Sample records for targeting tnox attenuates

  1. A site-directed mutagenesis analysis of tNOX functional domains

    NASA Technical Reports Server (NTRS)

    Chueh, Pin-Ju; Morre, Dorothy M.; Morre, D. James

    2002-01-01

    Constitutive NADH oxidase proteins of the mammalian cell surface exhibit two different activities, oxidation of hydroquinones (or NADH) and protein disulfide-thiol interchange which alternate to yield oscillatory patterns with period lengths of 24 min. A drug-responsive tNOX (tumor-associated NADH oxidase) has a period length of about 22 min. The tNOX cDNA has been cloned and expressed. These two proteins are representative of cycling oxidase proteins of the plant and animal cell surface. In this report, we describe a series of eight amino acid replacements in tNOX which, when expressed in Escherichia coli, were analyzed for enzymatic activity, drug response and period length. Replacement sites selected include six cysteines that lie within the processed plasma membrane (34 kDa) form of the protein, and amino acids located in putative drug and adenine nucleotide (NADH) binding domains. The latter, plus two of the cysteine replacements, resulted in a loss of enzymatic activity. The recombinant tNOX with the modified drug binding site retained activity but the activity was no longer drug-responsive. The four remaining cysteine replacements were of interest in that both activity and drug response were retained but the period length for both NADH oxidation and protein disulfide-thiol interchange was increased from 22 min to 36 or 42 min. The findings confirm the correctness of the drug and adenine nucleotide binding motifs within the tNOX protein and imply a potential critical role of cysteine residues in determining the period length.

  2. Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface

    NASA Technical Reports Server (NTRS)

    Chueh, Pin-Ju; Kim, Chinpal; Cho, NaMi; Morre, Dorothy M.; Morre, D. James

    2002-01-01

    NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit prion-like properties. The two enzymatic activities alternate to generate a regular period length of about 24 min. Here we report the expression, cloning, and characterization of a tumor-associated NADH oxidase (tNOX). The cDNA sequence of 1830 bp is located on gene Xq25-26 with an open reading frame encoding 610 amino acids. The activities of the bacterially expressed tNOX oscillate with a period length of 22 min as is characteristic of tNOX activities in situ. The activities are inhibited completely by capsaicin, which represents a defining characteristic of tNOX activity. Functional motifs identified by site-directed mutagenesis within the C-terminal portion of the tNOX protein corresponding to the processed plasma membrane-associated form include quinone (capsaicin), copper and adenine nucleotide binding domains, and two cysteines essential for catalytic activity. Four of the six cysteine to alanine replacements retained enzymatic activity, but the period lengths of the oscillations were increased. A single protein with two alternating enzymatic activities indicative of a time-keeping function is unprecedented in the biochemical literature.

  3. NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying G1 arrest and apoptosis.

    PubMed

    De Luca, Thomas; Morré, Dorothy M; Zhao, Haiyun; Morré, D James

    2005-01-01

    To elucidate possible biochemical links between growth arrest from antiproliferative chemotherapeutic agents and apoptosis, our work has focused on agents (EGCg, capsaicin, cis platinum, adriamycin, anti-tumor sulfonylureas, phenoxodiol) that target tNOX. tNOX is a cancer-specific cell surface NADH oxidase (ECTO-NOX protein), that functions in cancer cells as the terminal oxidase for plasma membrane electron transport. When tNOX is active, coenzyme Q(10) (ubiquinone) of the plasma membrane is oxidized and NADH is oxidized at the cytosolic surface of the plasma membrane. However, when tNOX is inhibited and plasma membrane electron transport is diminished, both reduced coenzyme Q(10) (ubiquinol) and NADH would be expected to accumulate. To relate inhibition of plasma membrane redox to increased ceramide levels and arrest of cell proliferation in G(1) and apoptosis, we show that neutral sphingomyelinase, a major contributor to plasma membrane ceramide, is inhibited by reduced glutathione and ubiquinone. Ubiquinol is without effect or stimulates. In contrast, sphingosine kinase, which generates anti-apoptotic sphingosine-1-phosphate, is stimulated by ubiquinone but inhibited by ubiquinol and NADH. Thus, the quinone and pyridine nucleotide products of plasma membrane redox, ubiquinone and ubiquinol, as well as NAD(+) and NADH, may directly modulate in a reciprocal manner two key plasma membrane enzymes, sphingomyelinase and sphingosine kinase, potentially leading to G(1) arrest (increase in ceramide) and apoptosis (loss of sphingosine-1-phosphate). As such, the findings provide potential links between coenzyme Q(10)-mediated plasma membrane electron transport and the anticancer action of several clinically-relevant anticancer agents.

  4. Calculated mammographic spectra confirmed with attenuation curves for molybdenum, rhodium, and tungsten targets.

    PubMed

    Blough, M M; Waggener, R G; Payne, W H; Terry, J A

    1998-09-01

    A model for calculating mammographic spectra independent of measured data and fitting parameters is presented. This model is based on first principles. Spectra were calculated using various target and filter combinations such as molybdenum/molybdenum, molybdenum/rhodium, rhodium/rhodium, and tungsten/aluminum. Once the spectra were calculated, attenuation curves were calculated and compared to measured attenuation curves. The attenuation curves were calculated and measured using aluminum alloy 1100 or high purity aluminum filtration. Percent differences were computed between the measured and calculated attenuation curves resulting in an average of 5.21% difference for tungsten/aluminum, 2.26% for molybdenum/molybdenum, 3.35% for rhodium/rhodium, and 3.18% for molybdenum/rhodium. Calculated spectra were also compared to measured spectra from the Food and Drug Administration [Fewell and Shuping, Handbook of Mammographic X-ray Spectra (U.S. Government Printing Office, Washington, D.C., 1979)] and a comparison will also be presented.

  5. Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

    PubMed Central

    Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

    2016-01-01

    Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

  6. Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

    PubMed

    Iezzi, Raymond; Guru, Bharath R; Glybina, Inna V; Mishra, Manoj K; Kennedy, Alexander; Kannan, Rangaramanujam M

    2012-01-01

    Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 μg of FA conjugated to 7 μg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. (−)-Epigallocatechin Gallate Targets Notch to Attenuate the Inflammatory Response in the Immediate Early Stage in Human Macrophages

    PubMed Central

    Wang, Tengfei; Xiang, Zemin; Wang, Ya; Li, Xi; Fang, Chongye; Song, Shuang; Li, Chunlei; Yu, Haishuang; Wang, Han; Yan, Liang; Hao, Shumei; Wang, Xuanjun; Sheng, Jun

    2017-01-01

    Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (−)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenuated the inflammatory response in the immediate early stage of EGCG treatment by shutting off Notch signaling and that the effect did not involve the 67-kDa laminin receptor, the common receptor for EGCG. EGCG eliminated mature Notch from the cell membrane and the nuclear Notch intercellular domain, the active form of Notch, within 2 min by rapid degradation via the proteasome pathway. Transcription of the Notch target gene was downregulated simultaneously. Knockdown of Notch 1/2 expression by RNA interference impaired the downregulation of the inflammatory response elicited by EGCG. Further study showed that EGCG inhibited lipopolysaccharide-induced inflammation and turned off Notch signaling in human primary macrophages. Taken together, our results show that EGCG targets Notch to regulate the inflammatory response in the immediate early stage. PMID:28443100

  8. RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

    PubMed

    Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

    2016-01-01

    Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

  9. Sera from cancer patients contain two oscillating ECTO-NOX activities with different period lengths

    NASA Technical Reports Server (NTRS)

    Wang, Sui; Morre, Dorothy M.; Morre, D. James

    2003-01-01

    ECTO-NOX protein's are cell surface-associated and growth-related hydroquinone oxidases with both protein disulfide-thiol interchange activity and the capacity to oxidize NAD(P)H. The activities of these ECTO-NOX proteins are not steady state but fluctuate to create a repeating pattern of oscillations. Two forms of ECTO-NOX activities have been distinguished. The constitutive ECTO-NOX (CNOX), is hormone responsive and refractory to quinone-site inhibitors. A tumor-associated NOX (tNOX) is unregulated, refractory to hormones and growth factors and responds to quinone-site inhibitors. CNOX proteins are widely distributed and exhibit oscillations in enzymatic activity with a period length of 24 min. tNOX proteins are cancer specific and exhibit oscillations with a period length of about 22 min. Our findings now demonstrate the presence of the novel oscillating tNOX activity in sera of patients with cancer whereas the constitutive NOX of non-cancer cells is present in sera of both cancer patients and healthy volunteers. We conclude that ECTO-NOX proteins in sera exhibit oscillatory characteristics similar to those of ECTO-NOX forms of the cell surface.

  10. Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension

    PubMed Central

    Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

    2012-01-01

    Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

  11. Attenuation of S. aureus-induced bacteremia by human mini-antibodies targeting the complement inhibitory protein Efb

    PubMed Central

    Georgoutsou-Spyridonos, Maria; Ricklin, Daniel; Pratsinis, Haris; Perivolioti, Eustathia; Pirmettis, Ioannis; Garcia, Brandon L.; Geisbrecht, Brian V.; Foukas, Periklis G.; Lambris, John D.; Mastellos, Dimitrios C.; Sfyroera, Georgia

    2015-01-01

    Staphylococcus aureus (S. aureus) can cause a broad range of potentially fatal inflammatory complications (e.g. sepsis, endocarditis). Its emerging antibiotic resistance and formidable immune evasion arsenal have emphasized the need for more effective antimicrobial approaches. Complement is an innate immune sensor that rapidly responds to bacterial infection eliciting C3-mediated opsonophagocytic and immunomodulatory responses. Extracellular Fibrinogen-binding Protein (Efb) is a key immune evasion protein of S. aureus that intercepts complement at the level of C3. To date, Efb has not been explored as a target for monoclonal antibody (mAb)-based antimicrobial therapeutics. Herein we have isolated donor-derived anti-Efb IgGs that attenuate S. aureus survival through enhanced neutrophil killing. A phage library screen yielded mAbs (miniAbs) that selectively inhibit the interaction of Efb with C3 partly by disrupting contacts essential for complex formation. Surface Plasmon Resonance-based kinetic analysis enabled the selection of miniAbs with favorable Efb-binding profiles as therapeutic leads. MiniAb-mediated blockade of Efb attenuated S aureus survival in a whole blood model of bacteremia. This neutralizing effect was associated with enhanced neutrophil-mediated killing of S. aureus, increased C5a release and modulation of IL-6 secretion. Finally, these miniAbs afforded protection from S. aureus-induced bacteremia in a murine renal abscess model, attenuating bacterial inflammation in kidneys. Overall, these findings are anticipated to pave the way towards novel antibody-based therapeutics for S. aureus-related diseases. PMID:26342032

  12. MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

    PubMed

    Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

    2018-01-15

    Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

  13. Defining wet season water quality target concentrations for ecosystem conservation using empirical light attenuation models: A case study in the Great Barrier Reef (Australia).

    PubMed

    Petus, Caroline; Devlin, Michelle; Teixera da Silva, Eduardo; Lewis, Stephen; Waterhouse, Jane; Wenger, Amelia; Bainbridge, Zoe; Tracey, Dieter

    2018-05-01

    Optically active water quality components (OAC) transported by flood plumes to nearshore marine environments affect light levels. The definition of minimum OAC concentrations that must be maintained to sustain sufficient light levels for conservation of light-dependant coastal ecosystems exposed to flood waters is necessary to guide management actions in adjacent catchments. In this study, a framework for defining OAC target concentrations using empirical light attenuation models is proposed and applied to the Wet Tropics region of the Great Barrier Reef (GBR) (Queensland, Australia). This framework comprises several steps: (i) light attenuation (Kd(PAR)) profiles and OAC measurements, including coloured dissolved organic matter (CDOM), chlorophyll-a (Chl-a) and suspended particulate matter (SPM) concentrations collected in flood waters; (ii) empirical light attenuation models used to define the contribution of CDOM, Chl-a and SPM to the light attenuation, and; (iii) translation of empirical models into manageable OAC target concentrations specific for wet season conditions. Results showed that (i) Kd(PAR) variability in the Wet Tropics flood waters is driven primarily by SPM and CDOM, with a lower contribution from Chl-a (r2 = 0.5, p < 0.01), (ii) the relative contributions of each OAC varies across the different water bodies existing along flood waters and strongest Kd(PAR) predictions were achieved when the in-situ data were clustered into water bodies with similar satellite-derived colour characteristics ('brownish flood waters', r2 = 0.8, p < 0.01, 'greenish flood waters', r2 = 0.5, p < 0.01), and (iii) that Kd(PAR) simulations are sensitive to the angular distribution of the light field in the clearest flood water bodies. Empirical models developed were used to translate regional light guidelines (established for the GBR) into manageable OAC target concentrations. Preliminary results suggested that a 90th percentile SPM concentration

  14. Attenuation of Staphylococcus aureus-Induced Bacteremia by Human Mini-Antibodies Targeting the Complement Inhibitory Protein Efb.

    PubMed

    Georgoutsou-Spyridonos, Maria; Ricklin, Daniel; Pratsinis, Haris; Perivolioti, Eustathia; Pirmettis, Ioannis; Garcia, Brandon L; Geisbrecht, Brian V; Foukas, Periklis G; Lambris, John D; Mastellos, Dimitrios C; Sfyroera, Georgia

    2015-10-15

    Staphylococcus aureus can cause a broad range of potentially fatal inflammatory complications (e.g., sepsis and endocarditis). Its emerging antibiotic resistance and formidable immune evasion arsenal have emphasized the need for more effective antimicrobial approaches. Complement is an innate immune sensor that rapidly responds to bacterial infection eliciting C3-mediated opsonophagocytic and immunomodulatory responses. Extracellular fibrinogen-binding protein (Efb) is a key immune evasion protein of S. aureus that intercepts complement at the level of C3. To date, Efb has not been explored as a target for mAb-based antimicrobial therapeutics. In this study, we have isolated donor-derived anti-Efb IgGs that attenuate S. aureus survival through enhanced neutrophil killing. A phage library screen yielded mini-Abs that selectively inhibit the interaction of Efb with C3 partly by disrupting contacts essential for complex formation. Surface plasmon resonance-based kinetic analysis enabled the selection of mini-Abs with favorable Efb-binding profiles as therapeutic leads. Mini-Ab-mediated blockade of Efb attenuated S. aureus survival in a whole blood model of bacteremia. This neutralizing effect was associated with enhanced neutrophil-mediated killing of S. aureus, increased C5a release, and modulation of IL-6 secretion. Finally, these mini-Abs afforded protection from S. aureus-induced bacteremia in a murine renal abscess model, attenuating bacterial inflammation in kidneys. Overall, these findings are anticipated to pave the way toward novel Ab-based therapeutics for S. aureus-related diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Lipid Emulsion Inhibits Vasodilation Induced by a Toxic Dose of Bupivacaine via Attenuated Dephosphorylation of Myosin Phosphatase Target Subunit 1 in Isolated Rat Aorta

    PubMed Central

    Ok, Seong-Ho; Byon, Hyo-Jin; Kwon, Seong-Chun; Park, Jungchul; Lee, Youngju; Hwang, Yeran; Baik, Jiseok; Choi, Mun-Jeoung; Sohn, Ju-Tae

    2015-01-01

    Lipid emulsions are widely used for the treatment of systemic toxicity that arises from local anesthetics. The goal of this in vitro study was to examine the cellular mechanism associated with the lipid emulsion-mediated attenuation of vasodilation induced by a toxic dose of bupivacaine in isolated endothelium-denuded rat aorta. The effects of lipid emulsion on vasodilation induced by bupivacaine, mepivacaine, and verapamil were assessed in isolated aorta precontracted with phenylephrine, the Rho kinase stimulant NaF, and the protein kinase C activator phorbol 12,13-dibutyrate (PDBu). The effects of Rho kinase inhibitor Y-27632 on contraction induced by phenylephrine or NaF were assessed. The effects of bupivacaine on intracellular calcium concentrations ([Ca2+]i) and tension induced by NaF were simultaneously measured. The effects of bupivacaine alone and lipid emulsion plus bupivacaine on myosin phosphatase target subunit 1 (MYPT1) phosphorylation induced by NaF were examined in rat aortic vascular smooth muscle cells. In precontracted aorta, the lipid emulsion attenuated bupivacaine-induced vasodilation but had no effect on mepivacaine-induced vasodilation. Y-27632 attenuated contraction induced by either phenylephrine or NaF. The lipid emulsion attenuated verapamil-induced vasodilation. Compared with phenylephrine-induced precontracted aorta, bupivacaine-induced vasodilation was slightly attenuated in NaF-induced precontracted aorta. The magnitude of the bupivacaine-induced vasodilation was higher than that of a bupivacaine-induced decrease in [Ca2+]i. Bupivacaine attenuated NaF-induced MYPT1 phosphorylation, whereas lipid emulsion pretreatment attenuated the bupivacaine-induced inhibition of MYPT1 phosphorylation induced by NaF. Taken together, these results suggest that lipid emulsions attenuate bupivacaine-induced vasodilation via the attenuation of inhibition of MYPT1 phosphorylation evoked by NaF. PMID:26664257

  16. P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: Implications for EEG models of working memory function.

    PubMed

    Hochberger, William C; Axelrod, Jenna L; Sarapas, Casey; Shankman, Stewart A; Hill, S Kristian

    2018-06-08

    Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTI) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct ("match") or incorrect ("non-match" or "oddball") stimuli. Moreover, the recall series included either a brief (500ms) or extended (2000ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in target-to-target interval (TTI). These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.

  17. Biological control via "ecological" damping: An approach that attenuates non-target effects.

    PubMed

    Parshad, Rana D; Quansah, Emmanuel; Black, Kelly; Beauregard, Matthew

    2016-03-01

    In this work we develop and analyze a mathematical model of biological control to prevent or attenuate the explosive increase of an invasive species population, that functions as a top predator, in a three-species food chain. We allow for finite time blow-up in the model as a mathematical construct to mimic the explosive increase in population, enabling the species to reach "disastrous", and uncontrollable population levels, in a finite time. We next improve the mathematical model and incorporate controls that are shown to drive down the invasive population growth and, in certain cases, eliminate blow-up. Hence, the population does not reach an uncontrollable level. The controls avoid chemical treatments and/or natural enemy introduction, thus eliminating various non-target effects associated with such classical methods. We refer to these new controls as "ecological damping", as their inclusion dampens the invasive species population growth. Further, we improve prior results on the regularity and Turing instability of the three-species model that were derived in Parshad et al. (2014). Lastly, we confirm the existence of spatiotemporal chaos. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Drug and tobacco detection using neutron transmission/attenuation

    NASA Astrophysics Data System (ADS)

    Miller, Thomas G.

    1994-10-01

    A neutron transmission/attenuation spectrometer has been used to obtain the neutron attenuation signature of cocaine, heroin, hashish, methamphetamine, pipe tobacco and chewing tobacco. A pulsed `white neutron' source was created by bombarding a thick beryllium target with a 5 MeV pulsed deuteron beam. The neutron intensity was measured from about 0.75 MeV to about 4 MeV with the suitcase in and out of the neutron beam to determine the neutron attenuation. Experiments were performed for drugs and tobacco alone and when imbedded in an `average suitcase'. The experimentally determined neutron attenuation curves were used to determine the atomic ratios C/O, N/O, and H/C through the samples using measured neutron cross sections.

  19. The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for oxidative stress, low-grade inflammation and nitric oxide production.

    PubMed

    Krause, Mauricio; Rodrigues-Krause, Josianne; O'Hagan, Ciara; Medlow, Paul; Davison, Gareth; Susta, Davide; Boreham, Colin; Newsholme, Philip; O'Donnell, Mark; Murphy, Colin; De Vito, Giuseppe

    2014-02-01

    To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM). Twenty-five sedentary, obese (BMI > 30 kg/m2) males (52.8 ± 7.2 years); 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max; 30-40% VO(2max)) or moderate (T(vent); 55-65 % VO(2max)) intensity. Before and after training, blood and muscle samples (v. lateralis) were collected. Baseline erythrocyte glutathione was lower (21.8 ± 2.8 vs. 32.7 ± 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 ± 52.1 vs. 75.5 ± 41.6 nmol/ml). Plasma catalase increased in T2DM after T(vent) training (from 0.98 ± 0.22 to 1.96 ± 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 ± 2.78 vs. 12.34 ± 3.56 μmol/l). Training at T(vent) increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers. Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T(vent). Non-diabetics responded to T(vent) training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention).

  20. Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

    PubMed

    Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

    2017-02-02

    Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Time for Genome Editing: Next-Generation Attenuated Malaria Parasites.

    PubMed

    Singer, Mirko; Frischknecht, Friedrich

    2017-03-01

    Immunization with malaria parasites that developmentally arrest in or immediately after the liver stage is the only way currently known to confer sterilizing immunity in both humans and rodent models. There are various ways to attenuate parasite development resulting in different timings of arrest, which has a significant impact on vaccination efficiency. To understand what most impacts vaccination efficiency, newly developed gain-of-function methods can now be used to generate a wide array of differently attenuated parasites. The combination of multiple attenuation approaches offers the potential to engineer efficiently attenuated Plasmodium parasites and learn about their fascinating biology at the same time. Here we discuss recent studies and the potential of targeted parasite manipulation using genome editing to develop live attenuated malaria vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Brain-Targeted (Pro)Renin Receptor Knockdown attenuates Angiotensin II-Dependent Hypertension

    PubMed Central

    Li, Wencheng; Peng, Hua; Cao, Theresa; Sato, Ryosuke; McDaniels, Sarah. J.; Kobori, Hiroyuki; Navar, L. Gabriel; Feng, Yumei

    2012-01-01

    The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor shRNA was used to knockdown (pro)renin receptor expression in the brain of non-transgenic normotensive and human renin-angiotensinogen double transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor and vasopressin mRNA levels. Plasma vasopressin levels were determined by Enzyme-Linked Immuno Sorbent Assay. Double transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor shRNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared to the control virus treatment in double transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease insympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with down-regulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice. PMID:22526255

  3. miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

    PubMed Central

    Xie, Wang; Lu, Qingchun; Wang, Kailing; Lu, Jingjing; Gu, Xia; Zhu, Dongyi; Liu, Fanglei

    2018-01-01

    Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS‐induced ALI. Here, we have investigated the potential roles of PGRN‐targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS‐induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR‐34b‐5p in ALI was determined by transfection of a miR‐34b‐5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT‐PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR‐34b‐5p levels were closely associated with PGRN expression in the lung homogenates. The gain‐ and loss‐of‐function analysis, dual‐luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR‐34b‐5p. Intravenous injection of miR‐34b‐5p antagomir in vivo significantly inhibited miR‐34b‐5p up‐regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR‐34b‐5p knockdown attenuates lung inflammation and apoptosis in an LPS‐induced ALI mouse model by targeting PGRN. This study shows that miR‐34b‐5p and PGRN may be potential targets for ALI treatments. PMID:29150939

  4. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

    DOE PAGES

    Polyzos, Aris; Holt, Amy; Brown, Christopher; ...

    2016-02-21

    Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

  5. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes

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

    Polyzos, Aris; Holt, Amy; Brown, Christopher

    Oxidative damage to mitochondria (MT) is a major mechanism for aging and neurodegeneration. We have developed a novel synthetic antioxidant, XJB-5-131, which directly targets MT, the primary site and primary target of oxidative damage. XJB-5-131 prevents the onset of motor decline in an HdhQ(150/150) mouse model for Huntington's disease (HD) if treatment starts early. Here, we report that XJB-5-131 attenuates or reverses disease progression if treatment occurs after disease onset. In animals with well-developed pathology, XJB-5-131 promotes weight gain, prevents neuronal death, reduces oxidative damage in neurons, suppresses the decline of motor performance or improves it, and reduces a grayingmore » phenotype in treated HdhQ(150/150) animals relative to matched littermate controls. XJB-5-131 holds promise as a clinical candidate for the treatment of HD.« less

  6. The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice.

    PubMed

    Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

    2016-01-01

    Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis.

  7. The mitochondria-targeted antioxidant MitoQ attenuates liver fibrosis in mice

    PubMed Central

    Rehman, Hasibur; Liu, Qinlong; Krishnasamy, Yasodha; Shi, Zengdun; Ramshesh, Venkat K; Haque, Khujista; Schnellmann, Rick G; Murphy, Michael P; Lemasters, John J; Rockey, Don C; Zhong, Zhi

    2016-01-01

    Oxidative stress plays an essential role in liver fibrosis. This study investigated whether MitoQ, an orally active mitochondrial antioxidant, decreases liver fibrosis. Mice were injected with corn oil or carbon tetrachloride (CCl4, 1:3 dilution in corn oil; 1 µl/g, ip) once every 3 days for up to 6 weeks. 4-Hydroxynonenal adducts increased markedly after CCl4 treatment, indicating oxidative stress. MitoQ attenuated oxidative stress after CCl4. Collagen 1α1 mRNA and hydroxyproline increased markedly after CCl4 treatment, indicating increased collagen formation and deposition. CCl4 caused overt pericentral fibrosis as revealed by both the sirius red staining and second harmonic generation microscopy. MitoQ blunted fibrosis after CCl4. Profibrotic transforming growth factor-β1 (TGF-β1) mRNA and expression of smooth muscle α-actin, an indicator of hepatic stellate cell (HSC) activation, increased markedly after CCl4 treatment. Smad 2/3, the major mediator of TGF-β fibrogenic effects, was also activated after CCl4 treatment. MitoQ blunted HSC activation, TGF-β expression, and Smad2/3 activation after CCl4 treatment. MitoQ also decreased necrosis, apoptosis and inflammation after CCl4 treatment. In cultured HSCs, MitoQ decreased oxidative stress, inhibited HSC activation, TGF-β1 expression, Smad2/3 activation, and extracellular signal-regulated protein kinase activation. Taken together, these data indicate that mitochondrial reactive oxygen species play an important role in liver fibrosis and that mitochondria-targeted antioxidants are promising potential therapies for prevention and treatment of liver fibrosis. PMID:27186319

  8. Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

    PubMed Central

    Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

    2014-01-01

    Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

  9. Combining Natural Attenuation Capacity and use of Targeted Technological Mitigation Measures for Reducing Diffuse Nutrient Emissions to Surface Waters: The Danish Way

    NASA Astrophysics Data System (ADS)

    Kronvang, B.; Højberg, A. L.; Hoffmann, C. C.; Windolf, J.; Blicher-Mathiesen, G.

    2015-12-01

    Excess nitrogen (N) and phosphorus (P) emissions to surface waters are a high priority environmental problem worldwide for protection of water resources in times of population growth and climate change. As clean water is a scarce resource the struggle for reducing nutrient emissions are an ongoing issue for many countries and regions. Since the mid1980s a wide range of national regulatory general measures have been implemented to reduce land based nitrogen (N) and phosphorus (P) loadings of the Danish aquatic environment. These measures have addressed both point source emissions and emissions from diffuse sources especially from agricultural production. Following nearly 4 decades of combating nutrient pollution our surface waters such as lakes and estuaries are only slowly responding on the 50% reduction in N and 56% reduction in P. Therefore, the implementation of the EU Water Framework Directive in Danish surface waters still call for further reductions of N and P loadings. Therefore, a new era of targeted implemented measures was the outcome of a Commission on Nature and Agriculture established by the Danish Government in 2013. Their White Book points to the need of increased growth and better environment through more targeted and efficient regulation using advanced technological mitigation methods that are implemented intelligently according to the local natural attenuation capacity for nutrients in the landscape. As a follow up a national consensus model for N was established chaining existing leaching, 3D groundwater and surface water models that enable a calculation of the N dynamics and attenuation capacity within a scale of 15 km2. Moreover, several research projects have been conducted to investigate the effect of a suite of targeted mitigation measures such as restored natural wetlands, constructed wetlands, controlled drainage, buffer strips and constructed buffer strips. The results of these studies will be shared in this presentation.

  10. Targeting nitrative stress for attenuating cisplatin-induced downregulation of cochlear LIM domain only 4 and ototoxicity.

    PubMed

    Jamesdaniel, Samson; Rathinam, Rajamani; Neumann, William L

    2016-12-01

    Cisplatin-induced ototoxicity remains a primary dose-limiting adverse effect of this highly effective anticancer drug. The clinical utility of cisplatin could be enhanced if the signaling pathways that regulate the toxic side-effects are delineated. In previous studies, we reported cisplatin-induced nitration of cochlear proteins and provided the first evidence for nitration and downregulation of cochlear LIM domain only 4 (LMO4) in cisplatin ototoxicity. Here, we extend these findings to define the critical role of nitrative stress in cisplatin-induced downregulation of LMO4 and its consequent ototoxic effects in UBOC1 cell cultures derived from sensory epithelial cells of the inner ear and in CBA/J mice. Cisplatin treatment increased the levels of nitrotyrosine and active caspase 3 in UBOC1 cells, which was detected by immunocytochemical and flow cytometry analysis, respectively. The cisplatin-induced nitrative stress and apoptosis were attenuated by co-treatment with SRI110, a peroxynitrite decomposition catalyst (PNDC), which also attenuated the cisplatin-induced downregulation of LMO4 in a dose-dependent manner. Furthermore, transient overexpression of LMO4 in UBOC1 cells prevented cisplatin-induced cytotoxicity while repression of LMO4 exacerbated cisplatin-induced cell death, indicating a direct link between LMO4 protein levels and cisplatin ototoxicity. Finally, auditory brainstem responses (ABR) recorded from CBA/J mice indicated that co-treatment with SRI110 mitigated cisplatin-induced hearing loss. Together, these results suggest that cisplatin-induced nitrative stress leads to a decrease in the levels of LMO4, downregulation of LMO4 is a critical determinant in cisplatin-induced ototoxicity, and targeting peroxynitrite could be a promising strategy for mitigating cisplatin-induced hearing loss. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy.

    PubMed

    Graham, Delyth; Huynh, Ngan N; Hamilton, Carlene A; Beattie, Elisabeth; Smith, Robin A J; Cochemé, Helena M; Murphy, Michael P; Dominiczak, Anna F

    2009-08-01

    Mitochondria are a major site of reactive oxygen species production, which may contribute to the development of cardiovascular disease. Protecting mitochondria from oxidative damage should be an effective therapeutic strategy; however, conventional antioxidants are ineffective, because they cannot penetrate the mitochondria. This study investigated the role of mitochondrial oxidative stress during development of hypertension in the stroke-prone spontaneously hypertensive rat, using the mitochondria-targeted antioxidant, MitoQ(10). Eight-week-old male stroke-prone spontaneously hypertensive rats were treated with MitoQ(10) (500 mumol/L; n=16), control compound decyltriphenylphosphonium (decylTPP; 500 mumol/L; n=8), or vehicle (n=9) in drinking water for 8 weeks. Systolic blood pressure was significantly reduced by approximately 25 mm Hg over the 8-week MitoQ(10) treatment period compared with decylTPP (F=5.94; P=0.029) or untreated controls (F=65.6; P=0.0001). MitoQ(10) treatment significantly improved thoracic aorta NO bioavailability (1.16+/-0.03 g/g; P=0.002, area under the curve) compared with both untreated controls (0.68+/-0.02 g/g) and decylTPP-treated rats (0.60+/-0.06 g/g). Cardiac hypertrophy was significantly reduced by MitoQ(10) treatment compared with untreated control and decylTPP treatment (MitoQ(10): 4.01+/-0.05 mg/g; control: 4.42+/-0.11 mg/g; and decylTPP: 4.40+/-0.09 mg/g; ANOVA P=0.002). Total MitoQ(10) content was measured in liver, heart, carotid artery, and kidney harvested from MitoQ(10)-treated rats by liquid chromatography-tandem mass spectrometry. All of the organs analyzed demonstrated detectable levels of MitoQ(10), with comparable accumulation in vascular and cardiac tissues. Administration of the mitochondria-targeted antioxidant MitoQ(10) protects against the development of hypertension, improves endothelial function, and reduces cardiac hypertrophy in young stroke-prone spontaneously hypertensive rats. MitoQ(10) provides a novel

  12. Chlorine signal attenuation in concrete.

    PubMed

    Naqvi, A A; Maslehuddin, M; Ur-Rehman, Khateeb; Al-Amoudi, O S B

    2015-11-01

    The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Mass attenuation coefficient of chromium and manganese compounds around absorption edge.

    PubMed

    Sharanabasappa; Kaginelli, S B; Kerur, B R; Anilkumar, S; Hanumaiah, B

    2009-01-01

    The total mass attenuation coefficient for Potassium dichromate, Potassium chromate and Manganese acetate compounds are measured at different photon energies 5.895, 6.404, 6.490, 7.058, 8.041 and 14.390 keV using Fe-55, Co-57 and 241Am source with Copper target, radioactive sources. The photon intensity is analyzed using a high resolution HPGe detector system coupled to MCA under good geometrical arrangement. The obtained values of mass attenuation coefficient values are compared with theoretical values. This study suggests that measured mass attenuation coefficient values at and near absorption edges differ from the theoretical value by about 5-28%.

  14. DC attenuation meter

    DOEpatents

    Hargrove, Douglas L.

    2004-09-14

    A portable, hand-held meter used to measure direct current (DC) attenuation in low impedance electrical signal cables and signal attenuators. A DC voltage is applied to the signal input of the cable and feedback to the control circuit through the signal cable and attenuators. The control circuit adjusts the applied voltage to the cable until the feedback voltage equals the reference voltage. The "units" of applied voltage required at the cable input is the system attenuation value of the cable and attenuators, which makes this meter unique. The meter may be used to calibrate data signal cables, attenuators, and cable-attenuator assemblies.

  15. Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

    PubMed Central

    Locke, Jeffrey B.; Aziz, Ramy K.; Vicknair, Mike R.; Nizet, Victor; Buchanan, John T.

    2008-01-01

    Background Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI). Methodology/Principal Findings S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the ΔsimA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development. Conclusions/Significance Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement

  16. Targeted Gene Silencing of Tumor Necrosis Factor Attenuates the Negative Inotropic Effects of Lipopolysaccharide in Isolated Contracting Cardiac Myocytes

    PubMed Central

    Ramabadran, R. S.; Chancey, Amanda; Vallejo, Jesus G.; Barger, Philip M.; Sivasubramanian, Natarajan; Mann, Douglas L.

