABELLA; DUDESCU, MIRCEA; MERIE, VIOLETA VALENTINA; PACURAR, MARIANA; BRATU, CRISTINA DANA

    2017-01-01

    Background and aims This experimental study mainly aims at comparing the most important mechanical properties of the new orthodontic archwires, those immersed in fluorinated solution, the as-retrieved ones and the intra-oral used ones. Methods A total of 270 arch wires were tested, using tensile testing and three-point bending tests. The tested archwires were made of Stainless Steel, Nickel Titanium, Beta-Titanium and physiognomic covered Nickel Titanium. The tested archwires were subjected to three types of treatments: immersion into fluorinated solution, immersion into carbonated drinks and intra-oral use. Results The immersion caused variations of the activation and deactivation forces of all arch wires. The most affected arch wires, in terms of bending characteristics, were the intra-oral used ones. Conclusions The alteration of mechanical properties of the orthodontic arch wires by their immersion into fluorinated solutions and soft drinks could not be statistically demonstrated. PMID:28781528

  14. Insomnia Disorder and Brain's Default-Mode Network.

    PubMed

    Marques, Daniel Ruivo; Gomes, Ana Allen; Caetano, Gina; Castelo-Branco, Miguel

    2018-06-09

    Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI). The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia. A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

  15. Rocky Flats Plant: Test bed for transitioning from weapons production mission to environmental restoration, waste management, and economic development missions

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

    Benjamin, A.; Murthy, K.S.; Krenzer, R.W.

    1993-01-07

    Redirection of Rocky Flats Plant's (RF) mission is an inevitable result of changes in the worldwide social, political, and environmental factors. These changes were exemplified in the cancellation of the W-88 Warhead in January 1992, by the President of the United States. These unprecedented changes have altered the RF's traditional nuclear weapons production mission to the transition mission, i.e., cleanup, preparation for deactivation and decontamination, decommissioning, dismantlement and demolition, and when appropriate, economic development, of the facilities. The purpose of this paper is to describe the essentials of the technical approach and management actions advanced by EG G Rocky Flats,more » Inc., to organize, staff, direct, and control the activities necessary to transition the RF from its historical weapons production mission to the transition mission.« less

  16. Rocky Flats Plant: Test bed for transitioning from weapons production mission to environmental restoration, waste management, and economic development missions

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

    Benjamin, A.; Murthy, K.S.; Krenzer, R.W.

    1993-01-07

    Redirection of Rocky Flats Plant`s (RF) mission is an inevitable result of changes in the worldwide social, political, and environmental factors. These changes were exemplified in the cancellation of the W-88 Warhead in January 1992, by the President of the United States. These unprecedented changes have altered the RF`s traditional nuclear weapons production mission to the transition mission, i.e., cleanup, preparation for deactivation and decontamination, decommissioning, dismantlement and demolition, and when appropriate, economic development, of the facilities. The purpose of this paper is to describe the essentials of the technical approach and management actions advanced by EG&G Rocky Flats, Inc.,more » to organize, staff, direct, and control the activities necessary to transition the RF from its historical weapons production mission to the transition mission.« less

  17. The recovery of gold from refractory ores by the use of carbon-in-chlorine leaching

    NASA Astrophysics Data System (ADS)

    Greaves, John N.; Palmer, Glenn R.; White, William W.

    1990-09-01

    Recently, the U.S. Bureau of Mines examined the recovery of gold by chlorination of refractory carbonaceous and sulfidic ores, comparing various treatment methods in which a ground ore pulp is contacted with chlorine gas and activated carbon is added to the pulp for a carbon-in-chlorine leach (CICL). The objective of this research was to demonstrate the basic feasibility of CICL technology. Results showed that the organic carbon deactivating environment of CICL lowers, but does not eliminate, the adsorption of gold on activated carbon. In this environment, the refractory ore is altered, and gold is extracted and then recovered on activated carbon. With highly carbonaceous ores, CICL achieved a higher recovery than with primarily sulfidic refractory ores. Basic cyanide amenability testing of two carbonaceous ores achieved recoveries of only 5.5% and 46%. With CICL treatment, recoveries on carbon were 90% and 92%.

  18. Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption

    PubMed Central

    Reinhardt, Martin; Parigi, Angelo Del; Chen, Kewei; Reiman, Eric M.; Thiyyagura, Pradeep; Krakoff, Jonathan; Hohenadel, Maximilian G.; Le, Duc Son N.T.; Weise, Christopher M.

    2016-01-01

    Background/Objectives Prader-Willi syndrome (PWS) a type of human genetic obesity may inform us about the physiology of non-syndromic obesity. Objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison to healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings. Subjects/Methods This study compared the central effects of food consumption in 9 individuals with PWS (7 men, 2 women; body fat 35.3%±10.0) and 7 controls (7 men; body fat 28.8%±7.6), matched for percentage body fat. H215O PET scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. Results Compared with obese controls, PWS showed altered (p<0.05 FWE cluster-level corrected; voxelwise p<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls DLPFC rCBF tended to remain unchanged. In more liberal analyses (voxelwise p<0.005) rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings. Conclusion The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior. PMID:27121248

  19. The binding of activated Gαq to phospholipase C-β exhibits anomalous affinity.

    PubMed

    Navaratnarajah, Punya; Gershenson, Anne; Ross, Elliott M

    2017-10-06

    Upon activation by the G q family of Gα subunits, Gβγ subunits, and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins, potentiating G q deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gα q FRET and fluorescence correlation spectroscopy, two physically distinct methods, both yielded K d values of about 200 nm for PLC-β3-Gα q binding. This K d is 50-100 times greater than the EC 50 for Gα q -mediated PLC-β3 activation and for the Gα q GTPase-activating protein activity of PLC-β. The measured K d was not altered either by the presence of phospholipid vesicles, phosphatidylinositol 4,5-bisphosphate and Ca 2+ , or by the identity of the fluorescent labels. FRET-based kinetic measurements were also consistent with a K d of 200 nm We determined that PLC-β3 hysteresis, whereby PLC-β3 remains active for some time following either Gα q -PLC-β3 dissociation or PLC-β3-potentiated Gα q deactivation, is not sufficient to explain the observed discrepancy between EC 50 and K d These results indicate that the mechanism by which Gα q and PLC-β3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

    PubMed

    Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

    2013-06-01

    Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

  1. Epileptic Discharges Affect the Default Mode Network – fMRI and Intracerebral EEG Evidence

    PubMed Central

    Fahoum, Firas; Zelmann, Rina; Tyvaert, Louise; Dubeau, François; Gotman, Jean

    2013-01-01

    Functional neuroimaging studies of epilepsy patients often show, at the time of epileptic activity, deactivation in default mode network (DMN) regions, which is hypothesized to reflect altered consciousness. We aimed to study the metabolic and electrophysiological correlates of these changes in the DMN regions. We studied six epilepsy patients that underwent scalp EEG-fMRI and later stereotaxic intracerebral EEG (SEEG) sampling regions of DMN (posterior cingulate cortex, Pre-cuneus, inferior parietal lobule, medial prefrontal cortex and dorsolateral frontal cortex) as well as non-DMN regions. SEEG recordings were subject to frequency analyses comparing sections with interictal epileptic discharges (IED) to IED-free baselines in the IED-generating region, DMN and non-DMN regions. EEG-fMRI and SEEG were obtained at rest. During IEDs, EEG-fMRI demonstrated deactivation in various DMN nodes in 5 of 6 patients, most frequently the pre-cuneus and inferior parietal lobule, and less frequently the other DMN nodes. SEEG analyses demonstrated decrease in gamma power (50–150 Hz), and increase in the power of lower frequencies (<30 Hz) at times of IEDs, in at least one DMN node in all patients. These changes were not apparent in the non-DMN regions. We demonstrate that, at the time of IEDs, DMN regions decrease their metabolic demand and undergo an EEG change consisting of decreased gamma and increased lower frequencies. These findings, specific to DMN regions, confirm in a pathological condition a direct relationship between DMN BOLD activity and EEG activity. They indicate that epileptic activity affects the DMN, and therefore may momentarily reduce the consciousness level and cognitive reserve. PMID:23840805

  2. Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption.

    PubMed

    Reinhardt, M; Parigi, A D; Chen, K; Reiman, E M; Thiyyagura, P; Krakoff, J; Hohenadel, M G; Le, D S N T; Weise, C M

    2016-09-01

    Prader-Willi syndrome (PWS) is a type of human genetic obesity that may give us information regarding the physiology of non-syndromic obesity. The objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison with healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings. This study compared the central effects of food consumption in nine individuals with PWS (7 men, 2 women; body fat 35.3±10.0%) and seven controls (7 men; body fat 28.8±7.6%), matched for percentage body fat. H2(15)O-PET (positron emission tomography) scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. Compared with obese controls, PWS showed altered (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls, DLPFC rCBF tended to remain unchanged. In more liberal analyses (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.005), rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings. The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal-induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior.

  3. An Analysis of Type IV Precision Measurement Equipment Laboratory Logistical Support Relative to the Implementation of F-15/F-16 Two-Level Maintenance

    DTIC Science & Technology

    1994-09-01

    wife, Margie, for her patience and understanding. Graduate school definitely affects the family . Margie allowed me to use many valuable family hours...Consolidations and reorganizations, in which the face of logistics is changing day -by- day , are taking place throughout the Department of Defense. Two...will focus on Type IV F-15 and Type IV F-16 PMELs. Imporane of Research The two-level maintenance concept significantly alters the structure of

  4. Research notes : methods for traffic stripe removal.

    DOT National Transportation Integrated Search

    2001-11-01

    Pavement marking removal due to changed traffic configurations is a continual construction and maintenance problem. Often the removal alters the texture and/or color of the pavement surface. The removed markings become visible under different lightin...

  5. Safe Deactivation of Energetic Materials and Use of By-products as Epoxy Curing Agents

    DTIC Science & Technology

    2001-11-01

    National Laboratory has developed a lab- scale synthesis to convert TNT to higher value products such as TATB. 3.2 Firing Range Clean-Up Due to...1000 2000 3000 4000 5000 TCD1 , of Nitrogen Nitric Oxide Nitrous oxide ammonia Water Figure 1. Reactant Products for the Reaction of...SAND2001-3344 Unlimited Release Printed November 2001 Safe Deactivation of Energetic Materials and Use of By- products as Epoxy Curing

  6. Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy.

    PubMed

    Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

    2013-07-21

    Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.

  7. Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.

    1994-01-01

    Research was conducted on: (1) design and construction of a continuous flow photoreactor to study oxidation of trace atmospheric contaminants; (2) kinetics of acetone oxidation including adsorption equilibrium, variation of oxidatiin rate with acetone concentration and water, and variation of rate and apparent quantum yield with light intensity, and (3) kinetics of butanol oxidation, including rate variations; and (4) kinetics of catalyst deactivation including deactivation rate, influence of dark conditions, and photocatalytic regeneration in alcohol-free air.

  8. The default mode network in chimpanzees (Pan troglodytes) is similar to that of humans.

    PubMed

    Barks, Sarah K; Parr, Lisa A; Rilling, James K

    2015-02-01

    The human default mode network (DMN), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. The DMN and social cognitive networks overlap significantly in humans. We previously demonstrated that chimpanzees (Pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human DMN. Human DMN is defined by task-induced deactivations, not absolute resting metabolic levels; ergo, resting activity is insufficient to define a DMN in chimpanzees. Here, we assessed the chimpanzee DMN's deactivations relative to rest during cognitive tasks and the effect of social content on these areas' activity. Chimpanzees performed a match-to-sample task with conspecific behavioral stimuli of varying sociality. Using [(18)F]-FDG PET, brain activity during these tasks was compared with activity during a nonsocial task and at rest. Cortical midline areas in chimpanzees deactivated in these tasks relative to rest, suggesting a chimpanzee DMN anatomically and functionally similar to humans. Furthermore, when chimpanzees make social discriminations, these same areas (particularly precuneus) are highly active relative to nonsocial tasks, suggesting that, as in humans, the chimpanzee DMN may play a role in social cognition. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Rad53 regulates replication fork restart after DNA damage in Saccharomyces cerevisiae

    PubMed Central

    Szyjka, Shawn J.; Aparicio, Jennifer G.; Viggiani, Christopher J.; Knott, Simon; Xu, Weihong; Tavaré, Simon; Aparicio, Oscar M.

    2008-01-01

    Replication fork stalling at a DNA lesion generates a damage signal that activates the Rad53 kinase, which plays a vital role in survival by stabilizing stalled replication forks. However, evidence that Rad53 directly modulates the activity of replication forks has been lacking, and the nature of fork stabilization has remained unclear. Recently, cells lacking the Psy2–Pph3 phosphatase were shown to be defective in dephosphorylation of Rad53 as well as replication fork restart after DNA damage, suggesting a mechanistic link between Rad53 deactivation and fork restart. To test this possibility we examined the progression of replication forks in methyl-methanesulfonate (MMS)-damaged cells, under different conditions of Rad53 activity. Hyperactivity of Rad53 in pph3Δ cells slows fork progression in MMS, whereas deactivation of Rad53, through expression of dominant-negative Rad53-KD, is sufficient to allow fork restart during recovery. Furthermore, combined deletion of PPH3 and PTC2, a second, unrelated Rad53 phosphatase, results in complete replication fork arrest and lethality in MMS, demonstrating that Rad53 deactivation is a key mechanism controlling fork restart. We propose a model for regulation of replication fork progression through damaged DNA involving a cycle of Rad53 activation and deactivation that coordinates replication restart with DNA repair. PMID:18628397

  10. Expertise-related deactivation of the right temporoparietal junction during musical improvisation.

    PubMed

    Berkowitz, Aaron L; Ansari, Daniel

    2010-01-01

    Musical training has been associated with structural changes in the brain as well as functional differences in brain activity when musicians are compared to nonmusicians on both perceptual and motor tasks. Previous neuroimaging comparisons of musicians and nonmusicians in the motor domain have used tasks involving prelearned motor sequences or synchronization with an auditorily presented sequence during the experiment. Here we use functional magnetic resonance imaging (fMRI) to examine expertise-related differences in brain activity between musicians and nonmusicians during improvisation--the generation of novel musical-motor sequences--using a paradigm that we previously used in musicians alone. Despite behaviorally matched performance, the two groups showed significant differences in functional brain activity during improvisation. Specifically, musicians deactivated the right temporoparietal junction (rTPJ) during melodic improvisation, while nonmusicians showed no change in activity in this region. The rTPJ is thought to be part of a ventral attentional network for bottom-up stimulus-driven processing, and it has been postulated that deactivation of this region occurs in order to inhibit attentional shifts toward task-irrelevant stimuli during top-down, goal-driven behavior. We propose that the musicians' deactivation of the rTPJ during melodic improvisation may represent a training-induced shift toward inhibition of stimulus-driven attention, allowing for a more goal-directed performance state that aids in creative thought.

  11. Visual cycle modulation in neurovascular retinopathy.

    PubMed

    Akula, James D; Hansen, Ronald M; Tzekov, Radouil; Favazza, Tara L; Vyhovsky, Tanya C; Benador, Ilan Y; Mocko, Julie A; McGee, David; Kubota, Ryo; Fulton, Anne B

    2010-08-01

    Rats with oxygen-induced retinopathy (OIR) model the pediatric retinal disease retinopathy of prematurity (ROP). Recent findings in OIR rats imply a causal role for the rods in the ROP disease process, although only experimental manipulation of rod function can establish this role conclusively. Accordingly, a visual cycle modulator (VCM) - with no known direct effect on retinal vasculature - was administered to "50/10 model" OIR Sprague-Dawley rats to test the hypotheses that it would 1) alter rod function and 2) consequently alter vascular outcome. Four litters of pups (N=46) were studied. For two weeks, beginning on postnatal day (P) 7, the first and fourth litters were administered 6 mg kg(-1) N-retinylacetamide (the VCM) intraperitoneally; the second and third litters received vehicle (DMSO) alone. Following a longitudinal design, retinal function was assessed by electroretinography (ERG) and the status of the retinal vessels was monitored using computerized fundus photograph analysis. Rod photoreceptor and post-receptor response amplitudes were significantly higher in VCM-treated than in vehicle-treated rats; deactivation of phototransduction was also significantly more rapid. Notably, the arterioles of VCM-treated rats showed significantly greater recovery from OIR. Presuming that the VCM did not directly affect the retinal vessels, a causal role for the neural retina - particularly the rod photoreceptors - in OIR was confirmed. There was no evidence of negative alteration of photoreceptor function consequent to VCM treatment. This finding implicates the rods as a possible therapeutic target in neurovascular diseases such as ROP. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. How do messenger RNA splicing alterations drive myelodysplasia?

    PubMed Central

    2017-01-01

    Mutations in RNA splicing factors are the single most common class of genetic alterations in myelodysplastic syndrome (MDS) patients. Although much has been learned about how these mutations affect splicing at a global- and transcript-specific level, critical questions about the role of these mutations in MDS development and maintenance remain. Here we present the questions to be addressed in order to understand the unique enrichment of these mutations in MDS. PMID:28348147

  13. 29 CFR 1926.60 - Methylenedianiline.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the following: (i) Construction, alteration, repair, maintenance, or renovation of structures... based are scientifically sound and were collected using methods that are sufficiently accurate and... are substantially similar. The data must be scientifically sound, the characteristics of the MDA...

  14. 29 CFR 1926.60 - Methylenedianiline.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the following: (i) Construction, alteration, repair, maintenance, or renovation of structures... based are scientifically sound and were collected using methods that are sufficiently accurate and... are substantially similar. The data must be scientifically sound, the characteristics of the MDA...

  15. 29 CFR 1926.60 - Methylenedianiline.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... the following: (i) Construction, alteration, repair, maintenance, or renovation of structures... based are scientifically sound and were collected using methods that are sufficiently accurate and... are substantially similar. The data must be scientifically sound, the characteristics of the MDA...

  16. 15 CFR 801.9 - Reports required.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...); industrial engineering services; industrial-type maintenance, installation, alteration, and training services... services; educational and training services; engineering, architectural, and surveying services; financial... assets covered by the BE-125 survey are rights related to: Industrial processes and products; books...

  17. 15 CFR 801.9 - Reports required.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...); industrial engineering services; industrial-type maintenance, installation, alteration, and training services... services; educational and training services; engineering, architectural, and surveying services; financial... assets covered by the BE-125 survey are rights related to: Industrial processes and products; books...

  18. 15 CFR 801.9 - Reports required.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...); industrial engineering services; industrial-type maintenance, installation, alteration, and training services... services; educational and training services; engineering, architectural, and surveying services; financial... assets covered by the BE-125 survey are rights related to: Industrial processes and products; books...

  19. Particle and Noise Exposure During Highway Maintenance Work

    EPA Science Inventory

    Background: Exposure to traffic is associated with increased cardiovascular morbidity and mortality. Traffic particles are associated with increased pro‑inflammatory and pro-thrombotic markers as well as altered heart rhythm (Riediker et al. 2004). Occupational noise exposu...

  20. The chlorophyllin-induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells is associated with ERK deactivation and Cyclin D1 depletion.

    PubMed

    Chiu, Lawrence C-M; Kong, Carrie K-L; Ooi, Vincent E-C

    2005-10-01

    Targeting the mitogen-activated protein kinases (MAPKs) has been suggested as a novel strategy to treat cancer. Chlorophyllin (CHL) is the sodium-copper salt of chlorophyll derivative and is a commonly used food dye for green coloration; CHL was found previously to retard growth of the human breast carcinoma MCF-7 cells. Extracellular signal-regulated kinases (ERKs) constitute a subfamily of MAPKs, participating in cell survival, proliferation and differentiation. We report here the first evidence that CHL deactivates ERKs to inhibit the breast cancer cell proliferation. The results from flow cytometry showed that 200 microg/ml CHL reduced the phosphorylated and activated ERK-positive cells in different cell cycle phases from the control of >96 to <38% at 24 h of incubation; the ERK deactivations occurred in both dose- and time-dependent manner, so that nearly all ERKs were de-activated by 400 microg/ml CHL at 72 h of treatment. Immunoblot studies, however, illustrated that the levels of total ERKs were not significantly affected by the CHL treatments, suggesting that the phytochemical retards the enzyme activation rather than its expression. Cyclin D1, but not its enzyme Cdk6, was also depleted after the CHL treatments; the depletions were associated with elevations of G0/G1 cells. Apoptosis occurred time-dependently with the ERK deactivations by 400 microg/ml CHL; the apoptotic cells elevated from 2.7-fold of the control level at 24 h, to 4.7-fold at 48 h and to 16.6-fold at 72 h of treatment. Bcl-2 was also depleted at 72 h when there was the most prominent elevation of the apoptotic cells, suggesting that it participates during the exacerbation rather than the initiation phases of the CHL-induced apoptosis. Results from this study support further research on CHL for preventing and treating those tumors with deregulated ERK activations.

  1. SU-F-T-35: Optimization of Bladder and Rectal Doses Using a Multi-Lumen Intracavitary Applicator for Gynecological Brachytherapy

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

    Laoui, S; Dietrich, S; Sehgal, V

    2016-06-15

    Purpose: Radiation dose delivery for endometrial cancer using HDR techniques is limited by dose to bladder and rectum. A dosimetric study was performed using Varian Capri vaginal brachytherapy applicator to determine the optimal channel configuration which minimizes dose to bladder and rectum, while providing good target coverage. Methods: A total of 17 patients, 63 plans clinically delivered, and 252 simulated plans using Varian BrachyVision planning system were generated to investigate optimal channel configuration which results in minimum dose to bladder and rectum while providing adequate target coverage. The Capri applicator consists of 13 lumens arranged in two concentric rings, onemore » central lumen and six lumens per ring. Manual dose shaping is invariably required to lower the dose to critical organs. Three-dimensional plans were simulated for 4 channel arrangements, all 13 channels, channel 12 o’clock (close to bladder) and 6 o’clock (close to rectum) deactivated, central channel deactivated, and central channel in addition to 12 o’clock and 6 o’clock deactivated. A relationship between V100, the volume that receives the prescribed dose, and the amount of curie-seconds required to deliver it, was established. Results: Using all 13 channels results in maximum dose to bladder and rectum. Deactivating central channel in addition to 12 o’clock and 6 o’clock resulted in minimizing bladder and rectum doses but compromised target coverage. The relationship between V100, the volume that receives the prescribed dose, and the curie seconds was found to be linear. Conclusion: Deactivating channels 12 o’clock and 6 o’clock was shown to be the optimal configuration leading to minimum dose to bladder and rectum without compromising target coverage. The linear relationship between V100 and the curie- seconds can be used as a verification parameter.« less

  2. Study of collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules in a hydrogen-oxygen mixture at high temperatures using laser-induced gratings

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

    Kozlov, D. N., E-mail: dnk@kapella.gpi.ru; Kobtsev, V. D.; Stel'makh, O. M.

    2013-07-15

    Collisional deactivation of O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) molecules resonantly excited by a 10 ns pulse of laser radiation with a wavelength of 762 nm in H{sub 2}/O{sub 2} mixtures is experimentally studied. The radiation intensity and hence the molecule excitation efficiency have a spatially periodic modulation that leads to the formation of laser-induced gratings (LIGs) of the refractive index. The study of LIG temporal evolution allows collisional relaxation rates of molecular excited states and gas temperature to be determined. In this work, the b{sup 1}{Sigma}{sub g}{sup +} state of O{sub 2} molecules deactivation rates are measured in a 4.3more » vol % H{sub 2} mixture at the number density of 2 amg in the temperature range 291-850 K. The physical deactivation is shown to dominate in the collisions of H{sub 2} with O{sub 2}(b{sup 1}{Sigma}{sub g}{sup +}) and O{sub 2}(a{sup 1}{Delta}{sub g}) up to temperatures of 780-790 K at time delays up to 10 {mu}s after the excitation pulse. The parameters of the obtained temperature dependence of the (b{sup 1}{Sigma}{sub g}{sup +} state deactivation rate agree well with the data of independent measurements performed earlier at lower temperatures (200-400 K). Tunable diode laser absorption spectroscopy is used to measure the temperature dependence of the number density of the H{sub 2}O molecules which appear as the mixture, as the result of the dark gross reaction with O{sub 2} molecules in the ground state, O{sub 2} + 2H{sub 2} {yields} 2H{sub 2}O. The measurements show that this reaction results in complete transformation of H{sub 2} into H{sub 2}O at temperatures of 790-810 K.« less

  3. Presynaptic elements involved in the maintenance of the neuromuscular junction

    NASA Technical Reports Server (NTRS)

    Burrows, G. H.

    1984-01-01

    Alterations in the neuromuscular junction were observed in rats preceding loss of muscle mass. In view of the possibility that these alterations involve changes in the secretion of myotrophic agents by presynaptic motor neurons, an investigation was undertaken to characterize a neuronall factor which is thought to be involved in the initiation and maintenance of cholinergic synapses. This factor, which is secreted into the incubation medium by NG108-15 neuroblastoma x glioma hybrid cells, induces the aggregation of nicotinic acetylcholine receptors on primary cultures of rat hindlimb myotubes. Previous attempts to purify this factor failed. Extensive washing of the NG108-15 cells with hepes-buffered salt solution followed by short (4 hour) collection times resulted in the collection of incubation medium containing maximal aggregation activity with as little as 5 ug secreted protein per ml of fresh medium. A three-fold increase in specific activity was obtained after anion exchange chromatography.

  4. Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia.

    PubMed

    Casellato, Claudia; Pedrocchi, Alessandra; Zorzi, Giovanna; Rizzi, Giorgio; Ferrigno, Giancarlo; Nardocci, Nardo

    2012-07-23

    Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions) and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A), constant disturbing force (B) and deactivation of the additive external force again (C). The path length for each trial was computed, from the recorded position data and interaction events. The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment.The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining of the existing but strongly imprecise motor scheme and sensorimotor patterns.

  5. Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia

    PubMed Central

    2012-01-01

    Background Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. Methods As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions) and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A), constant disturbing force (B) and deactivation of the additive external force again (C). The path length for each trial was computed, from the recorded position data and interaction events. Results The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment. The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. Conclusions The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining of the existing but strongly imprecise motor scheme and sensorimotor patterns. PMID:22824547

  6. Persistent modification of Na{sub v}1.9 following chronic exposure to insecticides and pyridostigmine bromide

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

    Nutter, Thomas J., E-mail: tnutter@dental.ufl.edu; Cooper, Brian Y., E-mail: bcooper@dental.ufl.edu

    Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60 day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Na{sub v}1.8, but increased K{sub v}7 mediated inhibitory currents 8 weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Na{sub v}1.9 expressed in muscle and vascular nociceptors. During a 60 day exposure to NTPB, rats exhibited lowered musclemore » pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12 weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Na{sub v}1.9, but significant increases in the amplitude of Na{sub v}1.9 were observed 8 weeks after exposure. Cellular studies, at the 8 week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22 °C). Acute application of permethrin (10 μM) also increased the amplitude of Na{sub v}1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Na{sub v}1.9 expressed in muscle and vascular nociceptors. The reported increases in K{sub v}7 amplitude may have been an adaptive response to increased Na{sub v}1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Na{sub v}1.9 and K{sub v}7 could release spontaneous discharge and produce chronic deep tissue pain. - Highlights: • Rats were treated 60 days with permethrin, chlorpyrifos and pyridostigmine bromide. • 8 weeks after treatments, Nav1.9 activation and deactivation were unchanged. • The amplitude and conductance of Nav1.9 were increased 8 weeks following exposure. • Nociceptors exhibit increased action potential duration and afterhyperpolarization. • Acute permethrin altered activation physiology and increased the amplitude of Nav1.9.« less

  7. Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study

    PubMed Central

    Farr, Olivia M.; Tsoukas, Michael A.; Triantafyllou, Georgios; Dincer, Fadime; Filippaios, Andreas; Ko, Byung-Joon; Mantzoros, Christos S.

    2016-01-01

    Background GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. Basic Procedures Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17 days (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days) of treatment, we also studied changes in fMRI responses to food cues. Main Findings By design, to avoid any confounding by weight changes, subjects were studied for 17 days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control-related thalamus and pre-SMA. Principal Conclusions We demonstrate herein short-term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that would over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials. PMID:27282865

  8. Extending operating range of a homogeneous charge compression ignition engine via cylinder deactivation

    DOEpatents

    Hergart, Carl-Anders [Peoria, IL; Hardy, William L [Peoria, IL; Duffy, Kevin P [Metamora, IL; Liechty, Michael P [Chillicothe, IL

    2008-05-27

    An HCCI engine has the ability to operate over a large load range by utilizing a lower cetane distillate diesel fuel to increase ignition delay. This permits more stable operation at high loads by avoidance of premature combustion before top dead center. During low load conditions, a portion of the engines cylinders are deactivated so that the remaining cylinders can operate at a pseudo higher load while the overall engine exhibits behavior typical of a relatively low load.

  9. Diagnosing Physical Plant Operation

    ERIC Educational Resources Information Center

    McKay, B. P.; Smith, H. W.

    1972-01-01

    Describes a survey designed to help administrators evaluate functional aspects, adequacy of employee work areas, quality of housekeeping methods, maintenance response, interior and exterior appearances, alteration and renovation satisfaction, employee feelings about parking adequacy, plant security, and attraction and function of roads and…

  10. Impacts of climate change and variability on transportation systems and infrastructure : Gulf Coast study, phase I

    DOT National Transportation Integrated Search

    2008-03-01

    Climate affects the design, construction, safety, operations, and maintenance of transportation : infrastructure and systems. The prospect of a changing climate raises critical questions : regarding how alterations in temperature, precipitation, stor...

  11. 15 CFR 301.10 - Importation of repair components and maintenance tools under HTSUS subheadings 9810.00.65 and...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC..., HTSUS (covering articles exported for repairs or alterations) or may be made the subject of a new...