    2008-01-01

    Bacterial endotoxin (lipopolysaccharide) depresses cardiovascular function; however, the mediators and signaling pathways that are responsible for the negative inotropic effects of lipopolysaccharide are not fully known. We used RNA interference to determine the relative role of tumor necrosis factor with respect to mediating the negative inotropic effects of lipopolysaccharide in isolated cardiac myocytes. Cardiac myocyte cultures were treated with lipopolysaccharide in the presence or absence of small interfering RNAs (siRNA) for tumor necrosis factor. We examined the effects of tumor necrosis factor siRNA on lipopolysaccharide-induced tumor necrosis factor messenger RNA (mRNA) and protein biosynthesis, as well as the negative inotropic effects of lipopolysaccharide in isolated contracting cardiac myocytes. Treatment of adult cardiac myocyte cultures with tumor necrosis factor siRNA significantly attenuated lipopolysaccharide-induced tumor necrosis factor mRNA and protein biosynthesis, whereas transfection with a double-stranded RNA that does not target mammalian mRNA had no effect. Pretreatment with tumor necrosis factor siRNA significantly attenuated, but did not abrogate, the lipopolysaccharide-induced decrease in sarcomere shortening in isolated contracting cardiac myocytes. In contrast, tumor necrosis factor siRNA had a comparatively smaller effect on improving sarcomere shortening once the negative inotropic effects of lipopolysaccharide were fully established. These results suggest that tumor necrosis factor plays an important upstream role in lipopolysaccharide-induced negative inotropic effects in isolated contracting cardiac myocytes and that other molecular mechanisms are responsible for the decrease in sarcomere shortening after sustained lipopolysaccharide signaling. PMID:18427645

  17. Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice.

    PubMed

    Townsend, Brigitte E; Johnson, Rodney W

    2016-01-01

    Increased neuroinflammation and oxidative stress resulting from heightened microglial activation are associated with age-related cognitive impairment. The objectives of this study were to examine the effects of the bioactive sulforaphane (SFN) on the nuclear factor E2-related factor 2 (Nrf2) pathway in BV2 microglia and primary microglia, and to evaluate proinflammatory cytokine expression in lipopolysaccharide (LPS)-stimulated primary microglia from adult and aged mice. BV2 microglia and primary microglia isolated from young adult and aged mice were treated with SFN and LPS. Changes in Nrf2 activity, expression of Nrf2 target genes, and levels of proinflammatory markers were assessed by quantitative PCR and immunoassay. SFN increased Nrf2 DNA-binding activity and upregulated Nrf2 target genes in BV2 microglia, while reducing LPS-induced interleukin (IL-)1β, IL-6, and inducible nitric oxide synthase (iNOS). In primary microglia from adult and aged mice, SFN increased expression of Nrf2 target genes and attenuated IL-1β, IL-6, and iNOS induced by LPS. These data indicate that SFN is a potential beneficial supplement that may be useful for reducing microglial mediated neuroinflammation and oxidative stress associated with aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2

    PubMed Central

    Wang, Jia; Cheng, Peng; Pavlyukov, Marat S.; Yu, Hai; Zhang, Zhuo; Kim, Sung-Hak; Minata, Mutsuko; Mohyeldin, Ahmed; Xie, Wanfu; Chen, Dongquan; Goidts, Violaine; Frett, Brendan; Hu, Wenhao; Li, Hongyu; Shin, Yong Jae; Lee, Yeri; Nam, Do-Hyun; Kornblum, Harley I.; Wang, Maode

    2017-01-01

    Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. Mechanistically, the formation of a protein complex comprising NEK2 and EZH2 in glioma spheres phosphorylated and then protected EZH2 from ubiquitination-dependent protein degradation in a NEK2 kinase activity–dependent manner. Clinically, NEK2 expression in patients with glioma was closely associated with EZH2 expression and correlated with a poor prognosis. NEK2 expression was also substantially elevated in recurrent tumors after therapeutic failure compared with primary untreated tumors in matched GBM patients. We designed a NEK2 kinase inhibitor, compound 3a (CMP3a), which efficiently attenuated GBM growth in a mouse model and exhibited a synergistic effect with radiotherapy. These data demonstrate a key role for NEK2 in maintaining GSCs in GBM by stabilizing the EZH2 protein and introduce the small-molecule inhibitor CMP3a as a potential therapeutic agent for GBM. PMID:28737508

  19. Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth

    PubMed Central

    Vittorio, Orazio; Brandl, Miriam; Cirillo, Giuseppe; Kimpton, Kathleen; Hinde, Elizabeth; Gaus, Katharina; Yee, Eugene; Kumar, Naresh; Duong, Hien; Fleming, Claudia; Haber, Michelle; Norris, Murray; Boyer, Cyrille; Kavallaris, Maria

    2016-01-01

    Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID:27374085

  20. Determination of rain rate from a spaceborne radar using measurements of total attenuation

    NASA Technical Reports Server (NTRS)

    Meneghini, R.; Eckerman, J.; Atlas, D.

    1981-01-01

    Studies shows that path-integrated rain rates can be determined by means of a direct measurement of attenuation. For ground based radars this is done by measuring the backscattering cross section of a fixed target in the presence and absence of rain along the radar beam. A ratio of the two measurements yields a factor proportional to the attenuation from which the average rain rate is deduced. The technique is extended to spaceborne radars by choosing the ground as reference target. The technique is also generalized so that both the average and range-profiled rain rates are determined. The accuracies of the resulting estimates are evaluated for a narrow beam radar located on a low earth orbiting satellite.

  1. Novel Intriguing Strategies Attenuating to Sarcopenia

    PubMed Central

    Sakuma, Kunihiro; Yamaguchi, Akihiko

    2012-01-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant. PMID:22500226

  2. Ultrasound-targeted microbubble destruction enhances delayed BMC delivery and attenuates post-infarction cardiac remodelling by inducing engraftment signals.

    PubMed

    Chen, Yanmei; Zhang, Chuanxi; Shen, Shuxin; Guo, Shengcun; Zhong, Lintao; Li, Xinzhong; Chen, Guojun; Chen, Gangbin; He, Xiang; Huang, Chixiong; He, Nvqin; Liao, Wangjun; Liao, Yulin; Bin, Jianping

    2016-12-01

    Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction (MI) does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. In the present study, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs and subsequently attenuate post-infarction cardiac remodelling. A myocardial ischaemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0-1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous haematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischaemic zone was greater in the group treated with both UTMD and delayed BMC transplantation than in the control groups (P<0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (both P<0.05). Histopathology demonstrated that UTMD combined with delayed BMC transplantation increased capillary density, myocardial cell proliferation and c-kit + cell proliferation. These findings indicated that UTMD treatment could induce engraftment signals and enhance homing of delayed BMCs to ischaemic myocardium, attenuating post-infarction cardiac remodelling by promoting neovascularization, cardiomyogenesis and expansion of cardiac c-kit + cells. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  3. Targeting the Transient Receptor Potential Vanilloid Type 1 (TRPV1) Assembly Domain Attenuates Inflammation-induced Hypersensitivity*

    PubMed Central

    Flynn, Robyn; Chapman, Kevin; Iftinca, Mircea; Aboushousha, Reem; Varela, Diego; Altier, Christophe

    2014-01-01

    The transient receptor potential channel vanilloid type 1 (TRPV1) is a non-selective cation channel expressed in sensory neurons of the dorsal root and trigeminal ganglia. TRPV1 is a polymodal channel activated by noxious heat, capsaicin, and protons. As a sensor for noxious stimuli, TRPV1 channel has been described as a key contributor to pain signaling. To form a functional channel, TRPV1 subunits must assemble into tetramers, and several studies have identified the TRPV1 C terminus as an essential element in subunit association. Here we combined biochemical assays with electrophysiology and imaging-based bimolecular fluorescence complementation (BiFC) and bioluminescence resonance energy transfer (BRET) in live cells to identify a short motif in the C-terminal tail of the TRPV1 subunit that governs channel assembly. Removing this region through early truncation or targeted deletion results in loss of subunit association and channel function. Importantly, we found that interfering with TRPV1 subunit association using a plasma membrane-tethered peptide attenuated mechanical and thermal hypersensitivity in two mouse models of inflammatory hyperalgesia. This represents a novel mechanism to disrupt TRPV1 subunit assembly and hence may offer a new analgesic tool for pain relief. PMID:24808184

  4. Targeting the transient receptor potential vanilloid type 1 (TRPV1) assembly domain attenuates inflammation-induced hypersensitivity.

    PubMed

    Flynn, Robyn; Chapman, Kevin; Iftinca, Mircea; Aboushousha, Reem; Varela, Diego; Altier, Christophe

    2014-06-13

    The transient receptor potential channel vanilloid type 1 (TRPV1) is a non-selective cation channel expressed in sensory neurons of the dorsal root and trigeminal ganglia. TRPV1 is a polymodal channel activated by noxious heat, capsaicin, and protons. As a sensor for noxious stimuli, TRPV1 channel has been described as a key contributor to pain signaling. To form a functional channel, TRPV1 subunits must assemble into tetramers, and several studies have identified the TRPV1 C terminus as an essential element in subunit association. Here we combined biochemical assays with electrophysiology and imaging-based bimolecular fluorescence complementation (BiFC) and bioluminescence resonance energy transfer (BRET) in live cells to identify a short motif in the C-terminal tail of the TRPV1 subunit that governs channel assembly. Removing this region through early truncation or targeted deletion results in loss of subunit association and channel function. Importantly, we found that interfering with TRPV1 subunit association using a plasma membrane-tethered peptide attenuated mechanical and thermal hypersensitivity in two mouse models of inflammatory hyperalgesia. This represents a novel mechanism to disrupt TRPV1 subunit assembly and hence may offer a new analgesic tool for pain relief. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Imaging of polarized target in underwater environment

    NASA Astrophysics Data System (ADS)

    Carrizo, Carlos; Foster, Robert; El-Habashi, Ahmed; Gray, Deric; Gilerson, Alex

    2017-10-01

    Imaging of underwater targets is challenging because of the significant attenuation of the propagating light field due to the absorption and scattering by water and suspended/dissolved matter. Some living and manmade objects in water have surfaces which partially polarize the light, whose properties can be used to camouflage or, conversely, to detect such objects. The attenuation of light by the intervening water (so-called veiling light) changes both the intensity and polarization characteristics at each pixel of the image, but does not contain any information about the target and contributes to image degradation and blurring. Its properties need to be understood in order to isolate the true optical signature of the target. The main goal of this study is to retrieve the polarization characteristics of the target from the image in different water environmental and illumination conditions by taking into account coincidentally measured inherent water optical properties (IOPs) during recent field campaigns outside the Chesapeake Bay and in New York Bight. Data, in the form of images and videos, were acquired using a green-band full-Stokes polarimetric video camera. Analysis of the acquired images show reasonable agreement in Stokes vector components with the measurements by the underwater polarimeter and modeled polarized signals. In addition, Stokes vector components of the veiling light were also estimated and compared with the models. Finally, retrieval of the attenuation coefficient for the light from the target is attempted from the measurements and compared with the results of the independent measurements of IOPs.

  6. Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr−/− mice by targeting the TGFβ-Smad3 pathway[S

    PubMed Central

    Lytle, Kelli A.; Depner, Christopher M.; Wong, Carmen P.; Jump, Donald B.

    2015-01-01

    DHA (22:6,ω3), but not EPA (20:5,ω3), attenuates Western diet (WD)-induced hepatic fibrosis in a Ldlr−/− mouse model of nonalcoholic steatohepatitis. We examined the molecular basis for the differential effect of dietary EPA and DHA on WD-induced hepatic fibrosis. DHA was more effective than EPA at preventing WD-induced effects on hepatic transcripts linked to fibrosis, including collagen 1A1 (Col1A1), transforming growth factor-β (TGFβ) signaling and proteins involved in remodeling the extracellular matrix, including metalloproteases, tissue inhibitors of metalloproteases, and lysyl oxidase subtypes. Examination of the TGFβ pathway showed that mice fed the WD supplemented with either olive oil or EPA had a significant (≥2.5-fold) increase in hepatic nuclear abundance of phospho-mothers against decapentaplegic homolog (Smad)3 when compared with mice fed the reference diet (RD); Smad3 is a key regulator of Col1A1 expression in stellate cells. In contrast, mice fed the WD supplemented with DHA had no increase in phospho-Smad3 when compared with mice fed the RD. Changes in hepatic phospho-Smad3 nuclear content correlated with proCol1A1 mRNA and protein abundance. Pretreatment of human LX2 stellate cells with DHA, but not other unsaturated fatty acids, blocked TGFβ1-mediated induction of Col1A1. In conclusion, DHA attenuates WD-induced fibrosis by targeting the TGFβ-Smad3-Col1A1 pathway in stellate cells. PMID:26315048

  7. Progression in attenuating myocardial reperfusion injury: an overview.

    PubMed

    Bernink, F J P; Timmers, L; Beek, A M; Diamant, M; Roos, S T; Van Rossum, A C; Appelman, Y

    2014-01-01

    Reperfusion by means of percutaneous coronary intervention or thrombolytic therapy is the most effective treatment for acute myocardial infarction, markedly reducing mortality and morbidity. Reperfusion however induces necrotic and apoptotic damages to cardiomyocytes, that were viable prior to reperfusion, a process called lethal reperfusion injury. This process, consisting of many single processes, may be responsible of up to half of the final infarct size. A myriad of therapies as an adjunct to reperfusion have been studied with the purpose to attenuate reperfusion injury. The majority of these studies have been disappointing or contradicting, but recent proof-of-concept trials show that reperfusion injury still is a legitimate target. This overview will discuss these trials, the progression in attenuating myocardial reperfusion injury, promising therapies, and future perspectives. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Analytical method for optimal source reduction with monitored natural attenuation in contaminated aquifers

    USGS Publications Warehouse

    Widdowson, M.A.; Chapelle, F.H.; Brauner, J.S.; ,

    2003-01-01

    A method is developed for optimizing monitored natural attenuation (MNA) and the reduction in the aqueous source zone concentration (??C) required to meet a site-specific regulatory target concentration. The mathematical model consists of two one-dimensional equations of mass balance for the aqueous phase contaminant, to coincide with up to two distinct zones of transformation, and appropriate boundary and intermediate conditions. The solution is written in terms of zone-dependent Peclet and Damko??hler numbers. The model is illustrated at a chlorinated solvent site where MNA was implemented following source treatment using in-situ chemical oxidation. The results demonstrate that by not taking into account a variable natural attenuation capacity (NAC), a lower target ??C is predicted, resulting in unnecessary source concentration reduction and cost with little benefit to achieving site-specific remediation goals.

  9. Using a LIDAR Vegetation Model to Predict UHF SAR Attenuation in Coniferous Forests

    PubMed Central

    Swanson, Alan; Huang, Shengli; Crabtree, Robert

    2009-01-01

    Attenuation of radar signals by vegetation can be a problem for target detection and GPS reception, and is an important parameter in models describing vegetation backscatter. Here we first present a model describing the 3D distribution of stem and foliage structure based on small footprint scanning LIDAR data. Secondly we present a model that uses ray-tracing methodology to record detailed interactions between simulated radar beams and vegetation components. These interactions are combined over the SAR aperture and used to predict two-way attenuation of the SAR signal. Accuracy of the model is demonstrated using UHF SAR observations of large trihedral corner reflectors in coniferous forest stands. Our study showed that the model explains between 66% and 81% of the variability in observed attenuation. PMID:22573972

  10. Control algorithms for dynamic attenuators

    PubMed Central

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-01-01

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  11. Control algorithms for dynamic attenuators.

    PubMed

    Hsieh, Scott S; Pelc, Norbert J

    2014-06-01

    The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

  12. The Groucho Co-repressor Is Primarily Recruited to Local Target Sites in Active Chromatin to Attenuate Transcription

    PubMed Central

    Jennings, Barbara H.

    2014-01-01

    Gene expression is regulated by the complex interaction between transcriptional activators and repressors, which function in part by recruiting histone-modifying enzymes to control accessibility of DNA to RNA polymerase. The evolutionarily conserved family of Groucho/Transducin-Like Enhancer of split (Gro/TLE) proteins act as co-repressors for numerous transcription factors. Gro/TLE proteins act in several key pathways during development (including Notch and Wnt signaling), and are implicated in the pathogenesis of several human cancers. Gro/TLE proteins form oligomers and it has been proposed that their ability to exert long-range repression on target genes involves oligomerization over broad regions of chromatin. However, analysis of an endogenous gro mutation in Drosophila revealed that oligomerization of Gro is not always obligatory for repression in vivo. We have used chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) to profile Gro recruitment in two Drosophila cell lines. We find that Gro predominantly binds at discrete peaks (<1 kilobase). We also demonstrate that blocking Gro oligomerization does not reduce peak width as would be expected if Gro oligomerization induced spreading along the chromatin from the site of recruitment. Gro recruitment is enriched in “active” chromatin containing developmentally regulated genes. However, Gro binding is associated with local regions containing hypoacetylated histones H3 and H4, which is indicative of chromatin that is not fully open for efficient transcription. We also find that peaks of Gro binding frequently overlap the transcription start sites of expressed genes that exhibit strong RNA polymerase pausing and that depletion of Gro leads to release of polymerase pausing and increased transcription at a bona fide target gene. Our results demonstrate that Gro is recruited to local sites by transcription factors to attenuate rather than silence gene expression by promoting histone deacetylation

  13. Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

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

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com

    ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccinemore » candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.« less

  14. Core disgust is attenuated by ingroup relations.

    PubMed

    Reicher, Stephen D; Templeton, Anne; Neville, Fergus; Ferrari, Lucienne; Drury, John

    2016-03-08

    We present the first experimental evidence to our knowledge that ingroup relations attenuate core disgust and that this helps explain the ability of groups to coact. In study 1, 45 student participants smelled a sweaty t-shirt bearing the logo of another university, with either their student identity (ingroup condition), their specific university identity (outgroup condition), or their personal identity (interpersonal condition) made salient. Self-reported disgust was lower in the ingroup condition than in the other conditions, and disgust mediated the relationship between condition and willingness to interact with target. In study 2, 90 student participants smelled a sweaty target t-shirt bearing either the logo of their own university, another university, or no logo, with either their student identity or their specific university identity made salient. Walking time to wash hands and pumps of soap indicated that disgust was lower where the relationship between participant and target was ingroup rather than outgroup or ambivalent (no logo).

  15. Core disgust is attenuated by ingroup relations

    PubMed Central

    Reicher, Stephen D.; Templeton, Anne; Neville, Fergus; Ferrari, Lucienne

    2016-01-01

    We present the first experimental evidence to our knowledge that ingroup relations attenuate core disgust and that this helps explain the ability of groups to coact. In study 1, 45 student participants smelled a sweaty t-shirt bearing the logo of another university, with either their student identity (ingroup condition), their specific university identity (outgroup condition), or their personal identity (interpersonal condition) made salient. Self-reported disgust was lower in the ingroup condition than in the other conditions, and disgust mediated the relationship between condition and willingness to interact with target. In study 2, 90 student participants smelled a sweaty target t-shirt bearing either the logo of their own university, another university, or no logo, with either their student identity or their specific university identity made salient. Walking time to wash hands and pumps of soap indicated that disgust was lower where the relationship between participant and target was ingroup rather than outgroup or ambivalent (no logo). PMID:26903640

  16. Tracer attenuation in groundwater

    NASA Astrophysics Data System (ADS)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  17. Variable laser attenuator

    DOEpatents

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  18. microRNA-212 promotes lipid accumulation and attenuates cholesterol efflux in THP-1 human macrophages by targeting SIRT1.

    PubMed

    Miao, Haiwei; Zeng, Honghui; Gong, Hui

    2018-02-15

    Macrophage foam cell formation is a key initiating event in the pathogenesis of atherosclerosis. This work was conducted to determine the role of microRNA (miR)-212 in the transformation of foam cells from macrophages. We examined the expression of miR-212 in atherosclerotic lesions in an apoE-deficient (apoE -/- ) mouse model. The effects of miR-212 overexpression and knockdown on lipid accumulation and cholesterol homeostasis in THP-1 macrophages after exposure to oxidized low-density lipoprotein (oxLDL). The mechanism underlying the activity of miR-212 was explored. It was found that miR-212 was downregulated in atherosclerotic lesions and macrophages from apoE -/- mice fed high-fat diet, compared to the equivalents from apoE -/- mice fed standard diet. Overexpression of miR-212 promoted lipid accumulation in oxLDL-treated THP-1 macrophages, whereas miR-212 depletion exerted an opposite effect. Macrophage cholesterol efflux to apolipoprotein A-I was significantly reduced by miR-212, which was accompanied by reduced ABCA1 expression. Mechanistically, miR-212 targeted sirtuin 1 (SIRT1) to repress the expression of ABCA1 in THP-1 macrophages. Rescue experiments confirmed that co-expression of SIRT1 attenuated lipid accumulation and restored cholesterol efflux in miR-212-overexpressing THP-1 macrophages. Collectively, miR-212 facilitates macrophage foam cell formation and suppresses ABCA1-dependent cholesterol efflux through downregulation of SIRT1. Targeting miR-212 may provide a potential therapeutic strategy for atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

    PubMed

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2015-11-01

    Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Variable laser attenuator

    DOEpatents

    Foltyn, S.R.

    1987-05-29

    The disclosure relates to low loss, high power variable attenuators comprising one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength. 9 figs.

  1. Seismic Linear Noise Attenuation with Use of Radial Transform

    NASA Astrophysics Data System (ADS)

    Szymańska-Małysa, Żaneta

    2018-03-01

    One of the goals of seismic data processing is to attenuate the recorded noise in order to enable correct interpretation of the image. Radial transform has been used as a very effective tool in the attenuation of various types of linear noise, both numerical and real (such as ground roll, direct waves, head waves, guided waves etc). The result of transformation from offset - time (X - T) domain into apparent velocity - time (R - T) domain is frequency separation between reflections and linear events. In this article synthetic and real seismic shot gathers were examined. One example was targeted at far offset area of dataset where reflections and noise had similar apparent velocities and frequency bands. Another example was a result of elastic modelling where linear artefacts were produced. Bandpass filtering and scaling operation executed in radial domain attenuated all discussed types of linear noise very effectively. After noise reduction all further processing steps reveal better results, especially velocity analysis, migration and stacking. In all presented cases signal-to-noise ratio was significantly increased and reflections covered previously by noise were revealed. Power spectra of filtered seismic records preserved real dynamics of reflections.

  2. Ultrasonic attenuation in pearlitic steel.

    PubMed

    Du, Hualong; Turner, Joseph A

    2014-03-01

    Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Attenuating effects of ecosystem management on coral reefs.

    PubMed

    Steneck, Robert S; Mumby, Peter J; MacDonald, Chancey; Rasher, Douglas B; Stoyle, George

    2018-05-01

    Managing diverse ecosystems is challenging because structuring drivers are often processes having diffuse impacts that attenuate from the people who were "managed" to the expected ecosystem-wide outcome. Coral reef fishes targeted for management only indirectly link to the ecosystem's foundation (reef corals). Three successively weakening interaction tiers separate management of fishing from coral abundance. We studied 12 islands along the 700-km eastern Caribbean archipelago, comparing fished and unfished coral reefs. Fishing reduced biomass of carnivorous (snappers and groupers) and herbivorous (parrotfish and surgeonfish) fishes. We document attenuating but important effects of managing fishing, which explained 37% of variance in parrotfish abundance, 20% of variance in harmful algal abundance, and 17% of variance in juvenile coral abundance. The explained variance increased when we quantified herbivory using area-specific bite rates. Local fisheries management resulted in a 62% increase in the archipelago's juvenile coral density, improving the ecosystem's recovery potential from major disturbances.

  4. Attenuating effects of ecosystem management on coral reefs

    PubMed Central

    Rasher, Douglas B.; Stoyle, George

    2018-01-01

    Managing diverse ecosystems is challenging because structuring drivers are often processes having diffuse impacts that attenuate from the people who were “managed” to the expected ecosystem-wide outcome. Coral reef fishes targeted for management only indirectly link to the ecosystem’s foundation (reef corals). Three successively weakening interaction tiers separate management of fishing from coral abundance. We studied 12 islands along the 700-km eastern Caribbean archipelago, comparing fished and unfished coral reefs. Fishing reduced biomass of carnivorous (snappers and groupers) and herbivorous (parrotfish and surgeonfish) fishes. We document attenuating but important effects of managing fishing, which explained 37% of variance in parrotfish abundance, 20% of variance in harmful algal abundance, and 17% of variance in juvenile coral abundance. The explained variance increased when we quantified herbivory using area-specific bite rates. Local fisheries management resulted in a 62% increase in the archipelago’s juvenile coral density, improving the ecosystem’s recovery potential from major disturbances. PMID:29750192

  5. LINE-ABOVE-GROUND ATTENUATOR

    DOEpatents

    Wilds, R.B.; Ames, J.R.

    1957-09-24

    The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

  6. Attenuator And Conditioner

    DOEpatents

    Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

    2006-04-04

    An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

  7. Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

    PubMed

    Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

    2015-10-22

    Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories

    PubMed Central

    Gräff, Johannes; Joseph, Nadine F.; Horn, Meryl E.; Samiei, Alireza; Meng, Jia; Seo, Jinsoo; Rei, Damien; Bero, Adam W.; Phan, Trongha X.; Wagner, Florence; Holson, Edward; Xu, Jinbin; Sun, Jianjun; Neve, Rachael L.; Mach, Robert H.; Haggarty, Stephen J.; Tsai, Li-Huei

    2014-01-01

    Summary Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. PMID:24439381

  9. Detection of attenuated plaque in stable angina with 64-multidetector computed tomography: a comparison with intravascular ultrasound.

    PubMed

    Jinzaki, Masahiro; Okabe, Teruo; Endo, Ayaka; Kawamura, Akio; Koga, Seiko; Yamada, Minoru; Fukuda, Keiichi; Kuribayashi, Sachio

    2012-01-01

    To clarify multidetector computed tomography (MDCT) findings of attenuated plaque detected by intravascular ultrasound (IVUS). One hundred and fifty-four patients with stable angina underwent MDCT before IVUS. The attenuated plaque was identified in the targeted artery with IVUS, and the same artery was analyzed with MDCT for the presence of a high density area (HDA) >130 Hounsfield units (HU), and a low density area (LDA) <30 HU. A HDA in attenuated plaque was compared with that in calcified plaque. Ten attenuated plaques and 15 calcified plaques were identified in 9 of 154 patients (males=9, 66.2 ± 9.5 years). Eight of the 10 attenuated plaques and all 15 calcified plaques were accompanied with a HDA on MDCT. The HDA ranged from 174 to 667 HU (mean 389.0 ± 148.3 HU) in the 8 attenuated plaques, and from 545 to 1,205 HU (mean 920.9 ± 215.9 HU) in 15 calcified plaques. There was a significant difference in CT density of the HDA between the attenuated and calcified plaque (P<0.001). All attenuated plaques contained LDA <30 HU in the portions without HDA. MDCT has the ability to demonstrate attenuated plaque as the combination of HDA (approximately 400 HU on average) and LDA <30 HU. The HDA can be differentiated from calcified plaque by its lower CT density value.

  10. A polymerase chain reaction assay for detection of virulent and attenuated strains of duck plague virus.

    PubMed

    Xie, Liji; Xie, Zhixun; Huang, Li; Wang, Sheng; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Luo, Sisi

    2017-11-01

    Sequence analysis of duck plague virus (DPV) revealed that there was a 528bp (B fragment) deletion within the UL2 gene of DPV attenuated vaccine strain in comparison with field virulent strains. The finding of gene deletion provides a potential differentiation test between DPV virulent strain and attenuated strain based on their UL2 gene sizes. Thus we developed a polymerase chain reaction (PCR) assay targeting to the DPV UL2 gene for simultaneous detection of DPV virulent strain and attenuated strain, 827bp for virulent strain and 299bp for attenuated strain. This newly developed PCR for DPV was highly sensitive and specific. It detected as low as 100fg of DNA on both DPV virulent and attenuated strains, no same size bands were amplified from other duck viruses including duck paramyxovirus, duck tembusu virus, duck circovirus, Muscovy duck parvovirus, duck hepatitis virus type I, avian influenza virus and gosling plague virus. Therefore, this PCR assay can be used for the rapid, sensitive and specific detection of DPV virulent and attenuated strains affecting ducks. Copyright © 2017. Published by Elsevier B.V.

  11. Gabor Deconvolution as Preliminary Method to Reduce Pitfall in Deeper Target Seismic Data

    NASA Astrophysics Data System (ADS)

    Oktariena, M.; Triyoso, W.

    2018-03-01

    Anelastic attenuation process during seismic wave propagation is the trigger of seismic non-stationary characteristic. An absorption and a scattering of energy are causing the seismic energy loss as the depth increasing. A series of thin reservoir layers found in the study area is located within Talang Akar Fm. Level, showing an indication of interpretation pitfall due to attenuation effect commonly occurred in deeper level seismic data. Attenuation effect greatly influences the seismic images of deeper target level, creating pitfalls in several aspect. Seismic amplitude in deeper target level often could not represent its real subsurface character due to a low amplitude value or a chaotic event nearing the Basement. Frequency wise, the decaying could be seen as the frequency content diminishing in deeper target. Meanwhile, seismic amplitude is the simple tool to point out Direct Hydrocarbon Indicator (DHI) in preliminary Geophysical study before a further advanced interpretation method applied. A quick-look of Post-Stack Seismic Data shows the reservoir associated with a bright spot DHI while another bigger bright spot body detected in the North East area near the field edge. A horizon slice confirms a possibility that the other bright spot zone has smaller delineation; an interpretation pitfall commonly occurs in deeper level of seismic. We evaluates this pitfall by applying Gabor Deconvolution to address the attenuation problem. Gabor Deconvolution forms a Partition of Unity to factorize the trace into smaller convolution window that could be processed as stationary packets. Gabor Deconvolution estimates both the magnitudes of source signature alongside its attenuation function. The enhanced seismic shows a better imaging in the pitfall area that previously detected as a vast bright spot zone. When the enhanced seismic is used for further advanced reprocessing process, the Seismic Impedance and Vp/Vs Ratio slices show a better reservoir delineation, in which the

  12. RADIO FREQUENCY ATTENUATOR

    DOEpatents

    Giordano, S.

    1963-11-12

    A high peak power level r-f attenuator that is readily and easily insertable along a coaxial cable having an inner conductor and an outer annular conductor without breaking the ends thereof is presented. Spaced first and second flares in the outer conductor face each other with a slidable cylindrical outer conductor portion therebetween. Dielectric means, such as water, contact the cable between the flares to attenuate the radio-frequency energy received thereby. The cylindrical outer conductor portion is slidable to adjust the voltage standing wave ratio to a low level, and one of the flares is slidable to adjust the attenuation level. An integral dielectric container is also provided. (AFC)

  13. Can attenuation of attentional blink also evoke removal of repetition blindness?

    PubMed

    Choi, Hoon; Watanabe, Takeo

    2014-06-01

    A recent study showed that attentional blink (AB), which has been considered to reflect the capacity limitation of visual temporal attention, can be attenuated after a short period of the color-salient training, in which the second target (T2) within the AB period is given a salient color (Choi et al., 2012). The current study explored whether the effect of the color-salient training could be transferred to another phenomenon. In addition to AB, repetition blindness (RB) was employed, which is phenomenologically similar to, but fundamentally different from AB. After completion of the color-salient training with a nonrepeated T2 (corresponding to AB), RB was still observed, whereas AB was completely removed. However, the color-salient training with a repeated T2 (similar to RB) induced not only a significant reduction of RB but also an attenuation of AB. This result provides further evidence for dissociation between AB and RB. In addition, it implies that the color-salient training improves the attentional control mechanism related to target-distractor discrimination rather than to the perceptual system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Optimization of coronary attenuation in coronary computed tomography angiography using diluted contrast material.

    PubMed

    Kawaguchi, Naoto; Kurata, Akira; Kido, Teruhito; Nishiyama, Yoshiko; Kido, Tomoyuki; Miyagawa, Masao; Ogimoto, Akiyoshi; Mochizuki, Teruhito

    2014-01-01

    The purpose of this study was to evaluate a personalized protocol with diluted contrast material (CM) for coronary computed tomography angiography (CTA). One hundred patients with suspected coronary artery disease underwent retrospective electrocardiogram-gated coronary CTA on a 256-slice multidetector-row CT scanner. In the diluted CM protocol (n=50), the optimal scan timing and CM dilution rate were determined by the timing bolus scan, with 20% CM dilution (5ml/s during 10s) being considered suitable to achieve the target arterial attenuation of 350 Hounsfield units (HU). In the body weight (BW)-adjusted protocol (n=50, 222mg iodine/kg), only the optimal scan timing was determined by the timing bolus scan. The injection rate and volume in the timing bolus scan and real scan were identical between the 2 protocols. We compared the means and variations in coronary attenuation between the 2 protocols. Coronary attenuation (mean±SD) in the diluted CM and BW-adjusted protocols was 346.1±23.9 HU and 298.8±45.2 HU, respectively. The diluted CM protocol provided significantly higher coronary attenuation and lower variance than did the BW-adjusted protocol (P<0.05, in each). The diluted CM protocol facilitates more uniform attenuation on coronary CTA in comparison with the BW-adjusted protocol.  

  15. Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.

    PubMed

    Yang, Emmy; Qian, Weiping; Cao, Zehong; Wang, Liya; Bozeman, Erica N; Ward, Christina; Yang, Bin; Selvaraj, Periasamy; Lipowska, Malgorzata; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2015-01-01

    Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.

  16. Increased expression of (immuno)proteasome subunits during epileptogenesis is attenuated by inhibition of the mammalian target of rapamycin pathway.

    PubMed

    Broekaart, Diede W M; van Scheppingen, Jackelien; Geijtenbeek, Karlijne W; Zuidberg, Mark R J; Anink, Jasper J; Baayen, Johannes C; Mühlebner, Angelika; Aronica, Eleonora; Gorter, Jan A; van Vliet, Erwin A

    2017-08-01

    Inhibition of the mammalian target of rapamycin (mTOR) pathway reduces epileptogenesis in various epilepsy models, possibly by inhibition of inflammatory processes, which may include the proteasome system. To study the role of mTOR inhibition in the regulation of the proteasome system, we investigated (immuno)proteasome expression during epileptogenesis, as well as the effects of the mTOR inhibitor rapamycin. The expression of constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits was investigated during epileptogenesis using immunohistochemistry in the electrical post-status epilepticus (SE) rat model for temporal lobe epilepsy (TLE). The effect of rapamycin was studied on (immuno)proteasome subunit expression in post-SE rats that were treated for 6 weeks. (Immuno)proteasome expression was validated in the brain tissue of patients who had SE or drug-resistant TLE and the effect of rapamycin was studied in primary human astrocyte cultures. In post-SE rats, increased (immuno)proteasome expression was detected throughout epileptogenesis in neurons and astrocytes within the hippocampus and piriform cortex and was most evident in rats that developed a progressive form of epilepsy. Rapamycin-treated post-SE rats had reduced (immuno)proteasome protein expression and a lower number of spontaneous seizures compared to vehicle-treated rats. (Immuno)proteasome expression was also increased in neurons and astrocytes within the human hippocampus after SE and in patients with drug-resistant TLE. In vitro studies using cultured human astrocytes showed that interleukin (IL)-1β-induced (immuno)proteasome gene expression could be attenuated by rapamycin. Because dysregulation of the (immuno)proteasome system is observed before the occurrence of spontaneous seizures in rats, is associated with progression of epilepsy, and can be modulated via the mTOR pathway, it may represent an interesting novel target for drug treatment in epilepsy. Wiley Periodicals, Inc. © 2017

  17. Projection-data based temporal maximum attenuation computed tomography: determination of internal target volume for lung cancer against intra-fraction motion

    NASA Astrophysics Data System (ADS)

    Mori, Shinichiro; Kanematsu, Nobuyuki; Asakura, Hiroshi; Endo, Masahiro

    2007-02-01

    The concept of internal target volume (ITV) is highly significant in radiotherapy for the lung, an organ which is hampered by organ motion. To date, different methods to obtain the ITV have been published and are therefore available. To define ITV, we developed a new method by adapting a time filter to the four-dimensional CT scan technique (4DCT) which is projection-data processing (4D projection data maximum attenuation (4DPM)), and compared it with reconstructed image processing (4D image maximum intensity projection (4DIM)) using a phantom and clinical evaluations. 4DIM and 4DPM captured accurate maximum intensity volume (MIV), that is tumour encompassing volume, easily. Although 4DIM increased the CT number 1.8 times higher than 4DPM, 4DPM provided the original tumour CT number for MIV via a reconstruction algorithm. In the patient with lung fibrosis honeycomb, the MIV with 4DIM is 0.7 cm larger than that for cine imaging in the cranio-caudal direction. 4DPM therefore provided an accurate MIV independent of patient characteristics and reconstruction conditions. These findings indicate the usefulness of 4DPM in determining ITV in radiotherapy.