  12. 14 CFR 145.151 - Personnel requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Personnel § 145.151 Personnel requirements. Each certificated repair station must— (a) Designate a repair station employee as the accountable manager; (b..., preventive maintenance, or alterations performed under the repair station certificate and operations...

  13. 14 CFR 145.151 - Personnel requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Personnel § 145.151 Personnel requirements. Each certificated repair station must— (a) Designate a repair station employee as the accountable manager; (b..., preventive maintenance, or alterations performed under the repair station certificate and operations...

  14. 14 CFR 145.151 - Personnel requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Personnel § 145.151 Personnel requirements. Each certificated repair station must— (a) Designate a repair station employee as the accountable manager; (b..., preventive maintenance, or alterations performed under the repair station certificate and operations...

  15. Deactivation of Streptococcus mutans Biofilms on a Tooth Surface Using He Dielectric Barrier Discharge at Atmospheric Pressure

    NASA Astrophysics Data System (ADS)

    Imola, Molnar; Judit, Papp; Alpar, Simon; Sorin, Dan Anghel

    2013-06-01

    This paper presents a study of the effect of the low temperature atmospheric helium dielectric barrier discharge (DBD) on the Streptococcus mutans biofilms formed on tooth surface. Pig jaws were also treated by plasma to detect if there is any harmful effect on the gingiva. The plasma was characterized by using optical emission spectroscopy. Experimental data indicated that the discharge is very effective in deactivating Streptococcus mutans biofilms. It can destroy them with an average decimal reduction time (D-time) of 19 s and about 98% of them were killed after a treatment time of 30 s. According to the survival curve kinetic an overall 32 s treatment time would be necessary to perform a complete sterilization. The experimental results presented in this study indicated that the helium dielectric barrier discharge, in plan-parallel electrode configuration, could be a very effective tool for deactivation of oral bacteria and might be a promising technique in various dental clinical applications.

  16. Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning

    PubMed Central

    Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

    2014-01-01

    Objective: Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. Methods: To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Results: Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Conclusions: Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning. PMID:25337240

  17. Interference Effects Redress over Power-Efficient Wireless-Friendly Mesh Networks for Ubiquitous Sensor Communications across Smart Cities.

    PubMed

    Santana, Jose; Marrero, Domingo; Macías, Elsa; Mena, Vicente; Suárez, Álvaro

    2017-07-21

    Ubiquitous sensing allows smart cities to take control of many parameters (e.g., road traffic, air or noise pollution levels, etc.). An inexpensive Wireless Mesh Network can be used as an efficient way to transport sensed data. When that mesh is autonomously powered (e.g., solar powered), it constitutes an ideal portable network system which can be deployed when needed. Nevertheless, its power consumption must be restrained to extend its operational cycle and for preserving the environment. To this end, our strategy fosters wireless interface deactivation among nodes which do not participate in any route. As we show, this contributes to a significant power saving for the mesh. Furthermore, our strategy is wireless-friendly, meaning that it gives priority to deactivation of nodes receiving (and also causing) interferences from (to) the rest of the smart city. We also show that a routing protocol can adapt to this strategy in which certain nodes deactivate their own wireless interfaces.

  18. Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study.

    PubMed

    Rahko, Jukka S; Vuontela, Virve A; Carlson, Synnöve; Nikkinen, Juha; Hurtig, Tuula M; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jussila, Katja K; Remes, Jukka J; Jansson-Verkasalo, Eira M; Aronen, Eeva T; Pauls, David L; Ebeling, Hanna E; Tervonen, Osmo; Moilanen, Irma K; Kiviniemi, Vesa J

    2016-06-01

    The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.

  19. Universal and reusable virus deactivation system for respiratory protection

    NASA Astrophysics Data System (ADS)

    Quan, Fu-Shi; Rubino, Ilaria; Lee, Su-Hwa; Koch, Brendan; Choi, Hyo-Jick

    2017-01-01

    Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.

  20. Effect of polymers on the retention and aging of enzyme on bioactive papers.

    PubMed

    Khan, Mohidus Samad; Haniffa, Sharon B M; Slater, Alison; Garnier, Gil

    2010-08-01

    The effect of polymer on the retention and the thermal stability of bioactive enzymatic papers was measured using a colorimetric technique quantifying the intensity of the enzyme-substrate product complex. Alkaline phosphatase (ALP) was used as model enzyme. Three water soluble polymers: a cationic polyacrylamide (CPAM), an anionic polyacrylic acid (PAA) and a neutral polyethylene oxide (PEO) were selected as retention aids. The model polymers increased the enzyme adsorption on paper by around 50% and prevented enzyme desorption upon rewetting of the papers. The thermal deactivation of ALP retained on paper with polymers follows two sequential first order reactions. This was also observed for ALP simply physisorbed on paper. The retention aid polymers instigated a rapid initial deactivation which significantly decreased the longevity of the enzymatic papers. This suggests some enzyme-polymer interaction probably affecting the enzyme tertiary structure. A deactivation mathematical model predicting the enzymatic paper half-life was developed. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  1. Universal and reusable virus deactivation system for respiratory protection

    PubMed Central

    Quan, Fu-Shi; Rubino, Ilaria; Lee, Su-Hwa; Koch, Brendan; Choi, Hyo-Jick

    2017-01-01

    Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases. PMID:28051158

  2. Interference Effects Redress over Power-Efficient Wireless-Friendly Mesh Networks for Ubiquitous Sensor Communications across Smart Cities

    PubMed Central

    Marrero, Domingo; Macías, Elsa; Mena, Vicente

    2017-01-01

    Ubiquitous sensing allows smart cities to take control of many parameters (e.g., road traffic, air or noise pollution levels, etc.). An inexpensive Wireless Mesh Network can be used as an efficient way to transport sensed data. When that mesh is autonomously powered (e.g., solar powered), it constitutes an ideal portable network system which can be deployed when needed. Nevertheless, its power consumption must be restrained to extend its operational cycle and for preserving the environment. To this end, our strategy fosters wireless interface deactivation among nodes which do not participate in any route. As we show, this contributes to a significant power saving for the mesh. Furthermore, our strategy is wireless-friendly, meaning that it gives priority to deactivation of nodes receiving (and also causing) interferences from (to) the rest of the smart city. We also show that a routing protocol can adapt to this strategy in which certain nodes deactivate their own wireless interfaces. PMID:28754013

  3. Method For Reactivating Solid Catalysts Used For Alklation Reactions

    DOEpatents

    Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

    2005-05-03

    A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

  4. Method for reactivating solid catalysts used in alkylation reactions

    DOEpatents

    Ginosar, Daniel M.; Thompson, David N.; Coates, Kyle; Zalewski, David J.; Fox, Robert V.

    2003-06-17

    A method for reactivating a solid alkylation catalyst is provided which can be performed within a reactor that contains the alkylation catalyst or outside the reactor. Effective catalyst reactivation is achieved whether the catalyst is completely deactivated or partially deactivated. A fluid reactivating agent is employed to dissolve catalyst fouling agents and also to react with such agents and carry away the reaction products. The deactivated catalyst is contacted with the fluid reactivating agent under pressure and temperature conditions such that the fluid reactivating agent is dense enough to effectively dissolve the fouling agents and any reaction products of the fouling agents and the reactivating agent. Useful pressures and temperatures for reactivation include near-critical, critical, and supercritical pressures and temperatures for the reactivating agent. The fluid reactivating agent can include, for example, a branched paraffin containing at least one tertiary carbon atom, or a compound that can be isomerized to a molecule containing at least one tertiary carbon atom.

  5. Unusually high fluorescence quantum yield of a homopolyfluorenylazomethine--towards a universal fluorophore.

    PubMed

    Mallet, Charlotte; Bolduc, Andréanne; Bishop, Sophie; Gautier, Yohan; Skene, W G

    2014-11-28

    The absolute fluorescence quantum yield (Φfl) of a polyfluorenyl azomethine homopolymer was measured as a function of solvent polarity. The solvent induced and temperature dependent fluorescence of the homopolymer were also investigated and they were compared to the corresponding monomer and copolymer. The Φfl of the homopolymer was consistent (45-70%), regardless of solvent polarity with Stokes shifts up to 7460 cm(-1) in ethanol. In contrast, the Φfl of its corresponding monomer decreased from 60% in ethanol to 1% in toluene, whereas a Φfl < 5% for its analogous copolymer was measured. Moderate fluorescence yields (Φfl ≈ 25%) were also possible in thin film when co-depositing the homopolymer with PMMA. Cryofluorescence was used to probe the excited state deactivation modes. Deactivation by internal conversion was found to compete with fluorescence. The fluorescence deactivation pathways of the homopolymer and its corresponding monomer could be suppressed at 77 K, resulting in fluorescence turn-on. Both fluorophores were found to detect nitroaromatics.

  6. Thermal stress analysis of sulfur deactivated solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Zeng, Shumao; Parbey, Joseph; Yu, Guangsen; Xu, Min; Li, Tingshuai; Andersson, Martin

    2018-03-01

    Hydrogen sulfide in fuels can deactivate catalyst for solid oxide fuel cells, which has become one of the most critical challenges to stability. The reactions between sulfur and catalyst will cause phase changes, leading to increase in cell polarization and mechanical mismatch. A three-dimensional computational fluid dynamics (CFD) approach based on the finite element method (FEM) is thus used to investigate the polarization, temperature and thermal stress in a sulfur deactivated SOFC by coupling equations for gas-phase species, heat, momentum, ion and electron transport. The results indicate that sulfur in fuels can strongly affect the cell polarization and thermal stresses, which shows a sharp decrease in the vicinity of electrolyte when 10% nickel in the functional layer is poisoned, but they remain almost unchanged even when the poisoned Ni content was increased to 90%. This investigation is helpful to deeply understand the sulfur poisoning effects and also benefit the material design and optimization of electrode structure to enhance cell performance and lifetimes in various hydrocarbon fuels containing impurities.

  7. Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy

    NASA Astrophysics Data System (ADS)

    Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

    2013-06-01

    Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy. Electronic supplementary information (ESI) available: Experimental details of the synthesis and in vitro and in vivo assays. See DOI: 10.1039/c3nr00227f

  8. RNA editing of the GABAA receptor α3 subunit alters the functional properties of recombinant receptors

    PubMed Central

    Nimmich, Mitchell L.; Heidelberg, Laura S.; Fisher, Janet L.

    2009-01-01

    RNA editing provides a post-transcriptional mechanism to increase structural heterogeneity of gene products. Recently, the α3 subunit of the GABAA receptors has been shown to undergo RNA editing. As a result, a highly conserved isoleucine residue in the third transmembrane domain is replaced with a methionine. To determine the effect of this structural change on receptor function, we compared the GABA sensitivity, pharmacological properties and macroscopic kinetics of recombinant receptors containing either the edited or unedited forms of the α3 subunit along with β3 and γ2L. Editing substantially altered the GABA sensitivity and deactivation rate of the receptors, with the unedited form showing a lower GABA EC50 and slower decay. Comparable effects were observed with a mutation at the homologous location in the α1 subunit, suggesting a common role for this site in regulation of channel gating. Except for the response to GABA, the pharmacological properties of the receptor were unaffected by editing, with similar enhancement by a variety of modulators. Since RNA editing of the α3 subunit increases through development, our findings suggest that GABAergic neurotransmission may be more effective early in development, with greater GABA sensitivity and slower decay rates conferred by the unedited α3 subunit. PMID:19367790

  9. Evaluation of changes arising in the pig mesenchymal stromal cells transcriptome following cryopreservation and Trichostatin A treatment

    PubMed Central

    Romanek, Joanna; Pawlina-Tyszko, Klaudia; Szmatoła, Tomasz

    2018-01-01

    Cryopreservation is an important procedure in maintenance and clinical applications of mesenchymal stem/stromal cells (MSCs). Although the methods of cell freezing using various cryoprotectants are well developed and allow preserving structurally intact living cells, the freezing process can be considered as a severe cellular stress associated with ice formation, osmotic damage, cryoprotectants migration/cytotoxicity or rapid cell shrinkage. The cellular response to freezing stress is aimed at the restoring of homeostasis and repair of cell damage and is crucial for cell viability. In this study we evaluated the changes arising in the pig mesenchymal stromal cell transcriptome following cryopreservation and showed the vast alterations in cell transcriptional activity (5,575 genes with altered expression) suggesting the engagement in post-thawing cell recovery of processes connected with cell membrane tension regulation, membrane damage repair, cell shape maintenance, mitochondria-connected energy homeostasis and apoptosis mediation. We also evaluated the effect of known gene expression stimulator—Trichostain A (TSA) on the frozen/thawed cells transcriptome and showed that TSA is able to counteract to a certain extent transcriptome alterations, however, its specificity and advantages for cell recovery after cryopreservation require further studies. PMID:29390033

  10. Hydrodeoxygenation of phenol over zirconia supported Pd bimetallic catalysts. The effect of second metal on catalyst performance

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

    Resende, Karen A.; Teles, Camila A.; Jacobs, Gary

    Here, this work investigated the effect of the addition of a second metal (Cu, Ag, Zn, Sn) on the performance of Pd/ZrO 2 catalyst for HDO of phenol at 573 K in the gas phase. The incorporation of dopants resulted in the formation of Pd–X (Cu, Ag, Zn) alloys, which reduced the reaction rate for HDO and increased the selectivity to hydrogenation products (cyclohexanone and cyclohexanol). The lower activity of the bimetallic catalysts was due to the segregation of the second metal on the surface of the Pd particle. For PdSn/ZrO 2, alloying was also observed but tin oxide wasmore » still present on the surface after reduction at 773 K. For Pd and PdSn/ZrO 2, the oxophilic sites represented by Zr and Sn cations promotes the hydrogenation of the carbonyl group of the keto-tautomer intermediate formed, producing benzene as the main product. All catalysts significantly deactivated during the reaction but the deactivation degree depended on the type of the metal. Pd/ZrO 2 and PdZn/ZrO 2 and PdAg/ZrO 2 exhibited approximately the same deactivation degree. However, the loss of activity was less pronounced for PdSn/ZrO2 catalyst. Finally, Pd dispersion significantly decreased during the reaction, indicating that the sintering of Pd particles is one of the causes for catalyst deactivation.« less

  11. Prevalence of Extracochlear Electrodes: Computerized Tomography Scans, Cochlear Implant Maps, and Operative Reports.

    PubMed

    Holder, Jourdan T; Kessler, David M; Noble, Jack H; Gifford, René H; Labadie, Robert F

    2018-06-01

    To quantify and compare the number of cochlear implant (CI) electrodes found to be extracochlear on postoperative computerized tomography (CT) scans, the number of basal electrodes deactivated during standard CI mapping (without knowledge of the postoperative CT scan), and the extent of electrode insertion noted by the surgeon. Retrospective. Academic Medical Center. Two hundred sixty-two patients underwent standard cochlear implantation and postoperative temporal bone CT scanning. Scans were analyzed to determine the number of extracochlear electrodes. Standard CI programming had been completed without knowledge of the extracochlear electrodes identified on the CT. These standard CI maps were reviewed to record the number of deactivated basal electrodes. Lastly, each operative report was reviewed to record the extent of reported electrode insertion. 13.4% (n = 35) of CIs were found to have at least one electrode outside of the cochlea on the CT scan. Review of CI mapping indicated that audiologists had deactivated extracochlear electrodes in 60% (21) of these cases. Review of operative reports revealed that surgeons correctly indicated the number of extracochlear electrodes in 6% (2) of these cases. Extracochlear electrodes were correctly identified audiologically in 60% of cases and in surgical reports in 6% of cases; however, it is possible that at least a portion of these cases involved postoperative electrode migration. Given these findings, postoperative CT scans can provide information regarding basal electrode location, which could help improve programming accuracy, associated frequency allocation, and audibility with appropriate deactivation of extracochlear electrodes.

  12. Decision-Making of Patients With Implantable Cardioverter-Defibrillators at End of Life: Family Members' Experiences.

    PubMed

    Lee, Mei Ching; Sulmasy, Daniel P; Gallo, Joseph; Kub, Joan; Hughes, Mark T; Russell, Stuart; Kellogg, Anela; Owens, Sharon G; Terry, Peter; Nolan, Marie T

    2017-07-01

    Many patients with advanced heart failure (HF) experience the life-extending benefits of implantable cardioverter-defibrillators (ICD), but at the end stage of HF, patients may experience shocks with increasing frequency and change the plan for end-of-life (EOL) care including the deactivation of the ICD. This report describes family members' experiences of patients with ICD making decisions at EOL. Understanding the decision-making of patients with ICD at EOL can promote informed decision-making and improve the quality of EOL care. This pilot study used a mixed methods approach to test the effects of a nurse-guided discussion in decision-making about ICD deactivation (turning off the defibrillation function) at the EOL. Interviews were conducted, audiotaped, and transcribed in 2012 to 2013 with 6 family members of patients with advanced HF and ICDs. Three researchers coded the data and identified themes in 2014. Three main themes described family members' experiences related to patients having HF with ICDs making health-care decision at EOL: decision-making preferences, patients' perception on ICD deactivation, and communication methods. Health-care providers need to have knowledge of patients' decision-making preferences. Preferences for decision-making include the allowing of appropriate people to involve and encourages direct conversation with family members even when advance directives is completed. Information of ICD function and the option of deactivation need to be clearly delivered to patients and family members. Education and guidelines will facilitate the communication of the preferences of EOL care.

  13. Hydrodeoxygenation of phenol over zirconia supported Pd bimetallic catalysts. The effect of second metal on catalyst performance

    DOE PAGES

    Resende, Karen A.; Teles, Camila A.; Jacobs, Gary; ...

    2018-03-21

    Here, this work investigated the effect of the addition of a second metal (Cu, Ag, Zn, Sn) on the performance of Pd/ZrO 2 catalyst for HDO of phenol at 573 K in the gas phase. The incorporation of dopants resulted in the formation of Pd–X (Cu, Ag, Zn) alloys, which reduced the reaction rate for HDO and increased the selectivity to hydrogenation products (cyclohexanone and cyclohexanol). The lower activity of the bimetallic catalysts was due to the segregation of the second metal on the surface of the Pd particle. For PdSn/ZrO 2, alloying was also observed but tin oxide wasmore » still present on the surface after reduction at 773 K. For Pd and PdSn/ZrO 2, the oxophilic sites represented by Zr and Sn cations promotes the hydrogenation of the carbonyl group of the keto-tautomer intermediate formed, producing benzene as the main product. All catalysts significantly deactivated during the reaction but the deactivation degree depended on the type of the metal. Pd/ZrO 2 and PdZn/ZrO 2 and PdAg/ZrO 2 exhibited approximately the same deactivation degree. However, the loss of activity was less pronounced for PdSn/ZrO2 catalyst. Finally, Pd dispersion significantly decreased during the reaction, indicating that the sintering of Pd particles is one of the causes for catalyst deactivation.« less

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

    Lara-Curzio, Edgar; Rios, Orlando; Marquez-Rossy, Andres Emilio

    ORNL collaborated with Faurecia Interior Systems to investigate the feasibility of developing a thermomagnetic preventive maintenance program for nickel tooling used in powder slush molding. It was found that thermal treatments at temperatures greater than 500°C can anneal strain hardening in nickel tooling and a range of temperatures and times for effective thermal annealing were identified. It was also observed that magnetic fields applied during thermal annealing do not alter the kinetics of strain hardening annealing. The results obtained in this investigation provide a foundation for establishing a preventive maintenance program for nickel tooling.

  15. Moving Species Redundancy Toward a More Predictive Framework

    EPA Science Inventory

    Human activities are driving rapid changes in species diversity in a wide range of habitats globally. These changes in species diversity raise questions about the ability of altered systems to continue to offer valuable ecosystem services. Maintenance of ecosystem services unde...

  16. Elements of Successful Plant Management.

    ERIC Educational Resources Information Center

    Sweitzer, John H.

    The physical plant administrator manages men, money and materials to create the best possible physical environment for the educational processes at his institution. Areas of concern of the plant administrator are administration, building maintenance, janitorial services, traffic, security and safety, utilities, grounds, alterations, and…

  17. Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

    PubMed Central

    Gerber, David E.; Schiller, Joan H.

    2013-01-01

    Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

  18. Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile.

    PubMed

    Jiménez, Gema; Hackenberg, Michael; Catalina, Purificación; Boulaiz, Houria; Griñán-Lisón, Carmen; García, María Ángel; Perán, Macarena; López-Ruiz, Elena; Ramírez, Alberto; Morata-Tarifa, Cynthia; Carrasco, Esther; Aguilera, Margarita; Marchal, Juan Antonio

    2018-08-10

    Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better stemness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo stemness properties. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. DNA-PKcs is critical for telomere capping

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

    Gilley, David; Tanaka, Hiromi; Hande, M. Prakash

    The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is critical for DNA repair via the non-homologous end joining (NHEJ) pathway. Previously, it was reported that bone marrow cells and spontaneously transformed fibroblasts from SCID (severe combined immunodeficiency) mice have defects in telomere maintenance. The genetically defective SCID mouse arose spontaneously from its parental strain CB17. One known genomic alteration in SCID mice is a truncation of the extreme carboxyl-terminus of DNA-PKcs, but other as yet unidentified alterations may also exist. We have used a defined system, the DNA-PKcs knockout mouse, to investigate specifically the role DNA-PKcs specifically plays in telomere maintenance.more » We report that primary mouse embryonic fibroblasts (MEFs) and primary cultured kidney cells from 6-8 month old DNA-PKcs deficient mice accumulate a large number of telomere fusions, yet still retain wildtype telomere length. Thus, the phenotype of this defect separates the two-telomere related phenotypes, capping and length maintenance. DNA-PKcs deficient MEFs also exhibit elevated levels of chromosome fragments and breaks, which correlate with increased telomere fusions. Based on the high levels of telomere fusions observed in DNA-PKcs deficient cells, we conclude that DNA-PKcs plays an important capping role at the mammalian telomere.« less

  20. Growth of metal phthalocyanine on deactivated semiconducting surfaces steered by selective orbital coupling

    DOE PAGES

    Wagner, Sean R.; Feng, Jiagui; Yoon, Mina; ...

    2015-08-25

    Using scanning tunneling microscopy and density functional theory, we show that the molecular ordering and orientation of metal phthalocyanine molecules on the deactivated Si surface display a strong dependency on the central transition-metal ion, driven by the degree of orbital hybridization at the heterointerface via selective p – d orbital coupling. As a result, this Letter identifies a selective mechanism for modifying the molecule-substrate interaction which impacts the growth behavior of transition-metal-incorporated organic molecules on a technologically relevant substrate for silicon-based devices.

  1. Defective downregulation of receptor tyrosine kinases in cancer

    PubMed Central

    Bache, Kristi G; Slagsvold, Thomas; Stenmark, Harald

    2004-01-01

    Most growth factors control cellular functions by activating specific receptor tyrosine kinases (RTKs). While overactivation of RTK signalling pathways is strongly associated with carcinogenesis, it is becoming increasingly clear that impaired deactivation of RTKs may also be a mechanism in cancer. A major deactivation pathway, receptor downregulation, involves ligand-induced endocytosis of the RTK and subsequent degradation in lysosomes. A complex molecular machinery that uses the small protein ubiquitin as a key regulator assures proper endocytosis and degradation of RTKs. Here we discuss evidence that implicates deregulation of this machinery in cancer. PMID:15229652

  2. Rupture loop annex ion exchange RLAIX vault deactivation

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

    Ham, J.E.; Harris, D.L., Westinghouse Hanford

    This engineering report documents the deactivation, stabilization and final conditions of the Rupture Loop Annex Ion Exchange (RLAIX) Vault located northwest of the 309 Building`s Plutonium Recycle Test Reactor (PRTR). Twelve ion exchange columns, piping debris, and column liquid were removed from the vault, packaged and shipped for disposal. The vault walls and floor were decontaminated, and portions of the vault were painted to fix loose contamination. Process piping and drains were plugged, and the cover blocks and rain cover were installed. Upon closure,the vault was empty, stabilized, isolated.

  3. Elucidation of the role of metal-to-ring charge-transfer excited states in the deactivation of photoexcited ruthenium porphyrin carbonyl complexes

    NASA Astrophysics Data System (ADS)

    Rodriguez, Juan; McDowell, Lynda; Holten, Dewey

    1988-06-01

    Deactivation of the lowest excited triplet state, 3(π, π*), of the Ru(II) porphyrins RuP(CO)(L) is more strongly dependent on temperature than decay of 3(π, π*) in Pt(II)P and H 2P (metal-free) complexes containing the same macrocycle P. This and other observations support the proposal that 3(π, π*) in the RuP(CO)(L) complexes decays in part via a metal-to-ring (d, π*) charge-transfer excited state at higher energy.

  4. Content of total iron, copper and manganese in liver of animals during hypokinesia, muscle activity and process of recovery

    NASA Technical Reports Server (NTRS)

    Potapovich, G. M.; Taneyeva, G. V.; Uteshev, A. B.

    1980-01-01

    It is shown that the content of total iron, copper and manganese in the liver of animals is altered depending on the intensity and duration of their swimming. Hypodynamia for 7 days does not alter the concentration of iron, but sufficiently increases the content of copper and manganese. The barometric factor effectively influences the maintenance of constancy in the content of microelements accumulated in the liver after intensive muscle activity.

  5. Role of Pterocarpus santalinus against mitochondrial dysfunction and membrane lipid changes induced by ulcerogens in rat gastric mucosa.

    PubMed

    Narayan, Shoba; Devi, R S; Devi, C S Shyamala

    2007-11-20

    Free radicals produced by ulcerogenic agents affect the TCA cycle enzymes located in the outer membrane of the mitochondria. Upon induction with ulcerogens, peroxidation of membrane lipids bring about alterations in the mitochondrial enzyme activity. This indicates an increase in the permeability levels of the mitochondrial membrane. The ability of PSE to scavenge the reactive oxygen species results in restoration of activities of TCA cycle enzymes. NSAIDs interfere with the mitochondrial beta-oxidation of fatty acids in vitro and in vivo, resulting in uncoupling of mitochondrial oxidative phosphorylation process. This usually results in diminished cellular ATP production. The recovery of gastric mucosal barrier function through maintenance of energy metabolism results in maintenance of ATP levels, as observed in this study upon treatment with PSE. Membrane integrity altered by peroxidation is known to have a modified fatty acid composition, a disruption of permeability, a decrease in electrical resistance, and increase in flip-flopping between monolayers and inactivated cross-linked proteins. The severe depletion of arachidonic acid in ulcer induced groups was prevented upon treatment with PSE. The acid inhibitory property of the herbal extract enables the maintenance of GL activity upon treatment with PSE. The ability to prevent membrane peroxidation has been traced to the presence of active constituents in the PSE. In essence, PSE has been found to prevent mitochondrial dysfunction, provide mitochondrial cell integrity, through the maintenance of lipid bilayer by its ability to provide a hydrophobic character to the gastric mucosa, further indicating its ability to reverse the action of NSAIDs and mast cell degranulators in gastric mucosa.

  6. State Revolving Fund American Iron and Steel (AIS) Requirement

    EPA Pesticide Factsheets

    The AIS provision requires CWSRF and DWSRF assistance recipients to use iron and steel products that are produced in the U.S. It applies to projects for the construction, alteration, maintenance, or repair of a public water system or treatment work.

  7. 41 CFR 105-53.147 - Public Buildings Service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for the design, construction, management, maintenance, operation, alteration, extension, remodeling... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Public Buildings Service. 105-53.147 Section 105-53.147 Public Contracts and Property Management Federal Property Management...

  8. 41 CFR 105-53.147 - Public Buildings Service.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... for the design, construction, management, maintenance, operation, alteration, extension, remodeling... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Public Buildings Service. 105-53.147 Section 105-53.147 Public Contracts and Property Management Federal Property Management...

  9. 41 CFR 105-53.147 - Public Buildings Service.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... for the design, construction, management, maintenance, operation, alteration, extension, remodeling... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Public Buildings Service. 105-53.147 Section 105-53.147 Public Contracts and Property Management Federal Property Management...

  10. 41 CFR 105-53.147 - Public Buildings Service.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... for the design, construction, management, maintenance, operation, alteration, extension, remodeling... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Public Buildings Service. 105-53.147 Section 105-53.147 Public Contracts and Property Management Federal Property Management...

  11. 14 CFR 169.3 - Application for recommendation and certification.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Application for recommendation and certification. 169.3 Section 169.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... the acquisition, establishment, construction, alteration, repair, maintenance, or operation of an...

  12. 14 CFR 169.3 - Application for recommendation and certification.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Application for recommendation and certification. 169.3 Section 169.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... the acquisition, establishment, construction, alteration, repair, maintenance, or operation of an...

  13. 14 CFR 169.3 - Application for recommendation and certification.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Application for recommendation and certification. 169.3 Section 169.3 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... the acquisition, establishment, construction, alteration, repair, maintenance, or operation of an...