  18. One registration multi-atlas-based pseudo-CT generation for attenuation correction in PET/MRI.

    PubMed

    Arabi, Hossein; Zaidi, Habib

    2016-10-01

    The outcome of a detailed assessment of various strategies for atlas-based whole-body bone segmentation from magnetic resonance imaging (MRI) was exploited to select the optimal parameters and setting, with the aim of proposing a novel one-registration multi-atlas (ORMA) pseudo-CT generation approach. The proposed approach consists of only one online registration between the target and reference images, regardless of the number of atlas images (N), while for the remaining atlas images, the pre-computed transformation matrices to the reference image are used to align them to the target image. The performance characteristics of the proposed method were evaluated and compared with conventional atlas-based attenuation map generation strategies (direct registration of the entire atlas images followed by voxel-wise weighting (VWW) and arithmetic averaging atlas fusion). To this end, four different positron emission tomography (PET) attenuation maps were generated via arithmetic averaging and VWW scheme using both direct registration and ORMA approaches as well as the 3-class attenuation map obtained from the Philips Ingenuity TF PET/MRI scanner commonly used in the clinical setting. The evaluation was performed based on the accuracy of extracted whole-body bones by the different attenuation maps and by quantitative analysis of resulting PET images compared to CT-based attenuation-corrected PET images serving as reference. The comparison of validation metrics regarding the accuracy of extracted bone using the different techniques demonstrated the superiority of the VWW atlas fusion algorithm achieving a Dice similarity measure of 0.82 ± 0.04 compared to arithmetic averaging atlas fusion (0.60 ± 0.02), which uses conventional direct registration. Application of the ORMA approach modestly compromised the accuracy, yielding a Dice similarity measure of 0.76 ± 0.05 for ORMA-VWW and 0.55 ± 0.03 for ORMA-averaging. The results of quantitative PET analysis

  19. Everolimus is better than rapamycin in attenuating neuroinflammation in kainic acid-induced seizures.

    PubMed

    Yang, Ming-Tao; Lin, Yi-Chin; Ho, Whae-Hong; Liu, Chao-Lin; Lee, Wang-Tso

    2017-01-21

    Microglia is responsible for neuroinflammation, which may aggravate brain injury in diseases like epilepsy. Mammalian target of rapamycin (mTOR) kinase is related to microglial activation with subsequent neuroinflammation. In the present study, rapamycin and everolimus, both as mTOR inhibitors, were investigated in models of kainic acid (KA)-induced seizure and lipopolysaccharide (LPS)-induced neuroinflammation. In vitro, we treated BV2 cells with KA and LPS. In vivo, KA was used to induce seizures on postnatal day 25 in B6.129P-Cx3cr1 tm1Litt /J mice. Rapamycin and everolimus were evaluated in their modulation of neuroinflammation detected by real-time PCR, Western blotting, and immunostaining. Everolimus was significantly more effective than rapamycin in inhibiting iNOS and mTOR signaling pathways in both models of neuroinflammation (LPS) and seizure (KA). Everolimus significantly attenuated the mRNA expression of iNOS by LPS and nitrite production by KA and LPS than that by rapamycin. Only everolimus attenuated the mRNA expression of mTOR by LPS and KA treatment. In the present study, we also found that the modulation of mTOR under LPS and KA treatment was not mediated by Akt pathway but was primarily mediated by ERK phosphorylation, which was more significantly attenuated by everolimus. This inhibition of ERK phosphorylation and microglial activation in the hippocampus by everolimus was also confirmed in KA-treated mice. Rapamycin and everolimus can block the activation of inflammation-related molecules and attenuated the microglial activation. Everolimus had better efficacy than rapamycin, possibly mediated by the inhibition of ERK phosphorylation. Taken together, mTOR inhibitor can be a potential pharmacological target of anti-inflammation and seizure treatment.

  20. Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model.

    PubMed

    Ohkawa, Sakae; Yanagida, Momoko; Uchikawa, Tsuyoshi; Yoshida, Takuya; Ikegaya, Naoki; Kumagai, Hiromichi

    2013-09-01

    The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model. © 2013.

  1. Plasma Parameters From Reentry Signal Attenuation

    DOE PAGES

    Statom, T. K.

    2018-02-27

    This study presents the application of a theoretically developed method that provides plasma parameter solution space information from measured RF attenuation that occurs during reentry. The purpose is to provide reentry plasma parameter information from the communication signal attenuation. The theoretical development centers around the attenuation and the complex index of refraction. The methodology uses an imaginary index of the refraction matching algorithm with a tolerance to find suitable solutions that satisfy the theory. The imaginary matching terms are then used to determine the real index of refraction resulting in the complex index of refraction. Then a filter is usedmore » to reject nonphysical solutions. Signal attenuation-based plasma parameter properties investigated include the complex index of refraction, plasma frequency, electron density, collision frequency, propagation constant, attenuation constant, phase constant, complex plasma conductivity, and electron mobility. RF plasma thickness attenuation is investigated and compared to the literature. Finally, similar plasma thickness for a specific signal attenuation can have different plasma properties.« less

  2. Plasma Parameters From Reentry Signal Attenuation

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

    Statom, T. K.

    This study presents the application of a theoretically developed method that provides plasma parameter solution space information from measured RF attenuation that occurs during reentry. The purpose is to provide reentry plasma parameter information from the communication signal attenuation. The theoretical development centers around the attenuation and the complex index of refraction. The methodology uses an imaginary index of the refraction matching algorithm with a tolerance to find suitable solutions that satisfy the theory. The imaginary matching terms are then used to determine the real index of refraction resulting in the complex index of refraction. Then a filter is usedmore » to reject nonphysical solutions. Signal attenuation-based plasma parameter properties investigated include the complex index of refraction, plasma frequency, electron density, collision frequency, propagation constant, attenuation constant, phase constant, complex plasma conductivity, and electron mobility. RF plasma thickness attenuation is investigated and compared to the literature. Finally, similar plasma thickness for a specific signal attenuation can have different plasma properties.« less

  3. Landing gear noise attenuation

    NASA Technical Reports Server (NTRS)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Abeysinghe, Amal (Inventor); Kwan, Hwa-Wan (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  4. Attenuation in gas-charged magma

    NASA Astrophysics Data System (ADS)

    Collier, L.; Neuberg, J. W.; Lensky, N.; Lyakhovsky, V.; Navon, O.

    2006-05-01

    Low frequency seismic events observed on volcanoes, such as Soufriere Hills Volcano, Montserrat, are thought to be caused by a resonating system. The modelling of seismic waves in gas-charged magma is critical for the understanding of seismic resonance effects in conduits, dykes and cracks. Seismic attenuation, which depends mainly on magma viscosity, gas and crystal content, is an essential factor in such modelling attempts. So far only two-phase gas-melt systems with the assumption of no diffusion and transport of volatiles between the melt and the gas bubbles have been considered. In this study, we develop a method of quantifying attenuation within gas-charged magma, including the effects of diffusion and exsolution of gas into the bubbles. The results show that by including such bubble growth processes attenuation levels are increased within magma. The resulting complex behaviour of attenuation with pressure and frequency indicates that two factors are controlling attenuation, the first due to viscous hindrance or the melt, and the second due diffusion processes. The level of attenuation within a gas-charged magma conduit suggests an upper limit on the length of a resonating conduit section of just a few hundred meters.

  5. Simultaneous inversion of intrinsic and scattering attenuation parameters incorporating multiple scattering effect

    NASA Astrophysics Data System (ADS)

    Ogiso, M.

    2017-12-01

    Heterogeneous attenuation structure is important for not only understanding the earth structure and seismotectonics, but also ground motion prediction. Attenuation of ground motion in high frequency range is often characterized by the distribution of intrinsic and scattering attenuation parameters (intrinsic Q and scattering coefficient). From the viewpoint of ground motion prediction, both intrinsic and scattering attenuation affect the maximum amplitude of ground motion while scattering attenuation also affect the duration time of ground motion. Hence, estimation of both attenuation parameters will lead to sophisticate the ground motion prediction. In this study, we try to estimate both parameters in southwestern Japan in a tomographic manner. We will conduct envelope fitting of seismic coda since coda has sensitivity to both intrinsic attenuation and scattering coefficients. Recently, Takeuchi (2016) successfully calculated differential envelope when these parameters have fluctuations. We adopted his equations to calculate partial derivatives of these parameters since we did not need to assume homogeneous velocity structure. Matrix for inversion of structural parameters would become too huge to solve in a straightforward manner. Hence, we adopted ART-type Bayesian Reconstruction Method (Hirahara, 1998) to project the difference of envelopes to structural parameters iteratively. We conducted checkerboard reconstruction test. We assumed checkerboard pattern of 0.4 degree interval in horizontal direction and 20 km in depth direction. Reconstructed structures well reproduced the assumed pattern in shallower part while not in deeper part. Since the inversion kernel has large sensitivity around source and stations, resolution in deeper part would be limited due to the sparse distribution of earthquakes. To apply the inversion method which described above to actual waveforms, we have to correct the effects of source and site amplification term. We consider these issues

  6. Adjustable Optical-Fiber Attenuator

    NASA Technical Reports Server (NTRS)

    Buzzetti, Mike F.

    1994-01-01

    Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

  7. Vaccination with live attenuated simian immunodeficiency virus causes dynamic changes in intestinal CD4+CCR5+ T cells

    PubMed Central

    2011-01-01

    Background Vaccination with live attenuated SIV can protect against detectable infection with wild-type virus. We have investigated whether target cell depletion contributes to the protection observed. Following vaccination with live attenuated SIV the frequency of intestinal CD4+CCR5+ T cells, an early target of wild-type SIV infection and destruction, was determined at days 3, 7, 10, 21 and 125 post inoculation. Results In naive controls, modest frequencies of intestinal CD4+CCR5+ T cells were predominantly found within the LPL TTrM-1 and IEL TTrM-2 subsets. At day 3, LPL and IEL CD4+CCR5+ TEM cells were dramatically increased whilst less differentiated subsets were greatly reduced, consistent with activation-induced maturation. CCR5 expression remained high at day 7, although there was a shift in subset balance from CD4+CCR5+ TEM to less differentiated TTrM-2 cells. This increase in intestinal CD4+CCR5+ T cells preceded the peak of SIV RNA plasma loads measured at day 10. Greater than 65.9% depletion of intestinal CD4+CCR5+ T cells followed at day 10, but overall CD4+ T cell homeostasis was maintained by increased CD4+CCR5- T cells. At days 21 and 125, high numbers of intestinal CD4+CCR5- naive TN cells were detected concurrent with greatly increased CD4+CCR5+ LPL TTrM-2 and IEL TEM cells at day 125, yet SIV RNA plasma loads remained low. Conclusions This increase in intestinal CD4+CCR5+ T cells, following vaccination with live attenuated SIV, does not correlate with target cell depletion as a mechanism of protection. Instead, increased intestinal CD4+CCR5+ T cells may correlate with or contribute to the protection conferred by vaccination with live attenuated SIV. PMID:21291552

  8. MRI-guided attenuation correction in whole-body PET/MR: assessment of the effect of bone attenuation.

    PubMed

    Akbarzadeh, A; Ay, M R; Ahmadian, A; Alam, N Riahi; Zaidi, H

    2013-02-01

    Hybrid PET/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies.

  9. miR-137 attenuates Aβ-induced neurotoxicity through inactivation of NF-κB pathway by targeting TNFAIP1 in Neuro2a cells.

    PubMed

    He, Dan; Tan, Jun; Zhang, Jiewen

    2017-08-26

    Accumulation of β-amyloid (Aβ) and neuroinflammation are implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miR-137 was aberrantly downregulated and may be associated with the pathogenesis of AD. However, the detailed function of miR-137 in AD pathogenesis and the molecular mechanism have not been elucidated. The expressions of miR-137 and tumor necrosis factor alpha (TNFα)-induced protein 1 (TNFAIP1) at mRNA and protein levels in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to different concentrations of Aβ 25-35 were examined by qRT-PCR and western blot. Luciferase reporter assay was used to confirm the potential target of miR-137. MTT assay, flow cytometry analysis, caspase-3 activity assay, Enzyme-linked immunosorbent assay (ELISA), and western blot were used to detect cell viability, apoptosis, caspase-3 activity, Nuclear factor-kappa B (NF-κB) activity and level, respectively. Aβ 25-35 downregulated miR-137 and upregulated TNFAIP1 in primary mouse cortical neurons and N2a cells. In addition, miR-137 was found to directly target TNFAIP1 and suppress its mRNA and protein levels. Moreover, miR-137 restoration and TNFAIP1 knockdown facilitate Aβ 25-35 -induced cell toxicity, apoptosis, caspase-3 activity, and activated NF-κB in N2a cells, which was partially abolished by TNFAIP1 overexpression. miR-137 attenuated Aβ-induced neurotoxicity through inactivation of NF-κB pathway by targeting TNFAIP1 in N2a cells, shedding light on the molecular mechanism of miR-137 underlying Aβ-induced neurotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Cross-species malaria immunity induced by chemically attenuated parasites

    PubMed Central

    Good, Michael F.; Reiman, Jennifer M.; Rodriguez, I. Bibiana; Ito, Koichi; Yanow, Stephanie K.; El-Deeb, Ibrahim M.; Batzloff, Michael R.; Stanisic, Danielle I.; Engwerda, Christian; Spithill, Terry; Hoffman, Stephen L.; Lee, Moses; McPhun, Virginia

    2013-01-01

    Vaccine development for the blood stages of malaria has focused on the induction of antibodies to parasite surface antigens, most of which are highly polymorphic. An alternate strategy has evolved from observations that low-density infections can induce antibody-independent immunity to different strains. To test this strategy, we treated parasitized red blood cells from the rodent parasite Plasmodium chabaudi with seco-cyclopropyl pyrrolo indole analogs. These drugs irreversibly alkylate parasite DNA, blocking their ability to replicate. After administration in mice, DNA from the vaccine could be detected in the blood for over 110 days and a single vaccination induced profound immunity to different malaria parasite species. Immunity was mediated by CD4+ T cells and was dependent on the red blood cell membrane remaining intact. The human parasite, Plasmodium falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo indole analogs. These data demonstrate that vaccination with chemically attenuated parasites induces protective immunity and provide a compelling rationale for testing a blood-stage parasite-based vaccine targeting human Plasmodium species. PMID:23863622

  11. A Compton scatter attenuation gamma ray spectrometer

    NASA Technical Reports Server (NTRS)

    Austin, W. E.

    1972-01-01

    A Compton scatter attenuation gamma ray spectrometer conceptual design is discussed for performing gamma spectral measurements in monodirectional gamma fields from 100 R per hour to 1,000,000 R per hour. Selectable Compton targets are used to scatter gamma photons onto an otherwise heavily shielded detector with changeable scattering efficiencies such that the count rate is maintained between 500 and 10,000 per second. Use of two sum-Compton coincident detectors, one for energies up to 1.5 MeV and the other for 600 keV to 10 MeV, will allow good peak to tail pulse height ratios to be obtained over the entire spectrum and reduces the neutron recoil background rate.

  12. Live attenuated tetravalent dengue vaccine.

    PubMed

    Bhamarapravati, N; Sutee, Y

    2000-05-26

    The development of a live attenuated tetravalent dengue vaccine is currently the best strategy to obtain a vaccine against dengue viruses. The Mahidol University group developed candidate live attenuated vaccines by attenuation through serial passages in certified primary cell cultures. Dengue serotype 1, 2 and 4 viruses were developed in primary dog kidney cells, whereas dengue serotype 3 was serially passaged in primary African green monkey kidney cells. Tissue culture passaged strain viruses were subjected to biological marker studies. Candidate vaccines have been tested as monovalent (single virus), bivalent (two viruses), trivalent (three viruses) and tetravalent (all four serotype viruses) vaccines in Thai volunteers. They were found to be safe and immunogenic in both adults and children. The Mahidol live attenuated dengue 2 virus was also tested in American volunteers and resulted in good immune response indistinguishable from those induced in Thai volunteers. The master seeds from the four live attenuated virus strains developed were provided to Pasteur Merieux Connaught of France for production on an industrial scale following good manufacturing practice guidelines.

  13. Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling.

    PubMed

    Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J

    2016-07-01

    The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  14. PET attenuation coefficients from CT images: experimental evaluation of the transformation of CT into PET 511-keV attenuation coefficients.

    PubMed

    Burger, C; Goerres, G; Schoenes, S; Buck, A; Lonn, A H R; Von Schulthess, G K

    2002-07-01

    The CT data acquired in combined PET/CT studies provide a fast and essentially noiseless source for the correction of photon attenuation in PET emission data. To this end, the CT values relating to attenuation of photons in the range of 40-140 keV must be transformed into linear attenuation coefficients at the PET energy of 511 keV. As attenuation depends on photon energy and the absorbing material, an accurate theoretical relation cannot be devised. The transformation implemented in the Discovery LS PET/CT scanner (GE Medical Systems, Milwaukee, Wis.) uses a bilinear function based on the attenuation of water and cortical bone at the CT and PET energies. The purpose of this study was to compare this transformation with experimental CT values and corresponding PET attenuation coefficients. In 14 patients, quantitative PET attenuation maps were calculated from germanium-68 transmission scans, and resolution-matched CT images were generated. A total of 114 volumes of interest were defined and the average PET attenuation coefficients and CT values measured. From the CT values the predicted PET attenuation coefficients were calculated using the bilinear transformation. When the transformation was based on the narrow-beam attenuation coefficient of water at 511 keV (0.096 cm(-1)), the predicted attenuation coefficients were higher in soft tissue than the measured values. This bias was reduced by replacing 0.096 cm(-1) in the transformation by the linear attenuation coefficient of 0.093 cm(-1) obtained from germanium-68 transmission scans. An analysis of the corrected emission activities shows that the resulting transformation is essentially equivalent to the transmission-based attenuation correction for human tissue. For non-human material, however, it may assign inaccurate attenuation coefficients which will also affect the correction in neighbouring tissue.

  15. Mass attenuation coefficients of several bio-adhesive based oil palm particleboards at 16.59-25.26 keV photon energies

    NASA Astrophysics Data System (ADS)

    Abdu Mustapa, U. A.; Yusof, M. F. Mohd; Hamid, P. N. K. Abd; Hashim, R.; Ahmad, M. Z.; Aziz, M. Z. Abd

    2018-01-01

    Particleboards made of oil palm with addition of polylactic acid (PLA), starch, and fish oil were fabricated with target density of 1.0 g/cm3. The mass attenuation coefficients of the particleboards were measured using x-ray fluorescence (XRF) configuration in conjunction with niobium, molybdenum, palladium and tin metal plates that provided Kα1 photon energies between 16.59 and 25.26 keV. The results were compared to the calculated value of water using XCOM. The results showed that all particleboards having mass attenuation coefficients near to the value of water with the mass attenuation coefficient different less than 0.25. The method of fabrication did not give significant different to the mass attenuation coefficients of the particleboards. The results had indicated the potential of bio-adhesive based palm oil particleboards to be developed as phantoms for low energy photons.

  16. Gas sensor with attenuated drift characteristic

    DOEpatents

    Chen, Ing-Shin [Danbury, CT; Chen, Philip S. H. [Bethel, CT; Neuner, Jeffrey W [Bethel, CT; Welch, James [Fairfield, CT; Hendrix, Bryan [Danbury, CT; Dimeo, Jr., Frank [Danbury, CT

    2008-05-13

    A sensor with an attenuated drift characteristic, including a layer structure in which a sensing layer has a layer of diffusional barrier material on at least one of its faces. The sensor may for example be constituted as a hydrogen gas sensor including a palladium/yttrium layer structure formed on a micro-hotplate base, with a chromium barrier layer between the yttrium layer and the micro-hotplate, and with a tantalum barrier layer between the yttrium layer and an overlying palladium protective layer. The gas sensor is useful for detection of a target gas in environments susceptible to generation or incursion of such gas, and achieves substantial (e.g., >90%) reduction of signal drift from the gas sensor in extended operation, relative to a corresponding gas sensor lacking the diffusional barrier structure of the invention

  17. Validation of attenuation, beam blockage, and calibration estimation methods using two dual polarization X band weather radars

    NASA Astrophysics Data System (ADS)

    Diederich, M.; Ryzhkov, A.; Simmer, C.; Mühlbauer, K.

    2011-12-01

    The amplitude a of radar wave reflected by meteorological targets can be misjudged due to several factors. At X band wavelength, attenuation of the radar beam by hydro meteors reduces the signal strength enough to be a significant source of error for quantitative precipitation estimation. Depending on the surrounding orography, the radar beam may be partially blocked when scanning at low elevation angles, and the knowledge of the exact amount of signal loss through beam blockage becomes necessary. The phase shift between the radar signals at horizontal and vertical polarizations is affected by the hydrometeors that the beam travels through, but remains unaffected by variations in signal strength. This has allowed for several ways of compensating for the attenuation of the signal, and for consistency checks between these variables. In this study, we make use of several weather radars and gauge network measuring in the same area to examine the effectiveness of several methods of attenuation and beam blockage corrections. The methods include consistency checks of radar reflectivity and specific differential phase, calculation of beam blockage using a topography map, estimating attenuation using differential propagation phase, and the ZPHI method proposed by Testud et al. in 2000. Results show the high effectiveness of differential phase in estimating attenuation, and potential of the ZPHI method to compensate attenuation, beam blockage, and calibration errors.

  18. Blockade and knock-out of CALHM1 channels attenuate ischemic brain damage.

    PubMed

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Ruiz, Asier; Chara, Juan C; Pérez-Samartín, Alberto; Marambaud, Philippe; Matute, Carlos

    2018-06-01

    Overactivation of purinergic receptors during cerebral ischemia results in a massive release of neurotransmitters, including adenosine triphosphate (ATP), to the extracellular space which leads to cell death. Some hypothetical pathways of ATP release are large ion channels, such as calcium homeostasis modulator 1 (CALHM1), a membrane ion channel that can permeate ATP. Since this transmitter contributes to postischemic brain damage, we hypothesized that CALHM1 activation may be a relevant target to attenuate stroke injury. Here, we analyzed the contribution of CALHM1 to postanoxic depolarization after ischemia in cultured neurons and in cortical slices. We observed that the onset of postanoxic currents in neurons in those preparations was delayed after its blockade with ruthenium red or silencing of Calhm1 gene by short hairpin RNA, as well as in slices from CALHM1 knockout mice. Subsequently, we used transient middle cerebral artery occlusion and found that ruthenium red, a blocker of CALHM1, or the lack of CALHM1, substantially attenuated the motor symptoms and reduced significantly the infarct volume. These results show that CALHM1 channels mediate postanoxic depolarization in neurons and brain damage after ischemia. Therefore, targeting CALHM1 may have a high therapeutic potential for treating brain damage after ischemia.

  19. The influence of CT based attenuation correction on PET/CT registration: an evaluation study

    NASA Astrophysics Data System (ADS)

    Yaniv, Ziv; Wong, Kenneth H.; Banovac, Filip; Levy, Elliot; Cleary, Kevin

    2007-03-01

    We are currently developing a PET/CT based navigation system for guidance of biopsies and radiofrequency ablation (RFA) of early stage hepatic tumors. For these procedures, combined PET/CT data can potentially improve current interventions. The diagnostic efficacy of biopsies can potentially be improved by accurately targeting the region within the tumor that exhibits the highest metabolic activity. For RFA procedures the system can potentially enable treatment of early stage tumors, targeting tumors before structural abnormalities are clearly visible on CT. In both cases target definition is based on the metabolic data (PET), and navigation is based on the spatial data (CT), making the system highly dependent upon accurate spatial alignment between these data sets. In our institute all clinical data sets include three image volumes: one CT, and two PET volumes, with and without CT-based attenuation correction. This paper studies the effect of the CT-based attenuation correction on the registration process. From comparing the pairs of registrations from five data sets we observe that the point motion magnitude difference between registrations is on the same scale as the point motion magnitude in each one of the registrations, and that visual inspection cannot identify this discrepancy. We conclude that using non-rigid registration to align the PET and CT data sets is too variable, and most likely does not provide sufficient accuracy for interventional procedures.

  20. Computer-controlled attenuator.

    PubMed

    Mitov, D; Grozev, Z

    1991-01-01

    Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

  1. A Citizen's Guide to Monitored Natural Attenuation

    EPA Pesticide Factsheets

    Citizen's Guide describing how natural attenuation relies on natural processes to decrease or attenuate concentrations of contaminants in soil and groundwater. Scientists monitor these conditions to make sure natural attenuation is working.

  2. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  3. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-11-10

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3 C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  4. Worker safety during operations with mobile attenuators.

    DOT National Transportation Integrated Search

    2013-05-01

    While most transportation agencies are very familiar with truck-mounted attenuators, trailer-mounted : attenuators are increasing in popularity. There is a concern for the level of protection that attenuators : provide for workers when they are mount...

  5. 3,3’-Diindolylmethane attenuates LPS-mediated acute liver failure by regulating miRNAs to target IRAK4 and suppress Toll-like receptor signalling

    PubMed Central

    Tomar, S; Nagarkatti, M; Nagarkatti, P S

    2015-01-01

    Background and Purpose Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. 3,3′-Diindolylmethane (DIM) is a natural plant-derived compound with anti-cancer activities. Recently, DIM has also been shown to have anti-inflammatory properties. Here, we tested the hypothesis that DIM would suppress endotoxin-induced ALF. Experimental Approach We investigated the therapeutic potential of DIM in a mouse model of D-galactosamine/Lipopolysaccharide (GalN/LPS)-induced ALF. The efficacy of DIM treatment was assessed by survival, liver histopathology, serum levels of alanine transaminase, pro-inflammatory cytokines and number of activated liver macrophages. Effects of DIM on the expression of two miRNAs, 106a and 20b, and their predicted target gene were measured by qRT-PCR and Western blotting. Effects of DIM on the release of TNF-α from RAW264.7 macrophages transfected with mimics of these miRNAs and activated by LPS was assessed by elisa. Key Results DIM treatment protected mice from ALF symptoms and reduced the number of activated liver macrophages. DIM increased expression of miR-106a and miR-20b in liver mononuclear cells and decreased expression of their predicted target gene IL-1 receptor-associated kinase 4 (IRAK4), involved in signalling from Toll-like receptor 4 (TLR4). In vitro transfection of RAW264.7 cells using miRNA mimics of miR-106a and 20b decreased expression of IRAK4 and of TNF-α secretion, following LPS stimulation. Conclusions and Implications DIM attenuated GalN/LPS-induced ALF by regulating the expression of unique miRNAs that target key molecules in the TLR4 inflammatory pathway. DIM may represent a potential novel hepatoprotective agent. PMID:25521277

  6. Attenuation of hippocampal mossy fiber long-term potentiation by low micromolar concentrations of zinc.

    PubMed

    Takeda, Atsushi; Kanno, Shingo; Sakurada, Naomi; Ando, Masaki; Oku, Naoto

    2008-10-01

    The role of zinc in long-term potentiation (LTP) at hippocampal mossy fiber synapses is controversial because of the contrary results obtained when using zinc chelators. On the basis of the postulation that exogenous zinc enhances the action of zinc released from mossy fibers, mossy fiber LTP after tetanic stimulation (100 Hz, 1 sec) was checked in the presence of exogenous zinc at low micromolar concentrations. Mossy fiber LTP was significantly attenuated in the presence of 5-30 microM ZnCl(2), and the amplitude of field excitatory postsynaptic potentials 60 min after tetanic stimulation was decreased to almost the basal level. Mossy fiber LTP was also attenuated in the presence of 5 microM ZnCl(2) 5 min after tetanic stimulation. The present study is the first to demonstrate that low micromolar concentrations of zinc attenuate mossy fiber LTP. When mossy fiber LTP was induced in the presence of CaEDTA and ZnAF-2 DA, a membrane-impermeable and a membrane-permeable zinc chelator, respectively, extracellular and intracellular chelation of zinc enhanced a transient posttetanic potentiation (PTP) without altering LTP. It is likely that zinc released by tetanic stimulation is immediately taken up into the mossy fibers and attenuates mossy fiber PTP. These results suggest that attenuation of PTP rather than LTP at mossy fiber synapses is a more physiological role for endogenous zinc. Targeting molecules of zinc in mossy fiber LTP seem to be different between during and after LTP induction because of the differential synaptic activity between them. (c) 2008 Wiley-Liss, Inc.

  7. Velocities and Attenuations of Gas Hydrate-Bearing Sediments

    USGS Publications Warehouse

    Lee, Myung W.

    2007-01-01

    Monopole and dipole logging data at the Mallik 5L-38, Mackenzie Delta, Canada, provide a challenge for sonic velocity and attenuation models used to remotely estimate pore-space gas hydrate content. Velocity and attenuation are linked, with velocity dispersion causing increased attenuation. Sonic waveforms for Mallik 5L-38, however, show no velocity dispersion in gas hydrate-bearing layers, yet are highly attenuated. Attenuation models applied to Mallik 5L-38 data are shown to be inconsistent with the observed velocity measurements, and therefore are suspect in their ability to predict gas hydrate content. A model explicitly linking velocity and attenuation data is presented, accurately predicting gas hydrate content from velocity data alone while demonstrating that the attenuation mechanisms at the Mallik 5L-38 site have not yet been identified.

  8. Comparison of high intensity focused ultrasound (HIFU) exposures using empirical and backscatter attenuation estimation methods

    NASA Astrophysics Data System (ADS)

    Civale, John; Ter Haar, Gail; Rivens, Ian; Bamber, Jeff

    2005-09-01

    Currently, the intensity to be used in our clinical HIFU treatments is calculated from the acoustic path lengths in different tissues measured on diagnostic ultrasound images of the patient in the treatment position, and published values of ultrasound attenuation coefficients. This yields an approximate value for the acoustic power at the transducer required to give a stipulated focal intensity in situ. Estimation methods for the actual acoustic attenuation have been investigated in large parts of the tissue path overlying the target volume from the backscattered ultrasound signal for each patient (backscatter attenuation estimation: BAE). Several methods have been investigated. The backscattered echo information acquired from an Acuson scanner has been used to compute the diffraction-corrected attenuation coefficient at each frequency using two methods: a substitution method and an inverse diffraction filtering process. A homogeneous sponge phantom was used to validate the techniques. The use of BAE to determine the correct HIFU exposure parameters for lesioning has been tested in ex vivo liver. HIFU lesions created with a 1.7-MHz therapy transducer have been studied using a semiautomated image processing technique. The reproducibility of lesion size for given in situ intensities determined using BAE and empirical techniques has been compared.

  9. Mode-independent attenuation in evanescent-field sensors

    NASA Astrophysics Data System (ADS)

    Gnewuch, Harald; Renner, Hagen

    1995-03-01

    Generally, the total power attenuation in multimode evanescent-field sensor waveguides is nonproportional to the bulk absorbance because the modal attenuation constants differ. Hence a direct measurement is difficult and is additionally aggravated because the waveguide absorbance is highly sensitive to the specific launching conditions at the waveguide input. A general asymptotic formula for the modal power attenuation in strongly asymmetric inhomogeneous planar waveguides with arbitrarily distributed weak absorption in the low-index superstrate is derived. Explicit expressions for typical refractive-index profiles are given. Except when very close to the cutoff, the predicted asymptotic attenuation behavior agrees well with exact calculations. The ratio of TM versus TE absorption has been derived to be (2 - n0 2/nf2 ) for arbitrary profiles. Waveguides with a linear refractive-index profile show mode-independent attenuation coefficients within each polarization. Further, the asymptotic sensitivity is independent of the wavelength, so that it should be possible to directly measure the spectral variation of the bulk absorption. The mode independence of the attenuation has been verified experimentally for a second-order polynomial profile, which is close to a linear refractive-index distribution. In contrast, the attenuation in the step-profile waveguide has been found to depend strongly on the mode number, as predicted by theory. A strong spread of the modal attenuation coefficients is also predicted for the parabolic-profile waveguide sensor.

  10. Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine.

    PubMed

    Cong, Wei; Jin, Hong; Jiang, Chengda; Yan, Weiyao; Liu, Mingqiu; Chen, Jiulian; Zuo, Xiaoping; Zheng, Zhaoxin

    2010-01-01

    In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets. These sequences are highly conserved among different serotype viruses based on sequence analysis. Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively. The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice. The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells. In suckling mice, p3D-NT56 and p2B-NT25 delayed the death of mice. Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I. We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV. We used guinea pigs to evaluate the inhibitory effects of recombinant S. cho (p3D-NT56/S. cho) on FMDV infection. The results show that 80% of guinea pigs inoculated with 10(9) CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID(50) of homologous FMDV were protected. We also measured the antiviral activity of p3D-NT56/S. cho in swine. The results indicate that 100% of the animals treated with 5 x 10(9) CFU of p3D-NT56/S. cho were protected in 9 days. INRA, EDP Sciences, 2010.

  11. Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine

    PubMed Central

    Cong, Wei; Jin, Hong; Jiang, Chengda; Yan, Weiyao; Liu, Mingqiu; Chen, Jiulian; Zuo, Xiaoping; Zheng, Zhaoxin

    2010-01-01

    In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets. These sequences are highly conserved among different serotype viruses based on sequence analysis. Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively. The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice. The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells. In suckling mice, p3D-NT56 and p2B-NT25 delayed the death of mice. Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I. We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV. We used guinea pigs to evaluate the inhibitory effects of recombinant S. cho (p3D-NT56/S. cho) on FMDV infection. The results show that 80% of guinea pigs inoculated with 109 CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID50 of homologous FMDV were protected. We also measured the antiviral activity of p3D-NT56/S. cho in swine. The results indicate that 100% of the animals treated with 5 × 109 CFU of p3D-NT56/S. cho were protected in 9 days. PMID:20167192

  12. Traffic Noise Ground Attenuation Algorithm Evaluation

    NASA Astrophysics Data System (ADS)

    Herman, Lloyd Allen

    The Federal Highway Administration traffic noise prediction program, STAMINA 2.0, was evaluated for its accuracy. In addition, the ground attenuation algorithm used in the Ontario ORNAMENT method was evaluated to determine its potential to improve these predictions. Field measurements of sound levels were made at 41 sites on I-440 in Nashville, Tennessee in order to both study noise barrier effectiveness and to evaluate STAMINA 2.0 and the performance of the ORNAMENT ground attenuation algorithm. The measurement sites, which contain large variations in terrain, included several cross sections. Further, all sites contain some type of barrier, natural or constructed, which could more fully expose the strength and weaknesses of the ground attenuation algorithms. The noise barrier evaluation was accomplished in accordance with American National Standard Methods for Determination of Insertion Loss of Outdoor Noise Barriers which resulted in an evaluation of this standard. The entire 7.2 mile length of I-440 was modeled using STAMINA 2.0. A multiple run procedure was developed to emulate the results that would be obtained if the ORNAMENT algorithm was incorporated into STAMINA 2.0. Finally, the predicted noise levels based on STAMINA 2.0 and STAMINA with the ORNAMENT ground attenuation algorithm were compared with each other and with the field measurements. It was found that STAMINA 2.0 overpredicted noise levels by an average of over 2 dB for the receivers on I-440, whereas, the STAMINA with ORNAMENT ground attenuation algorithm overpredicted noise levels by an average of less than 0.5 dB. The mean errors for the two predictions were found to be statistically different from each other, and the mean error for the prediction with the ORNAMENT ground attenuation algorithm was not found to be statistically different from zero. The STAMINA 2.0 program predicts little, if any, ground attenuation for receivers at typical first-row distances from highways where noise barriers

  13. Light attenuation characteristics of glacially-fed lakes

    NASA Astrophysics Data System (ADS)

    Rose, Kevin C.; Hamilton, David P.; Williamson, Craig E.; McBride, Chris G.; Fischer, Janet M.; Olson, Mark H.; Saros, Jasmine E.; Allan, Mathew G.; Cabrol, Nathalie

    2014-07-01

    Transparency is a fundamental characteristic of aquatic ecosystems and is highly responsive to changes in climate and land use. The transparency of glacially-fed lakes may be a particularly sensitive sentinel characteristic of these changes. However, little is known about the relative contributions of glacial flour versus other factors affecting light attenuation in these lakes. We sampled 18 glacially-fed lakes in Chile, New Zealand, and the U.S. and Canadian Rocky Mountains to characterize how dissolved absorption, algal biomass (approximated by chlorophyll a), water, and glacial flour contributed to attenuation of ultraviolet radiation (UVR) and photosynthetically active radiation (PAR, 400-700 nm). Variation in attenuation across lakes was related to turbidity, which we used as a proxy for the concentration of glacial flour. Turbidity-specific diffuse attenuation coefficients increased with decreasing wavelength and distance from glaciers. Regional differences in turbidity-specific diffuse attenuation coefficients were observed in short UVR wavelengths (305 and 320 nm) but not at longer UVR wavelengths (380 nm) or PAR. Dissolved absorption coefficients, which are closely correlated with diffuse attenuation coefficients in most non-glacially-fed lakes, represented only about one quarter of diffuse attenuation coefficients in study lakes here, whereas glacial flour contributed about two thirds across UVR and PAR. Understanding the optical characteristics of substances that regulate light attenuation in glacially-fed lakes will help elucidate the signals that these systems provide of broader environmental changes and forecast the effects of climate change on these aquatic ecosystems.

  14. Crustal structure of the Alps as seen by attenuation tomography

    NASA Astrophysics Data System (ADS)

    Mayor, Jessie; Calvet, Marie; Margerin, Ludovic; Vanderhaeghe, Olivier; Traversa, Paola

    2016-04-01

    We develop a simple tomographic approach exploiting the decay rate of coda waves to map the absorption properties of the crust in a region delimited approximately by the Rhine Graben to the North, the Apennines to the South, the Massif Central to the West and the Dinarides to the East. Our dataset comprises 40 000 coda records of about 2000 weak to moderate crustal earthquakes, with magnitude ranging from 2.8 to 6 and recorded by broad-band, accelerometric and short-period stations. After proper choice of a coda window minimizing the effects of variable epicentral distances, we measure the coda quality factor Qc in five non-overlapping frequency windows covering the 1-32 Hz band for all available source station pairs. These measurements are subsequently converted into maps of absorption quality factor (Qi) using a linearized, approximate relation between Qc and Qi. In practice the following procedure is applied in each frequency band: (1) we divide the target region into 40 × 40 km cells; (2) for each source-station pair, we assign the measured Qc value to each pixel intercepted by the direct ray path; (3) the results are averaged over all paths and subsequently smoothed with a 3 × 3 pixels moving window. Our approach is consistent with the high sensitivity of Qc to the value of Qi between source and station. Our tomographic approach reveals strong lateral variations of absorption with length scales ranging from 100 km to 1000 km. At low frequency (∼ 1 Hz), the correlation with the surface geology is clear, Cenozoic and Mesozoic sedimentary basins (resp. crystalline massifs) being recognized as high (resp. low)-absorption regions. Furthermore the Qi map delineates finer geological features such as the Ivrea Body, the Rhône Valley, or felsic intrusions in the central Alps. At high-frequency (>16 Hz), only the thickest Cenozoic sedimentary deposits show up as high-attenuation regions and a north/south dichotomy is apparent in the absorption structure. The limit

  15. Pressure-dependent attenuation with microbubbles at low mechanical index.

    PubMed

    Tang, Meng-Xing; Eckersley, Robert J; Noble, J Alison

    2005-03-01

    It has previously been shown that the attenuation of ultrasound (US) by microbubble contrast agents is dependent on acoustic pressure (Chen et al. 2002). Although previous studies have modelled the pressure-dependence of attenuation in single bubbles, this paper investigates this subject by considering a bulk volume of bubbles together with other linear attenuators. Specifically, a new pressure-dependent attenuation model for an inhomogeneous volume of attenuators is proposed. In this model, the effect of the attenuation on US propagation is considered. The model was validated using experimental measurements on the US contrast agent Sonovue. The results indicate, at low acoustic pressures, a linear relationship between the attenuation of Sonovue, measured in dB, and the insonating acoustic pressure.

  16. The Dipeptidyl Peptidases 4, 8, and 9 in Mouse Monocytes and Macrophages: DPP8/9 Inhibition Attenuates M1 Macrophage Activation in Mice.

    PubMed

    Waumans, Yannick; Vliegen, Gwendolyn; Maes, Lynn; Rombouts, Miche; Declerck, Ken; Van Der Veken, Pieter; Vanden Berghe, Wim; De Meyer, Guido R Y; Schrijvers, Dorien; De Meester, Ingrid

    2016-02-01

    Atherosclerosis remains the leading cause of death in Western countries. Dipeptidyl peptidase (DPP) 4 has emerged as a novel target for the prevention and treatment of atherosclerosis. Family members DPP8 and 9 are abundantly present in macrophage-rich regions of atherosclerotic plaques, and DPP9 inhibition attenuates activation of human M1 macrophages in vitro. Studying this family in a mouse model for atherosclerosis would greatly advance our knowledge regarding their potential as therapeutic targets. We found that DPP4 is downregulated during mouse monocyte-to-macrophage differentiation. DPP8 and 9 expression seems relatively low in mouse monocytes and macrophages. Viability of primary mouse macrophages is unaffected by DPP4 or DPP8/9 inhibition. Importantly, DPP8/9 inhibition attenuates macrophage activation as IL-6 secretion is significantly decreased. Mouse macrophages respond similarly to DPP inhibition, compared to human macrophages. This shows that the mouse could become a valid model species for the study of DPPs as therapeutic targets in atherosclerosis.

  17. Extrinsic Versus Intrinsic Seismic Anisotropy and Attenuation

    NASA Astrophysics Data System (ADS)

    Montagner, J. P.; Ricard, Y. R.; Capdeville, Y.; Bodin, T.; Wang, N.

    2015-12-01

    The apparent large scale anisotropy is the mixing of intrinsic anisotropic minerals (LPO) and extrinsic anisotropy due to materials with fine layering, fluid inclusions, cracks (SPO) . The same issue arises for attenuation (with many different anelastic processes). The proportion of extrinsic and intrinsic anisotropy and attenuation in the Earth mantle is still an open question. The interpretation of observations of seismic anisotropy and attenuation is the subject of controversies and often contradictory according to their intrinsic or extrinsic nature. Fine layering is a good candidate for explaining at the same time a large part of observed radial anisotropy (Wang et al., Geophys. Res. Lett., 2013) and attenuation (Ricard et al., Earth Planet. Sci. Lett., 2014). A plausible model of mixing of materials in a chaotic convecting fluid creates a spectrum of heterogeneity varying like 1/k (k wavenumber of the heterogeneity). A body wave propagating in a finely layered medium will be scattered and its distorted waveform can be interpreted as due to attenuation with a quality factor Q. We showed that, with the specific 1/k spectrum and only 6-9% RMS heterogeneity, the resulting apparent attenuation Q is frequency independent. Aggregates of randomly orientated anisotropic minerals are good candidates for giving rise to this extrinsic apparent attenuation. The relationship for a 1/k spectrum with apparent seismic anisotropy is also explored.

  18. Spinal activation of alpha7-nicotinic acetylcholine receptor attenuates posttraumatic stress disorder-related chronic pain via suppression of glial activation.

    PubMed

    Sun, Rao; Zhang, Wei; Bo, Jinhua; Zhang, Zuoxia; Lei, Yishan; Huo, Wenwen; Liu, Yue; Ma, Zhengliang; Gu, Xiaoping

    2017-03-06

    The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain. The experiments were conducted in a rat model of single prolonged stress (SPS), an established model of PTSD-pain comorbidity. We found that SPS exposure produced persistent mechanical allodynia. Immunohistochemical and enzyme-linked immuno sorbent assay analysis showed that SPS also induced elevated activation of glia cells (including microglia and astrocytes) and accumulation of pro-inflammatory cytokines in spinal cord. In another experiment, we found that intrathecal injection of PHA-543613, a selective α7 nAchR agonist, attenuated the SPS-evoked allodynia in a dose dependent manner. However, this anti-hyperalgesic effect was blocked by pretreatment with methyllycaconitine (MLA), a selective α7 nAchR antagonist. Further analyses showed that PHA-543613 suppressed SPS-induced spinal glial activation and SPS-elevated spinal pro-inflammatory cytokines, and these were abolished by MLA. Taken together, the present study showed that spinal activation of α7 nAChR by PHA-543613 attenuated mechanical allodynia induced by PTSD-like stress, and the suppression of spinal glial activation may underlie this anti-hyperalgesic effect. Our study demonstrated the therapeutic potential of targeting α7 nAChR in the treatment of PTSD-related chronic pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Muscarinic receptor M4 positive allosteric modulators attenuate central effects of cocaine.

    PubMed

    Dall, Camilla; Weikop, Pia; Dencker, Ditte; Molander, Anna C; Wörtwein, Gitta; Conn, P Jeffrey; Fink-Jensen, Anders; Thomsen, Morgane

    2017-07-01

    Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the hypothesis that specific muscarinic M 4 receptor stimulation can attenuate the discriminative stimulus effects and conditioned rewarding effects of cocaine, measures believed to predict the ability of cocaine and cocaine-associated cues to elicit relapse to drug taking. We tested the M 4 -selective positive allosteric modulators VU0152100 and VU0467154 in a drug discrimination assay and a conditioned place preference assay, including extinction and reinstatement of place preference. Specificity of the cocaine discrimination effect was verified using knockout mice lacking either M 1 or M 4 receptors (M 1 -/- , M 4 -/- ). We also replicated previous findings in cocaine-induced locomotor hyperactivity and striatal dopamine microdialysis assays. VU0152100 attenuated the discriminative stimulus effect of cocaine in wild-type mice and M 1 -/- mice, but not in M 4 -/- mice, without affecting rates of responding. As previously shown with VU0152100, VU0467154 almost eliminated cocaine-induced hyperactivity and striatal dopamine efflux. VU0467154 failed to attenuate acquisition of cocaine-conditioned place preference, but facilitated extinction and prevented reinstatement of the conditioned place preference. These findings further support the notion that M 4 receptors are promising targets for the treatment of cocaine addiction, by showing that results can be replicated using distinct ligands, and that in addition to blocking reinforcing effects of cocaine relevant to ongoing drug taking, M 4 positive allosteric modulators can also attenuate subjective and conditioned effects relevant to relapse. Copyright © 2017. Published by Elsevier B.V.

  20. Targeting polyamine metabolism for cancer therapy and prevention

    PubMed Central

    Murray-Stewart, Tracy R.; Woster, Patrick M.; Casero, Robert A.

    2017-01-01

    The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. PMID:27679855

  1. Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis.

    PubMed

    Wu, Mei-Ping; Zhang, Yi-Shuai; Xu, Xiangbin; Zhou, Qian; Li, Jian-Dong; Yan, Chen

    2017-04-01

    Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling.

  2. Is non-attenuation-corrected PET inferior to body attenuation-corrected PET or PET/CT in lung cancer?

    NASA Astrophysics Data System (ADS)

    Maintas, Dimitris; Houzard, Claire; Ksyar, Rachid; Mognetti, Thomas; Maintas, Catherine; Scheiber, Christian; Itti, Roland

    2006-12-01

    It is considered that one of the great strengths of PET imaging is the ability to correct for body attenuation. This enables better lesion uptake quantification and quality of PET images. The aim of this work is to compare the sensitivity of non-attenuation-corrected (NAC) PET images, the gamma photons (GPAC) and CT attenuation-corrected (CTAC) images in detecting and staging of lung cancer. We have studied 66 patients undergoing PET/CT examinations for detecting and staging NSC lung cancer. The patients were injected with 18-FDG; 5 MBq/kg under fasting conditions and examination was started 60 min later. Transmission data were acquired by a spiral CT X-ray tube and by gamma photons emitting Cs-137l source and were used for the patient body attenuation correction without correction for respiratory motion. In 55 of 66 patients we performed both attenuation correction procedures and in 11 patients only CT attenuation correction. In seven patients with solitary nodules PET was negative and in 59 patients with lung cancer PET/CT was positive for pulmonary or other localization. In the group of 55 patients we found 165 areas of focal increased 18-FDG uptake in NAC, 165 in CTAC and 164 in GPAC PET images.In the patients with only CTAC we found 58 areas of increased 18-FDG uptake on NAC and 58 areas lesions on CTAC. In the patients with positive PET we found 223 areas of focal increased uptake in NAC and 223 areas in CTAC images. The sensitivity of NAC was equal to the sensitivity of CTAC and GPAC images. The visualization of peripheral lesions was better in NAC images and the lesions were better localized in attenuation-corrected images. In three lesions of the thorax the localization was better in GPAC and fused images than in CTAC images.

  3. General relationships between ultrasonic attenuation and dispersion

    NASA Technical Reports Server (NTRS)

    Odonnell, M.; Jaynes, E. T.; Miller, J. G.

    1978-01-01

    General relationships between the ultrasonic attenuation and dispersion are presented. The validity of these nonlocal relationships hinges only on the properties of causality and linearity, and does not depend upon details of the mechanism responsible for the attenuation and dispersion. Approximate, nearly local relationships are presented and are demonstrated to predict accurately the ultrasonic dispersion in solutions of hemoglobin from the results of attenuation measurements.

  4. Skull's acoustic attenuation and dispersion modeling on photoacoustic signal

    NASA Astrophysics Data System (ADS)

    Mohammadi, Leila; Behnam, Hamid; Tavakkoli, Jahan; Nasiriavanaki, Mohammadreza

    2018-02-01

    Despite the promising results of the recent novel transcranial photoacoustic (PA) brain imaging technology, it has been demonstrated that the presence of the skull severely affects the performance of this imaging modality. We theoretically investigate the effects of acoustic heterogeneity induced by skull on the PA signals generated from single particles, with firstly developing a mathematical model for this phenomenon and then explore experimental validation of the results. The model takes into account the frequency dependent attenuation and dispersion effects occur with wave reflection, refraction and mode conversion at the skull surfaces. Numerical simulations based on the developed model are performed for calculating the propagation of photoacoustic waves through the skull. The results show a strong agreement between simulation and ex-vivo study. The findings are as follow: The thickness of the skull is the most PA signal deteriorating factor that affects both its amplitude (attenuation) and phase (distortion). Also we demonstrated that, when the depth of target region is low and it is comparable to the skull thickness, however, the skull-induced distortion becomes increasingly severe and the reconstructed image would be strongly distorted without correcting these effects. It is anticipated that an accurate quantification and modeling of the skull transmission effects would ultimately allow for aberration correction in transcranial PA brain imaging.

  5. Perceptibility curve test for digital radiographs before and after correction for attenuation and correction for attenuation and visual response.

    PubMed

    Li, G; Welander, U; Yoshiura, K; Shi, X-Q; McDavid, W D

    2003-11-01

    Two digital image processing methods, correction for X-ray attenuation and correction for attenuation and visual response, have been developed. The aim of the present study was to compare digital radiographs before and after correction for attenuation and correction for attenuation and visual response by means of a perceptibility curve test. Radiographs were exposed of an aluminium test object containing holes ranging from 0.03 mm to 0.30 mm with increments of 0.03 mm. Fourteen radiographs were exposed with the Dixi system (Planmeca Oy, Helsinki, Finland) and twelve radiographs were exposed with the F1 iOX system (Fimet Oy, Monninkylä, Finland) from low to high exposures covering the full exposure ranges of the systems. Radiographs obtained from the Dixi and F1 iOX systems were 12 bit and 8 bit images, respectively. Original radiographs were then processed for correction for attenuation and correction for attenuation and visual response. Thus, two series of radiographs were created. Ten viewers evaluated all the radiographs in the same random order under the same viewing conditions. The object detail having the lowest perceptible contrast was recorded for each observer. Perceptibility curves were plotted according to the mean of observer data. The perceptibility curves for processed radiographs obtained with the F1 iOX system are higher than those for originals in the exposure range up to the peak, where the curves are basically the same. For radiographs exposed with the Dixi system, perceptibility curves for processed radiographs are higher than those for originals for all exposures. Perceptibility curves show that for 8 bit radiographs obtained from the F1 iOX system, the contrast threshold was increased in processed radiographs up to the peak, while for 12 bit radiographs obtained with the Dixi system, the contrast threshold was increased in processed radiographs for all exposures. When comparisons were made between radiographs corrected for attenuation and

  6. Light attenuation in estuarine mangrove lakes

    NASA Astrophysics Data System (ADS)

    Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.

    2017-01-01

    Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (<2 m depth) mangrove-surrounded lakes in two sub-estuaries in the coastal Everglades, Florida USA. Turbidity, chromophoric dissolved organic matter (CDOM), and phytoplankton chlorophyll a (chl a) were measured concurrently and their respective contributions to the light attenuation rate were estimated. Light transmission to the benthos relative to literature estimates of minimum requirements for SAV growth indicated that the underwater light environment was often unsuitable for SAV. Light attenuation rates (n = 417) corrected for solar elevation angles ranged from 0.16 m-1 to 9.83 m-1 with a mean of 1.73 m-1. High concentrations of CDOM with high specific light absorption contributed the most to light attenuation followed by turbidity and chl a. CDOM alone sufficiently reduces light transmission beyond the estimated limits for SAV growth, making it difficult for ecosystem managers to increase SAV abundance by management activities. Light limitation of SAV in these areas may be a persistent feature because of their proximity to CDOM source materials from the surrounding mangrove swamp. Increasing freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

  7. LONG TERM MONITORING FOR NATURAL ATTENUATION

    EPA Science Inventory

    We have good statistical methods to: (1) determine whether concentrations of a contaminant are attenuating over time, (2) determine the rate of attenuation and confidence interval on the rate, and (3) determine whether concentrations have met a particular clean up goal. We do no...

  8. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

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

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzedmore » effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.« less

  9. DNA-launched live-attenuated vaccines for biodefense applications

    PubMed Central

    Pushko, Peter; Lukashevich, Igor S.; Weaver, Scott C.; Tretyakova, Irina

    2016-01-01

    Summary A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses. PMID:27055100

  10. Multispectral infrared target detection: phenomenology and modeling

    NASA Astrophysics Data System (ADS)

    Cederquist, Jack N.; Rogne, Timothy J.; Schwartz, Craig R.

    1993-10-01

    Many targets of interest provide only very small signature differences from the clutter background. The ability to detect these small difference targets should be improved by using data which is diverse in space, time, wavelength or some other observable. Target materials often differ from background materials in the variation of their reflectance or emittance with wavelength. A multispectral sensor is therefore considered as a means to improve detection of small signal targets. If this sensor operates in the thermal infrared, it will not need solar illumination and will be useful at night as well as during the day. An understanding of the phenomenology of the spectral properties of materials and an ability to model and simulate target and clutter signatures is needed to understand potential target detection performance from multispectral infrared sensor data. Spectral variations in material emittance are due to vibrational energy transitions in molecular bonds. The spectral emittances of many materials of interest have been measured. Examples are vegetation, soil, construction and road materials, and paints. A multispectral infrared signature model has been developed which includes target and background temperature and emissivity, sky, sun, cloud and background irradiance, multiple reflection effects, path radiance, and atmospheric attenuation. This model can be used to predict multispectral infrared signatures for small signal targets.

  11. Attenuation correction in 4D-PET using a single-phase attenuation map and rigidity-adaptive deformable registration

    PubMed Central

    Kalantari, Faraz; Wang, Jing

    2017-01-01

    Purpose Four-dimensional positron emission tomography (4D-PET) imaging is a potential solution to the respiratory motion effect in the thoracic region. Computed tomography (CT)-based attenuation correction (AC) is an essential step toward quantitative imaging for PET. However, due to the temporal difference between 4D-PET and a single attenuation map from CT, typically available in routine clinical scanning, motion artifacts are observed in the attenuation-corrected PET images, leading to errors in tumor shape and uptake. We introduced a practical method to align single-phase CT with all other 4D-PET phases for AC. Methods A penalized non-rigid Demons registration between individual 4D-PET frames without AC provides the motion vectors to be used for warping single-phase attenuation map. The non-rigid Demons registration was used to derive deformation vector fields (DVFs) between PET matched with the CT phase and other 4D-PET images. While attenuated PET images provide useful data for organ borders such as those of the lung and the liver, tumors cannot be distinguished from the background due to loss of contrast. To preserve the tumor shape in different phases, an ROI-covering tumor was excluded from non-rigid transformation. Instead the mean DVF of the central region of the tumor was assigned to all voxels in the ROI. This process mimics a rigid transformation of the tumor along with a non-rigid transformation of other organs. A 4D-XCAT phantom with spherical lung tumors, with diameters ranging from 10 to 40 mm, was used to evaluate the algorithm. The performance of the proposed hybrid method for attenuation map estimation was compared to 1) the Demons non-rigid registration only and 2) a single attenuation map based on quantitative parameters in individual PET frames. Results Motion-related artifacts were significantly reduced in the attenuation-corrected 4D-PET images. When a single attenuation map was used for all individual PET frames, the normalized root mean

  12. Natural Attenuation of Persistent Chemical Warfare Agent VX ...

    EPA Pesticide Factsheets

    Report Natural attenuation of persistent CWAs such as VX was investigated and occurs, given sufficient time (days to weeks). Natural attenuation was found to be faster at warmer temperatures (i.e., 35 °C and 25 °C) than cooler temperatures (i.e., 10 °C). Attenuation of VX was material dependent with a general trend of faster to slower attenuation in the order ceramic tile - galvanized metal - silanized glass - painted drywall. Trace amounts of VX may still be present weeks to months after a contamination event.

  13. Calculation Of Pneumatic Attenuation In Pressure Sensors

    NASA Technical Reports Server (NTRS)

    Whitmore, Stephen A.

    1991-01-01

    Errors caused by attenuation of air-pressure waves in narrow tubes calculated by method based on fundamental equations of flow. Changes in ambient pressure transmitted along narrow tube to sensor. Attenuation of high-frequency components of pressure wave calculated from wave equation derived from Navier-Stokes equations of viscous flow in tube. Developed to understand and compensate for frictional attenuation in narrow tubes used to connect aircraft pressure sensors with pressure taps on affected surfaces.

  14. Tick Passage Results in Enhanced Attenuation of Babesia bovis

    PubMed Central

    McElwain, Terry F.; Ueti, Massaro W.; Scoles, Glen A.; Reif, Kathryn E.; Lau, Audrey O. T.

    2014-01-01

    Serial blood passage of virulent Babesia bovis in splenectomized cattle results in attenuated derivatives that do not cause neurologic disease. Tick transmissibility can be lost with attenuation, but when retained, attenuated B. bovis can revert to virulence following tick passage. This study provides data showing that tick passage of the partially attenuated B. bovis T2Bo derivative strain further decreased virulence compared with intravenous inoculation of the same strain in infected animals. Ticks that acquired virulent or attenuated parasites by feeding on infected cattle were transmission fed on naive, splenectomized animals. While there was no significant difference between groups in the number of parasites in the midgut, hemolymph, or eggs of replete female ticks after acquisition feeding, animals infected with the attenuated parasites after tick transmission showed no clinical signs of babesiosis, unlike those receiving intravenous challenge with the same attenuated strain prior to tick passage. Additionally, there were significantly fewer parasites in blood and tissues of animals infected with tick-passaged attenuated parasites. Sequencing analysis of select B. bovis genes before and after tick passage showed significant differences in parasite genotypes in both peripheral blood and cerebral samples. These results provide evidence that not only is tick transmissibility retained by the attenuated T2Bo strain, but also it results in enhanced attenuation and is accompanied by expansion of parasite subpopulations during tick passage that may be associated with the change in disease phenotype. PMID:25114111

  15. Selective Blockade of Herpesvirus Entry Mediator–B and T Lymphocyte Attenuator Pathway Ameliorates Acute Graft-versus-Host Reaction

    PubMed Central

    del Rio, Maria-Luisa; Jones, Nick D.; Buhler, Leo; Norris, Paula; Shintani, Yasushi; Ware, Carl F.; Rodriguez-Barbosa, Jose-Ignacio

    2013-01-01

    The cosignaling network mediated by the herpesvirus entry mediator (HVEM; TNFRSF14) functions as a dual directional system that involves proinflammatory ligand, lymphotoxin that exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT; TNFSF14), and the inhibitory Ig family member B and T lymphocyte attenuator (BTLA). To dissect the differential contributions of HVEM/BTLA and HVEM/LIGHT interactions, topographically-specific, competitive, and nonblocking anti-HVEM Abs that inhibit BTLA binding, but not LIGHT, were developed. We demonstrate that a BTLA-specific competitor attenuated the course of acute graft-versus-host reaction in a murine F1 transfer semiallogeneic model. Selective HVEM/BTLA blockade did not inhibit donor T cell infiltration into graft-versus-host reaction target organs, but decreased the functional activity of the alloreactive T cells. These results highlight the critical role of HVEM/BTLA pathway in the control of the allogeneic immune response and identify a new therapeutic target for transplantation and autoimmune diseases. PMID:22490863

  16. Seismic attenuation system for a nuclear reactor

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

    Liszkai, Tamas; Cadell, Seth

    A system for attenuating seismic forces includes a reactor pressure vessel containing nuclear fuel and a containment vessel that houses the reactor pressure vessel. Both the reactor pressure vessel and the containment vessel include a bottom head. Additionally, the system includes a base support to contact a support surface on which the containment vessel is positioned in a substantially vertical orientation. An attenuation device is located between the bottom head of the reactor pressure vessel and the bottom head of the containment vessel. Seismic forces that travel from the base support to the reactor pressure vessel via the containment vesselmore » are attenuated by the attenuation device in a direction that is substantially lateral to the vertical orientation of the containment vessel.« less

  17. Heating of solid targets with laser pulses

    NASA Technical Reports Server (NTRS)

    Bechtel, J. H.

    1975-01-01

    Analytical and numerical solutions to the heat-conduction equation are obtained for the heating of absorbing media with pulsed lasers. The spatial and temporal form of the temperature is determined using several different models of the laser irradiance. Both surface and volume generation of heat are discussed. It is found that if the depth of thermal diffusion for the laser-pulse duration is large compared to the optical-attenuation depth, the surface- and volume-generation models give nearly identical results. However, if the thermal-diffusion depth for the laser-pulse duration is comparable to or less than the optical-attenuation depth, the surface-generation model can give significantly different results compared to the volume-generation model. Specific numerical results are given for a tungsten target irradiated by pulses of different temporal durations and the implications of the results are discussed with respect to the heating of metals by picosecond laser pulses.

  18. Mass attenuation coefficient of tannin-added Rhizophora spp. particleboards at 16.59-25.56 keV photons, and 137Cs and 60Co gamma energies.

    PubMed

    Yusof, Mohd Fahmi Mohd; Hamid, Puteri Nor Khatijah Abd; Tajuddin, Abd Aziz; Hashim, Rokiah; Bauk, Sabar; Isa, Norriza Mohd; Isa, Muhammad Jamal Md

    2017-09-01

    The aim of this study was to determine the suitability of tannin-added Rhizophora spp. particleboards as phantom materials in the application of low- and high-energy photons. The tannin-added Rhizophora spp. particleboards and density plug phantoms were created with a target density of 1.0 g/cm 3 . The elemental composition and effective atomic number of the particleboards were measured using energy dispersive X-ray analysis. The mass attenuation coefficient of the particleboards for low-energy photons were measured using the attenuation of X-ray fluorescence. The mass attenuation coefficients of high-energy photons were measured using the attenuation of 137 Cs and 60 Co gamma energies. The results were compared to the calculated value of water using XCOM calculations. The results showed that the effective atomic number and mass attenuation coefficients of tannin-added Rhizophora spp. particleboards were similar to those of water, indicating the suitability of tannin-added Rhizophora spp. particleboards as phantom materials for low- and high-energy photons.

  19. Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes

    PubMed Central

    Issaenko, Olga A.; Amerik, Alexander Yu

    2012-01-01

    The ubiquitin-proteasome system (UPS) is usurped by many if not all cancers to regulate their survival, proliferation, invasion, angiogenesis and metastasis. Bioflavonoids curcumin and chalcones exhibit anti-neoplastic selectivity through inhibition of the 26S proteasome-activity within the UPS. Here, we provide evidence for a novel mechanism of action of chalcone-based derivatives AM146, RA-9 and RA-14, which exert anticancer activity by targeting deubiquitinating enzymes (DUB) without affecting 20S proteasome catalytic-core activity. The presence of the α,β-unsaturated carbonyl group susceptible to nucleophilic attack from the sulfhydryl of cysteines in the active sites of DUB determines the capacity of novel small-molecules to act as cell-permeable, partly selective DUB inhibitors and induce rapid accumulation of polyubiquitinated proteins and deplete the pool of free ubiquitin. These chalcone-derivatives directly suppress activity of DUB UCH-L1, UCH-L3, USP2, USP5 and USP8, which are known to regulate the turnover and stability of key regulators of cell survival and proliferation. Inhibition of DUB-activity mediated by these compounds downregulates cell-cycle promoters, e.g., cyclin D1 and upregulates tumor suppressors p53, p27Kip1 and p16Ink4A. These changes are associated with arrest in S-G2/M, abrogated anchorage-dependent growth and onset of apoptosis in breast, ovarian and cervical cancer cells without noticeable alterations in primary human cells. Altogether, this work provides evidence of antitumor activity of novel chalcone-based derivatives mediated by their DUB-targeting capacity; supports the development of pharmaceuticals to directly target DUB as a most efficient strategy compared with proteasome inhibition and also provides a clear rationale for the clinical evaluation of these novel small-molecule DUB inhibitors. PMID:22510564

  20. Electron Effective-Attenuation-Length Database

    National Institute of Standards and Technology Data Gateway

    SRD 82 NIST Electron Effective-Attenuation-Length Database (PC database, no charge)   This database provides values of electron effective attenuation lengths (EALs) in solid elements and compounds at selected electron energies between 50 eV and 2,000 eV. The database was designed mainly to provide EALs (to account for effects of elastic-eletron scattering) for applications in surface analysis by Auger-electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS).

  1. Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer

    PubMed Central

    Seshacharyulu, Parthasarathy; Ponnusamy, Moorthy P.; Rachagani, Satyanarayana; Lakshmanan, Imayavaramban; Haridas, Dhanya; Yan, Ying; Ganti, Apar K.; Batra, Surinder K.

    2015-01-01

    Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, migration and survival of pancreatic cancer cells by attenuation of signaling events including pERK1/2 (T202/Y204), cyclin D1, cyclin A, pFAK (Y925) and pAKT (Ser473). Using in vivo bioluminescent imaging, we demonstrated that canertinib treatment significantly reduced tumor burden (P=0.0164) and metastasis to various organs. Further, reduced expression of MUC4 and EGFR family members were confirmed in xenografts. Our results for the first time demonstrated the targeting of EGFR family members along with MUC4 by using pan-EGFR inhibitors. In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer. PMID:25686822

  2. Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer.

    PubMed

    Seshacharyulu, Parthasarathy; Ponnusamy, Moorthy P; Rachagani, Satyanarayana; Lakshmanan, Imayavaramban; Haridas, Dhanya; Yan, Ying; Ganti, Apar K; Batra, Surinder K

    2015-03-10

    Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, migration and survival of pancreatic cancer cells by attenuation of signaling events including pERK1/2 (T202/Y204), cyclin D1, cyclin A, pFAK (Y925) and pAKT (Ser473). Using in vivo bioluminescent imaging, we demonstrated that canertinib treatment significantly reduced tumor burden (P=0.0164) and metastasis to various organs. Further, reduced expression of MUC4 and EGFR family members were confirmed in xenografts. Our results for the first time demonstrated the targeting of EGFR family members along with MUC4 by using pan-EGFR inhibitors. In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer.