  14. Ca2+/calmodulin-dependent transcriptional pathways: potential mediators of skeletal muscle growth and development.

    PubMed

    Al-Shanti, Nasser; Stewart, Claire E

    2009-11-01

    The loss of muscle mass with age and disuse has a significant impact on the physiological and social well-being of the aged; this is an increasingly important problem as the population becomes skewed towards older age. Exercise has psychological benefits but it also impacts on muscle protein synthesis and degradation, increasing muscle tissue volume in both young and older individuals. Skeletal muscle hypertrophy involves an increase in muscle mass and cross-sectional area and associated increased myofibrillar protein content. Attempts to understand the molecular mechanisms that underlie muscle growth, development and maintenance, have focused on characterising the molecular pathways that initiate, maintain and regenerate skeletal muscle. Such understanding may aid in improving targeted interventional therapies for age-related muscle loss and muscle wasting associated with diseases. Two major routes through which skeletal muscle development and growth are regulated are insulin-like growth factor I (IGF-I) and Ca(2+)/calmodulin-dependent transcriptional pathways. Many reviews have focused on understanding the signalling pathways of IGF-I and its receptor, which govern skeletal muscle hypertrophy. However, alternative molecular signalling pathways such as the Ca(2+)/calmodulin-dependent transcriptional pathways should also be considered as potential mediators of muscle growth. These latter pathways have received relatively little attention and the purpose herein is to highlight the progress being made in the understanding of these pathways and associated molecules: calmodulin, calmodulin kinases (CaMKs), calcineurin and nuclear factor of activated T-cell (NFAT), which are involved in skeletal muscle regulation. We describe: (1) how conformational changes in the Ca(2+) sensor calmodulin result in the exposure of binding pockets for the target proteins (CaMKs and calcineurin). (2) How Calmodulin consequently activates either the Ca(2+)/calmodulin-dependent kinases pathways (via CaMKs) or calmodulin-dependent serine/threonine phosphatases (via calcineurin). (3) How calmodulin kinases alter transcription in the nucleus through the phosphorylation, deactivation and translocation of histone deacetylase 4 (HDAC4) from the nucleus to the cytoplasm. (4) How calcineurin transmits signals to the nucleus through the dephosphorylation and translocation of NFAT from the cytoplasm to the nucleus.

  15. Transient Shifts of Incubation Temperature Reveal Immediate and Long-Term Transcriptional Response in Chicken Breast Muscle Underpinning Resilience and Phenotypic Plasticity.

    PubMed

    Naraballobh, Watcharapong; Trakooljul, Nares; Murani, Eduard; Brunner, Ronald; Krischek, Carsten; Janisch, Sabine; Wicke, Michael; Ponsuksili, Siriluck; Wimmers, Klaus

    2016-01-01

    Variations in egg incubation temperatures can have acute or long-term effects on gene transcription in avian species. Altered gene expression may, in turn, affect muscle traits in poultry and indirectly influence commercial production. To determine how changes in eggshell temperature affect gene expression, incubation temperatures were varied [36.8°C (low), 37.8°C (control), 38.8°C (high)] at specific time periods reflecting two stages of myogenesis [embryonic days (ED) 7-10 and 10-13]. Gene expression was compared between interventions and matching controls by microarrays in broiler breast muscle at ED10 or ED13 and post-hatch at day 35. Early (ED7-10) high incubation temperature (H10ΔC) resulted in 1370 differentially expressed genes (DEGs) in embryos. Ingenuity pathway analysis revealed temporary activation of cell maintenance, organismal development, and survival ability genes, but these effects were not maintained in adults. Late high incubation temperature (ED10-13) (H13ΔC) had slightly negative impacts on development of cellular components in embryos, but a cumulative effect was observed in adults, in which tissue development and nutrition metabolism were affected. Early low incubation temperature (L10ΔC) produced 368 DEGs, most of which were down-regulated and involved in differentiation and formation of muscle cells. In adults, this treatment down-regulated pathways of transcriptional processes, but up-regulated cell proliferation. Late low temperature incubation (L13ΔC) produced 795 DEGs in embryos, and activated organismal survival and post-transcriptional regulation pathways. In adults this treatment activated cellular and organ development, nutrition and small molecule activity, and survival rate, but deactivated size of body and muscle cells. Thermal interventions during incubation initiate immediate and delayed transcriptional responses that are specific for timing and direction of treatment. Interestingly, the transcriptional response to transiently decreased incubation temperature, which did not affect the phenotypes, prompts compensatory effects reflecting resilience. In contrast, higher incubation temperature triggers gene expression and has long-term effects on the phenotype. These mechanisms of considerable phenotypic plasticity contribute to the biodiversity and broaden the basis for managing poultry populations.

  16. Evaluation of Earthquake Detection Performance in Terms of Quality and Speed in SEISCOMP3 Using New Modules Qceval, Npeval and Sceval

    NASA Astrophysics Data System (ADS)

    Roessler, D.; Weber, B.; Ellguth, E.; Spazier, J.

    2017-12-01

    The geometry of seismic monitoring networks, site conditions and data availability as well as monitoring targets and strategies typically impose trade-offs between data quality, earthquake detection sensitivity, false detections and alert times. Network detection capabilities typically change with alteration of the seismic noise level by human activity or by varying weather and sea conditions. To give helpful information to operators and maintenance coordinators, gempa developed a range of tools to evaluate earthquake detection and network performance including qceval, npeval and sceval. qceval is a module which analyzes waveform quality parameters in real-time and deactivates and reactivates data streams based on waveform quality thresholds for automatic processing. For example, thresholds can be defined for latency, delay, timing quality, spikes and gaps count and rms. As changes in the automatic processing have a direct influence on detection quality and speed, another tool called "npeval" was designed to calculate in real-time the expected time needed to detect and locate earthquakes by evaluating the effective network geometry. The effective network geometry is derived from the configuration of stations participating in the detection. The detection times are shown as an additional layer on the map and updated in real-time as soon as the effective network geometry changes. Yet another new tool, "sceval", is an automatic module which classifies located seismic events (Origins) in real-time. sceval evaluates the spatial distribution of the stations contributing to an Origin. It confirms or rejects the status of Origins, adds comments or leaves the Origin unclassified. The comments are passed to an additional sceval plug-in where the end user can customize event types. This unique identification of real and fake events in earthquake catalogues allows to lower network detection thresholds. In real-time monitoring situations operators can limit the processing to events with unclassified Origins, reducing their workload. Classified Origins can be treated specifically by other procedures. These modules have been calibrated and fully tested by several complex seismic monitoring networks in the region of Indonesia and Northern Chile.

  17. Food, stress, and reproduction: short-term fasting alters endocrine physiology and reproductive behavior in the zebra finch.

    PubMed

    Lynn, Sharon E; Stamplis, Teresa B; Barrington, William T; Weida, Nicholas; Hudak, Casey A

    2010-07-01

    Stress is thought to be a potent suppressor of reproduction. However, the vast majority of studies focus on the relationship between chronic stress and reproductive suppression, despite the fact that chronic stress is rare in the wild. We investigated the role of fasting in altering acute stress physiology, reproductive physiology, and reproductive behavior of male zebra finches (Taeniopygia guttata) with several goals in mind. First, we wanted to determine if acute fasting could stimulate an increase in plasma corticosterone and a decrease in corticosteroid binding globulin (CBG) and testosterone. We then investigated whether fasting could alter expression of undirected song and courtship behavior. After subjecting males to fasting periods ranging from 1 to 10h, we collected plasma to measure corticosterone, CBG, and testosterone. We found that plasma corticosterone was elevated, and testosterone was decreased after 4, 6, and 10h of fasting periods compared with samples collected from the same males during nonfasted (control) periods. CBG was lower than control levels only after 10h of fasting. We also found that, coincident with these endocrine changes, males sang less and courted females less vigorously following short-term fasting relative to control conditions. Our data demonstrate that acute fasting resulted in rapid changes in endocrine physiology consistent with hypothalamo-pituitary-adrenal axis activation and hypothalamo-pituitary-gonadal axis deactivation. Fasting also inhibited reproductive behavior. We suggest that zebra finches exhibit physiological and behavioral flexibility that makes them an excellent model system for studying interactions of acute stress and reproduction. Copyright 2010 Elsevier Inc. All rights reserved.

  18. Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide.

    PubMed

    Vanyukov, P M; Szanto, K; Hallquist, M N; Siegle, G J; Reynolds, C F; Forman, S D; Aizenstein, H J; Dombrovski, A Y

    2016-01-01

    Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters' inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior. A total of 48 participants aged 46-90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls. More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses. Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.

  19. Mediator kinase module and human tumorigenesis.

    PubMed

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  20. Mediator kinase module and human tumorigenesis

    PubMed Central

    Clark, Alison D.; Oldenbroek, Marieke; Boyer, Thomas G.

    2016-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit “kinase” module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways. PMID:26182352

  1. Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions.

    PubMed

    La, Christian; Garcia-Ramos, Camille; Nair, Veena A; Meier, Timothy B; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E; Prabhakaran, Vivek

    2016-01-01

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.

  2. Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions

    PubMed Central

    La, Christian; Garcia-Ramos, Camille; Nair, Veena A.; Meier, Timothy B.; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E.; Prabhakaran, Vivek

    2016-01-01

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the “default-mode” network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently. PMID:27242519

  3. Influence of the Reaction Temperature on the Nature of the Active and Deactivating Species During Methanol-to-Olefins Conversion over H-SAPO-34

    PubMed Central

    2017-01-01

    The selectivity toward lower olefins during the methanol-to-olefins conversion over H-SAPO-34 at reaction temperatures between 573 and 773 K has been studied with a combination of operando UV–vis diffuse reflectance spectroscopy and online gas chromatography. It was found that the selectivity toward propylene increases in the temperature range of 573–623 K, while it decreases in the temperature range of 623–773 K. The high degree of incorporation of olefins, mainly propylene, into the hydrocarbon pool affects the product selectivity at lower reaction temperatures. The nature and dynamics of the active and deactivating hydrocarbon species with increasing reaction temperature were revealed by a non-negative matrix factorization of the time-resolved operando UV–vis diffuse reflectance spectra. The active hydrocarbon pool species consist of mainly highly methylated benzene carbocations at temperatures between 573 and 598 K, of both highly methylated benzene carbocations and methylated naphthalene carbocations at 623 K, and of only methylated naphthalene carbocations at temperatures between 673 and 773 K. The operando spectroscopy results suggest that the nature of the active species also influences the olefin selectivity. In fact, monoenylic and highly methylated benzene carbocations are more selective to the formation of propylene, whereas the formation of the group of low methylated benzene carbocations and methylated naphthalene carbocations at higher reaction temperatures (i.e., 673 and 773 K) favors the formation of ethylene. At reaction temperatures between 573 and 623 K, catalyst deactivation is caused by the gradual filling of the micropores with methylated naphthalene carbocations, while between 623 and 773 K the formation of neutral poly aromatics and phenanthrene/anthracene carbocations are mainly responsible for catalyst deactivation, their respective contribution increasing with increasing reaction temperature. Methanol pulse experiments at different temperatures demonstrate the dynamics between methylated benzene and methylated naphthalene carbocations. It was found that methylated naphthalene carbocations species are deactivating and block the micropores at low reaction temperatures, while acting as the active species at higher reaction temperatures, although they give rise to the formation of extended hydrocarbon deposits. PMID:28824823

  4. Enhancement of Glycerol Steam Reforming Activity and Thermal Stability by Incorporating CeO2 and TiO2 in Ni- and Co-MCM-41 Catalysts

    NASA Astrophysics Data System (ADS)

    Dade, William N.

    Hydrogen (H2) has many applications in industry with current focus shifted to production of hydrocarbon fuels and valuable oxygenates using the Fischer-Tropsch technology and direct use in proton exchange membrane fuel cell (PEMFC). Hydrogen is generally produced via steam reforming of natural gas or alcohols like methanol and ethanol. Glycerol, a by-product of biodiesel production process, is currently considered to be one of the most attractive sources of sustainable H2 due to its high H/C ratio and bio-based origin. Ni and Co based catalysts have been reported to be active in glycerol steam reforming (GSR); however, deactivation of the catalysts by carbon deposition and sintering under GSR operating conditions is a major challenge. In this study, a series of catalysts containing Ni and Co nanoparticles incorporated in CeO2 and TiO2 modified high surface area MCM-41 have been synthesized using one-pot method. The catalysts are tested for GSR (at H2O/Glycerol mole ratio of 12 and GHSV of 2200 h-1) to study the effect of support modification and reaction temperature (450 - 700 °C) on the product selectivity and long term stability. GSR results revealed that all the catalysts performed significantly well exhibiting over 85% glycerol conversion at 650 °C except Ni catalysts that showed better low temperature activities. Deactivation studies of the catalysts conducted at 650 °C indicated that the Ni-TiO2-MCM-41 and Ni-CeO 2-MCM-41 were resistant to deactivation with ˜100% glycerol conversion for 40 h. In contrast, Co-TiO2-MCM-41 perform poorly as the catalyst rapidly deactivated after 12 h to yield ˜20% glycerol conversion after 40 h. The WAXRD and TGA-DSC analyses of spent catalysts showed a significant amount of coke deposition that might explain catalysts deactivation. The flattening shape of the original BET type IV isotherm with drastic reduction of catalyst surface area can also be responsible for observed drop in catalysts activities.

  5. The default mode network and the working memory network are not anti-correlated during all phases of a working memory task.

    PubMed

    Piccoli, Tommaso; Valente, Giancarlo; Linden, David E J; Re, Marta; Esposito, Fabrizio; Sack, Alexander T; Di Salle, Francesco

    2015-01-01

    The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time. To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks. We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between "task-positive" and "task-negative" brain networks. Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.

  6. The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

    PubMed Central

    Piccoli, Tommaso; Valente, Giancarlo; Linden, David E. J.; Re, Marta; Esposito, Fabrizio; Sack, Alexander T.; Salle, Francesco Di

    2015-01-01

    Introduction The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time. Methods To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks. Results We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks. Conclusions Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network. PMID:25848951

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

    PubMed

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

    2014-03-01

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

  8. Ethical challenges of deactivation of cardiac devices in advanced heart failure.

    PubMed

    Chamsi-Pasha, Hassan; Chamsi-Pasha, Mohammed A; Albar, Mohammed Ali

    2014-06-01

    More than 23 million adults worldwide have heart failure (HF). Although survival after heart failure diagnosis has improved over time, mortality from heart failure remains high. At the end of life, the chronic HF patient often becomes increasingly symptomatic, and may have other life-limiting comorbidities as well. Multiple trials have shown a clear mortality benefit with the use of implantable cardioverter defibrillators (ICDs) in patients with cardiomyopathy and ventricular arrhythmia. However, patients who have an ICD may be denied the chance of a sudden cardiac death, and instead are committed to a slower terminal decline, with frequent DC shocks that can be painful and decrease the quality of life, greatly contributing to their distress and that of their families during this period. While patients with ICDs are routinely counseled with regard to the benefits of ICDs, they have a poor understanding of the options for device deactivation and related ethical and legal implications. Deactivating an ICD or not performing a generator change is both legal and ethical, and is supported by guidelines from both sides of the Atlantic. Patient autonomy is paramount, and no patient is committed to any therapy that they no longer wish to receive. Left ventricular assist devices (LVADs) were initially used as bridge in patients awaiting heart transplantation, but they are currently implanted as destination therapy (DT) in patients with end-stage heart failure who have failed to respond to optimal medical therapy and who are ineligible for cardiac transplantation. The decision-making process for initiation and deactivation of LVAD is becoming more and more ethically and clinically challenging, particularly for elderly patients.