  3. Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

    PubMed Central

    Ortiz-Abalia, Jon; Sahún, Ignasi; Altafaj, Xavier; Andreu, Núria; Estivill, Xavier; Dierssen, Mara; Fillat, Cristina

    2008-01-01

    Genetic-dissection studies carried out with Down syndrome (DS) murine models point to the critical contribution of Dyrk1A overexpression to the motor abnormalities and cognitive deficits displayed in DS individuals. In the present study we have used a murine model overexpressing Dyrk1A (TgDyrk1A mice) to evaluate whether functional CNS defects could be corrected with an inhibitory RNA against Dyrk1A, delivered by bilateral intrastriatal injections of adeno-associated virus type 2 (AAVshDyrk1A). We report that AAVshDyrk1A efficiently transduced HEK293 cells and primary neuronal cultures, triggering the specific inhibition of Dyrk1A expression. Injecting the vector into the striata of TgDyrk1A mice resulted in a restricted, long-term transduction of the striatum. This gene therapy was found to be devoid of toxicity and succeeded in normalizing Dyrk1A protein levels in TgDyrk1A mice. Importantly, the behavioral studies of the adult TgDyrk1A mice treated showed a reversal of corticostriatal-dependent phenotypes, as revealed by the attenuation of their hyperactive behavior, the restoration of motor-coordination defects, and an improvement in sensorimotor gating. Taken together, the data demonstrate that normalizing Dyrk1A gene expression in the striatum of adult TgDyrk1A mice, by means of AAVshRNA, clearly reverses motor impairment. Furthermore, these results identify Dyrk1A as a potential target for therapy in DS. PMID:18940310

  4. Vinpocetine Attenuates Pathological Cardiac Remodeling by Inhibiting Cardiac Hypertrophy and Fibrosis

    PubMed Central

    Wu, Mei-ping; Zhang, Yi-shuai; Xu, Xiangbin; Zhou, Qian

    2017-01-01

    Purpose Pathological cardiac remodeling, characterized by cardiac hypertrophy and fibrosis, is a pathological feature of many cardiac disorders that leads to heart failure and cardiac arrest. Vinpocetine, a derivative of the alkaloid vincamine, has been used for enhancing cerebral blood flow to treat cognitive impairment. However, its role in pathological cardiac remodeling remains unknown. The aim of this study is to examine the effect of vinpocetine on pathological cardiac remodeling induced by chronic stimulation with angiotensin II (Ang II). Methods Mice received Ang II infusion via osmotic pumps in the presence of vehicle or vinpocetine. Cardiac hypertrophy and fibrosis were assessed by morphological, histological, and biochemical analyses. Mechanistic studies were carried out in vitro with isolated mouse adult cardiac myocytes and fibroblasts. Results We showed that chronic Ang II infusion caused cardiac hypertrophy and fibrosis, which were all significantly attenuated by systemic administration of vinpocetine. In isolated adult mouse cardiomyocytes, vinpocetine suppressed Ang II-stimulated myocyte hypertrophic growth. In cultured cardiac fibroblasts, vinpocetine suppressed TGFβ-induced fibroblast activation and matrix gene expression, consistent with its effect in attenuating cardiac fibrosis. The effects of vinpocetine on cardiac myocyte hypertrophy and fibroblast activation are likely mediated by targeting cyclic nucleotide phosphodiesterase 1 (PDE1). Conclusions Our results reveal a novel protective effect of vinpocetine in attenuating pathological cardiac remodeling through suppressing cardiac myocyte hypertrophic growth and fibroblast activation and fibrotic gene expression. These studies may also shed light on developing novel therapeutic agents for antagonizing pathological cardiac remodeling. PMID:28321644

  5. Inner Core Anisotropy in Attenuation

    NASA Astrophysics Data System (ADS)

    Yu, W.; Wen, L.

    2004-12-01

    It is now well established that the compressional velocity in the Earth's inner core varies in both direction and geographic location. The compressional waves travel faster along the polar directions than along the equatorial directions. Such polar-equatorial difference is interpreted as a result of inner core anisotropy in velocity (with a magnitude of about 3%) and such anisotropy appears to be stronger in the ``western hemisphere" (180oW -40oE) than in the ``eastern hemisphere" (40oE-180oE). Along the equatorial paths, the compressional velocity also exhibits a hemispheric pattern with the eastern hemisphere being about 1% higher than the western hemisphere. Possible explanations for the causes of the velocity in anisotropy and the hemispheric difference in velocity along the equatorial paths include different geometric inclusions of melt or different alignments of iron crystals which are known to be anisotropic in velocities. Here, we report an observation of ubiquitous correlation between small (large) amplitude and fast (slow) travel time of the PKIKP waves sampling the top 300 km of the inner core. We study this correlation by jointly analyzing the differential travel times and amplitude ratios of the PKiKP-PKIKP and the PKPbc-PKIKP phases recorded by the Global Seismographic Network (1990-2001), various regional seismic networks (BANJO, BLSP, FREESIA, GEOFON, GEOSCOPE, Kazakhstan, Kyrgyz, MEDNET, and OHP), and several PASSCAL Networks deployed in Alaska and Antarctica (XE: 1999-2001, XF: 1995-1996, and YI: 1998-1999). Our dataset consists of 310 PKiKP-PKIKP and 240 PKPbc-PKIKP phases, selected from a total of more than 16,000 observations. PKIKP waves exhibit relatively smaller amplitudes for those sampling the eastern hemisphere along the equatorial paths and even smaller amplitudes for those sampling the polar paths in the western hemisphere. One simple explanation for the velocity-attenuation relation is that the inner core is anisotropic in attenuation

  6. Ultrasound attenuation estimation using backscattered echoes from multiple sources.

    PubMed

    Bigelow, Timothy A

    2008-08-01

    The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Deltaf=mf(o)+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation, and f(o) is the center frequency of the source as measured from a reference echo. Therefore, the total attenuation can be determined independent of the scatterer correlation length by measuring the downshift in center frequency from multiple sources (i.e., different f(o)) and fitting a line to the measured shifts versus f(o). The intercept of the line gives the total attenuation along the propagation path. The calculations were verified using computer simulations of five spherically focused sources with 50% bandwidths and center frequencies of 6, 8, 10, 12, and 14 MHz. The simulated tissue had Gaussian scattering structures with effective radii of 25 mum placed at a density of 250 mm(3). The attenuation of the tissue was varied from 0.1 to 0.9 dB / cm-MHz. The error in the attenuation along the propagation path ranged from -3.5+/-14.7% for a tissue attenuation of 0.1 dB / cm-MHz to -7.0+/-3.1% for a tissue attenuation of 0.9 dB / cm-MHz demonstrating that the attenuation along the propagation path could be accurately determined using backscattered echoes from multiple sources using the derived algorithm.

  7. GPR measurements of attenuation in concrete

    NASA Astrophysics Data System (ADS)

    Eisenmann, David; Margetan, Frank J.; Pavel, Brittney

    2015-03-01

    Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena, and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.

  8. Identifying Attenuating Mutations: Tools for a New Vaccine Design against Flaviviruses.

    PubMed

    Khou, Cécile; Pardigon, Nathalie

    2017-01-01

    Emerging Flaviviruses pose an increasing threat to global human health. To date, human vaccines against yellow fever virus (YFV), Japanese encephalitis virus (JEV), dengue virus (DV), and tick-borne encephalitis virus (TBEV) exist. However, there is no human vaccine against other Flaviviruses such as Zika virus (ZIKV) and West Nile virus (WNV). In order to restrict their spread and to protect populations against the diseases they induce, vaccines against these emerging viruses must be designed. Obtaining new live attenuated Flavivirus vaccines using molecular biology methods is now possible. Molecular infectious clones of the parental viruses are relatively easy to generate. Key mutations present in live attenuated vaccines or mutations known to have a key role in the Flavivirus life cycle and/or interactions with their hosts can be identified by sequencing, and are then inserted in infectious clones by site-directed mutagenesis. More recently, the use of chimeric viruses and large-scale reencoding and introduction of microRNA target sequences have also been tested. Indeed, a combination of these methods will help in designing new generations of vaccines against emerging and reemerging Flaviviruses. © 2017 S. Karger AG, Basel.

  9. Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats.

    PubMed

    Liu, Chi; Yang, Chuan-Xi; Chen, Xi-Ru; Liu, Bo-Xun; Li, Yong; Wang, Xiao-Zhi; Sun, Wei; Li, Peng; Kong, Xiang-Qing

    2018-05-12

    Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

  10. Fat Attenuation at CT in Anorexia Nervosa

    PubMed Central

    Gill, Corey M.; Torriani, Martin; Murphy, Rachel; Harris, Tamara B.; Miller, Karen K.; Klibanski, Anne

    2016-01-01

    Purpose To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. Materials and Methods This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age ± standard deviation, 26 years ± 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. Results Women with AN had higher fat attenuation than did control subjects (−100.1 to −46.7 HU vs −117.6 to −61.8 HU, P < .0001), despite lower fat CSA (2.0–62.8 cm2 vs 5.5–185.9 cm2, P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = −0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = −0.34 to −0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42–0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = −0.44 to −0.58, P = .04 to .02). Conclusion Women with AN have differences in fat

  11. Quantifying contributions to light attenuation in estuaries and ...

    EPA Pesticide Factsheets

    In Narragansett Bay, light attenuation by total suspended sediments (TSS), colored dissolved organic matter (CDOM), and phytoplankton chlorophyll-a (chl-a) pigment is 129, 97, and 70%, respectively, of that by pure seawater. Spatial distribution of light attenuation indicates higher values in the upper Bay, where rivers with sediment and nutrient-rich waters enter and elevate TSS, CDOM, and chl-a concentrations. The temporal trends of light attenuation during the summer months (July–August) differed at various locations in the Bay, having the highest values in July. For the same period, spectral methods overestimated attenuation throughout the Bay. These findings quantify the behavior of light attenuation in space and time, providing information that can guide decisions related to improving water clarity and help understanding the effects of various environmental and management scenarios on it. The methods developed can be used to study the effect of various environmental and management scenarios on the recovery efforts for SAV beds in estuarine and coastal systems. An innovative normalization for light attenuation is presented to validate comparison between water clarity of the same or different systems in space and time.

  12. Rain attenuation measurements: Variability and data quality assessment

    NASA Technical Reports Server (NTRS)

    Crane, Robert K.

    1989-01-01

    Year to year variations in the cumulative distributions of rain rate or rain attenuation are evident in any of the published measurements for a single propagation path that span a period of several years of observation. These variations must be described by models for the prediction of rain attenuation statistics. Now that a large measurement data base has been assembled by the International Radio Consultative Committee, the information needed to assess variability is available. On the basis of 252 sample cumulative distribution functions for the occurrence of attenuation by rain, the expected year to year variation in attenuation at a fixed probability level in the 0.1 to 0.001 percent of a year range is estimated to be 27 percent. The expected deviation from an attenuation model prediction for a single year of observations is estimated to exceed 33 percent when any of the available global rain climate model are employed to estimate the rain rate statistics. The probability distribution for the variation in attenuation or rain rate at a fixed fraction of a year is lognormal. The lognormal behavior of the variate was used to compile the statistics for variability.

  13. Examination of the Lateral Attenuation of Aircraft Noise

    NASA Technical Reports Server (NTRS)

    Plotkin, Kenneth J.; Hobbs, Christopher M.; Bradley, Kevin A.; Shepherd, Kevin P. (Technical Monitor)

    2000-01-01

    Measurements of the lateral attenuation of noise from aircraft operations at Denver International Airport were made at distances up to 2000 feet and elevation angles up to 27 degrees. Attenuation Calculated from modem ground impedance theory agrees well with average measured attenuation. The large variability between measured and predicted levels observed at small elevation angles is demonstrated to be due to refraction by wind and temperature gradients.

  14. Seismic attenuation of the inner core: Viscoelastic or stratigraphic?

    USGS Publications Warehouse

    Cormier, V.F.; Xu, L.; Choy, G.L.

    1998-01-01

    Broadband velocity waveforms of PKIKP in the distance range 150??to 180??are inverted for inner core attenuation. A mean Q?? of 244 is determined at 1 Hz from 8 polar and 9 equatorial paths. The scatter in measured Q-1 exceeds individual error estimates, suggesting significant variation in attenuation with path. These results are interpreted by (1) viscoelasticity, in which the relaxation spectrum has a low-frequency corner near or slightly above the frequency band of short-period body waves, and by (2) stratigraphic (scattering) attenuation, in which attenuation and pulse broadening are caused by the interference of scattered multiples in a velocity structure having rapid fluctuations along a PKIKP path. In the scattering interpretation, PKIKP attenuation is only weakly affected by the intrinsic shear attenuation measured in the free-oscillation band. Instead, its frequency dependence, path variations, and fluctuations are all explained by scattering attenuation in a heterogeneous fabric resulting from solidification texturing of intrinsically anisotropic iron. The requisite fabric may consist of either single or ordered groups of crystals with P velocity differences of at least 5% and as much as 12% between two crystallographic axes at scale lengths of 0.5 to 2 km in the direction parallel to the axis of rotation and longer in the cylindrically radial direction, perpendicular to the axis of rotation.Broadband velocity waveforms of PKIKP in the distance range 150?? to 180?? are inverted for inner core attenuation. A mean Q?? of 244 is determined at 1 Hz from 8 polar and 9 equatorial paths. The scatter in the measured Q-1 exceeds individual error estimates, indicating significant variation in attenuation with path. The results are interpreted by viscoelasticity and stratigraphic (scattering) attenuation.

  15. A description of shock attenuation for children running.

    PubMed

    Mercer, John A; Dufek, Janet S; Mangus, Brent C; Rubley, Mack D; Bhanot, Kunal; Aldridge, Jennifer M

    2010-01-01

    A growing number of children are participating in organized sport activities, resulting in a concomitant increase in lower extremity injuries. Little is known about the impact generated when children are running or how this impact is attenuated in child runners. To describe shock attenuation characteristics for children running at different speeds on a treadmill and at a single speed over ground. Prospective cohort study. Biomechanics laboratory. Eleven boys (age = 10.5 +/- 0.9 years, height = 143.7 +/- 8.3 cm, mass = 39.4 +/- 10.9 kg) and 7 girls (age = 9.9 +/- 1.1 years, height = 136.2 +/- 7.7 cm, mass = 35.1 +/- 9.6 kg) participated. Participants completed 4 running conditions, including 3 treadmill (TM) running speeds (preferred, fast [0.5 m/s more than preferred], and slow [0.5 m/s less than preferred]) and 1 overground (OG) running speed. We measured leg peak impact acceleration (LgPk), head peak impact acceleration (HdPk), and shock attenuation (ratio of LgPk to HdPk). Shock attenuation (F(2,16) = 4.80, P = .01) was influenced by the interaction of speed and sex. Shock attenuation increased across speeds (slow, preferred, fast) for boys (P < .05) but not for girls (P > .05). Both LgPk (F(1,16) = 5.04, P = .04) and HdPk (F(1,16) = 6.04, P = .03) were different across speeds, and both were greater for girls than for boys. None of the dependent variables were influenced by the interaction of setting (TM, OG) and sex (P >or= .05). Shock attenuation (F(1,16) = 33.51, P < .001) and LgPk (F(1,16) = 31.54, P < .001) were different between TM and OG, and each was greater when running OG than on the TM, regardless of sex. Shock attenuation was between 66% and 76% for children running under a variety of conditions. Girls had greater peak impact accelerations at the leg and head levels than boys but achieved similar shock attenuation. We do not know how these shock attenuation characteristics are related to overuse injuries.

  16. Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents.

    PubMed

    Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B; Radhakrishnan, Kirthi; Griffin, Joseph K; Huang, Shao-Ling; McPherson, David D; Holland, Christy K

    2014-02-01

    The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95-103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. Action-related auditory ERP attenuation: Paradigms and hypotheses.

    PubMed

    Horváth, János

    2015-11-11

    A number studies have shown that the auditory N1 event-related potential (ERP) is attenuated when elicited by self-induced or self-generated sounds. Because N1 is a correlate of auditory feature- and event-detection, it was generally assumed that N1-attenuation reflected the cancellation of auditory re-afference, enabled by the internal forward modeling of the predictable sensory consequences of the given action. Focusing on paradigms utilizing non-speech actions, the present review summarizes recent progress on action-related auditory attenuation. Following a critical analysis of the most widely used, contingent paradigm, two further hypotheses on the possible causes of action-related auditory ERP attenuation are presented. The attention hypotheses suggest that auditory ERP attenuation is brought about by a temporary division of attention between the action and the auditory stimulation. The pre-activation hypothesis suggests that the attenuation is caused by the activation of a sensory template during the initiation of the action, which interferes with the incoming stimulation. Although each hypothesis can account for a number of findings, none of them can accommodate the whole spectrum of results. It is suggested that a better understanding of auditory ERP attenuation phenomena could be achieved by systematic investigations of the types of actions, the degree of action-effect contingency, and the temporal characteristics of action-effect contingency representation-buildup and -deactivation. This article is part of a Special Issue entitled SI: Prediction and Attention. Copyright © 2015. Published by Elsevier B.V.

  18. Range estimation of passive infrared targets through the atmosphere

    NASA Astrophysics Data System (ADS)

    Cho, Hoonkyung; Chun, Joohwan; Seo, Doochun; Choi, Seokweon

    2013-04-01

    Target range estimation is traditionally based on radar and active sonar systems in modern combat systems. However, jamming signals tremendously degrade the performance of such active sensor devices. We introduce a simple target range estimation method and the fundamental limits of the proposed method based on the atmosphere propagation model. Since passive infrared (IR) sensors measure IR signals radiating from objects in different wavelengths, this method has robustness against electromagnetic jamming. The measured target radiance of each wavelength at the IR sensor depends on the emissive properties of target material and various attenuation factors (i.e., the distance between sensor and target and atmosphere environment parameters). MODTRAN is a tool that models atmospheric propagation of electromagnetic radiation. Based on the results from MODTRAN and atmosphere propagation-based modeling, the target range can be estimated. To analyze the proposed method's performance statistically, we use maximum likelihood estimation (MLE) and evaluate the Cramer-Rao lower bound (CRLB) via the probability density function of measured radiance. We also compare CRLB and the variance of MLE using Monte-Carlo simulation.

  19. Silibinin Attenuates Sulfur Mustard Analog-Induced Skin Injury by Targeting Multiple Pathways Connecting Oxidative Stress and Inflammation

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants. PMID:23029417

  20. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  1. Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.

    PubMed

    Chao, Dongman; Bazzy-Asaad, Alia; Balboni, Gianfranco; Salvadori, Severo; Xia, Ying

    2008-09-01

    We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.

  2. Rollover of Apparent Wave Attenuation in Ice Covered Seas

    NASA Astrophysics Data System (ADS)

    Li, Jingkai; Kohout, Alison L.; Doble, Martin J.; Wadhams, Peter; Guan, Changlong; Shen, Hayley H.

    2017-11-01

    Wave attenuation from two field experiments in the ice-covered Southern Ocean is examined. Instead of monotonically increasing with shorter waves, the measured apparent attenuation rate peaks at an intermediate wave period. This "rollover" phenomenon has been postulated as the result of wind input and nonlinear energy transfer between wave frequencies. Using WAVEWATCH III®, we first validate the model results with available buoy data, then use the model data to analyze the apparent wave attenuation. With the choice of source parameterizations used in this study, it is shown that rollover of the apparent attenuation exists when wind input and nonlinear transfer are present, independent of the different wave attenuation models used. The period of rollover increases with increasing distance between buoys. Furthermore, the apparent attenuation for shorter waves drops with increasing separation between buoys or increasing wind input. These phenomena are direct consequences of the wind input and nonlinear energy transfer, which offset the damping caused by the intervening ice.

  3. GPR measurements of attenuation in concrete

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

    Eisenmann, David, E-mail: djeisen@cnde.iastate.edu; Margetan, Frank J., E-mail: djeisen@cnde.iastate.edu; Pavel, Brittney, E-mail: djeisen@cnde.iastate.edu

    2015-03-31

    Ground-penetrating radar (GPR) signals from concrete structures are affected by several phenomenon, including: (1) transmission and reflection coefficients at interfaces; (2) the radiation patterns of the antenna(s) being used; and (3) the material properties of concrete and any embedded objects. In this paper we investigate different schemes for determining the electromagnetic (EM) attenuation of concrete from measured signals obtained using commercially-available GPR equipment. We adapt procedures commonly used in ultrasonic inspections where one compares the relative strengths of two or more signals having different travel paths through the material of interest. After correcting for beam spread (i.e., diffraction), interface phenomena,more » and equipment amplification settings, any remaining signal differences are assumed to be due to attenuation thus allowing the attenuation coefficient (say, in dB of loss per inch of travel) to be estimated. We begin with a brief overview of our approach, and then discuss how diffraction corrections were determined for our two 1.6 GHz GPR antennas. We then present results of attenuation measurements for two types of concrete using both pulse/echo and pitch/catch measurement setups.« less

  4. Seismic Attenuation Structure and Intraplate Deformation

    NASA Astrophysics Data System (ADS)

    Bezada, M.; Kowalke, S.; Smale, J.

    2017-12-01

    It has been suggested that intraplate deformation and seismicity is localized at weak zones in the lithosphere and at rheological boundaries. Comparisons of intraplate deformation regions with mantle seismic velocity structure suggest a correlation, but are not universally accepted as compelling evidence. We present P-wave attenuation models built from records of teleseismic deep-focus earthquakes in three different regions that show significant correlation between attenuation structure and intraplate seismicity and deformation. In the eastern United States, the New Madrid, Wabash Valley, Eastern Tennessee, Central Virginia, and Carolina seismic zones all occur at or near the edges of high-Q (low attenuation) regions. In Spain, intraplate seismicity is absent from high-Q regions but relatively abundant in surrounding low-Q regions where intraplate orogeny is also observed. In Australia, where our model resolution is relatively poor owing to sparse and uneven station coverage, the Petermann and Alice Springs intraplate orogens occur near the edge of a high-Q feature roughly coinciding with the undeformed Amadeus basin. Our results suggest that lithospheric structure exerts important controls on the localization of intraplate deformation and seismicity and that seismic attenuation is a useful proxy for lithospheric strength.

  5. Entanglement sensitivity to signal attenuation and amplification

    NASA Astrophysics Data System (ADS)

    Filippov, Sergey N.; Ziman, Mário

    2014-07-01

    We analyze general laws of continuous-variable entanglement dynamics during the deterministic attenuation and amplification of the physical signal carrying the entanglement. These processes are inevitably accompanied by noises, so we find fundamental limitations on noise intensities that destroy entanglement of Gaussian and non-Gaussian input states. The phase-insensitive amplification Φ1⊗Φ2⊗⋯ΦN with the power gain κi≥2 (≈3 dB, i =1,...,N) is shown to destroy entanglement of any N-mode Gaussian state even in the case of quantum-limited performance. In contrast, we demonstrate non-Gaussian states with the energy of a few photons such that their entanglement survives within a wide range of noises beyond quantum-limited performance for any degree of attenuation or gain. We detect entanglement preservation properties of the channel Φ1⊗Φ2, where each mode is deterministically attenuated or amplified. Gaussian states of high energy are shown to be robust to very asymmetric attenuations, whereas non-Gaussian states are at an advantage in the case of symmetric attenuation and general amplification. If Φ1=Φ2, the total noise should not exceed 1/2√κ2+1 to guarantee entanglement preservation.

  6. Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain

    PubMed Central

    Chitlaru, Theodor; Israeli, Ma’ayan; Bar-Haim, Erez; Elia, Uri; Rotem, Shahar; Ehrlich, Sharon; Cohen, Ofer; Shafferman, Avigdor

    2016-01-01

    Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel B. anthracis SterneΔhtrA strain secretes functional anthrax toxins but is 10–104-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with SterneΔhtrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization. PMID:26732659

  7. A depolarization and attenuation experiment using the COMSTAR and CTS satellites

    NASA Technical Reports Server (NTRS)

    Bostian, C. W.; Manus, E. A.; Marshall, R. E.; Overstreet, W. P.; Persinger, R. R.; Powell, J. D.; Santago, P.; Stutzman, W. L.; Wiley, P. H.

    1978-01-01

    Monthly statistical data are presented on ground rainfall rate and attenuation of satellite downlinks at 11.7 GHz, 19.04 GHz, and 28.56 GHz and on cross-polarization isolation at 11.7 GHz. Regression equations for relating isolation to attenuation, attenuation to rain rate, and attenuation at one frequency to attenuation at another frequency are also included. Longer-term statistics are also presented and discussed.

  8. Visual Search of Experts in Medical Image Reading: The Effect of Training, Target Prevalence, and Expert Knowledge

    PubMed Central

    Nakashima, Ryoichi; Kobayashi, Kazufumi; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

    2013-01-01

    The aims of this study are (a) To determine the effect of training on the multiple-target lesion search performance; and (b) To examine the effect of target prevalence on the performance of radiologists and novices. We conducted four sessions of 500 trials in a lesion search on a medical image task in which participants searched for three different target lesions. Participants were 10 radiologists and novices. In each session, the prevalence of the different target lesions varied from low (2%) to high (40%). The sensitivity of novices was higher in the later sessions than in the first session, whereas there were no differences among sessions in radiologists. The improvement on sensitivity of novices was largely due to attenuations of false alarm (FA) errors. In addition, miss rates of the three targets did not differ in data of novices, whereas radiologists produced a higher miss rate for the highest prevalence target lesion (non-serious lesion) than for the other two lesions (serious lesions). The conclusions are (a) The training for the multiple-target lesion search task can be effective to reduce FA errors; and (b) The prevalence effect on lesion search can be attenuated by the multiple-target identification and the knowledge about seriousness of lesions. This suggests that acquired knowledge about normal cases and serious lesions is an important aspect of a radiologists’ skill in searching for medical lesions and their high performance levels. PMID:23576997

  9. Visual search of experts in medical image reading: the effect of training, target prevalence, and expert knowledge.

    PubMed

    Nakashima, Ryoichi; Kobayashi, Kazufumi; Maeda, Eriko; Yoshikawa, Takeharu; Yokosawa, Kazuhiko

    2013-01-01

    The aims of this study are (a) To determine the effect of training on the multiple-target lesion search performance; and (b) To examine the effect of target prevalence on the performance of radiologists and novices. We conducted four sessions of 500 trials in a lesion search on a medical image task in which participants searched for three different target lesions. Participants were 10 radiologists and novices. In each session, the prevalence of the different target lesions varied from low (2%) to high (40%). The sensitivity of novices was higher in the later sessions than in the first session, whereas there were no differences among sessions in radiologists. The improvement on sensitivity of novices was largely due to attenuations of false alarm (FA) errors. In addition, miss rates of the three targets did not differ in data of novices, whereas radiologists produced a higher miss rate for the highest prevalence target lesion (non-serious lesion) than for the other two lesions (serious lesions). The conclusions are (a) The training for the multiple-target lesion search task can be effective to reduce FA errors; and (b) The prevalence effect on lesion search can be attenuated by the multiple-target identification and the knowledge about seriousness of lesions. This suggests that acquired knowledge about normal cases and serious lesions is an important aspect of a radiologists' skill in searching for medical lesions and their high performance levels.

  10. Frequency-domain ultrasound waveform tomography breast attenuation imaging

    NASA Astrophysics Data System (ADS)

    Sandhu, Gursharan Yash Singh; Li, Cuiping; Roy, Olivier; West, Erik; Montgomery, Katelyn; Boone, Michael; Duric, Neb

    2016-04-01

    Ultrasound waveform tomography techniques have shown promising results for the visualization and characterization of breast disease. By using frequency-domain waveform tomography techniques and a gradient descent algorithm, we have previously reconstructed the sound speed distributions of breasts of varying densities with different types of breast disease including benign and malignant lesions. By allowing the sound speed to have an imaginary component, we can model the intrinsic attenuation of a medium. We can similarly recover the imaginary component of the velocity and thus the attenuation. In this paper, we will briefly review ultrasound waveform tomography techniques, discuss attenuation and its relations to the imaginary component of the sound speed, and provide both numerical and ex vivo examples of waveform tomography attenuation reconstructions.

  11. Seismic velocity and attenuation structures in the Earth's inner core

    NASA Astrophysics Data System (ADS)

    Yu, Wen-Che

    2007-12-01

    I study seismic velocity and attenuation structures in the top 400 km of the Earth's inner core along equatorial paths, velocity-attenuation relationship, and seismic anisotropy in the top of the inner core beneath Africa. Seismic observations exhibit "east-west" hemispheric differences in seismic velocity, attenuation, and anisotropy. Joint modeling of the PKiKP-PKIKP and PKPbc-PKIKP phases is used to constrain seismic velocity and attenuation structures in the top 400 km of the inner core for the eastern and western hemispheres. The velocity and attenuation models for the western hemisphere are simple, having a constant velocity gradient and a Q value of 600 in the top 400 km of the inner core. The velocity and attenuation models for the eastern hemisphere appear complex. The velocity model for the eastern hemisphere has a small velocity gradient in the top 235 km, a steeper velocity gradient at the depth range of 235 - 375 km, and a gradient similar to PREM in the deeper portion of the inner core. The attenuation model for the eastern hemisphere has a Q value of 300 in the top 300 km and a Q value of 600 in the deeper portion of the inner core. The study of velocity-attenuation relationship reveals that inner core is anisotropic in both velocity and attenuation, and the direction of high attenuation corresponding to that of high velocity. I hypothesize that the hexagonal close packed (hcp) iron crystal is anisotropic in attenuation, with the axis of high attenuation corresponding to that of high velocity. Anisotropy in the top of the inner core beneath Africa is complex. Beneath eastern Africa, the thickness of the isotropic upper inner core is about 0 km. Beneath central and western Africa, the thickness of the isotropic upper inner core increases from 20 to 50 km. The velocity increase across the isotropic upper inner core and anisotropic lower inner core boundary is sharp, laterally varying from 1.6% - 2.2%. The attenuation model has a Q value of 600 for the

  12. WE-H-207A-02: Attenuation Correction in 4D-PET Using a Single-Phase Attenuation Map

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

    Kalantari, F; Wang, J

    2016-06-15

    Purpose: 4D-PET imaging has been proposed as a potential solution to the respiratory motion effect in thoracic region. CT-based attenuation correction (AC) is an essential step toward quantitative imaging for PET. However, due to the temporal difference of 4D-PET and a single breath-hold CT, motion artifacts are observed in the attenuation-corrected PET images that can lead to error in tumor shape and uptake. We introduce a practical method for aligning single-phase CT to all other 4D-PET phases using a penalized non-rigid demons registration. Methods: Individual 4D-PET frames were reconstructed without AC. Non-rigid Demons registration was used to derive deformation vectormore » fields (DVFs) between the PET matched with CT phase and other 4D-PET images. While attenuated PET images provide enough useful data for organ borders such as lung and liver, tumors are not distinguishable from background due to loss of contrast. To preserve tumor shape in different phases, from CT image an ROI covering tumor was excluded from non-rigid transformation. Mean DVF of the central region of the tumor was assigned to all voxels in the ROI. This process mimics a rigid transformation of tumor along with a non-rigid transformation of other organs. 4D XCAT phantom with spherical tumors in lung with diameters ranging from 10 to 40 mm was used to evaluate the algorithm. Results: Motion related induced artifacts in attenuation-corrected 4D-PET images were significantly reduced. For tumors smaller than 20 mm, non-rigid transformation was capable to provide quantitative results. However, for larger tumors, where tumor self-attenuation is considerable, our combined method yields superior results. Conclusion: We introduced a practical method for deforming a single CT to match all 4D-PET images for accurate AC. Although 4D-PET data include insignificant anatomical information, we showed that they are still useful to estimate DVFs for aligning attenuation map and accurate AC.« less

  13. Severe Acute Respiratory Syndrome Coronaviruses with Mutations in the E Protein Are Attenuated and Promising Vaccine Candidates

    PubMed Central

    Regla-Nava, Jose A.; Nieto-Torres, Jose L.; Jimenez-Guardeño, Jose M.; Fernandez-Delgado, Raul; Fett, Craig; Castaño-Rodríguez, Carlos; Perlman, Stanley; DeDiego, Marta L.

    2015-01-01

    . Previously, we demonstrated that a SARS-CoV lacking the E protein was attenuated in vivo. Here, we show that small deletions and modifications within the E protein led to virus attenuation, manifested by minimal lung injury, limited neutrophil influx to the lungs, reduced expression of proinflammatory cytokines, increased anti-inflammatory cytokine levels, and enhanced CD4+ and CD8+ T cell counts in vivo, suggesting that these phenomena contribute to virus attenuation. The attenuated mutants fully protected mice from challenge with virulent virus. These studies show that mutations in the E protein are not well tolerated and indicate that this protein is an excellent target for vaccine development. PMID:25609816

  14. Cognitive enhancement as a pharmacotherapy target for stimulant addiction.

    PubMed

    Sofuoglu, Mehmet

    2010-01-01

    No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha(2)-adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction.

  15. Spatially resolved ultrasonic attenuation in resistance spot welds: implications for nondestructive testing.

    PubMed

    Mozurkewich, George; Ghaffari, Bita; Potter, Timothy J

    2008-09-01

    Spatial variation of ultrasonic attenuation and velocity has been measured in plane parallel specimens extracted from resistance spot welds. In a strong weld, attenuation is larger in the nugget than in the parent material, and the region of increased attenuation is surrounded by a ring of decreased attenuation. In the center of a stick weld, attenuation is even larger than in a strong weld, and the low-attenuation ring is absent. These spatial variations are interpreted in terms of differences in grain size and martensite formation. Measured frequency dependences indicate the presence of an additional attenuation mechanism besides grain scattering. The observed attenuations do not vary as commonly presumed with weld quality, suggesting that the common practice of using ultrasonic attenuation to indicate weld quality is not a reliable methodology.

  16. Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol, attenuates mast cell degranulation.

    PubMed

    Oka, T; Fujimoto, M; Nagasaka, R; Ushio, H; Hori, M; Ozaki, H

    2010-02-01

    IgE-targeting therapy could provide significant progress in the treatment of allergic inflammation. In this study, we examined the effect of cycloartenyl ferulate (cycloartenol ferulic acid ester; CAF), a natural product from rice bran oil-derived gamma-oryzanol, on allergic reaction. When CAF and gamma-oryzanol were injected intradermally with anti-DNP IgE into the dorsal skin of rats, the passive cutaneous anaphylaxis reaction induced by DNP-HSA was attenuated. CAF and gamma-oryzanol also inhibited the degranulation of DNP-IgE sensitized RBL-2H3 mast cells stimulated with anti-DNP-HSA. IgE conjugated with CAF could not be detected by anti-IgE antibody in the ELISA analysis. Although incubation of IgE with CAF did not decrease the amount of IgE, it was possible to precipitate IgE by centrifugation. These results demonstrate that CAF captures IgE, prevents it from binding to FcepsilonRI, and attenuates mast cell degranulation. Copyright 2009 Elsevier GmbH. All rights reserved.

  17. Measurement of the attenuation length of argon scintillation light in the ArDM LAr TPC

    NASA Astrophysics Data System (ADS)

    Calvo, J.; Cantini, C.; Crivelli, P.; Daniel, M.; Di Luise, S.; Gendotti, A.; Horikawa, S.; Molina-Bueno, L.; Montes, B.; Mu, W.; Murphy, S.; Natterer, G.; Nguyen, K.; Periale, L.; Quan, Y.; Radics, B.; Regenfus, C.; Romero, L.; Rubbia, A.; Santorelli, R.; Sergiampietri, F.; Viant, T.; Wu, S.

    2018-01-01

    We report on a measurement of the attenuation length for the scintillation light in the tonne size liquid argon target of the ArDM dark matter experiment. The data was recorded in the first underground operation of the experiment in single-phase operational mode. The results were achieved by comparing the light yield spectra from 39Ar and 83mKr to a description of the ArDM setup with a model of full light ray tracing. A relatively low value close to 0.5 m was found for the attenuation length of the liquid argon bulk to its own scintillation light. We interpret this result as a presence of optically active impurities in the liquid argon which are not filtered by the installed purification systems. We also present analyses of the argon gas employed for the filling and discuss cross sections in the vacuum ultraviolet of various molecules in respect to purity requirements in the context of large liquid argon installations.

  18. Monitored natural attenuation and enhanced attenuation for chlorinated solvent plumes - It's all about balance

    USGS Publications Warehouse

    Adams, K.A.; Vangelas, K.M.; Looney, B.B.; Chapelle, F.; Early, T.; Gilmore, T.; Sink, C.H.

    2005-01-01

    Nature's inherent ability to cleanse itself is at the heart of Monitored Natural Attenuation (MNA). The complexity comes when one attempts to measure and calculate this inherent ability, called the Natural Attenuation Capacity (NAC), and determine if it is sufficient to cleanse the system to agreed upon criteria. An approach that is simple in concept for determining whether the NAC is sufficient for MNA to work is the concept of a mass balance. Mass balance is a robust framework upon which all decisions can be made. The inflows to and outflows from the system are balanced against the NAC of the subsurface system. For MNA to be acceptable, the NAC is balanced against the contaminant loading to the subsurface system with the resulting outflow from the system being in a range that is acceptable to the regulating and decision-making parties. When the system is such that the resulting outflow is not within an acceptable range, the idea of taking actions that are sustainable and that will bring the system within the acceptable range of outflows is evaluated. These sustainable enhancements are being developed under the Enhanced Attenuation (EA) concept. Copyright ASCE 2005.

  19. On the suitability of broadband attenuation measurement for characterizing contrast microbubbles.

    PubMed

    Chatterjee, Dhiman; Sarkar, Kausik; Jain, Pankaj; Schreppler, Nathan E

    2005-06-01

    Broadband attenuation measurement has been widely used for characterizing ultrasound contrast agents. Chen et al. (2002) recently suggested that broadband attenuation data depend on the center frequency of the broadband excitation pulse and, therefore, that they are not a reliable measure of the bubble behavior. We investigated the suitability of measurement of broadband attenuation as a characterizing tool using the contrast agent Definity as a test case. Analyzing the attenuation data obtained with three broadband unfocused transducers with different center frequencies (2.25, 3.5 and 5 MHz), we found that attenuation is independent of the transducer used and matches in the overlap regions of any two transducers. Attenuation does not depend on excitation pressure amplitude as long as the excitation amplitude remains below a critical value ( approximately 0.26 MPa), indicating that the measurement of broadband attenuation below critical excitation can, indeed, be used for characterization. Furthermore, the linear relationship of attenuation with concentrations of Definity is also investigated.

  20. METHODS AND ANALYSES FOR IMPLEMENTING NATURAL ATTENUATION PROTOCOLS

    EPA Science Inventory

    Technical protocols for evaluating natural attenuation at petroleum hydrocarbon and chlorinated solvent contaminated sites specify the analysis of electron acceptors and metabolic by-products for identifying and quantifying natural attenuation processes. However, these protocols ...

  1. Live-Attenuated Lentivirus Immunization Modulates Innate Immunity and Inflammation while Protecting Rhesus Macaques from Vaginal Simian Immunodeficiency Virus Challenge

    PubMed Central

    Genescà, Meritxell; Ma, Zhong-Min; Wang, Yichuan; Assaf, Basel; Qureshi, Huma; Fritts, Linda; Huang, Ying; McChesney, Michael B.

    2012-01-01

    Immunization with attenuated lentiviruses is the only reliable method of protecting rhesus macaques (RM) from vaginal challenge with pathogenic simian immunodeficiency virus (SIV). CD8+ lymphocyte depletion prior to SIVmac239 vaginal challenge demonstrated that a modest, Gag-specific CD8+ T cell response induced by immunization with simian-human immunodeficiency virus 89.6 (SHIV89.6) protects RM. Although CD8+ T cells are required for protection, there is no anamnestic expansion of SIV-specific CD8+ T cells in any tissues except the vagina after challenge. Further, SHIV immunization increased the number of viral target cells in the vagina and cervix, suggesting that the ratio of target cells to antiviral CD8+ T cells was not a determinant of protection. We hypothesized that persistent replication of the attenuated vaccine virus modulates inflammatory responses and limits T cell activation and expansion by inducing immunoregulatory T cell populations. We found that attenuated SHIV infection decreased the number of circulating plasmacytoid dendritic cells, suppressed T cell activation, decreased mRNA levels of proinflammatory mediators, and increased mRNA levels of immunoregulatory molecules. Three days after SIV vaginal challenge, SHIV-immunized RM had significantly more T regulatory cells in the vagina than the unimmunized RM. By day 14 postchallenge, immune activation and inflammation were characteristic of unimmunized RM but were minimal in SHIV-immunized RM. Thus, a modest vaccine-induced CD8+ T cell response in the context of immunoregulatory suppression of T cell activation may protect against vaginal HIV transmission. PMID:22696662

  2. Generation of growth arrested Leishmania amastigotes: a tool to develop live attenuated vaccine candidates against visceral leishmaniasis.

    PubMed

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Gannavaram, Sreenivas; Solanki, Sumit; Salotra, Poonam; Nakhasi, Hira L

    2014-06-30

    Visceral leishmaniasis (VL) is fatal if not treated and is prevalent widely in the tropical and sub-tropical regions of world. VL is caused by the protozoan parasite Leishmania donovani or Leishmania infantum. Although several second generation vaccines have been licensed to protect dogs against VL, there are no effective vaccines against human VL [1]. Since people cured of leishmaniasis develop lifelong protection, development of live attenuated Leishmania parasites as vaccines, which can have controlled infection, may be a close surrogate to leishmanization. This can be achieved by deletion of genes involved in the regulation of growth and/or virulence of the parasite. Such mutant parasites generally do not revert to virulence in animal models even under conditions of induced immune suppression due to complete deletion of the essential gene(s). In the Leishmania life cycle, the intracellular amastigote form is the virulent form and causes disease in the mammalian hosts. We developed centrin gene deleted L. donovani parasites that displayed attenuated growth only in the amastigote stage and were found safe and efficacious against virulent challenge in the experimental animal models. Thus, targeting genes differentially expressed in the amastigote stage would potentially attenuate only the amastigote stage and hence controlled infectivity may be effective in developing immunity. This review lays out the strategies for attenuation of the growth of the amastigote form of Leishmania for use as live vaccine against leishmaniasis, with a focus on visceral leishmaniasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Attenuation of the influenza virus by microRNA response element in vivo and protective efficacy against 2009 pandemic H1N1 virus in mice.

    PubMed

    Feng, Chunlai; Tan, Mingming; Sun, Wenkui; Shi, Yi; Xing, Zheng

    2015-09-01

    The 2009 influenza pandemics underscored the need for effective vaccines to block the spread of influenza virus infection. Most live attenuated vaccines utilize cold-adapted, temperature-sensitive virus. An alternative to live attenuated virus is presented here, based on microRNA-induced gene silencing. In this study, miR-let-7b target sequences were inserted into the H1N1 genome to engineer a recombinant virus - miRT-H1N1. Female BALB/c mice were vaccinated intranasally with the miRT-H1N1 and challenged with a lethal dose of homologous virus. This miRT-H1N1 virus was attenuated in mice, while it exhibited wild-type characteristics in chicken embryos. Mice vaccinated intranasally with the miRT-H1N1 responded with robust immunity that protected the vaccinated mice from a lethal challenge with the wild-type 2009 pandemic H1N1 virus. These results indicate that the influenza virus containing microRNA response elements (MREs) is attenuated in vivo and can be used to design a live attenuated vaccine. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Stratification of chlorinated ethenes natural attenuation in an alluvial aquifer assessed by hydrochemical and biomolecular tools.

    PubMed

    Němeček, Jan; Dolinová, Iva; Macháčková, Jiřina; Špánek, Roman; Ševců, Alena; Lederer, Tomáš; Černík, Miroslav

    2017-10-01

    Biomolecular and hydrochemical tools were used to evaluate natural attenuation of chlorinated ethenes in a Quaternary alluvial aquifer located close to a historical source of large-scale tetrachloroethylene (PCE) contamination. Distinct stratification of redox zones was observed, despite the aquifer's small thickness (2.8 m). The uppermost zone of the target aquifer was characterised by oxygen- and nitrate-reducing conditions, with mixed iron- to sulphate-reducing conditions dominant in the lower zone, along with indications of methanogenesis. Natural attenuation of PCE was strongly influenced by redox heterogeneity, while higher levels of PCE degradation coincided with iron- to sulphate reducing conditions. Next generation sequencing of the middle and/or lower zones identified anaerobic bacteria (Firmicutes, Chloroflexi, Actinobacteria and Bacteroidetes) associated with reductive dechlorination. The relative abundance of dechlorinators (Dehalococcoides mccartyi, Dehalobacter sp.) identified by real-time PCR in soil from the lower levels supports the hypothesis that there is a significant potential for reductive dechlorination of PCE. Local conditions were insufficiently reducing for rapid complete dechlorination of PCE to harmless ethene. For reliable assessment of natural attenuation, or when designing monitoring or remedial systems, vertical stratification of key biological and hydrochemical markers should be analysed as standard, even in shallow aquifers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Effects of Grain Size on Ultrasonic Attenuation in Type 316L Stainless Steel

    PubMed Central

    Wan, Tao; Wakui, Takashi; Futakawa, Masatoshi; Obayashi, Hironari

    2017-01-01

    A lead bismuth eutectic (LBE) spallation target will be installed in the Target Test Facility (TEF-T) in the Japan Proton Accelerator Research Complex (J-PARC). The spallation target vessel filled with LBE is made of type 316L stainless steel. However, various damages, such as erosion/corrosion damage and liquid metal embrittlement caused by contact with flowing LBE at high temperature, and irradiation hardening caused by protons and neutrons, may be inflicted on the target vessel, which will deteriorate the steel and might break the vessel. To monitor the target vessel for prevention of an accident, an ultrasonic technique has been proposed to establish off-line evaluation for estimating vessel material status during the target maintenance period. Basic R&D must be carried out to clarify the dependency of ultrasonic wave propagation behavior on material microstructures and obtain fundamental knowledge. As a first step, ultrasonic waves scattered by the grains of type 316L stainless steel are investigated using new experimental and numerical approaches in the present study. The results show that the grain size can be evaluated exactly and quantitatively by calculating the attenuation coefficient of the ultrasonic waves scattered by the grains. The results also show that the scattering regimes of ultrasonic waves depend heavily on the ratio of wavelength to average grain size, and are dominated by grains of extraordinarily large size along the wave propagation path. PMID:28773115

  6. Attenuation correction strategies for multi-energy photon emitters using SPECT

    NASA Astrophysics Data System (ADS)

    Pretorius, P. H.; King, M. A.; Pan, T.-S.; Hutton, B. F.

    1997-06-01

    The aim of this study was to investigate whether the photopeak window projections from different energy photons can be combined into a single window for reconstruction or if it is better to not combine the projections due to differences in the attenuation maps required for each photon energy. The mathematical cardiac torso (MCAT) phantom was modified to simulate the uptake of Ga-67 in the human body. Four spherical hot tumors were placed in locations which challenged attenuation correction. An analytical 3D projector with attenuation and detector response included was used to generate projection sets. Data were reconstructed using filtered backprojection (FBP) reconstruction with Butterworth filtering in conjunction with one iteration of Chang attenuation correction, and with 5 and 10 iterations of ordered-subset maximum-likelihood expectation maximization (ML-OS) reconstruction. To serve as a standard for comparison, the projection sets obtained from the two energies were first reconstructed separately using their own attenuation maps. The emission data obtained from both energies were added and reconstructed using the following attenuation strategies: 1) the 93 keV attenuation map for attenuation correction, 2) the 185 keV attenuation map for attenuation correction, 3) using a weighted mean obtained from combining the 93 keV and 185 keV maps, and 4) an ordered subset approach which combines both energies. The central count ratio (CCR) and total count ratio (TCR) were used to compare the performance of the different strategies. Compared to the standard method, results indicate an over-estimation with strategy 1, an under-estimation with strategy 2 and comparable results with strategies 3 and 4. In all strategies, the CCRs of sphere 4 (in proximity to the liver, spleen and backbone) were under-estimated, although TCRs were comparable to that of the other locations. The weighted mean and ordered subset strategies for attenuation correction were of comparable

  7. Attenuation correction strategies for multi-energy photon emitters using SPECT

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

    Pretorius, P.H.; King, M.A.; Pan, T.S.

    1996-12-31

    The aim of this study was to investigate whether the photopeak window projections from different energy photons can be combined into a single window for reconstruction or if it is better to not combine the projections due to differences in the attenuation maps required for each photon energy. The mathematical cardiac torso (MCAT) phantom was modified to simulate the uptake of Ga-67 in the human body. Four spherical hot tumors were placed in locations which challenged attenuation correction. An analytical 3D projector with attenuation and detector response included was used to generate projection sets. Data were reconstructed using filtered backprojectionmore » (FBP) reconstruction with Butterworth filtering in conjunction with one iteration of Chang attenuation correction, and with 5 and 10 iterations of ordered-subset maximum-likelihood expectation-maximization reconstruction. To serve as a standard for comparison, the projection sets obtained from the two energies were first reconstructed separately using their own attenuation maps. The emission data obtained from both energies were added and reconstructed using the following attenuation strategies: (1) the 93 keV attenuation map for attenuation correction, (2) the 185 keV attenuation map for attenuation correction, (3) using a weighted mean obtained from combining the 93 keV and 185 keV maps, and (4) an ordered subset approach which combines both energies. The central count ratio (CCR) and total count ratio (TCR) were used to compare the performance of the different strategies. Compared to the standard method, results indicate an over-estimation with strategy 1, an under-estimation with strategy 2 and comparable results with strategies 3 and 4. In all strategies, the CCR`s of sphere 4 were under-estimated, although TCR`s were comparable to that of the other locations. The weighted mean and ordered subset strategies for attenuation correction were of comparable accuracy to reconstruction of the windows

  8. Earth-Space Link Attenuation Estimation via Ground Radar Kdp

    NASA Technical Reports Server (NTRS)

    Bolen, Steven M.; Benjamin, Andrew L.; Chandrasekar, V.

    2003-01-01

    A method of predicting attenuation on microwave Earth/spacecraft communication links, over wide areas and under various atmospheric conditions, has been developed. In the area around the ground station locations, a nearly horizontally aimed polarimetric S-band ground radar measures the specific differential phase (Kdp) along the Earth-space path. The specific attenuation along a path of interest is then computed by use of a theoretical model of the relationship between the measured S-band specific differential phase and the specific attenuation at the frequency to be used on the communication link. The model includes effects of rain, wet ice, and other forms of precipitation. The attenuation on the path of interest is then computed by integrating the specific attenuation over the length of the path. This method can be used to determine statistics of signal degradation on Earth/spacecraft communication links. It can also be used to obtain real-time estimates of attenuation along multiple Earth/spacecraft links that are parts of a communication network operating within the radar coverage area, thereby enabling better management of the network through appropriate dynamic routing along the best combination of links.

  9. A depolarization and attenuation experiment using the COMSTAR and CTS satellites

    NASA Technical Reports Server (NTRS)

    Bostian, C. W.; Kauffman, S. R.; Manus, E. A.; Marshall, R. E.; Overstreet, W. P.; Persinger, R. R.; Stutzman, W. L.; Wiley, P. H.

    1978-01-01

    An experiment for measuring precipitation attenuation and depolarization on the CTS 11.7 and the COMSTAR 19.04 and 28.56 GHz downlinks is described. Attenuation scaling, effective path length, and the relationship between isolation and attenuation are discussed. Attenuation and effective path data are presented for the months of July, August, and September, 1977.

  10. Identification of an attenuated barley stripe mosaic virus for the virus-induced gene silencing of pathogenesis-related wheat genes.

    PubMed

    Buhrow, Leann M; Clark, Shawn M; Loewen, Michele C

    2016-01-01

    Virus-induced gene silencing (VIGS) has become an emerging technology for the rapid, efficient functional genomic screening of monocot and dicot species. The barley stripe mosaic virus (BSMV) has been described as an effective VIGS vehicle for the evaluation of genes involved in wheat and barley phytopathogenesis; however, these studies have been obscured by BSMV-induced phenotypes and defense responses. The utility of BSMV VIGS may be improved using a BSMV genetic background which is more tolerable to the host plant especially upon secondary infection of highly aggressive, necrotrophic pathogens such as Fusarium graminearum. BSMV-induced VIGS in Triticum aestivum (bread wheat) cv. 'Fielder' was assessed for the study of wheat genes putatively related to Fusarium Head Blight (FHB), the necrotrophism of wheat and other cereals by F. graminearum. Due to the lack of 'Fielder' spike viability and increased accumulation of Fusarium-derived deoxynivalenol contamination upon co-infection of BSMV and FHB, an attenuated BSMV construct was generated by the addition of a glycine-rich, C-terminal peptide to the BSMV γ b protein. This attenuated BSMV effectively silenced target wheat genes while limiting disease severity, deoxynivalenol contamination, and yield loss upon Fusarium co-infection compared to the original BSMV construct. The attenuated BSMV-infected tissue exhibited reduced abscisic, jasmonic, and salicylic acid defense phytohormone accumulation upon secondary Fusarium infection. Finally, the attenuated BSMV was used to investigate the role of the salicylic acid-responsive pathogenesis-related 1 in response to FHB. The use of an attenuated BSMV may be advantageous in characterizing wheat genes involved in phytopathogenesis, including Fusarium necrotrophism, where minimal viral background effects on defense are required. Additionally, the attenuated BSMV elicits reduced defense hormone accumulation, suggesting that this genotype may have applications for the

  11. The Seismic Attenuation Structure of the East Pacific Rise

    DTIC Science & Technology

    1992-02-27

    Kanamori, R. W. Clayton, Three- dimensional attenuation structure of Kilauea -East rift zone, Hawaii , J. Geophys. Res., submitted, 1990. Holt, M., Underwater...and J. J. Zucca, Active high-resolution seismic tomography of compressional wave velocity and attenuation at Medicine Lake volcano , northern California...zones of anomalously high S-wave attenuation in the upper crust near Ruapehu and Ngauruhoe volcanoes , New Zealand, J. Volcanol. Geotherm. Res., 10, 125

  12. Lateral Attenuation of Aircraft Flight Noise.

    DTIC Science & Technology

    1985-03-01

    levels with elevation angle. Comparisons of different Imodels are made in terms of the differences in A - levels for a flyover with the observer directly...attenuation adjustment to be applied to the basic noise data is the same when applied to maximum levels (maximum A - levels for example) or to integrated...attenuation values were applied to sets of one-third octave band spectra for different aircraft The resulting differences in A - levels for these noise spectra

  13. Attenuation Measurements of Cell Pellets Using Through Transmission

    NASA Astrophysics Data System (ADS)

    Vadas, Justin; Greene, Claudia; Grygotis, Emma; Kuhn, Stephen; Mahlalela, Sanele; Newland, Tinisha; Ovutmen, Idil; Herd, Maria-Teresa

    2011-10-01

    A better understanding of differences in ultrasound tissue characteristics (such as speed of sound, attenuation, and backscatter coefficients) of benign compared to malignant cells could lead to improved cancer detection and diagnosis. A narrow band technique for measuring ultrasonic speed of sound and attenuation of small biological materials was developed and tested. Several mechanical improvements were made to the system to drastically improve alignment, allowing for accurate measurements of small cell pellets. Narrow band attenuation measurements were made first with tissue-mimicking phantoms and then with three different types of cell pellets: Chinese hamster ovary cells, healthy human prostate cells, and cancerous human prostate cells. Attenuation and speed of sound results for all three cell types, as well as the culture medium and tissue mimicking phantoms, are presented for a frequency range of 5 to 25 MHz.

  14. Differences in attenuation among the stable continental regions

    USGS Publications Warehouse

    Bakun, W.H.; McGarr, A.

    2002-01-01

    There are systematic differences in the attenuation of damaging earthquake ground motions between different stable continental regions (SCRs). Seismic intensity and weak-motion data show that the attenuation in seismic waves for eastern North America (ENA) is less than for India, Africa, Australia, and northwest Europe. If ENA ground-motion attenuation relations are used in seismic hazard models for other SCRs, as is commonly done, then the estimated ground motions and resulting hazard may be too large. If an attenuation model that averages observations from ENA and the other SCRs is used to estimate the magnitudes of large historical earthquakes in ENA, as is the case for recent estimates of M for the 1811-1812 New Madrid, Missouri and the 1886 Charleston, South Carolina events, then the magnitude estimates for these events will be too large, as will be the resulting hazard.

  15. X-Ray Form Factor, Attenuation and Scattering Tables

    National Institute of Standards and Technology Data Gateway

    SRD 66 X-Ray Form Factor, Attenuation and Scattering Tables (Web, free access)   This database collects tables and graphs of the form factors, the photoabsorption cross section, and the total attenuation coefficient for any element (Z <= 92).

  16. Image quality assessment of automatic three-segment MR attenuation correction vs. CT attenuation correction.

    PubMed

    Partovi, Sasan; Kohan, Andres; Gaeta, Chiara; Rubbert, Christian; Vercher-Conejero, Jose L; Jones, Robert S; O'Donnell, James K; Wojtylak, Patrick; Faulhaber, Peter

    2013-01-01

    The purpose of this study is to systematically evaluate the usefulness of Positron emission tomography/Magnetic resonance imaging (PET/MRI) images in a clinical setting by assessing the image quality of Positron emission tomography (PET) images using a three-segment MR attenuation correction (MRAC) versus the standard CT attenuation correction (CTAC). We prospectively studied 48 patients who had their clinically scheduled FDG-PET/CT followed by an FDG-PET/MRI. Three nuclear radiologists evaluated the image quality of CTAC vs. MRAC using a Likert scale (five-point scale). A two-sided, paired t-test was performed for comparison purposes. The image quality was further assessed by categorizing it as acceptable (equal to 4 and 5 on the five-point Likert scale) or unacceptable (equal to 1, 2, and 3 on the five-point Likert scale) quality using the McNemar test. When assessing the image quality using the Likert scale, one reader observed a significant difference between CTAC and MRAC (p=0.0015), whereas the other readers did not observe a difference (p=0.8924 and p=0.1880, respectively). When performing the grouping analysis, no significant difference was found between CTAC vs. MRAC for any of the readers (p=0.6137 for reader 1, p=1 for reader 2, and p=0.8137 for reader 3). All three readers more often reported artifacts on the MRAC images than on the CTAC images. There was no clinically significant difference in quality between PET images generated on a PET/MRI system and those from a Positron emission tomography/Computed tomography (PET/CT) system. PET images using the automatic three-segmented MR attenuation method provided diagnostic image quality. However, future research regarding the image quality obtained using different MR attenuation based methods is warranted before PET/MRI can be used clinically.

  17. Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

    PubMed Central

    Zhang, Jing; Fan, Ying; Zeng, Chuchu; He, Li; Wang, Niansong

    2016-01-01

    Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN). Endoplasmic reticulum (ER) stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA) is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p.) twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN. PMID:27669287

  18. MLAA-based RF surface coil attenuation estimation in hybrid PET/MR imaging

    NASA Astrophysics Data System (ADS)

    Heußer, Thorsten; Rank, Christopher M.; Freitag, Martin T.; Kachelrieß, Marc

    2017-03-01

    Attenuation correction (AC) for both patient and hardware attenuation of the 511 keV annihilation photons is required for accurate PET quantification. In hybrid PET/MR imaging, AC for stationary hardware components such as patient table and MR head coil is performed using CT{derived attenuation templates. AC for flexible hardware components such as MR radiofrequency (RF) surface coils is more challenging. Registration{based approaches, aligning scaled CT{derived attenuation templates with the current patient position, have been proposed but are not used in clinical routine. Ignoring RF coil attenuation has been shown to result in regional activity underestimation values of up to 18 %. We propose to employ a modified version of the maximum{ likelihood reconstruction of attenuation and activity (MLAA) algorithm to obtain an estimate of the RF coil attenuation. Starting with an initial attenuation map not including the RF coil, the attenuation update of MLAA is applied outside the body outline only, allowing to estimate RF coil attenuation without changing the patient attenuation map. Hence, the proposed method is referred to as external MLAA (xMLAA). In this work, xMLAA for RF surface coil attenuation estimation is investigated using phantom and patient data acquired with a Siemens Biograph mMR. For the phantom data, average activity errors compared to the ground truth was reduced from -8:1% to +0:8% when using the proposed method. Patient data revealed an average activity underestimation of -6:1% for the abdominal region and -5:3% for the thoracic region when ignoring RF coil attenuation.

  19. Ionotropic and metabotropic glutamate receptor antagonism attenuates cue-induced cocaine seeking.

    PubMed

    Bäckström, Pia; Hyytiä, Petri

    2006-04-01

    Neuroanatomical and pharmacological evidence implicates glutamate transmission in drug-environment conditioning that partly controls drug seeking and relapse. Glutamate receptors could be targets for pharmacological attenuation of the motivational properties of drug-paired cues and for relapse prevention. The purpose of the present study was therefore to investigate the involvement of ionotropic and metabotropic glutamate receptor subtypes in cue-induced reinstatement of cocaine-seeking behavior. Rats were trained to self-administer cocaine using a second-order schedule of reinforcement (FR4(FR5:S)) under which a compound stimulus (light and tone) associated with cocaine infusions was presented contingently. Following extinction, the effects of the competitive NMDA receptor antagonist CGP 39551 (0, 2.5, 5, 10 mg/kg intraperitoneally (i.p.)), two competitive AMPA/kainate antagonists, CNQX (0, 0.75, 1.5, 3 mg/kg i.p.) and NBQX (0, 1.25, 2.5, 5 mg/kg i.p.), the NMDA/glycine site antagonist L-701,324 (0, 0.63, 1.25, 2.5 mg/kg i.p.), and the mGluR5 antagonist MPEP (0, 1.25, 2.5, 5 mg/kg i.p.) on cue-induced reinstatement of cocaine seeking were examined. The AMPA/kainate receptor antagonists CNQX and NBQX, the NMDA/glycine site antagonist L-701,324, and the mGluR5 antagonist MPEP attenuated significantly cue-induced reinstatement. The NMDA antagonist CGP 39551 failed to affect reinstatement. Additional control experiments indicated that attenuation of cue-induced reinstatement by CNQX, NBQX, L-701,324, and MPEP was not accompanied by significant suppression of spontaneous locomotor activity. These results suggest that conditioned influences on cocaine seeking depend on glutamate transmission. Accordingly, drugs with antagonist properties at various glutamate receptor subtypes could be useful in prevention of relapse induced by conditioned stimuli.

  20. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

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

    Yu, Xiao-Jing; Zhang, Dong-Mei; Jia, Lin-Lin

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocytemore » diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of

  1. A two-component rain model for the prediction of attenuation statistics

    NASA Technical Reports Server (NTRS)

    Crane, R. K.

    1982-01-01

    A two-component rain model has been developed for calculating attenuation statistics. In contrast to most other attenuation prediction models, the two-component model calculates the occurrence probability for volume cells or debris attenuation events. The model performed significantly better than the International Radio Consultative Committee model when used for predictions on earth-satellite paths. It is expected that the model will have applications in modeling the joint statistics required for space diversity system design, the statistics of interference due to rain scatter at attenuating frequencies, and the duration statistics for attenuation events.

  2. Determination of the temperature of bremsstrahlung photon generated by ultraintense laser using various thickness attenuators

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

    Hasegawa, Shuichi; Takashima, Ryuta; Todoriki, Masaru

    2011-03-15

    We evaluate the simplified method using the Lambert-Beer law to measure the temperature of bremsstrahlung photon generated by an ultraintense laser. Analytical values are compared to the results of the Monte Carlo calculation of GEANT4 and they agreed very well on the condition of the appropriate distance between the attenuator and the detector. We performed the experiment to measure the temperature of bremsstrahlung x-ray emitted from a metal target irradiated by a Ti:sapphire laser with 76 mJ, 72 fs, 2.2 x 10{sup 18} W/cm{sup 2}. For a Cu target of 30 {mu}m thick, the photon temperature was reasonably determined tomore » be 0.18 MeV, which is in good agreement with previous studies.« less

  3. Impact of Scattering Model on Disdrometer Derived Attenuation Scaling

    NASA Technical Reports Server (NTRS)

    Zemba, Michael; Luini, Lorenzo; Nessel, James; Riva, Carlo (Compiler)

    2016-01-01

    NASA Glenn Research Center (GRC), the Air Force Research Laboratory (AFRL), and the Politecnico di Milano (POLIMI) are currently entering the third year of a joint propagation study in Milan, Italy utilizing the 20 and 40 GHz beacons of the Alphasat TDP5 Aldo Paraboni scientific payload. The Ka- and Q-band beacon receivers were installed at the POLIMI campus in June of 2014 and provide direct measurements of signal attenuation at each frequency. Collocated weather instrumentation provides concurrent measurement of atmospheric conditions at the receiver; included among these weather instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which records droplet size distributions (DSD) and droplet velocity distributions (DVD) during precipitation events. This information can be used to derive the specific attenuation at frequencies of interest and thereby scale measured attenuation data from one frequency to another. Given the ability to both predict the 40 GHz attenuation from the disdrometer and the 20 GHz timeseries as well as to directly measure the 40 GHz attenuation with the beacon receiver, the Milan terminal is uniquely able to assess these scaling techniques and refine the methods used to infer attenuation from disdrometer data.In order to derive specific attenuation from the DSD, the forward scattering coefficient must be computed. In previous work, this has been done using the Mie scattering model, however, this assumes a spherical droplet shape. The primary goal of this analysis is to assess the impact of the scattering model and droplet shape on disdrometer derived attenuation predictions by comparing the use of the Mie scattering model to the use of the T-matrix method, which does not assume a spherical droplet. In particular, this paper will investigate the impact of these two scattering approaches on the error of the resulting predictions as well as on the relationship between prediction error and rain rate.

  4. Impact of Scattering Model on Disdrometer Derived Attenuation Scaling

    NASA Technical Reports Server (NTRS)

    Zemba, Michael; Luini, Lorenzo; Nessel, James; Riva, Carlo

    2016-01-01

    NASA Glenn Research Center (GRC), the Air Force Research Laboratory (AFRL), and the Politecnico di Milano (POLIMI) are currently entering the third year of a joint propagation study in Milan, Italy utilizing the 20 and 40 GHz beacons of the Alphasat TDP#5 Aldo Paraboni scientific payload. The Ka- and Q-band beacon receivers were installed at the POLIMI campus in June of 2014 and provide direct measurements of signal attenuation at each frequency. Collocated weather instrumentation provides concurrent measurement of atmospheric conditions at the receiver; included among these weather instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which records droplet size distributions (DSD) and droplet velocity distributions (DVD) during precipitation events. This information can be used to derive the specific attenuation at frequencies of interest and thereby scale measured attenuation data from one frequency to another. Given the ability to both predict the 40 gigahertz attenuation from the disdrometer and the 20 gigahertz time-series as well as to directly measure the 40 gigahertz attenuation with the beacon receiver, the Milan terminal is uniquely able to assess these scaling techniques and refine the methods used to infer attenuation from disdrometer data. In order to derive specific attenuation from the DSD, the forward scattering coefficient must be computed. In previous work, this has been done using the Mie scattering model, however, this assumes a spherical droplet shape. The primary goal of this analysis is to assess the impact of the scattering model and droplet shape on disdrometer-derived attenuation predictions by comparing the use of the Mie scattering model to the use of the T-matrix method, which does not assume a spherical droplet. In particular, this paper will investigate the impact of these two scattering approaches on the error of the resulting predictions as well as on the relationship between prediction error and rain rate.

  5. Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments

    PubMed Central

    Hill, Terence E.; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Slack, Olga A. L.; Ly, Hoai J.; Lokugamage, Nandadeva; Freiberg, Alexander N.

    2015-01-01

    ABSTRACT Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. IMPORTANCE Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to

  6. Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments.

    PubMed

    Ikegami, Tetsuro; Hill, Terence E; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Slack, Olga A L; Ly, Hoai J; Lokugamage, Nandadeva; Freiberg, Alexander N

    2015-07-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to spread into other

  7. On the estimation of risk associated with an attenuation prediction

    NASA Technical Reports Server (NTRS)

    Crane, R. K.

    1992-01-01

    Viewgraphs from a presentation on the estimation of risk associated with an attenuation prediction is presented. Topics covered include: link failure - attenuation exceeding a specified threshold for a specified time interval or intervals; risk - the probability of one or more failures during the lifetime of the link or during a specified accounting interval; the problem - modeling the probability of attenuation by rainfall to provide a prediction of the attenuation threshold for a specified risk; and an accounting for the inadequacy of a model or models.

  8. Using seismic coda waves to resolve intrinsic and scattering attenuation

    NASA Astrophysics Data System (ADS)

    Wang, W.; Shearer, P. M.

    2016-12-01

    Seismic attenuation is caused by two factors, scattering and intrinsic absorption. Characterizing scattering and absorbing properties and the power spectrum of crustal heterogeneity is a fundamental problem for informing strong ground motion estimates at high frequencies, where scattering and attenuation effects are critical. Determining the relative amount of attenuation caused by scattering and intrinsic absorption has been a long-standing problem in seismology. The wavetrain following the direct body wave phases is called the coda, which is caused by scattered energy. Many studies have analyzed the coda of local events to constrain crustal and upper-mantle scattering strength and intrinsic attenuation. Here we examine two popular attenuation inversion methods, the Multiple Lapse Time Window Method (MLTWM) and the Coda Qc Method. First, based on our previous work on California attenuation structure, we apply an efficient and accurate method, the Monte Carlo Approach, to synthesize seismic envelope functions. We use this code to generate a series of synthetic data based on several complex and realistic forward models. Although the MLTWM assumes a uniform whole space, we use the MLTWM to invert for both scattering and intrinsic attenuation from the synthetic data to test how accurately it can recover the attenuation models. Results for the coda Qc method depend on choices for the length and starting time of the coda-wave time window. Here we explore the relation between the inversion results for Qc, the windowing parameters, and the intrinsic and scattering Q structure of our synthetic model. These results should help assess the practicality and accuracy of the Multiple Lapse Time Window Method and Coda Qc Method when applied to realistic crustal velocity and attenuation models.