  9. Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

    PubMed

    Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

    2011-04-01

    Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

  10. Brain processing of rectal sensation in adolescents with functional defecation disorders and healthy controls.

    PubMed

    Mugie, S M; Koppen, I J N; van den Berg, M M; Groot, P F C; Reneman, L; de Ruiter, M B; Benninga, M A

    2018-03-01

    Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross-sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs). We included 15 adolescents with FC, 10 adolescents with FNRFI, and 15 young adult HCs. Rectal barostat was performed prior to functional magnetic resonance imaging (fMRI) to determine individual pressure thresholds for urge sensation. Subjects received 2 sessions of 5 × 30 seconds of barostat stimulation during the acquisition of blood oxygenation level-dependent fMRI. Functional magnetic resonance imaging signal differences were analyzed using SPM8 in Matlab. Functional constipation and FNRFI patients had higher thresholds for urgency than HCs (P < .001). During rectal distension, FC patients showed activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior parietal lobule, and putamen. No activations were observed in controls and FNRFI patients. Functional nonretentive fecal incontinence patients showed deactivation in the hippocampus, parahippocampal gyrus, fusiform gyrus (FFG), lingual gyrus, posterior parietal cortex, and precentral gyrus. In HCs, deactivated areas were detected in the hippocampus, amygdala, FFG, insula, thalamus, precuneus, and primary somatosensory cortex. In contrast, no regions with significant deactivation were detected in FC patients. Children with FC differ from children with FNRFI and HCs with respect to patterns of cerebral activation and deactivation during rectal distension. Functional nonretentive fecal incontinence patients seem to resemble HCs when it comes to brain processing of rectal distension. © 2017 John Wiley & Sons Ltd.

  11. Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint Arthroplasty Surgery.

    PubMed

    Patel, Suhani; Fine, Janelle M; Lim, Michael J; Copp, Steven N; Rosen, Adam S; West, John B; Prisk, G Kim

    2017-08-01

    To protect both the surgeon and patient during procedures, hooded protection shields are used during joint arthroplasty procedures. Headache, malaise, and dizziness, consistent with increased carbon dioxide (CO 2 ) exposure, have been anecdotally reported by surgeons using hoods. We hypothesized that increased CO 2 concentrations were causing reported symptoms. Six healthy subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered during arthroplasty. Inspired O 2 and CO 2 concentrations at the nares were continuously measured at rest, 12 W, and 25 W. At each activity level, the fan was deactivated and the times for CO 2 to reach 0.5% and 1.0% were measured. At rest, inspired CO 2 was 0.14% ± 0.04%. Exercise had significant effect on CO 2 compared with rest (0.26% ± 0.08% at 12 W, P = .04; 0.31% ± 0.05% at 25 W, P = .003). Inspired CO 2 concentration increased rapidly with fan deactivation, with the time for CO 2 to increase to 0.5% and 1.0% after fan deactivation being rapid but variable (0.5%, 12 ± 9 seconds; 1%, 26 ± 15 seconds). Time for CO 2 to return below 0.5% after fan reactivation was 20 ± 37 seconds. During simulated joint arthroplasty, CO 2 remained within Occupational Safety and Health Administration (OSHA) standards with the fan at the highest setting. With fan deactivation, CO 2 concentration rapidly exceeds OSHA standards. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men.

    PubMed

    Schulte, Tilman; Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf

    2012-02-01

    Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity. We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict. Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity. Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Temperature and Voltage Coupling to Channel Opening in Transient Receptor Potential Melastatin 8 (TRPM8)*♦

    PubMed Central

    Raddatz, Natalia; Castillo, Juan P.; Gonzalez, Carlos; Alvarez, Osvaldo; Latorre, Ramon

    2014-01-01

    Expressed in somatosensory neurons of the dorsal root and trigeminal ganglion, the transient receptor potential melastatin 8 (TRPM8) channel is a Ca2+-permeable cation channel activated by cold, voltage, phosphatidylinositol 4,5-bisphosphate, and menthol. Although TRPM8 channel gating has been characterized at the single channel and macroscopic current levels, there is currently no consensus regarding the extent to which temperature and voltage sensors couple to the conduction gate. In this study, we extended the range of voltages where TRPM8-induced ionic currents were measured and made careful measurements of the maximum open probability the channel can attain at different temperatures by means of fluctuation analysis. The first direct measurements of TRPM8 channel temperature-driven conformational rearrangements provided here suggest that temperature alone is able to open the channel and that the opening reaction is voltage-independent. Voltage is a partial activator of TRPM8 channels, because absolute open probability values measured with fully activated voltage sensors are less than 1, and they decrease as temperature rises. By unveiling the fast temperature-dependent deactivation process, we show that TRPM8 channel deactivation is well described by a double exponential time course. The fast and slow deactivation processes are temperature-dependent with enthalpy changes of 27.2 and 30.8 kcal mol−1. The overall Q10 for the closing reaction is about 33. A three-tiered allosteric model containing four voltage sensors and four temperature sensors can account for the complex deactivation kinetics and coupling between voltage and temperature sensor activation and channel opening. PMID:25352597

  14. 40 CFR 86.010-38 - Maintenance instructions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., excluding any research and development costs incurred in designing and implementing, upgrading or altering... months lead time to meet this requirement. Each manufacturer Web site shall: (i) Provide access in full... same time as manufacturer-franchised dealership World Wide Web sites; (iii) Provide users with a...

  15. 40 CFR 86.010-38 - Maintenance instructions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., excluding any research and development costs incurred in designing and implementing, upgrading or altering... months lead time to meet this requirement. Each manufacturer Web site shall: (i) Provide access in full... same time as manufacturer-franchised dealership World Wide Web sites; (iii) Provide users with a...

  16. 40 CFR 86.010-38 - Maintenance instructions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., excluding any research and development costs incurred in designing and implementing, upgrading or altering... months lead time to meet this requirement. Each manufacturer Web site shall: (i) Provide access in full... same time as manufacturer-franchised dealership World Wide Web sites; (iii) Provide users with a...

  17. 40 CFR 86.010-38 - Maintenance instructions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., excluding any research and development costs incurred in designing and implementing, upgrading or altering... months lead time to meet this requirement. Each manufacturer Web site shall: (i) Provide access in full... same time as manufacturer-franchised dealership World Wide Web sites; (iii) Provide users with a...

  18. Gravity and body mass regulation

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Horwitz, B. A.; Fuller, C. A.

    1997-01-01

    The effects of altered gravity on body mass, food intake, energy expenditure, and body composition are examined. Metabolic adjustments are reviewed in maintenance of energy balance, neural regulation, and humoral regulation are discussed. Experiments with rats indicate that genetically obese rats respond differently to hypergravity than lean rats.

  19. 14 CFR 135.439 - Maintenance recording requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... alterations and repairs to each airframe, engine, propeller, rotor, and appliance. (b) Each certificate holder... the records of the last complete overhaul of each airframe, engine, propeller, rotor, and appliance...

  20. 14 CFR 135.439 - Maintenance recording requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... alterations and repairs to each airframe, engine, propeller, rotor, and appliance. (b) Each certificate holder... the records of the last complete overhaul of each airframe, engine, propeller, rotor, and appliance...

  1. 14 CFR 135.439 - Maintenance recording requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... alterations and repairs to each airframe, engine, propeller, rotor, and appliance. (b) Each certificate holder... the records of the last complete overhaul of each airframe, engine, propeller, rotor, and appliance...

  2. 14 CFR 135.439 - Maintenance recording requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... alterations and repairs to each airframe, engine, propeller, rotor, and appliance. (b) Each certificate holder... the records of the last complete overhaul of each airframe, engine, propeller, rotor, and appliance...

  3. 14 CFR 135.439 - Maintenance recording requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... alterations and repairs to each airframe, engine, propeller, rotor, and appliance. (b) Each certificate holder... the records of the last complete overhaul of each airframe, engine, propeller, rotor, and appliance...

  4. 15 CFR 801.10 - Rules and regulations for the BE-120, Benchmark Survey of Transactions in Selected Services and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... engineering services; industrial-type maintenance, installation, alteration, and training services; legal... services; (17) Financial services (purchases only); (18) Industrial engineering services; (19) Industrial...; educational and training services; engineering, architectural, and surveying services; financial services...

  5. Ecodriving and carbon footprinting : understanding how public education can reduce greenhouse gas emissions and fuel use [research brief].

    DOT National Transportation Integrated Search

    2012-04-01

    Ecodriving, the concept of altering driving behavior and vehicle maintenance practices in existing vehicles, has gained recent prominence as a strategy for drivers to reduce gasoline consumption and greenhouse gas (GHG) emissions. Ecodriving is gaini...

  6. 40 CFR 89.321 - Oxides of nitrogen analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... (b) Prior to its introduction into service, and monthly thereafter, the chemiluminescent oxides of... periodic calibration. Prior to its introduction into service, after any maintenance which could alter... represent good engineering practice. For each range calibrated, if the deviation from a least-squares best...

  7. Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover.

    PubMed

    Westera, Liset; van Hoeven, Vera; Drylewicz, Julia; Spierenburg, Gerrit; van Velzen, Jeroen F; de Boer, Rob J; Tesselaar, Kiki; Borghans, José A M

    2015-04-01

    In healthy humans, lymphocyte populations are maintained at a relatively constant size throughout life, reflecting a balance between lymphocyte production and loss. Given the profound immunological changes that occur during healthy aging, including a significant decline in T-cell production by the thymus, lymphocyte maintenance in the elderly is generally thought to require homeostatic alterations in lymphocyte dynamics. Surprisingly, using in vivo (2) H2 O labeling, we find similar dynamics of most lymphocyte subsets between young adult and elderly healthy individuals. As the contribution of thymic output to T-cell production is only minor from young adulthood onward, compensatory increases in peripheral T-cell division rates are not required to maintain the T-cell pool, despite a tenfold decline in thymic output. These fundamental insights will aid the interpretation of further research into aging and clinical conditions related to disturbed lymphocyte dynamics. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Implementation of a Peltier-based cooling device for localized deep cortical deactivation during in vivo object recognition testing

    NASA Astrophysics Data System (ADS)

    Marra, Kyle; Graham, Brett; Carouso, Samantha; Cox, David

    2012-02-01

    While the application of local cortical cooling has recently become a focus of neurological research, extended localized deactivation deep within brain structures is still unexplored. Using a wirelessly controlled thermoelectric (Peltier) device and water-based heat sink, we have achieved inactivating temperatures (<20 C) at greater depths (>8 mm) than previously reported. After implanting the device into Long Evans rats' basolateral amygdala (BLA), an inhibitory brain center that controls anxiety and fear, we ran an open field test during which anxiety-driven behavioral tendencies were observed to decrease during cooling, thus confirming the device's effect on behavior. Our device will next be implanted in the rats' temporal association cortex (TeA) and recordings from our signal-tracing multichannel microelectrodes will measure and compare activated and deactivated neuronal activity so as to isolate and study the TeA signals responsible for object recognition. Having already achieved a top performing computational face-recognition system, the lab will utilize this TeA activity data to generalize its computational efforts of face recognition to achieve general object recognition.

  9. Random one-of-N selector

    DOEpatents

    Kronberg, J.W.

    1993-04-20

    An apparatus for selecting at random one item of N items on the average comprising counter and reset elements for counting repeatedly between zero and N, a number selected by the user, a circuit for activating and deactivating the counter, a comparator to determine if the counter stopped at a count of zero, an output to indicate an item has been selected when the count is zero or not selected if the count is not zero. Randomness is provided by having the counter cycle very often while varying the relatively longer duration between activation and deactivation of the count. The passive circuit components of the activating/deactivating circuit and those of the counter are selected for the sensitivity of their response to variations in temperature and other physical characteristics of the environment so that the response time of the circuitry varies. Additionally, the items themselves, which may be people, may vary in shape or the time they press a pushbutton, so that, for example, an ultrasonic beam broken by the item or person passing through it will add to the duration of the count and thus to the randomness of the selection.

  10. Deactivation of cisplatin-resistant human lung/ovary cancer cells with pyropheophorbide-α methyl ester-photodynamic therapy.

    PubMed

    Qian, Guanhua; Wang, Li; Zheng, Xueling; Yu, Tinghe

    2017-12-02

    The aim of this study was to determine whether photodynamic therapy (PDT) alone or combined with cisplatin (DDP), can deactivate cisplatin-resistant cancer cells. Human cancer cell lines A549 and SKOV3, and chemoresistant sublines A549/DDP and SKOV3/DDP, were subjected to PDT, DDP, or PDT combined with DDP. Cell viability and apoptosis were analyzed, and then intracellular reactive oxygen species (ROS) and proteins related to apoptosis were determined. PDT caused cell death, and PDT combined with DDP led to the highest percentage of dead cells in 4 cell lines; similar results were detected in ROS; a quantification evaluation manifested that the combined effect was addition. DDP increased the percentage of apoptotic cells, and the ROS level in A549 and SKOV3 cells, which was not observed in A549/DDP and SKOV3/DDP cells. Western blot revealed an increase of caspase 3 and Bax, and a decrease of Bcl-2, demonstrating the occurrence of apoptosis. The data suggest that PDT can efficiently deactivate resistant cells and enhance the action of DDP against resistant cancer cells.

  11. Random one-of-N selector

    DOEpatents

    Kronberg, James W.

    1993-01-01

    An apparatus for selecting at random one item of N items on the average comprising counter and reset elements for counting repeatedly between zero and N, a number selected by the user, a circuit for activating and deactivating the counter, a comparator to determine if the counter stopped at a count of zero, an output to indicate an item has been selected when the count is zero or not selected if the count is not zero. Randomness is provided by having the counter cycle very often while varying the relatively longer duration between activation and deactivation of the count. The passive circuit components of the activating/deactivating circuit and those of the counter are selected for the sensitivity of their response to variations in temperature and other physical characteristics of the environment so that the response time of the circuitry varies. Additionally, the items themselves, which may be people, may vary in shape or the time they press a pushbutton, so that, for example, an ultrasonic beam broken by the item or person passing through it will add to the duration of the count and thus to the randomness of the selection.

  12. Activation-deactivation of self-healing in supramolecular rubbers

    NASA Astrophysics Data System (ADS)

    Corte, Laurent; Maes, Florine; Montarnal, Damien; Cantournet, Sabine; Tournilhac, Francois; Leibler, Ludwik; Mines-Paristech Cnrs (Umr7633) Team; Espci-Paristech Cnrs (Umr7167) Team

    2011-03-01

    Self-healing materials have the ability to restore autonomously their structural integrity after damage. Such a remarkable property was obtained recently in supramolecular rubbers formed by a network of small molecules associated via hydrogen bonds. Here we explore this self-healing through an original tack experiment where two parts of supramolecular rubber are brought into contact and then separated. These experiments reveal that a strong self-healing ability is activated by damage even though the surfaces of a molded part are weakly self-adhesive. In our testing conditions, a five minute contact between crack faces is sufficient to recover most mechanical properties of the bulk while days are required to obtain such adhesion levels with melt-pressed surfaces. We show that the deactivation of this self-healing ability seems unexpectedly slow as compared to the predicted dynamics of supramolecular networks. Fracture faces stored apart at room temperature still self-heal after days but are fully deactivated within hours by annealing. Combining these results with microstructural observations gives us a deeper insight into the mechanisms involved in this self-healing process.