  9. DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

    PubMed Central

    Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

    2013-01-01

    Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

  10. Quantitative analysis of MRI-guided attenuation correction techniques in time-of-flight brain PET/MRI.

    PubMed

    Mehranian, Abolfazl; Arabi, Hossein; Zaidi, Habib

    2016-04-15

    In quantitative PET/MR imaging, attenuation correction (AC) of PET data is markedly challenged by the need of deriving accurate attenuation maps from MR images. A number of strategies have been developed for MRI-guided attenuation correction with different degrees of success. In this work, we compare the quantitative performance of three generic AC methods, including standard 3-class MR segmentation-based, advanced atlas-registration-based and emission-based approaches in the context of brain time-of-flight (TOF) PET/MRI. Fourteen patients referred for diagnostic MRI and (18)F-FDG PET/CT brain scans were included in this comparative study. For each study, PET images were reconstructed using four different attenuation maps derived from CT-based AC (CTAC) serving as reference, standard 3-class MR-segmentation, atlas-registration and emission-based AC methods. To generate 3-class attenuation maps, T1-weighted MRI images were segmented into background air, fat and soft-tissue classes followed by assignment of constant linear attenuation coefficients of 0, 0.0864 and 0.0975 cm(-1) to each class, respectively. A robust atlas-registration based AC method was developed for pseudo-CT generation using local weighted fusion of atlases based on their morphological similarity to target MR images. Our recently proposed MRI-guided maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm was employed to estimate the attenuation map from TOF emission data. The performance of the different AC algorithms in terms of prediction of bones and quantification of PET tracer uptake was objectively evaluated with respect to reference CTAC maps and CTAC-PET images. Qualitative evaluation showed that the MLAA-AC method could sparsely estimate bones and accurately differentiate them from air cavities. It was found that the atlas-AC method can accurately predict bones with variable errors in defining air cavities. Quantitative assessment of bone extraction accuracy based on

  11. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction

    PubMed Central

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2016-01-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  12. Patient position alters attenuation effects in multipinhole cardiac SPECT

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

    Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn, E-mail: gwells@ottawaheart.ca

    2015-03-15

    Purpose: Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Methods: Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic andmore » a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Results: Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of <1.5 for the water phantom but up to 4.2 in the anthropomorphic phantom. Changes were larger for axial than for transverse translations. These results were supported by SPS changes of up to six seen in the physical anthropomorphic phantom for axial translations. Defect width was also seen to significantly increase

  13. Targeting Epigenetics to Prevent Obesity Promoted Cancers.

    PubMed

    Berger, Nathan A; Scacheri, Peter C

    2018-03-01

    Epigenetic changes in DNA and associated chromatin proteins are increasingly being considered as important mediators of the linkage between obesity and cancer. Although multiple agents, targeted at epigenetic changes, are being tested for therapy of established cancers, this issue of Cancer Prevention Research carries two articles demonstrating that the bromodomain inhibitor I-BET-762 can attenuate adipose tissue-promoted cancers. Although I-BET-762 significantly delayed, rather than completely prevented, the onset of adiposity-promoted transformation and malignancy, these experiments provide important proof of principle for the strategies of targeting epigenetic changes to disrupt the obesity-cancer linkage. Because bromodomain proteins represent only one of multiple epigenetic mediators, it is probable that targeting other epigenetic processes, alone or in combination, may serve to even more effectively disrupt the obesity promotion of cancer. Given the magnitude of the current obesity pandemic and its impact on cancer, preventive measures to disrupt this linkage are critically important. Cancer Prev Res; 11(3); 125-8. ©2018 AACR See related article by Chakraborty et al., p. 129 . ©2018 American Association for Cancer Research.

  14. Intensity attenuation in the Pannonian Basin

    NASA Astrophysics Data System (ADS)

    Győri, Erzsébet; Gráczer, Zoltán; Szanyi, Gyöngyvér

    2015-04-01

    Ground motion prediction equations play a key role in seismic hazard assessment. Earthquake hazard has to be expressed in macroseismic intensities in case of seismic risk estimations where a direct relation to the damage associated with ground shaking is needed. It can be also necessary for shake map generation where the map is used for prompt notification to the public, disaster management officers and insurance companies. Although only few instrumental strong motion data are recorded in the Pannonian Basin, there are numerous historical reports of past earthquakes since the 1763 Komárom earthquake. Knowing the intensity attenuation and comparing them with relations of other areas - where instrumental strong motion data also exist - can help us to choose from the existing instrumental ground motion prediction equations. The aim of this work is to determine an intensity attenuation formula for the inner part of the Pannonian Basin, which can be further used to find an adaptable ground motion prediction equation for the area. The crust below the Pannonian Basin is thin and warm and it is overlain by thick sediments. Thus the attenuation of seismic waves here is different from the attenuation in the Alp-Carpathian mountain belt. Therefore we have collected intensity data only from the inner part of the Pannonian Basin and defined the boundaries of the studied area by the crust thickness of 30 km (Windhoffer et al., 2005). 90 earthquakes from 1763 until 2014 have sufficient number of macroseismic data. Magnitude of the events varies from 3.0 to 6.6. We have used individual intensity points to eliminate the subjectivity of drawing isoseismals, the number of available intensity data is more than 3000. Careful quality control has been made on the dataset. The different types of magnitudes of the used earthquake catalogue have been converted to local and momentum magnitudes using relations determined for the Pannonian Basin. We applied the attenuation formula by Sorensen

  15. Attenuation of sonic waves in water-saturated alluvial sediments due to wave-induced fluid flow at microscopic, mesoscopic and macroscopic scales

    NASA Astrophysics Data System (ADS)

    Milani, Marco; Rubino, J. Germán; Baron, Ludovic; Sidler, Rolf; Holliger, Klaus

    2015-10-01

    The attenuation and velocity dispersion of sonic waves contain valuable information on the mechanical and hydraulic properties of the probed medium. An inherent complication arising in the interpretation of corresponding measurements is, however, that there are multiple physical mechanisms contributing to the energy dissipation and that the relative importance of the various contributions is difficult to unravel. To address this problem for the practically relevant case of terrestrial alluvial sediments, we analyse the attenuation and velocity dispersion characteristics of broad-band multifrequency sonic logs with dominant source frequencies ranging between 1 and 30 kHz. To adequately compensate for the effects of geometrical spreading, which is critical for reliable attenuation estimates, we simulate our experimental setup using a correspondingly targeted numerical solution of the poroelastic equations. After having applied the thus inferred corrections, the broad-band sonic log data set, in conjunction with a comprehensive suite of complementary logging data, allows for assessing the relative importance of a range of pertinent attenuation mechanisms. In doing so, we focus on the effects of wave-induced fluid flow over a wide range of scales. Our results indicate that the levels of attenuation due to the presence of mesoscopic heterogeneities in unconsolidated clastic sediments fully saturated with water are expected to be largely negligible. Conversely, Monte-Carlo-type inversions indicate that Biot's classical model permits to explain most of the considered data. Refinements with regard to the fitting of the observed attenuation and velocity dispersion characteristics are locally provided by accounting for energy dissipation at the microscopic scale, although the nature of the underlying physical mechanism remains speculative.

  16. Nutrient attenuation in rivers and streams, Puget Sound Basin, Washington

    USGS Publications Warehouse

    Sheibley, Rich W.; Konrad, Christopher P.; Black, Robert W.

    2015-01-01

    From a management perspective, preservation and improvement of instream nutrient attenuation should focus on increasing the travel time through a reach and contact time of water sediment (reactive) surfaces and lowering nutrient concentrations (and loads) to avoid saturation of instream attenuation and increase attenuation efficiency. These goals can be reached by maintaining and restoring channel-flood plain connectivity, maintaining and restoring healthy riparian zones along streams, managing point and nonpoint nutrient loads to streams and rivers, and restoring channel features that promote attenuation such as the addition of woody debris and maintaining pool-riffle morphologies. Many of these management approaches are already being undertaken during projects aimed to restore quality salmon habitat. Therefore, there is a dual benefit to these projects that also may lead to enhanced potential for nitrogen and phosphorus attenuation.

  17. MicroRNA-mediated species-specific attenuation of influenza A virus.

    PubMed

    Perez, Jasmine T; Pham, Alissa M; Lorini, Maria H; Chua, Mark A; Steel, John; tenOever, Benjamin R

    2009-06-01

    Influenza A virus leads to yearly epidemics and sporadic pandemics. Present prophylactic strategies focus on egg-grown, live, attenuated influenza vaccines (LAIVs), in which attenuation is generated by conferring temperature sensitivity onto the virus. Here we describe an alternative approach to attenuating influenza A virus based on microRNA-mediated gene silencing. By incorporating nonavian microRNA response elements (MREs) into the open-reading frame of the viral nucleoprotein, we generate reassortant LAIVs for H1N1 and H5N1 that are attenuated in mice but not in eggs. MRE-based LAIVs show a greater than two-log reduction in mortality compared with control viruses lacking MREs and elicit a diverse antibody response. This approach might be combined with existing LAIVs to increase attenuation and improve vaccine safety.

  18. CT-based attenuation and scatter correction compared with uniform attenuation correction in brain perfusion SPECT imaging for dementia

    NASA Astrophysics Data System (ADS)

    Gillen, Rebecca; Firbank, Michael J.; Lloyd, Jim; O'Brien, John T.

    2015-09-01

    This study investigated if the appearance and diagnostic accuracy of HMPAO brain perfusion SPECT images could be improved by using CT-based attenuation and scatter correction compared with the uniform attenuation correction method. A cohort of subjects who were clinically categorized as Alzheimer’s Disease (n=38 ), Dementia with Lewy Bodies (n=29 ) or healthy normal controls (n=30 ), underwent SPECT imaging with Tc-99m HMPAO and a separate CT scan. The SPECT images were processed using: (a) correction map derived from the subject’s CT scan or (b) the Chang uniform approximation for correction or (c) no attenuation correction. Images were visually inspected. The ratios between key regions of interest known to be affected or spared in each condition were calculated for each correction method, and the differences between these ratios were evaluated. The images produced using the different corrections were noted to be visually different. However, ROI analysis found similar statistically significant differences between control and dementia groups and between AD and DLB groups regardless of the correction map used. We did not identify an improvement in diagnostic accuracy in images which were corrected using CT-based attenuation and scatter correction, compared with those corrected using a uniform correction map.

  19. Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration.

    PubMed

    Zhang, Duo; Li, Xihua; Chen, Chuchu; Li, Yuyin; Zhao, Lei; Jing, Yanyan; Liu, Wei; Wang, Xiaoyun; Zhang, Ying; Xia, Hongfeng; Chang, Yaning; Gao, Xiang; Yan, Jun; Ying, Hao

    2012-01-01

    Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration.

  20. Rain attenuation statistics over millimeter wave bands in South Korea

    NASA Astrophysics Data System (ADS)

    Shrestha, Sujan; Choi, Dong-You

    2017-01-01

    Rain induced degradations are significant for terrestrial microwave links operating at frequencies higher than 10 GHz. Paper presents analyses done on rain attenuation and rainfall data for three years between 2013 till 2015, in 3.2 km experimental link of 38 GHz and 0.1 km link at 75 GHz. The less link distance is maintained for 75 GHz operating frequency in order to have better recording of propagation effect as such attenuation induced by rain. OTT Parsivel is used for collection of rain rate database which show rain rate of about 50 mm/h and attenuation values of 20.89 and 28.55 dB are obtained at 0.01% of the time for vertical polarization under 38 and 75 GHz respectively. Prediction models, namely, ITU-R P. 530-16, Da Silva Mello, Moupfouma, Abdulrahman, Lin and differential equation approach are analyzed. This studies help to identify most suitable rain attenuation model for higher microwave bands. While applying ITU-R P. 530-16, the relative error margin of about 3%, 38% and 42% along with 80, 70, 61% were obtained in 0.1%, 0.01% and 0.001% of the time for vertical polarization under 38 and 75 GHz respectively. Interestingly, ITU-R P. 530-16 shows relatively closer estimation to measured rain attenuation at 75 GHz with relatively less error probabilities and additionally, Abdulrahman and ITU-R P. 530-16 results in better estimation to the measured rain attenuation at 38 GHz link. The performance of prominent rain attenuation models are judged with different error matrices as recommended by ITU-R P. 311-15. Furthermore, the efficacy of frequency scaling technique of rain attenuation between links distribution are also discussed. This study shall be useful for making good considerations in rain attenuation predictions for terrestrial link operating at higher frequencies.

  1. Shock wave attenuation in a micro-channel

    NASA Astrophysics Data System (ADS)

    Giordano, J.; Perrier, P.; Meister, L.; Brouillette, M.

    2018-05-01

    This work presents optical measurements of shock wave attenuation in a glass micro-channel. This transparent facility, with a cross section ranging from 1 mm× 150 μm to 1 mm× 500 μm, allowed for the use of high-speed schlieren videography to visualize the propagation of a shock wave within the entire micro-channel and to quantify velocity attenuation of the wave due to wall effects. In this paper, we present the experimental technique and the relevant data treatment we have used to increase the sensitivity of shock wave detection. Then, we compared our experimental results for different channel widths, lengths, and shock wave velocities with the analytical model for shock attenuation proposed by Russell (J Fluid Mech 27(2):305-314, 1967), which assumes laminar flow, and by Mirels (Attenuation in a shock tube due to unsteady-boundary-layer action, NACA Report 1333, 1957) for turbulent flow. We found that these models are inadequate to predict the observed data, owing to the presence of fully developed flow which violates the basic assumption of these models. The data are also compared with the empirical shock attenuation models proposed by Zeitoun (Phys Fluids 27(1):011701, 2015) and Deshpande and Puranik (Shock Waves 26(4):465-475, 2016), where better agreement is observed. Finally, we presented experimental data for the flow field behind the shock wave from measurements of the Mach wave angle which shows globally decreasing flow Mach numbers due to viscous wall effects.

  2. MODIS Solar Diffuser Attenuation Screen Modeling Results

    NASA Technical Reports Server (NTRS)

    Waluschka, Eugene; Xuong, Xiaoxiong; Guenther, Bruce; Barnes, William

    2004-01-01

    On-orbit calibration of the reflected solar bands on the EOS Moderate Resolution Imaging Spectroradiometer (MODIS) is accomplished by have the instrument view a high reflectance diffuse surface illuminated by the sun. For some of the spectral bands this proves to be much too bright a signal that results in the saturation of detectors designed for measuring low reflectance (ocean) surfaces signals. A mechanical attenuation device in the form of a pin hole screen is used to reduce the signals to calibrate these bands. The sensor response to solar illumination of the SD with and without the attenuation screen in place will be presented. The MODIS detector response to the solar diffuser is smooth when the attenuation screen is absent, but has structures up to a few percent when the attenuation screen is present. This structure corresponds to non-uniform illumination from the solar diffuser. Each pin hole produces a pin-hole image of the sun on the solar diffuser, and there are very many pin hole images of the sun on the solar diffuser for each MODIS detector. Even though there are very many pin-hole images of the sun on the solar diffuser, it is no longer perfectly uniformly illuminated. This non-uniformly illuminated solar diffuser produces intensity variation on the focal planes. The results of a very detailed simulation will be discussed which show how the illumination of the focal plane changes as a result of the attenuation, and the impacts on the calibration will be discussed.

  3. Kissing-loop interaction between 5′ and 3′ ends of tick-borne Langat virus genome ‘bridges the gap’ between mosquito- and tick-borne flaviviruses in mechanisms of viral RNA cyclization: applications for virus attenuation and vaccine development

    PubMed Central

    Tsetsarkin, Konstantin A.; Liu, Guangping; Shen, Kui; Pletnev, Alexander G.

    2016-01-01

    Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective pressure, restricting their use in vaccine development. To overcome this limitation, we developed a new approach for miRNA-targeting of tick-borne flavivirus (Langat virus, LGTV) in the duplicated capsid gene region (DCGR). Genetic stability of viruses with DCGR was ensured by the presence of multiple cis-acting elements within the N-terminal capsid coding region, including the stem-loop structure (5′SL6) at the 3′ end of the promoter. We found that the 5′SL6 functions as a structural scaffold for the conserved hexanucleotide motif at its tip and engages in a complementary interaction with the region present in the 3′ NCR to enhance viral RNA replication. The resulting kissing-loop interaction, common in tick-borne flaviviruses, supports a single pair of cyclization elements (CYC) and functions as a homolog of the second pair of CYC that is present in the majority of mosquito-borne flaviviruses. Placing miRNA targets into the DCGR results in superior attenuation of LGTV in the CNS and does not interfere with development of protective immunity in immunized mice. PMID:26850640

  4. A funny thing happened on the way to articulation: N400 attenuation despite behavioral interference in picture naming

    PubMed Central

    Blackford, Trevor; Holcomb, Phillip J.; Grainger, Jonathan; Kuperberg, Gina R.

    2013-01-01

    We measured Event-Related Potentials (ERPs) and naming times to picture targets preceded by masked words (stimulus onset asynchrony: 80 ms) that shared one of three different types of relationship with the names of the pictures: (1) Identity related, in which the prime was the name of the picture (“socks” – ), (2) Phonemic Onset related, in which the initial segment of the prime was the same as the name of the picture (“log” – ), and (3) Semantically related in which the prime was a co–category exemplar and associated with the name of the picture (“cake” – ). Each type of related picture target was contrasted with an Unrelated picture target, resulting in a 3 × 2 design that crossed Relationship Type between the word and the target picture (Identity, Phonemic Onset and Semantic) with Relatedness (Related and Unrelated). Modulation of the N400 component to related (versus unrelated) pictures was taken to reflect semantic processing at the interface between the picture's conceptual features and its lemma, while naming times reflected the end product of all stages of processing. Both attenuation of the N400 and shorter naming times were observed to pictures preceded by Identity related (versus Unrelated) words. No ERP effects within 600 ms, but shorter naming times, were observed to pictures preceded by Phonemic Onset related (versus Unrelated) words. An attenuated N400 (electrophysiological semantic priming) but longer naming times (behavioral semantic interference) were observed to pictures preceded by Semantically related (versus Unrelated) words. These dissociations between ERP modulation and naming times suggest that (a) phonemic onset priming occurred late, during encoding of the articulatory response, and (b) semantic behavioral interference was not driven by competition at the lemma level of representation, but rather occurred at a later stage of production. PMID:22245030

  5. Radiance and atmosphere propagation-based method for the target range estimation

    NASA Astrophysics Data System (ADS)

    Cho, Hoonkyung; Chun, Joohwan

    2012-06-01

    Target range estimation is traditionally based on radar and active sonar systems in modern combat system. However, the performance of such active sensor devices is degraded tremendously by jamming signal from the enemy. This paper proposes a simple range estimation method between the target and the sensor. Passive IR sensors measures infrared (IR) light radiance radiating from objects in dierent wavelength and this method shows robustness against electromagnetic jamming. The measured target radiance of each wavelength at the IR sensor depends on the emissive properties of target material and is attenuated by various factors, in particular the distance between the sensor and the target and atmosphere environment. MODTRAN is a tool that models atmospheric propagation of electromagnetic radiation. Based on the result from MODTRAN and measured radiance, the target range is estimated. To statistically analyze the performance of proposed method, we use maximum likelihood estimation (MLE) and evaluate the Cramer-Rao Lower Bound (CRLB) via the probability density function of measured radiance. And we also compare CRLB and the variance of and ML estimation using Monte-Carlo.

  6. Deep magnetic capture of magnetically loaded cells for spatially targeted therapeutics.

    PubMed

    Huang, Zheyong; Pei, Ning; Wang, Yanyan; Xie, Xinxing; Sun, Aijun; Shen, Li; Zhang, Shuning; Liu, Xuebo; Zou, Yunzeng; Qian, Juying; Ge, Junbo

    2010-03-01

    Magnetic targeting has recently demonstrated potential in promoting magnetically loaded cell delivery to target lesion, but its application is limited by magnetic attenuation. For deep magnetic capture of cells for spatial targeting therapeutics, we designed a magnetic pole, in which the magnetic field density can be focused at a distance from the pole. As flowing through a tube served as a model of blood vessels, the magnetically loaded mesenchymal stem cells (MagMSCs) were highly enriched at the site distance from the magnetic pole. The cell capture efficiency was positively influenced by the magnetic flux density, and inversely influenced by the flow velocity, and well-fitted with the deductive value by theoretical considerations. It appeared to us that the spatially-focused property of the magnetic apparatus promises a new deep targeting strategy to promote homing and engraftment for cellular therapy. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  7. Cement-based materials' characterization using ultrasonic attenuation

    NASA Astrophysics Data System (ADS)

    Punurai, Wonsiri

    The quantitative nondestructive evaluation (NDE) of cement-based materials is a critical area of research that is leading to advances in the health monitoring and condition assessment of the civil infrastructure. Ultrasonic NDE has been implemented with varying levels of success to characterize cement-based materials with complex microstructure and damage. A major issue with the application of ultrasonic techniques to characterize cement-based materials is their inherent inhomogeneity at multiple length scales. Ultrasonic waves propagating in these materials exhibit a high degree of attenuation losses, making quantitative interpretations difficult. Physically, these attenuation losses are a combination of internal friction in a viscoelastic material (ultrasonic absorption), and the scattering losses due to the material heterogeneity. The objective of this research is to use ultrasonic attenuation to characterize the microstructure of heterogeneous cement-based materials. The study considers a real, but simplified cement-based material, cement paste---a common bonding matrix of all cement-based composites. Cement paste consists of Portland cement and water but does not include aggregates. First, this research presents the findings of a theoretical study that uses a set of existing acoustics models to quantify the scattered ultrasonic wavefield from a known distribution of entrained air voids. These attenuation results are then coupled with experimental measurements to develop an inversion procedure that directly predicts the size and volume fraction of entrained air voids in a cement paste specimen. Optical studies verify the accuracy of the proposed inversion scheme. These results demonstrate the effectiveness of using attenuation to measure the average size, volume fraction of entrained air voids and the existence of additional larger entrapped air voids in hardened cement paste. Finally, coherent and diffuse ultrasonic waves are used to develop a direct

  8. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

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

    Ma, Li; Mao, Rurong; Shen, Ke

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led tomore » the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.« less

  9. Deficiency of the Bax gene attenuates denervation-induced apoptosis

    PubMed Central

    Siu, P. M.; Alway, S. E.

    2015-01-01

    Apoptosis has been implicated in mediating denervation-induced muscle wasting. In this study we determined the effect of interference of apoptosis on muscle wasting during denervation by using mice genetically deficient in pro-apoptotic Bax. After denervation, muscle wasting was evident in both wild-type and Bax−/− muscles but reduction of muscle weight was attenuated in Bax−/− mice. Apoptotic DNA fragmentation increased in wild-type denervated muscles whereas there was no statistical increase in DNA fragmentation in denervated muscles from Bax−/− mice. Mitochondrial AIF and Smac/DIABLO releases and Bcl-2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a similar extent in muscles from wild-type and Bax−/− mice following denervation. Mitochondrial cytochrome c release was elevated in denervated muscles from wild-type mice but the increase was suppressed in muscles from Bax−/− mice. Increases in caspase-3 and -9 activities and oxidative stress markers H2O2, MDA/4-HAE and nitrotyrosine were all evident in denervated muscles from wild-type mice but these changes were absent in muscles from Bax−/− mice. Moreover, ARC increased exclusively in denervated Bax−/− muscle. Our data indicate that under conditions of denervation, pro-apoptotic signalling is suppressed and muscle wasting is attenuated when the Bax gene is lacking. These findings suggest that interventions targeting apoptosis may be valuable in ameliorating denervation-associated pathologic muscle wasting in certain neuromuscular disorders that involve partial or full denervation. PMID:16763784

  10. Mycophenolic acid attenuates tumor necrosis factor-alpha-induced endothelin-1 production in human aortic endothelial cells.

    PubMed

    Yang, Won Seok; Lee, Joo Mi; Han, Nam Jeong; Kim, Yoon Ji; Chang, Jai Won; Park, Su-Kil

    2010-07-01

    Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated in the pathogenesis of atherosclerosis and is one of the potential therapeutic targets. This study was conducted to evaluate the effect of mycophenolic acid (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells. In cultured human aortic endothelial cells, TNF-alpha increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not extracellular signal-regulated kinase. N-acetylcysteine that downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation, but attenuated p65 Ser276 phosphorylation. MPA attenuated TNF-alpha-induced ET-1 production through inhibitions of ROS-dependent JNK and ROS-independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings suggest that MPA could have an effect of amelioration of atherosclerosis. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Significant Attenuation of Lightly Damped Resonances Using Particle Dampers

    NASA Technical Reports Server (NTRS)

    Smith, Andrew; LaVerde, Bruce; Hunt, Ron; Knight, Joseph Brent

    2015-01-01

    When equipment designs must perform in a broad band vibration environment it can be difficult to avoid resonances that affect life and performance. This is especially true when an organization seeks to employ an asset from a heritage design in a new, more demanding vibration environment. Particle dampers may be used to provide significant attenuation of lightly damped resonances to assist with such a deployment of assets by including only a very minor set of modifications. This solution may be easier to implement than more traditional attenuation schemes. Furthermore, the cost in additional weight to the equipment can be very small. Complexity may also be kept to a minimum, because the particle dampers do not require tuning. Attenuating the vibratory response with particle dampers may therefore be simpler (in a set it and forget it kind of way) than tuned mass dampers. The paper will illustrate the use of an "equivalent resonance test jig" that can assist designers in verifying the potential resonance attenuation that may be available to them during the early trade stages of the design. An approach is suggested for transforming observed attenuation in the jig to estimated performance in the actual service design. KEY WORDS: Particle Damper, Performance in Vibration Environment, Damping, Resonance, Attenuation, Mitigation of Vibration Response, Response Estimate, Response Verification.

  12. Attenuation of midinfrared free electron laser energy with eyewear

    NASA Astrophysics Data System (ADS)

    Joos, Karen M.; Gabella, William

    2005-04-01

    Purpose: To determine the attenuation of free electron laser (FEL) energy at several wavelengths through microscope objective and eyeglass lenses. Materials and Methods: The FEL at wavelengths of 2.3 um, 2.5 um, 3.0 um, 3.5 um, 4.0 um, 4.5 um, 5.0 um, 6.45 um, 7.0 um, 7.5 um, and 8.0 um was telescoped using a 500 mm nominal focal length lens and a 200 mm focal length lens. The beam had a final spot of about 3 mm and was passed through a 3 mm aperture and onto the 8 mm active area of a J9LP Molectron detector. The eyeglass sample was placed 3 cm in front of the detector. Energy readings were averaged over multiple pulses. Results: Attenuation varied greatly with wavelength and sample from a low attenuation of 0.46 dB, 90% transmission, for short wavelengths through common glass to greater than 60 dB attenuation (transmission at the detector noise level) for IR safe glass by Aura, Inc. Conclusion: Only the designated laser safety goggles effectively attenuate free electron laser energy at 2.3 um and 2.5 um. A microscope objective lens, polycarbonate, and silica glass eyewear is capable of effectively attenuating FEL energy at wavelengths greater than 4.5 um, but the polycarbonate lenses demonstrated material damage.

  13. Global Attenuation Tomography and Implications for Upper-Mantle Thermal Structure

    NASA Astrophysics Data System (ADS)

    Dalton, C. A.; Ekström, G.; Dziewonski, A. M.

    2007-12-01

    Observation of seismic-wave attenuation provides a direct measure of the Earth's anelasticity. The sensitivity of attenuation to temperature, composition, partial melt, and water content is different from that of seismic velocity, and joint interpretation of elastic and anelastic models may be used to improve constraints on these properties throughout the Earth. Historically, the development of attenuation models has lagged behind velocity models. However, the availability of large seismic datasets and improved techniques to treat these data have recently led to better and higher-resolution attenuation models. We have developed a new 3-D global model of shear attenuation in the upper mantle. This new model, QRFSI12, is derived from > 30,000 fundamental-mode Rayleigh wave amplitude measurements at each period (period range 50-250 s). The amplitudes are inverted simultaneously for the coefficients of the 3-D model as well as frequency-dependent amplitude correction factors for each source and receiver. We have found that focusing by elastic heterogeneity can significantly influence surface-wave amplitudes and that this effect can be modeled at long periods using ray-theoretical approximations. We therefore subtract focusing effects from the data prior to inversion by using phase-velocity maps determined from jointly inverting amplitude and phase-delay datasets. In the shallow mantle, QRFSI12 exhibits a strong correlation with tectonic features, and different tectonic provinces are characterized by distinct attenuative properties. At depths > 250 km, the model is dominated by high attenuation beneath the southeastern Pacific and eastern Africa and low attenuation associated with subduction zones in the western Pacific. Comparison of QRFSI12 with global shear-velocity models shows a strong anti-correlation throughout the upper mantle. At 100-km depth, a clear trend of increasing velocity and decreasing attenuation with increasing age of the seafloor is apparent, and

  14. Measuring coronary calcium on CT images adjusted for attenuation differences.

    PubMed

    Nelson, Jennifer Clark; Kronmal, Richard A; Carr, J Jeffrey; McNitt-Gray, Michael F; Wong, Nathan D; Loria, Catherine M; Goldin, Jonathan G; Williams, O Dale; Detrano, Robert

    2005-05-01

    To quantify scanner and participant variability in attenuation values for computed tomographic (CT) images assessed for coronary calcium and define a method for standardizing attenuation values and calibrating calcium measurements. Institutional review board approval and participant informed consent were obtained at all study sites. An image attenuation adjustment method involving the use of available calibration phantom data to define standard attenuation values was developed. The method was applied to images from two population-based multicenter studies: the Coronary Artery Risk Development in Young Adults study (3041 participants) and the Multi-Ethnic Study of Atherosclerosis (6814 participants). To quantify the variability in attenuation, analysis of variance techniques were used to compare the CT numbers of standardized torso phantom regions across study sites, and multivariate linear regression models of participant-specific calibration phantom attenuation values that included participant age, race, sex, body mass index (BMI), smoking status, and site as covariates were developed. To assess the effect of the calibration method on calcium measurements, Pearson correlation coefficients between unadjusted and attenuation-adjusted calcium measurements were computed. Multivariate models were used to examine the effect of sex, race, BMI, smoking status, unadjusted score, and site on Agatston score adjustments. Mean attenuation values (CT numbers) of a standard calibration phantom scanned beneath participants varied significantly according to scanner and participant BMI (P < .001 for both). Values were lowest for Siemens multi-detector row CT scanners (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese (BMI, > or =40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0-39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and

  15. Millimeter wave attenuation prediction using a piecewise uniform rain rate model

    NASA Technical Reports Server (NTRS)

    Persinger, R. R.; Stutzman, W. L.; Bostian, C. W.; Castle, R. E., Jr.

    1980-01-01

    A piecewise uniform rain rate distribution model is introduced as a quasi-physical model of real rain along earth-space millimeter wave propagation paths. It permits calculation of the total attenuation from specific attenuation in a simple fashion. The model predications are verified by comparison with direct attenuation measurements for several frequencies, elevation angles, and locations. Also, coupled with the Rice-Holmberg rain rate model, attenuation statistics are predicated from rainfall accumulation data.

  16. Metabotropic glutamate receptor 5 as a potential target for smoking cessation.

    PubMed

    Chiamulera, Cristiano; Marzo, Claudio Marcello; Balfour, David J K

    2017-05-01

    Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high, and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence, they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many "off-target" effects to be used clinically. However, newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence.

  17. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequentmore » challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.« less

  18. Compensating for Attenuation Differences in Ultrasonic Inspections of Titanium-Alloy Billets

    NASA Astrophysics Data System (ADS)

    Margetan, F. J.; Thompson, R. B.; Keller, Michael; Hassan, Waled

    2004-02-01

    Cylindrical billets of Titanium alloy are ultrasonically inspected prior to use in fabricating rotating jet-engine components. Although each billet has a cylindrical geometry, its ultrasonic properties are not cylindrically symmetric due to asymmetries in the process used to produce the billet from the original cast ingot. In the inspection process, a calibration standard of the same diameter containing flat-bottomed hole (FBH) reflectors is used to set the initial inspection gain (i.e., the signal amplification level). If the ultrasonic attenuation of the billet to be inspected differs significantly from that of the calibration standard, the inspection gain must be adjusted to maintain the desired defect detection sensitivity. In this paper we investigate several schemes for attenuation compensation. The gain adjustments fall into two broad categories: "global" adjustments (in dB/inch units), which are applied uniformly throughout the billet under inspection; and "local adjustments", which vary with axial and circumferential position. The schemes make use of the patterns of reflected back-wall amplitude and backscattered grain noise seen in the calibration standard and test billet. The various compensation schemes are tested using specimens of 6″-diameter Ti-6A1-4V billet into which many FBH targets were drilled. Results are summarized and tentative recommendations for improving billet inspection practices are offered.

  19. Blockade of CCN4 attenuates CCl4-induced liver fibrosis.

    PubMed

    Li, Xiaofei; Chen, Yongxin; Ye, Weiwei; Tao, Xingfei; Zhu, Jinhong; Wu, Shuang; Lou, Lianqing

    2015-06-19

    CCN4, also termed WNT-inducible signaling pathway protein-1 (WISP-1), has important roles in inflammation and tissue injury. This study aimed to investigate the effect of CCN4 inhibition using monoclonal anti-CCN4 antibody (CCN4mAb) on the liver injury and fibrosis in a mouse model of liver fibrosis. The mouse liver fibrosis model was induced by carbon tetrachloride (CCl4). Mice received vehicle (saline/olive oil) by subcutaneous injection, CCl4 by subcutaneous injection or CCl4 (subcutaneous) plus CCN4mAb by subcutaneous injection. The pro-inflammatory and pro-fibrotic factors were determined by Western blot. The biochemistry and histopathology, collagen deposition and nuclear factor (NF)-κB activity were also assessed. Chronic CCl4 treatment caused liver injury and collagen accumulation. The expression levels of CCN4, pro-inflammatory and pro-fibrotic mediators as well as the activity of NF-κB were markedly increased. Treatment with CCN4mAb significantly inhibited CCl4-induced CCN4 expression, leading to attenuated CCl4-induced liver injury and the inflammatory response. CCN4 blockade also significantly reduced the formation of collagen in the liver and the expression of α-smooth muscle actin and transforming growth factor β1. CCN4 inhibition by CCN4mAb in vivo significantly attenuated the CCl4-induced liver injury and the progression of liver fibrosis. CCN4 may represent a novel therapeutic target for liver injury and fibrosis.

  20. GOODS-Herschel: dust attenuation properties of UV selected high redshift galaxies

    NASA Astrophysics Data System (ADS)

    Buat, V.; Noll, S.; Burgarella, D.; Giovannoli, E.; Charmandaris, V.; Pannella, M.; Hwang, H. S.; Elbaz, D.; Dickinson, M.; Magdis, G.; Reddy, N.; Murphy, E. J.