  13. Effect of Feedstock and Catalyst Impurities on the Methanol‐to‐Olefin Reaction over H‐SAPO‐34

    PubMed Central

    Vogt, Charlotte; Ruiz‐Martínez, Javier

    2016-01-01

    Abstract Operando UV/Vis spectroscopy with on‐line mass spectrometry was used to study the effect of different types of impurities on the hydrocarbon pool species and the activity of H‐SAPO‐34 as a methanol‐to‐olefins (MTO) catalyst. Successive reaction cycles with different purity feedstocks were studied, with an intermittent regeneration step. The combined study of two distinct impurity types (i.e., feed and internal impurities) leads to new insights into MTO catalyst activation and deactivation mechanisms. In the presence of low amounts of feed impurities, the induction and active periods of the process are prolonged. Feed impurities are thus beneficial in the formation of the initial hydrocarbon pool, but also aid in the unwanted formation of deactivating coke species by a separate, competing mechanism favoring coke species over olefins. Further, feedstock impurities strongly influence the location of coke deposits, and thus influence the deactivation mechanism, whereas a study of the organic impurities retained after calcination reveals that these species are less relevant for catalyst activity and function as “seeds” for coke formation only. PMID:28163792

  14. Deactivation of Cellulase at the Air-Liquid Interface Is the Main Cause of Incomplete Cellulose Conversion at Low Enzyme Loadings.

    PubMed

    Bhagia, Samarthya; Dhir, Rachna; Kumar, Rajeev; Wyman, Charles E

    2018-01-22

    Amphiphilic additives such as bovine serum albumin (BSA) and Tween have been used to improve cellulose hydrolysis by cellulases. However, there has been a lack of clarity to explain their mechanism of action in enzymatic hydrolysis of pure or low-lignin cellulosic substrates. In this work, a commercial Trichoderma reesei enzyme preparation and the amphiphilic additives BSA and Tween 20 were applied for hydrolysis of pure Avicel cellulose. The results showed that these additives only had large effects on cellulose conversion at low enzyme to substrate ratios when the reaction flasks were shaken. Furthermore, changes in the air-liquid interfacial area profoundly affected cellulose conversion, but surfactants reduced or prevented cellulase deactivation at the air-liquid interface. Not shaking the flasks or adding low amounts of surfactant resulted in near theoretical cellulose conversion at low enzyme loadings given enough reaction time. At low enzyme loadings, hydrolysis of cellulose in lignocellulosic biomass with low lignin content suffered from enhanced enzyme deactivation at the air-liquid interface.

  15. Patient Comprehension and Attitudes toward Maintenance Chemotherapy for Lung Cancer

    PubMed Central

    Gerber, David E.; Hamann, Heidi A.; Rasco, Drew W.; Woodruff, Sharon; Craddock Lee, Simon J.

    2012-01-01

    Objective Maintenance chemotherapy is a recently approved approach to the treatment of advanced non-small cell lung cancer (NSCLC). We sought to gain insight into patients’ perceptions of maintenance chemotherapy using qualitative methods. Methods We conducted thematic content analysis of focus groups at a freestanding cancer center and at an associated safety-net county hospital. Patients with advanced NSCLC who had started but not yet completed first-line platinum doublet chemotherapy were provided visual and written explanations of maintenance chemotherapy before being guided in group discussion. Results Key themes to emerge for consideration of maintenance chemotherapy included (1) survival benefits, disease control, and “buying time”; (2) the importance of “doing something”; (3) quality of life concerns; (4) the role of provider opinion/preference; and (5) the importance of logistics. Conclusions Patients undergoing first-line chemotherapy for advanced NSCLC were able to understand the concept of maintenance chemotherapy, distinguish it from traditional treatment paradigms, identify pros and cons of this approach, and convey reasons for considering it. Practice Implications Advances in oncology care that alter therapy modalities and delivery may significantly impact patient perceptions and treatment experiences. Clinical team members may wish to elicit treatment preferences of first-line patients through clinical discussions that anticipate these considerations. PMID:22632736

  16. Emerging role of lipid metabolism alterations in Cancer stem cells.

    PubMed

    Yi, Mei; Li, Junjun; Chen, Shengnan; Cai, Jing; Ban, Yuanyuan; Peng, Qian; Zhou, Ying; Zeng, Zhaoyang; Peng, Shuping; Li, Xiaoling; Xiong, Wei; Li, Guiyuan; Xiang, Bo

    2018-06-15

    Cancer stem cells (CSCs) or tumor-initiating cells (TICs) represent a small population of cancer cells with self-renewal and tumor-initiating properties. Unlike the bulk of tumor cells, CSCs or TICs are refractory to traditional therapy and are responsible for relapse or disease recurrence in cancer patients. Stem cells have distinct metabolic properties compared to differentiated cells, and metabolic rewiring contributes to self-renewal and stemness maintenance in CSCs. Recent advances in metabolomic detection, particularly in hyperspectral-stimulated raman scattering microscopy, have expanded our knowledge of the contribution of lipid metabolism to the generation and maintenance of CSCs. Alterations in lipid uptake, de novo lipogenesis, lipid droplets, lipid desaturation, and fatty acid oxidation are all clearly implicated in CSCs regulation. Alterations on lipid metabolism not only satisfies the energy demands and biomass production of CSCs, but also contributes to the activation of several important oncogenic signaling pathways, including Wnt/β-catenin and Hippo/YAP signaling. In this review, we summarize the current progress in this attractive field and describe some recent therapeutic agents specifically targeting CSCs based on their modulation of lipid metabolism. Increased reliance on lipid metabolism makes it a promising therapeutic strategy to eliminate CSCs. Targeting key players of fatty acids metabolism shows promising to anti-CSCs and tumor prevention effects.

  17. Numerical modelling to assess maintenance strategy management options for a small tidal inlet

    NASA Astrophysics Data System (ADS)

    Shaeri, Saeed; Tomlinson, Rodger; Etemad-Shahidi, Amir; Strauss, Darrell

    2017-03-01

    Small tidal inlets are found to be more sensitive to anthropogenic alteration than their larger counterparts. Such alterations, although typically supported by technical design reports, sometimes require amendments or modification. One of the most suitable tools to conduct the necessary studies in this regard is numerical modelling, since the behaviour of the inlet system in response to proposed remedial actions, can easily be identified. In this paper, various alternative proposals are investigated to determine the most practical and viable option to mitigate the need for ongoing maintenance at a typical small, jettied tidal inlet. The main tool to investigate the alternatives is the hydro-sedimentological modelling of the inlet system, which was performed using the Delft3D software package. The proposed alternative entrance modifications were based upon structural alterations of the inlet system (such as a jetty extension or submerged weir) and non-structural scenarios (such as a change of the time of the dredging campaign or the deposition location of the dredged material). It was concluded that whilst a detailed study is inevitable in order to achieve a comprehensive design plan, based upon the results of this study the construction of a submerged weir at the entrance channel can satisfy the needs of most of the stakeholders, with justifiable costs over a longer period.

  18. Receptor Tyrosine Kinase Signaling – A Proteomic Perspective

    PubMed Central

    Biarc, Jordane; Chalkley, Robert J.; Burlingame, A. L.; Bradshaw, Ralph A.

    2011-01-01

    The stimulation of various cellular processes through extracellular signals is of paramount importance in biological systems and is a central focus in the diagnosis, treatment and prevention of disease. The information transfer is accomplished in a variety of ways by the interaction of soluble, matrix-associated and cell bound ligands that either bind specifically to plasma membrane-associated proteins that act as receptors, or penetrate to the cytoplasmic/nuclear compartments to bind and activate receptors located there. The former class of entities generates intracellular signals that are transmitted and amplified by chemical modifications that are manifested as protein post-translational modifications (PTMs). These are both reversible and irreversible and range from phosphorylation of tyrosine, threonine and serine residues to endoproteolytic cleavages. Although the PTMs alter the activity and functions of many of the proteins in these cascades, the major outcomes of most of the signaling pathways are the activation/deactivation of transcriptional regulators with the concomitant changes in gene expression that generally underlie biological responses. PMID:21056590

  19. Major bleeding caused by warfarin in a genetically susceptible patient.

    PubMed

    Bloch, Aharon; Ben-Chetrit, Eldad; Muszkat, Mordechai; Caraco, Yoseph

    2002-01-01

    A 90-year-old woman was hospitalized for gastrointestinal bleeding. Although she had been receiving only warfarin 5 mg/day, her international normalized ratio (INR) was 66. Warfarin was discontinued, and her INR fell to 3.7 after transfusion of fresh-frozen plasma. However, it rose again spontaneously to 7.5. Eleven days after the last dose of warfarin had been administered, it was still detectable in the patient's plasma, indicating that impaired warfarin clearance may have caused an enhanced anticoagulation effect. Genetic analysis of the cytochrome P450 (CYP) isoenzyme 2C9, which mediates the major deactivating pathway of S-warfarin, revealed that the patient was a compound heterozygote carrying two variant alleles: CYP2C9*2 and CYP2C9*3. The patient's enhanced sensitivity to warfarin 5 mg/day can be ascribed to decreased clearance of S-warfarin secondary to genetic alteration of the gene encoding CYP2C9, resulting in a life-threatening complication.

  20. Use of low energy hydrogen ion implants in high efficiency crystalline silicon solar cells

    NASA Technical Reports Server (NTRS)

    Fonash, S. J.; Singh, R.

    1985-01-01

    This program is a study of the use of low energy hydrogen ion implantation for high efficiency crystalline silicon solar cells. The first quarterly report focuses on two tasks of this program: (1) an examination of the effects of low energy hydrogen implants on surface recombination speed; and (2) an examination of the effects of hydrogen on silicon regrowth and diffusion in silicon. The first part of the project focussed on the measurement of surface properties of hydrogen implanted silicon. Low energy hydrogen ions when bombarded on the silicon surface will create structural damage at the surface, deactivate dopants and introduce recombination centers. At the same time the electrically active centers such as dangling bonds will be passivated by these hydrogen ions. Thus hydrogen is expected to alter properties such as the surface recombination velocity, dopant profiles on the emitter, etc. In this report the surface recombination velocity of a hydrogen emplanted emitter was measured.

  1. Characteristics of a commercially aged Ni-Mo/Al2O3 hydrotreating catalyst: component distribution, nature of coke and effects of regeneration

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

    Bogdanor, J.M.

    1984-01-01

    Information concerning the morphology and behavior of active components on commercially aged catalyst, the effects of regeneration conditions on activity, and insights into the nature of coke and contaminant metal deposits could lead to improved catalysts and operating conditions , yielding significant economic returns. Spent Ni-Mo/Al2O3 hydrotreating catalyst from a commercial hydrotreater was examined using TGA, SEM, STEM, XPS, and a microreactor. Information concerning intraparticle distributions of active components, characteristics of the coke and metal deposits, and catalytic activity for fresh, spent and regenerated catalyst was used to draw general conclusions concerning hydrotreating catalyst deactivation. It was found that catalyticmore » activity was reduced and the nature of the hydrogenation function was altered due to bulk migration and agglomeration of molybdenum. This process was found to be accelerated by high-temperature regeneration. Results also indicated that iron deposits might catalyze formation of coke. Tentative generalizations and suggestions on improved reactor operation are presented.« less

  2. Multiple molecular dynamics simulations of human LOX-1 and Trp150Ala mutant reveal the structural determinants causing the full deactivation of the receptor.

    PubMed

    Iacovelli, Federico; Tucci, Fabio Giovanni; Macari, Gabriele; Falconi, Mattia

    2017-10-01

    Multiple classical molecular dynamics simulations have been applied to the human LOX-1 receptor to clarify the role of the Trp150Ala mutation in the loss of binding activity. Results indicate that the substitution of this crucial residue, located at the dimer interface, markedly disrupts the wild-type receptor dynamics. The mutation causes an irreversible rearrangement of the subunits interaction pattern that in the wild-type protein allows the maintaining of a specific symmetrical motion of the monomers. The subunits dislocation determines a loss of linearity of the arginines residues composing the basic spine and a consequent alteration of the long-range electrostatic attraction of the substrate. Moreover, the anomalous subunits arrangement observed in the mutated receptor also affects the integrity of the hydrophobic tunnel, actively involved in the short-range hydrophobic recognition of the substrate. The combined effect of these structural rearrangements generates the impairing of the receptor function. © 2017 Wiley Periodicals, Inc.

  3. The effect of nanofiber based filter morphology on bacteria deactivation during water filtration

    NASA Astrophysics Data System (ADS)

    Kimmer, Dusan; Vincent, Ivo; Lev, Jaroslav; Kalhotka, Libor; Mikula, Premysl; Korinkova, Radka; Sambaer, Wannes; Zatloukal, Martin

    2013-04-01

    Procedures permitting to prepare homogeneous functionalized nanofibre structures based on polyurethanes modified by phthalocyanines (PCs) by employing a suitable combination of variables during the electrospinning process are presented. Compared are filtration and bacteria deactivation properties of open and planar nanostructures with PCs embedded into polyurethane chain by a covalent bond protecting the release of active organic compound during the filtration process. Finding that the morphology of functionalized nanofibre structures have an effect on bacterial growth was confirmed by microbiological and physico-chemical analyses, such as the inoculation in a nutrient agar culture medium and flow cytometry.

  4. Heterogeneous photocatalytic oxidation of atmospheric trace contaminants

    NASA Technical Reports Server (NTRS)

    Ollis, David F.; Peral, Jose

    1991-01-01

    The following subject areas are covered: (1) design and construction of continuous flow photoreactor for study of oxidation of trace atmospheric contaminants; (2) establishment of kinetics of acetone oxidation including adsorption equilibration, variation of oxidation rate with acetone concentration and water (inhibitor), and variation of rate and apparent quantum yield with light intensity; (3) exploration of kinetics of butanol oxidation, including rate variation with concentration of butanol, and lack of inhibition by water; and (4) exploration of kinetics of catalyst deactivation during oxidation of butanol, including deactivation rate, influence of dark conditions, and establishment of photocatalytic regeneration of activity in alcohol-free air.

  5. 48 CFR Appendix F to Chapter 2 - Material Inspection and Receiving Report

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... items are maintenance, repair, alteration, rehabilitation, engineering, research, development, training... slashes. Show the descriptive noun of the item nomenclature and if provided, the Government assigned..., engineering, research, development, training, and testing. Do not complete Blocks 4, 13, and 14 when there is...

  6. 77 FR 42964 - Airworthiness Directives; The Boeing Company Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-23

    ... the potential for ignition sources inside fuel tanks caused by latent failures, alterations, repairs, or maintenance actions, which, in combination with flammable fuel vapors, could result in a fuel tank... for fuel tank systems to satisfy Special Federal Aviation Regulation No. 88 requirements. That AD also...

  7. 40 CFR 89.320 - Carbon monoxide analyzer calibration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... introduction into service and annually thereafter, the NDIR carbon monoxide analyzer shall be checked for... to its introduction into service, after any maintenance which could alter calibration, and every two... engineering practice. For each range calibrated, if the deviation from a least-squares best-fit straight line...

  8. 14 CFR 65.131 - Records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Records. 65.131 Section 65.131 Aeronautics... CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Parachute Riggers § 65.131 Records. (a) Each certificated parachute rigger shall keep a record of the packing, maintenance, and alteration of parachutes performed or...

  9. 14 CFR 65.131 - Records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Records. 65.131 Section 65.131 Aeronautics... CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Parachute Riggers § 65.131 Records. (a) Each certificated parachute rigger shall keep a record of the packing, maintenance, and alteration of parachutes performed or...

  10. 14 CFR 65.131 - Records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Records. 65.131 Section 65.131 Aeronautics... CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Parachute Riggers § 65.131 Records. (a) Each certificated parachute rigger shall keep a record of the packing, maintenance, and alteration of parachutes performed or...

  11. 14 CFR 65.131 - Records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Records. 65.131 Section 65.131 Aeronautics... CERTIFICATION: AIRMEN OTHER THAN FLIGHT CREWMEMBERS Parachute Riggers § 65.131 Records. (a) Each certificated parachute rigger shall keep a record of the packing, maintenance, and alteration of parachutes performed or...

  12. 75 FR 37350 - Endangered and Threatened Wildlife and Plants; Designation of Critical Habitat for Vermilion Darter

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-29

    ... with economic activities, including future development, road construction, wastewater treatment, stream... development, road construction, wastewater treatment, stream alteration, and water withdrawal. In order to... activities such as construction and maintenance activities; impoundments (five within the Turkey Creek and...

  13. Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial.

    PubMed

    El-Sayed, Y Y; Holbrook, R H; Gibson, R; Chitkara, U; Druzin, M L; Baba, D

    1998-01-01

    The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

  14. Anatomy and Physiology of the Blood-Brain Barrier

    PubMed Central

    Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon

    2015-01-01

    Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. PMID:25681530

  15. Attention Alters Neural Responses to Evocative Faces in Behaviorally Inhibited Adolescents

    PubMed Central

    Pérez-Edgar, Koraly; Roberson-Nay, Roxann; Hardin, Michael G.; Poeth, Kaitlin; Guyer, Amanda E.; Nelson, Eric E.; McClure, Erin B.; Henderson, Heather A.; Fox, Nathan A.; Pine, Daniel S.; Ernst, Monique

    2007-01-01

    Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N=10, mean 12.8 years) and BN (N=17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety. PMID:17376704

  16. Pain-mediated affect regulation is reduced after dialectical behavior therapy in borderline personality disorder: a longitudinal fMRI study.

    PubMed

    Niedtfeld, Inga; Schmitt, Ruth; Winter, Dorina; Bohus, Martin; Schmahl, Christian; Herpertz, Sabine C

    2017-05-01

    Borderline Personality Disorder (BPD) is characterized by affective instability, but self-injurious behavior appears to have an emotion-regulating effect. We investigated whether pain-mediated affect regulation can be altered at the neural level by residential Dialectical Behavior Therapy (DBT), providing adaptive emotion regulation techniques. Likewise, we investigated whether pain thresholds or the appraisal of pain change after psychotherapy. We investigated 28 patients with BPD undergoing DBT (self-referral), 15 patients with treatment as usual and 23 healthy control subjects at two time points 12 weeks apart. We conducted an fMRI experiment eliciting negative emotions with picture stimuli and induced heat pain to investigate the role of pain in emotion regulation. Additionally, we assessed heat and cold pain thresholds.At first measurement, patients with BPD showed amygdala deactivation in response to painful stimulation, as well as altered connectivity between left amygdala and dorsal anterior cingulate cortex. These effects were reduced after DBT, as compared with patients with treatment as usual. Pain thresholds did not differ between the patient groups. We replicated the role of pain as a means of affect regulation in BPD, indicated by increased amygdala coupling. For the first time, we could demonstrate that pain-mediated affect regulation can be changed by DBT. © The Author (2017). Published by Oxford University Press.

  17. 40 CFR 94.1004 - Maintenance, repair, adjustment, and recordkeeping.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... alteration before the emission-control system is restored to proper functioning. The provisions of paragraph... be signed by the executive with responsibility for marine activities of the owner. If the vessel is... executive(s) may authorize a captain or other primary operator to conduct this review and submit the...

  18. 33 CFR 277.6 - Basic policies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... maintenance costs. That part of the cost attributable to the requirements of railroad or highway traffic shall... cost of a bridge alteration shall be limited to providing a functional facility equal in every respect... procedures in this regulation, shall be cost shared on the basis of 50 percent Federal and 50 percent non...

  19. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... alteration and records of the 100-hour, annual, progressive, and other required or approved inspections, as... propeller, and each rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... are required to be overhauled on a specified time basis. (iv) The current inspection status of the...

  20. 14 CFR 91.417 - Maintenance records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... alteration and records of the 100-hour, annual, progressive, and other required or approved inspections, as... propeller, and each rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller... are required to be overhauled on a specified time basis. (iv) The current inspection status of the...

  1. 14 CFR 91.1439 - CAMP: Maintenance recording requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... service of the airframe, engine, propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller, rotor, and appliance. (iii) The time since last overhaul of each item... required. (vi) A list of current major alterations and repairs to each airframe, engine, propeller, rotor...

  2. 14 CFR 91.1439 - CAMP: Maintenance recording requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... service of the airframe, engine, propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller, rotor, and appliance. (iii) The time since last overhaul of each item... required. (vi) A list of current major alterations and repairs to each airframe, engine, propeller, rotor...

  3. 14 CFR 121.380 - Maintenance recording requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... section, the total time in service of each engine and propeller. (iii) The current status of life-limited parts of each airframe, engine, propeller, and appliance. (iv) The time since last overhaul of all items... required. (vii) A list of current major alterations to each airframe, engine, propeller, and appliance. (b...

  4. 14 CFR 121.380 - Maintenance recording requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... section, the total time in service of each engine and propeller. (iii) The current status of life-limited parts of each airframe, engine, propeller, and appliance. (iv) The time since last overhaul of all items... required. (vii) A list of current major alterations to each airframe, engine, propeller, and appliance. (b...

  5. 14 CFR 121.380 - Maintenance recording requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... section, the total time in service of each engine and propeller. (iii) The current status of life-limited parts of each airframe, engine, propeller, and appliance. (iv) The time since last overhaul of all items... required. (vii) A list of current major alterations to each airframe, engine, propeller, and appliance. (b...

  6. 14 CFR 91.1439 - CAMP: Maintenance recording requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... service of the airframe, engine, propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller, rotor, and appliance. (iii) The time since last overhaul of each item... required. (vi) A list of current major alterations and repairs to each airframe, engine, propeller, rotor...

  7. 14 CFR 121.380 - Maintenance recording requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... section, the total time in service of each engine and propeller. (iii) The current status of life-limited parts of each airframe, engine, propeller, and appliance. (iv) The time since last overhaul of all items... required. (vii) A list of current major alterations to each airframe, engine, propeller, and appliance. (b...

  8. 14 CFR 91.1439 - CAMP: Maintenance recording requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... service of the airframe, engine, propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller, rotor, and appliance. (iii) The time since last overhaul of each item... required. (vi) A list of current major alterations and repairs to each airframe, engine, propeller, rotor...

  9. 14 CFR 121.380 - Maintenance recording requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... section, the total time in service of each engine and propeller. (iii) The current status of life-limited parts of each airframe, engine, propeller, and appliance. (iv) The time since last overhaul of all items... required. (vii) A list of current major alterations to each airframe, engine, propeller, and appliance. (b...

  10. 14 CFR 91.1439 - CAMP: Maintenance recording requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... service of the airframe, engine, propeller, and rotor. (ii) The current status of life-limited parts of each airframe, engine, propeller, rotor, and appliance. (iii) The time since last overhaul of each item... required. (vi) A list of current major alterations and repairs to each airframe, engine, propeller, rotor...

  11. 15 CFR 801.10 - Rules and regulations for the BE-120, Benchmark Survey of Transactions in Selected Services and...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...; educational and training services; engineering, architectural, and surveying services; financial services (purchases only, by companies or parts of companies that are not financial services providers); industrial engineering services; industrial-type maintenance, installation, alteration, and training services; legal...

  12. 15 CFR 801.10 - Rules and regulations for the BE-120, Benchmark Survey of Transactions in Selected Services and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...; educational and training services; engineering, architectural, and surveying services; financial services (purchases only, by companies or parts of companies that are not financial services providers); industrial engineering services; industrial-type maintenance, installation, alteration, and training services; legal...

  13. 40 CFR 86.516-90 - Calibrations, frequency and overview.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... be checked at a frequency consistent with observed column life or when the indicator of the column... Regulations for 1978 and Later New Motorcycles; Test Procedures § 86.516-90 Calibrations, frequency and...) At least monthly or after any maintenance which could alter calibration, the following calibrations...

  14. 40 CFR 86.516-90 - Calibrations, frequency and overview.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... be checked at a frequency consistent with observed column life or when the indicator of the column... Regulations for 1978 and Later New Motorcycles; Test Procedures § 86.516-90 Calibrations, frequency and...) At least monthly or after any maintenance which could alter calibration, the following calibrations...

  15. 29 CFR 570.67 - Occupations in roofing operations and on or about a roof (Order 16).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... proximity to a roof, including carpentry and metal work, alterations, additions, maintenance and repair... or metal), including roof trusses or joists; gutter and downspout work; the installation and... work performed in connection with the installation of roofs, including related metal work such as...

  16. Dual Layer Monolith ATR of Pyrolysis Oil for Distributed Synthesis Gas Production

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

    Lawal, Adeniyi

    We have successfully demonstrated a novel reactor technology, based on BASF dual layer monolith catalyst, for miniaturizing the autothermal reforming of pyrolysis oil to syngas, the second and most critical of the three steps for thermochemically converting biomass waste to liquid transportation fuel. The technology was applied to aged as well as fresh samples of pyrolysis oil derived from five different biomass feedstocks, namely switch-grass, sawdust, hardwood/softwood, golden rod and maple. Optimization of process conditions in conjunction with innovative reactor system design enabled the minimization of carbon deposit and control of the H2/CO ratio of the product gas. A comprehensivemore » techno-economic analysis of the integrated process using in part, experimental data from the project, indicates (1) net energy recovery of 49% accounting for all losses and external energy input, (2) weight of diesel oil produced as a percent of the biomass to be ~14%, and (3) for a demonstration size biomass to Fischer-Tropsch liquid plant of ~ 2000 daily barrels of diesel, the price of the diesel produced is ~$3.30 per gallon, ex. tax. However, the extension of catalyst life is critical to the realization of the projected economics. Catalyst deactivation was observed and the modes of deactivation, both reversible and irreversible were identified. An effective catalyst regeneration strategy was successfully demonstrated for reversible catalyst deactivation while a catalyst preservation strategy was proposed for preventing irreversible catalyst deactivation. Future work should therefore be focused on extending the catalyst life, and a successful demonstration of an extended (> 500 on-stream hours) catalyst life would affirm the commercial viability of the process.« less

  17. Visual Space and Object Space in the Cerebral Cortex of Retinal Disease Patients

    PubMed Central

    Spileers, Werner; Wagemans, Johan; Op de Beeck, Hans P.

    2014-01-01

    The lower areas of the hierarchically organized visual cortex are strongly retinotopically organized, with strong responses to specific retinotopic stimuli, and no response to other stimuli outside these preferred regions. Higher areas in the ventral occipitotemporal cortex show a weak eccentricity bias, and are mainly sensitive for object category (e.g., faces versus buildings). This study investigated how the mapping of eccentricity and category sensitivity using functional magnetic resonance imaging is affected by a retinal lesion in two very different low vision patients: a patient with a large central scotoma, affecting central input to the retina (juvenile macular degeneration), and a patient where input to the peripheral retina is lost (retinitis pigmentosa). From the retinal degeneration, we can predict specific losses of retinotopic activation. These predictions were confirmed when comparing stimulus activations with a no-stimulus fixation baseline. At the same time, however, seemingly contradictory patterns of activation, unexpected given the retinal degeneration, were observed when different stimulus conditions were directly compared. These unexpected activations were due to position-specific deactivations, indicating the importance of investigating absolute activation (relative to a no-stimulus baseline) rather than relative activation (comparing different stimulus conditions). Data from two controls, with simulated scotomas that matched the lesions in the two patients also showed that retinotopic mapping results could be explained by a combination of activations at the stimulated locations and deactivations at unstimulated locations. Category sensitivity was preserved in the two patients. In sum, when we take into account the full pattern of activations and deactivations elicited in retinotopic cortex and throughout the ventral object vision pathway in low vision patients, the pattern of (de)activation is consistent with the retinal loss. PMID:24505449

  18. Plasticity of spatial hearing: behavioural effects of cortical inactivation

    PubMed Central

    Nodal, Fernando R; Bajo, Victoria M; King, Andrew J

    2012-01-01

    The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex. PMID:22547635

  19. Reconstructed Serine 288 in the Left Flipper Region of the Rat P2X7 Receptor Stabilizes Nonsensitized States.

    PubMed

    Ishchenko, Yevheniia; Novosolova, Nataliia; Khafizov, Kamil; Bart, Geneviève; Timonina, Arina; Fayuk, Dmitriy; Skorinkin, Andrei; Giniatullin, Rashid

    2017-07-05

    Serine 275, a conserved residue of the left flipper region of ATP-gated P2X3 receptors, plays a key role in both agonist binding and receptor desensitization. It is conserved in most of the P2X receptors except P2X7 and P2X6. By combining experimental patch-clamp and modeling approaches, we explored the role of the corresponding residue in the rat P2X7 receptor (rP2X7) by replacing the phenylalanine at position 288 with serine and characterizing the membrane currents generated by either the wild-type (WT) or the mutated rP2X7 receptor. F288S, an rP2X7 mutation, slowed the deactivation subsequent to 2 and 20 s applications of 1 mM ATP. F288S also prevented sensitization (a progressive current growth) observed with the WT in response to a 20 s application of 1 mM ATP. Increasing the ATP concentration to 5 mM promoted sensitization also in the mutated rP2X7 receptor, accelerating the deactivation rate to typical WT values. YO-PRO1 uptake in cells expressing either the WT or the F288S P2X7 receptor was consistent with recorded membrane current data. Interestingly, in the human P2X7 (hP2X7) receptor, substitution Y288S did not change the deactivation rate, while the Y288F mutant generated a "rat-like" phenotype with a fast deactivation rate. Our combined experimental, kinetic, and molecular modeling data suggest that the rat F288S novel phenotype is due to a slower rate of ATP binding and/or unbinding and stabilization of nonsensitized receptor states.

  20. Psychosocial versus physiological stress – meta-analyses on deactivations and activations of the neural correlates of stress reactions

    PubMed Central

    Kogler, Lydia; Mueller, Veronika I.; Chang, Amy; Eickhoff, Simon B.; Fox, Peter T.; Gur, Ruben C.; Derntl, Birgit

    2015-01-01

    Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended. PMID:26123376

Top