    2012-09-01

    Context. Dust attenuation in galaxies is poorly known, especially at high redshift. And yet the amount of dust attenuation is a key parameter to deduce accurate star formation rates from ultraviolet (UV) rest-frame measurements. The wavelength dependence of the dust attenuation is also of fundamental importance to interpret the observed spectral energy distributions (SEDs) and to derive photometric redshifts or physical properties of galaxies. Aims: We want to study dust attenuation at UV wavelengths at high redshift, where the UV is redshifted to the observed visible light wavelength range. In particular, we search for a UV bump and related implications for dust attenuation determinations. Methods: We use photometric data in the Chandra Deep Field South (CDFS), obtained in intermediate and broad band filters by the MUSYC project, to sample the UV rest-frame of 751 galaxies with 0.95 < z < 2.2. When available, infrared (IR) Herschel/PACS data from the GOODS-Herschel project, coupled with Spitzer/MIPS measurements, are used to estimate the dust emission and to constrain dust attenuation. The SED of each source is fit using the CIGALE code. The amount of dust attenuation and the characteristics of the dust attenuation curve are obtained as outputs of the SED fitting process, together with other physical parameters linked to the star formation history. Results: The global amount of dust attenuation at UV wavelengths is found to increase with stellar mass and to decrease as UV luminosity increases. A UV bump at 2175 Å is securely detected in 20% of the galaxies, and the mean amplitude of the bump for the sample is similar to that observed in the extinction curve of the LMC supershell region. This amplitude is found to be lower in galaxies with very high specific star formation rates, and 90% of the galaxies exhibiting a secure bump are at z < 1.5. The attenuation curve is confirmed to be steeper than that of local starburst galaxies for 20% of the galaxies. The large

  1. Infrared attenuation of thallium bromo-iodide fibers

    NASA Technical Reports Server (NTRS)

    Magilavy, B.; Goebel, J.

    1986-01-01

    Analysis of attenuation measurements in the near infrared of an unclad fiber of Thallium Bromo-Iodide (Th(Br,I)), a polycrystalline thallium halide, is presented. A general overview is given of the properties of fiber optics. Two groups of attenuation measurements, for the region 1.2 to 3.4 and for 3 to 11 microns, respectively, are presented, analyzed, and compared with those of two other groups of researchers.

  2. MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis

    PubMed Central

    Lippai, Dora; Kodys, Karen; Catalano, Donna; Iracheta-Vellve, Arvin; Szabo, Gyongyi

    2015-01-01

    Background & Aim MicroRNAs (miRs) regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis. Methods Wild type (WT) and miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed. Results MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear factor κ beta (NF-κB) activation and enhanced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and monocyte chemoattractant protein-1 (MCP1) in MCD diet-fed mice. We found a significant attenuation of apoptosis (cleaved caspase-3) and reduction in collagen and α smooth muscle actin (αSMA) levels in miR-155 KO mice compared to WTs on MCD diet. In addition, we found attenuation of platelet derived growth factor (PDGF), a pro-fibrotic cytokine; SMAD family member 3 (Smad3), a protein involved in transforming growth factor-β (TGFβ) signal transduction and vimentin, a mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition (EMT) in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein β (C/EBPβ) a miR-155 target involved in EMT was significantly increased in miR-155 KO compared to WT mice. Conclusions Our novel data demonstrate that miR-155 deficiency can reduce steatosis and fibrosis without decreasing inflammation in steatohepatitis. PMID:26042593

  3. Thin-Layering Effect On Estimating Seismic Attenuation In Methane Hydrate-Bearing Sediments

    NASA Astrophysics Data System (ADS)

    Lee, K.; Matsushima, J.

    2012-12-01

    Seismic attenuation is one of the important parameters that provide information concerning both the detection and quantitative assessment of gas-hydrates. We estimated seismic attenuation (1/Q) from surface seismic data acquired at Nankai Trough in Japan. We adapt the Q-versus offset (QVO) method to calculate robust and continuous interval attenuations from CMP gathers. We could observe high attenuation in methane hydrate bearing sediments over the BSR region. However some negative 1/Q values are also shown. This means that the amplitude of high frequency components is increasing with depth. Such results may be due to tuning effect. Here, we carried out numerical test to see how thin-layering effect influences on seismic attenuation results. The results showed that tuning considerably influences the attenuation results, and causes the lower 1/Q values (lower attenuation) and negative 1/Q values.

  4. Curcumin Attenuates N-Nitrosodiethylamine-Induced Liver Injury in Mice by Utilizing the Method of Metabonomics.

    PubMed

    Qiu, Peiyu; Sun, Jiachen; Man, Shuli; Yang, He; Ma, Long; Yu, Peng; Gao, Wenyuan

    2017-03-08

    N-Nitrosodiethylamine (DEN) exists as a food additive in cheddar cheese, processed meats, beer, water, and so forth. It is a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination of liver tissues and biomarker detection in serum and livers, it was demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level, and COX-2/PGE2 pathway. Furthermore, curcumin attenuated metabolic disorders via increasing concentration of glucose and fructose, and decreasing levels of glycine and proline, and mRNA expression of GLUT1, PKM and FASN. Docking study indicated that curcumin presented strong affinity with key metabolism enzymes such as GLUT1, PKM, FASN and LDHA. There were a number of amino acid residues involved in curcumin-targeting enzymes of hydrogen bonds and hydrophobic interactions. All in all, curcumin exhibited a potent liver protective agent inhibiting chemically induced liver injury through suppressing liver cellular metabolism in the prospective application.

  5. Environmental assessments on schools located on or near former industrial facilities: Feedback on attenuation factors for the prediction of indoor air quality.

    PubMed

    Derycke, Virginie; Coftier, Aline; Zornig, Clément; Léprond, Hubert; Scamps, Mathilde; Gilbert, Dominique

    2018-06-01

    One of the goals of the French national campaign called "Etablissements Sensibles (Sensitive Establishments)" is to evaluate indoor air degradation in schools because of vapor intrusion of volatile compounds from soil gases towards the indoor air, related to the presence of former industrial sites on or near the establishment. During this campaign, as recommended by the United States of Environmental Protection Agency (US EPA), indoor air quality was evaluated from soil gas concentrations using generic attenuation factors, and extra investigations into soil gases and indoor air were performed when the estimated values exceeded target indoor air concentrations. This study exploits matched data on subsurface soil gases and indoor air that came from the "Sensitive Establishments" campaign. It aims to consolidate and refine the use of attenuation factors as a function of environmental variables acquired routinely during environmental assessments. We have been able to select the measured environmental variables that have the most influence on vapor intrusion using Principal Components Analysis and hypotheses tests. Since the collected data are mainly related to weak sources (only 15% schools required risk management measures related to vapor intrusion), halogenated volatile organic compounds (HVOC) were selected as tracer compounds for vapor intrusion for this study. This choice enables the exclusion or minimization of background sources contributions. From the results we have calculated the descriptive statistics of the attenuation factors distribution for the subslab-to-indoor air pathway and refined the attenuation factors for this pathway through an easily obtained parameter, building age. Qualitative comparison of attenuation factors according to the building age shows that attenuation factors observed for building less than 50 years are lower than attenuation factors for buildings 50 years old and above. These results show the utility of creating databases for

  6. INDIRECT MEASUREMENT OF BIOLOGICAL ACTIVITY TO MONITOR NATURAL ATTENUATION

    EPA Science Inventory

    The remediation of ground water contamination by natural attenuation, specifically biodegradation, requires continual monitoring. This research is aimed at improving methods for evaluating the long-term performance of Monitored Natural Attenuation (MNA), specifically changes in ...

  7. Genetic diversity of Babesia bovis in virulent and attenuated strains.

    PubMed

    Mazuz, M L; Molad, T; Fish, L; Leibovitz, B; Wolkomirsky, R; Fleiderovitz, L; Shkap, V

    2012-03-01

    The aim of this study was to compare the genetic diversity of the single copy Bv80 gene sequences of Babesia bovis in populations of attenuated and virulent parasites. PCR/ RT-PCR followed by cloning and sequence analyses of 4 attenuated and 4 virulent strains were performed. Multiple fragments in the range of 420 to 744 bp were amplified by PCR or RT-PCR. Cloning of the PCR fragments and sequence analyses revealed the presence of mixed subpopulations in either virulent or attenuated parasites with a total of 19 variants with 12 different sequences that differed in number and type of tandem repeats. High levels of intra- and inter-strain diversity of the Bv80 gene, with the presence of mixed populations of parasites were found in both the virulent field isolates and the attenuated vaccine strains. In addition, during the attenuation process, sequence analyses showed changes in the pattern of the parasite subpopulations. Despite high polymorphism found by sequence analyses, the patterns observed and the number of repeats, order, or motifs found could not discriminate between virulent field isolates and attenuated vaccine strains of the parasite.

  8. Theoretical Analysis of Rain Attenuation Probability

    NASA Astrophysics Data System (ADS)

    Roy, Surendra Kr.; Jha, Santosh Kr.; Jha, Lallan

    2007-07-01

    Satellite communication technologies are now highly developed and high quality, distance-independent services have expanded over a very wide area. As for the system design of the Hokkaido integrated telecommunications(HIT) network, it must first overcome outages of satellite links due to rain attenuation in ka frequency bands. In this paper theoretical analysis of rain attenuation probability on a slant path has been made. The formula proposed is based Weibull distribution and incorporates recent ITU-R recommendations concerning the necessary rain rates and rain heights inputs. The error behaviour of the model was tested with the loading rain attenuation prediction model recommended by ITU-R for large number of experiments at different probability levels. The novel slant path rain attenuastion prediction model compared to the ITU-R one exhibits a similar behaviour at low time percentages and a better root-mean-square error performance for probability levels above 0.02%. The set of presented models exhibits the advantage of implementation with little complexity and is considered useful for educational and back of the envelope computations.

  9. Attenuating the Systemic Inflammatory Response to Adult Cardiopulmonary Bypass: A Critical Review of the Evidence Base

    PubMed Central

    Landis, R. Clive; Brown, Jeremiah R.; Fitzgerald, David; Likosky, Donald S.; Shore-Lesserson, Linda; Baker, Robert A.; Hammon, John W.

    2014-01-01

    Abstract: A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based review exists to cover the scope of anti-inflammatory interventions deployed. We therefore conducted an evidence-based review to capture “self-identified” anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the “Outcomes 2010” consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory response. However, only a minority of papers (35 of 98 [35.7%]) demonstrated any clinical improvement to one or more of the predefined outcome measures (most frequently myocardial protection or length of intensive care unit stay). No single intervention was supported by strong level A evidence (multiple randomized controlled trials [RCTs] or meta-analysis) for clinical benefit. Interventions at level A evidence included off-pump surgery, minimized circuits, biocompatible circuit coatings, leukocyte filtration, complement C5 inhibition, preoperative aspirin, and corticosteroid prophylaxis. Interventions at level B evidence (single RCT) for minimizing inflammation included nitric oxide donors, C1 esterase inhibition, neutrophil elastase inhibition, propofol, propionyl-L-carnitine, and intensive insulin therapy. A secondary analysis revealed that suppression of at least one inflammatory marker was necessary but not sufficient to confer clinical benefit. The most effective interventions were those that targeted multiple inflammatory pathways. These observations are consistent with a “multiple hit” hypothesis, whereby clinically effective suppression of the systemic inflammatory response

  10. [Progress in application of targeting viral vector regulated by microRNA in gene therapy: a review].

    PubMed

    Zhang, Guohai; Wang, Qizhao; Zhang, Jinghong; Xu, Ruian

    2010-06-01

    A safe and effective targeting viral vector is the key factor for successful clinical gene therapy. microRNA, a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The discovery of these kind regulatory elements provides a new approach to regulate gene expression more accurately. In this review, we elucidated the principle of microRNA in regulation of targeting viral vector. The applications of microRNA in the fields of elimination contamination from replication competent virus, reduction of transgene-specific immunity, promotion of cancer-targeted gene therapy and development of live attenuated vaccines were also discussed.

  11. Laser Doppler Radar System Calibration and Rainfall Attenuation Measurements

    DOT National Transportation Integrated Search

    1978-10-01

    The atmospheric attenuation and backscatter coefficients have been measured at the 10.6-micrometers wavelength of the CO2 laser in rainstorms. Data are presented to show the increase in attenuation coefficient with rainfall rate. Backscatter coeffici...

  12. Long-Term Memories Bias Sensitivity and Target Selection in Complex Scenes

    PubMed Central

    Patai, Eva Zita; Doallo, Sonia; Nobre, Anna Christina

    2014-01-01

    In everyday situations we often rely on our memories to find what we are looking for in our cluttered environment. Recently, we developed a new experimental paradigm to investigate how long-term memory (LTM) can guide attention, and showed how the pre-exposure to a complex scene in which a target location had been learned facilitated the detection of the transient appearance of the target at the remembered location (Summerfield, Lepsien, Gitelman, Mesulam, & Nobre, 2006; Summerfield, Rao, Garside, & Nobre, 2011). The present study extends these findings by investigating whether and how LTM can enhance perceptual sensitivity to identify targets occurring within their complex scene context. Behavioral measures showed superior perceptual sensitivity (d′) for targets located in remembered spatial contexts. We used the N2pc event-related potential to test whether LTM modulated the process of selecting the target from its scene context. Surprisingly, in contrast to effects of visual spatial cues or implicit contextual cueing, LTM for target locations significantly attenuated the N2pc potential. We propose that the mechanism by which these explicitly available LTMs facilitate perceptual identification of targets may differ from mechanisms triggered by other types of top-down sources of information. PMID:23016670

  13. Temperature and frequency dependence of ultrasonic attenuation in selected tissues

    NASA Technical Reports Server (NTRS)

    Gammell, P. M.; Croissette, D. H. L.; Heyser, R. C.

    1979-01-01

    Ultrasonic attenuation over the frequency range of 1.5-10 MHz has been measured as a function of temperature for porcine liver, backfat, kidney and spleen as well as for a single specimen of human liver. The attenuation in these excised specimens increases nearly linearly with frequency. Over the temperature range of approximately 4-37 C the attenuation decreases with increasing temperature for most soft tissue studied.

  14. Monitored Natural Attenuation and Enhanced Attenuation for Chlorinated Solvent Plumes - It’s All About Balance

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

    VANGELAS, KAREN

    2005-05-19

    Nature's inherent ability to cleanse itself is at the heart of Monitored Natural Attenuation (MNA). The complexity comes when one attempts to measure and calculate this inherent ability, called the Natural Attenuation Capacity (NAC), and determine if it is sufficient to cleanse the system to agreed upon criteria. An approach that is simple in concept for determining whether the NAC is sufficient for MNA to work is the concept of a mass balance. Mass balance is a robust framework upon which all decisions can be made. The inflows to and outflows from the system are balanced against the NAC ofmore » the subsurface system. For MNA to be acceptable, the NAC is balanced against the contaminant loading to the subsurface system with the resulting outflow from the system being in a range that is acceptable to the regulating and decision-making parties. When the system is such that the resulting outflow is not within an acceptable range, the idea of taking actions that are sustainable and that will bring the system within the acceptable range of outflows is evaluated. These sustainable enhancements are being developed under the Enhanced Attenuation (EA) concept.« less

  15. Two-photon coincident emission from thick targets for 70-keV incident electrons

    NASA Astrophysics Data System (ADS)

    Liu, J.; Kahler, D. L.; Quarles, C. A.

    1993-04-01

    Two-photon coincidence yields have been measured in thick targets of C, Al, Ag, and Ta for 70 keV incident electrons and photons radiated at +/-45° to the incident beam. A theoretical model, which is more rigorous, has been developed to simulate the two-photon processes of coherent thick-target double bremsstrahlung (TTDB) and the incoherent emission of two single-bremsstrahlung (SBSB) photons in a thick-target environment. The model is based on an integration of the thin-target cross sections over the target thickness taking into account electron energy loss, electron backscattering, and photon attenuation. It predicts a yield that is much lower than that of the previous model. The prediction of the model fits the present experimental data well by adjusting the relative weight of the two competing processes, and we find that TTDB dominates at low Z and incoherent SBSB dominates at higher Z.

  16. THE NATIONAL RESEARCH COUNCIL REPORT ON MONITORED NATURAL ATTENUATION

    EPA Science Inventory

    The National Research Council recently released a report titled Natural Attenuation for Groundwater Remediation, available from the National Academy Press(http://www.nap.edu>). The report made a number of observations and recommedations, including the following. -Natural attenu...

  17. Masked priming by misspellings: Word frequency moderates the effects of SOA and prime-target similarity.

    PubMed

    Burt, Jennifer S

    2016-02-01

    University students made lexical decisions to eight- or nine-letter words preceded by masked primes that were the target, an unrelated word, or a typical misspelling of the target. At a stimulus onset asynchrony (SOA) of 47 ms, primes that were misspellings of the target produced a priming benefit for low-, medium-, and high-frequency words, even when the misspelled primes were changed to differ phonologically from their targets. At a longer SOA of 80 ms, misspelled primes facilitated lexical decisions only to medium- and low-frequency targets, and a phonological change attenuated the benefit for medium-frequency targets. The results indicate that orthographic similarity can be preserved over changes in letter position and word length, and that the priming effect of misspelled words at the shorter SOA is orthographically based. Orthographic-priming effects depend on the quality of the orthographic learning of the target word.

  18. Measurement of acoustic attenuation in South Pole ice

    NASA Astrophysics Data System (ADS)

    IceCube Collaboration; Abbasi, R.; Abdou, Y.; Abu-Zayyad, T.; Adams, J.; Aguilar, J. A.; Ahlers, M.; Andeen, K.; Auffenberg, J.; Bai, X.; Baker, M.; Barwick, S. W.; Bay, R.; Bazo Alba, J. L.; Beattie, K.; Beatty, J. J.; Bechet, S.; Becker, J. K.; Becker, K.-H.; Benabderrahmane, M. L.; Berdermann, J.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Bissok, M.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Böser, S.; Botner, O.; Bradley, L.; Braun, J.; Buitink, S.; Carson, M.; Chirkin, D.; Christy, B.; Clem, J.; Clevermann, F.; Cohen, S.; Colnard, C.; Cowen, D. F.; D'Agostino, M. V.; Danninger, M.; de Clercq, C.; Demirörs, L.; Depaepe, O.; Descamps, F.; Desiati, P.; de Vries-Uiterweerd, G.; Deyoung, T.; Díaz-Vélez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Engdegård, O.; Euler, S.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Feusels, T.; Filimonov, K.; Finley, C.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Franke, R.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Geisler, M.; Gerhardt, L.; Gladstone, L.; Glüsenkamp, T.; Goldschmidt, A.; Goodman, J. A.; Grant, D.; Griesel, T.; Groß, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Gustafsson, L.; Ha, C.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Helbing, K.; Herquet, P.; Hickford, S.; Hill, G. C.; Hoffman, K. D.; Homeier, A.; Hoshina, K.; Hubert, D.; Huelsnitz, W.; Hülß, J.-P.; Hulth, P. O.; Hultqvist, K.; Hussain, S.; Imlay, R. L.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kelley, J. L.; Kemming, N.; Kenny, P.; Kiryluk, J.; Kislat, F.; Klein, S. R.; Knops, S.; Köhne, J.-H.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Koskinen, D. J.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Krings, T.; Kroll, G.; Kuehn, K.; Kuwabara, T.; Labare, M.; Lafebre, S.; Laihem, K.; Landsman, H.; Lauer, R.; Lehmann, R.; Lennarz, D.; Lünemann, J.; Madsen, J.; Majumdar, P.; Maruyama, R.; Mase, K.; Matis, H. S.; Matusik, M.; Meagher, K.; Merck, M.; Mészáros, P.; Meures, T.; Middell, E.; Milke, N.; Montaruli, T.; Morse, R.; Movit, S. M.; Nahnhauer, R.; Nam, J. W.; Naumann, U.; Nießen, P.; Nygren, D. R.; Odrowski, S.; Olivas, A.; Olivo, M.; Ono, M.; Panknin, S.; Paul, L.; Pérez de Los Heros, C.; Petrovic, J.; Piegsa, A.; Pieloth, D.; Porrata, R.; Posselt, J.; Price, P. B.; Prikockis, M.; Przybylski, G. T.; Rawlins, K.; Redl, P.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Rodrigues, J. P.; Roth, P.; Rothmaier, F.; Rott, C.; Roucelle, C.; Ruhe, T.; Rutledge, D.; Ruzybayev, B.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Schatto, K.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Schukraft, A.; Schultes, A.; Schulz, O.; Schunck, M.; Seckel, D.; Semburg, B.; Seo, S. H.; Sestayo, Y.; Seunarine, S.; Silvestri, A.; Slipak, A.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Stephens, G.; Stezelberger, T.; Stokstad, R. G.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sullivan, G. W.; Swillens, Q.; Taboada, I.; Tamburro, A.; Tarasova, O.; Tepe, A.; Ter-Antonyan, S.; Tilav, S.; Toale, P. A.; Tosi, D.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; van Overloop, A.; van Santen, J.; Voigt, B.; Walck, C.; Waldenmaier, T.; Wallraff, M.; Walter, M.; Wendt, C.; Westerhoff, S.; Whitehorn, N.; Wiebe, K.; Wiebusch, C. H.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, C.; Xu, X. W.; Yanez, J. P.; Yodh, G.; Yoshida, S.; Zarzhitsky, P.; IceCube Collaboration

    2011-01-01

    Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient α = 3.20 ± 0.57 km-1 between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for λ ≡ 1/α of ˜300 m with 20% uncertainty. No significant depth or frequency dependence has been found.

  19. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR

    NASA Astrophysics Data System (ADS)

    Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander

    2017-04-01

    In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This

  20. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR.

    PubMed

    Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A; Costes, Nicolas; Hammers, Alexander

    2017-04-07

    In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [ 18 F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [ 18 F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BP ND ). On static [ 18 F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [ 18 F]MPPF, most regional errors on BP ND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation

  1. Stratospheric mountain wave attenuation in positive and negative ambient wind shear

    NASA Astrophysics Data System (ADS)

    Kruse, C. G.; Smith, R. B.

    2016-12-01

    Recently, much has been learned about the vertical propagation and attenuation of mountain waves launched by the Southern Alps of New Zealand (NZ) from the Deep Propagating Gravity Wave Experiment (DEEPWAVE) field campaign. Over NZ, approximately half of mountain wave events are strongly attenuated in a lower-stratospheric "valve layer," defined as a layer of reduced wind with no critical levels. Within a valve layer, negative wind shear causes mountain waves steepen and attenuate, with the amount of transmitted momentum flux controlled by the minimum wind speed within the layer. The other half of wave events are deep (propagating to 35+ km), usually with positive wind shear. Within these deep events, increasing amplitude with decreasing density causes mountain waves to attenuate gradually (after spatial/temporal averaging). Global reanalyses indicate that this valve layer is a climatological feature in the wintertime mid-latitudes above the subtropical jet, while deep events and gradual attenuation occur over higher latitudes below the polar stratospheric jet. The local physics of mountain wave attenuation in positive and negative ambient wind shear are investigated using realistic winter-long (JJA) 6-km resolution Weather Research and Forecasting (WRF) model simulations over the Andes. Attention is given to the spatiotemporal variability of wave attenuation and the various factors driving this variability (e.g. variability in wave generation, ambient conditions at attenuation level, inherent wave-induced instabilities). Mesoscale potential vorticity generation is used as an indicator of wave attenuation. Additionally, regionally integrated wave momentum flux and gravity wave drag (GWD) within WRF are quantified and compared with parameterized quantities in the MERRA1 and 2 reanalyses.

  2. Attenuation of Ricin Toxin under Ambient Conditions and ...

    EPA Pesticide Factsheets

    Report This study focused on the attenuation of ricin toxin on six types of materials representative of a mail sorting facility and/or indoor building materials. Attenuation tests were conducted under various combinations of temperature, relative humidity (RH), and contact time, using two forms of ricin toxin: a commercially-available pure preparation and a crude preparation from castor beans.

  3. Adaptive attenuation of aliased ground roll using the shearlet transform

    NASA Astrophysics Data System (ADS)

    Hosseini, Seyed Abolfazl; Javaherian, Abdolrahim; Hassani, Hossien; Torabi, Siyavash; Sadri, Maryam

    2015-01-01

    Attenuation of ground roll is an essential step in seismic data processing. Spatial aliasing of the ground roll may cause the overlap of the ground roll with reflections in the f-k domain. The shearlet transform is a directional and multidimensional transform that separates the events with different dips and generates subimages in different scales and directions. In this study, the shearlet transform was used adaptively to attenuate aliased and non-aliased ground roll. After defining a filtering zone, an input shot record is divided into segments. Each segment overlaps adjacent segments. To apply the shearlet transform on each segment, the subimages containing aliased and non-aliased ground roll, the locations of these events on each subimage are selected adaptively. Based on these locations, mute is applied on the selected subimages. The filtered segments are merged together, using the Hanning function, after applying the inverse shearlet transform. This adaptive process of ground roll attenuation was tested on synthetic data, and field shot records from west of Iran. Analysis of the results using the f-k spectra revealed that the non-aliased and most of the aliased ground roll were attenuated using the proposed adaptive attenuation procedure. Also, we applied this method on shot records of a 2D land survey, and the data sets before and after ground roll attenuation were stacked and compared. The stacked section after ground roll attenuation contained less linear ground roll noise and more continuous reflections in comparison with the stacked section before the ground roll attenuation. The proposed method has some drawbacks such as more run time in comparison with traditional methods such as f-k filtering and reduced performance when the dip and frequency content of aliased ground roll are the same as those of the reflections.

  4. Wave attenuation across a tidal marsh in San Francisco Bay

    USGS Publications Warehouse

    Foster-Martinez, Madeline R.; Lacy, Jessica; Ferner, Matthew C.; Variano, Evan A.

    2018-01-01

    Wave attenuation is a central process in the mechanics of a healthy salt marsh. Understanding how wave attenuation varies with vegetation and hydrodynamic conditions informs models of other marsh processes that are a function of wave energy (e.g. sediment transport) and allows for the incorporation of marshes into coastal protection plans. Here, we examine the evolution of wave height across a tidal salt marsh in San Francisco Bay. Instruments were deployed along a cross-shore transect, starting on the mudflat and crossing through zones dominated by Spartina foliosa and Salicornia pacifica. This dataset is the first to quantify wave attenuation for these vegetation species, which are abundant in the intertidal zone of California estuaries. Measurements were collected in the summer and winter to assess seasonal variation in wave attenuation. Calculated drag coefficients of S. foliosa and S. pacifica were similar, indicating equal amounts of vegetation would lead to similar energy dissipation; however, S. pacifica has much greater biomass close to the bed (<20 cm) and retains biomass throughout the year, and therefore, it causes more total attenuation. S. foliosa dies back in the winter, and waves often grow across this section of the marsh. For both vegetation types, attenuation was greatest for low water depths, when the vegetation was emergent. For both seasons, attenuation rates across S. pacifica were the highest and were greater than published attenuation rates across similar (Spartina alterniflora) salt marshes for the comparable depths. These results can inform designs for marsh restorations and management plans in San Francisco Bay and other estuaries containing these species.

  5. Monitored natural attenuation forum: MNA of metals and radionuclides

    EPA Science Inventory

    While the natural attenuation of many organic compounds is established and accepted by the regulated and regulatory communities, there is some debate whether monitored natural attenuation (MNA) of metals and radionuclides is a reasonable remedial alternative to consider. Do you...

  6. Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in Iberian rivers.

    PubMed

    Acuña, Vicenç; von Schiller, Daniel; García-Galán, Maria Jesús; Rodríguez-Mozaz, Sara; Corominas, Lluís; Petrovic, Mira; Poch, Manel; Barceló, Damià; Sabater, Sergi

    2015-01-15

    A multitude of pharmaceuticals enter surface waters via discharges of wastewater treatment plants (WWTPs), and many raise environmental and health concerns. Chemical fate models predict their concentrations using estimates of mass loading, dilution and in-stream attenuation. However, current comprehension of the attenuation rates remains a limiting factor for predictive models. We assessed in-stream attenuation of 75 pharmaceuticals in 4 river segments, aiming to characterize in-stream attenuation variability among different pharmaceutical compounds, as well as among river segments differing in environmental conditions. Our study revealed that in-stream attenuation was highly variable among pharmaceuticals and river segments and that none of the considered pharmaceutical physicochemical and molecular properties proved to be relevant in determining the mean attenuation rates. Instead, the octanol-water partition coefficient (Kow) influenced the variability of rates among river segments, likely due to its effect on sorption to sediments and suspended particles, and therefore influencing the balance between the different attenuation mechanisms (biotransformation, photolysis, sorption, and volatilization). The magnitude of the measured attenuation rates urges scientists to consider them as important as dilution when aiming to predict concentrations in freshwater ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets.

    PubMed

    Rajendran, Peramaiyan; Rengarajan, Thamaraiselvan; Nandakumar, Natarajan; Divya, H; Nishigaki, Ikuo

    2015-02-01

    A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

  8. Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice.

    PubMed

    Gioscia-Ryan, Rachel A; Battson, Micah L; Cuevas, Lauren M; Eng, Jason S; Murphy, Michael P; Seals, Douglas R

    2018-05-01

    Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes-including collagen overabundance and elastin degradation-and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness

  9. Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice

    PubMed Central

    Gioscia-Ryan, Rachel A.; Battson, Micah L.; Cuevas, Lauren M.; Eng, Jason S.; Murphy, Michael P.

    2018-01-01

    Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes—including collagen overabundance and elastin degradation—and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness

  10. Application of non-attenuating frequency radars for prediction of rain attenuation and space diversity performance

    NASA Technical Reports Server (NTRS)

    Goldhirsh, J.

    1979-01-01

    In order to establish transmitter power and receiver sensitivity levels at frequencies above 10 GHz, the designers of earth-satellite telecommunication systems are interested in cumulative rain fade statistics at variable path orientations, elevation angles, climatological regions, and frequencies. They are also interested in establishing optimum space diversity performance parameters. In this work are examined the many elements involved in the employment of single non-attenuating frequency radars for arriving at the desired information. The elements examined include radar techniques and requirements, phenomenological assumptions, path attenation formulations and procedures, as well as error budgeting and calibration analysis. Included are the pertinent results of previous investigators who have used radar for rain attenuation modeling. Suggestions are made for improving present methods.

  11. Frequency graded 1D metamaterials: A study on the attenuation bands

    NASA Astrophysics Data System (ADS)

    Banerjee, Arnab; Das, Raj; Calius, Emilio P.

    2017-08-01

    Depending on the frequency, waves can either propagate (transmission band) or be attenuated (attenuation band) while travelling through a one-dimensional spring-mass chain with internal resonators. The literature on wave propagation through a 1D mass-in-mass chain is vast and continues to proliferate because of its versatile applicability in condensed matter physics, optics, chemistry, acoustics, and mechanics. However, in all these areas, a uniformly periodic arrangement of identical linear resonating units is normally used which limits the attenuation band to a narrow frequency range. To counter this limitation of linear uniformly periodic metamaterials, the attenuation bandwidth in a one-dimensional finite chain with frequency graded linear internal resonators are investigated in this paper. The result shows that a properly tuned frequency graded arrangement of resonating units can extend the upper part of the attenuation band of 1D metamaterial theoretically up to infinity and also increases the lower part of the attenuation bandwidth by around 40% of an equivalent uniformly periodic metamaterial without increasing the mass. Therefore, the frequency graded metamaterials can be a potential solution towards low frequency and wideband acoustic or vibration insulation. In addition, this paper provides analytical expressions for the attenuation and transmission frequency limits for a periodic mass-in-mass metamaterial and demonstrates the attenuation band is generated by the high absolute value of the effective mass not only due to the negative effective mass.

  12. Characterizing X-ray Attenuation of Containerized Cargo

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

    Birrer, N.; Divin, C.; Glenn, S.

    X-ray inspection systems can be used to detect radiological and nuclear threats in imported cargo. In order to better understand performance of these systems, the attenuation characteristics of imported cargo need to be determined. This project focused on developing image processing algorithms for segmenting cargo and using x-ray attenuation to quantify equivalent steel thickness to determine cargo density. These algorithms were applied to over 450 cargo radiographs. The results are summarized in this report.

  13. Damping factor estimation using spin wave attenuation in permalloy film

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

    Manago, Takashi, E-mail: manago@fukuoka-u.ac.jp; Yamanoi, Kazuto; Kasai, Shinya

    2015-05-07

    Damping factor of a Permalloy (Py) thin film is estimated by using the magnetostatic spin wave propagation. The attenuation lengths are obtained by the dependence of the transmission intensity on the antenna distance, and decrease with increasing magnetic fields. The relationship between the attenuation length, damping factor, and external magnetic field is derived theoretically, and the damping factor was determined to be 0.0063 by fitting the magnetic field dependence of the attenuation length, using the derived equation. The obtained value is in good agreement with the general value of Py. Thus, this estimation method of the damping factor using spinmore » waves attenuation can be useful tool for ferromagnetic thin films.« less

  14. Rational design of human metapneumovirus live attenuated vaccine candidates by inhibiting viral mRNA cap methyltransferase.

    PubMed

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan; Li, Jianrong

    2014-10-01

    The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising

  15. P-selectin is a nanotherapeutic delivery target in the tumor microenvironment.

    PubMed

    Shamay, Yosi; Elkabets, Moshe; Li, Hongyan; Shah, Janki; Brook, Samuel; Wang, Feng; Adler, Keren; Baut, Emily; Scaltriti, Maurizio; Jena, Prakrit V; Gardner, Eric E; Poirier, John T; Rudin, Charles M; Baselga, José; Haimovitz-Friedman, Adriana; Heller, Daniel A

    2016-06-29

    Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin. The nanoparticles targeted the tumor microenvironment to localize chemotherapeutics and a targeted MEK (mitogen-activated protein kinase kinase) inhibitor at tumor sites in both primary and metastatic models, resulting in superior antitumor efficacy. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression. Radiation concomitantly produced an abscopal-like phenomenon wherein P-selectin appeared in unirradiated tumor vasculature, suggesting a potential strategy to target disparate drug classes to almost any tumor. Copyright © 2016, American Association for the Advancement of Science.

  16. Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain.

    PubMed

    Van Bockstaele, Elisabeth J; Qian, Yaping; Sterling, Robert C; Page, Michelle E

    2008-05-15

    , animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration.

  17. Effect of attenuation correction on image quality in emission tomography

    NASA Astrophysics Data System (ADS)

    Denisova, N. V.; Ondar, M. M.

    2017-10-01

    In this paper, mathematical modeling and computer simulations of myocardial perfusion SPECT imaging are performed. The main factors affecting the quality of reconstructed images in SPECT are anatomical structures, the diastolic volume of a myocardium and attenuation of gamma rays. The purpose of the present work is to study the effect of attenuation correction on image quality in emission tomography. The basic 2D model describing a Tc-99m distribution in a transaxial slice of the thoracic part of a patient body was designed. This model was used to construct four phantoms simulated various anatomical shapes: 2 male and 2 female patients with normal, obese and subtle physique were included in the study. Data acquisition model which includes the effect of non-uniform attenuation, collimator-detector response and Poisson statistics was developed. The projection data were calculated for 60 views in accordance with the standard myocardial perfusion SPECT imaging protocol. Reconstructions of images were performed using the OSEM algorithm which is widely used in modern SPECT systems. Two types of patient's examination procedures were simulated: SPECT without attenuation correction and SPECT/CT with attenuation correction. The obtained results indicate a significant effect of the attenuation correction on the SPECT images quality.

  18. Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

    PubMed Central

    Mukherjee, Uma A.; Ong, Sang-Bing; Ong, Sang-Ging; Hausenloy, Derek J.

    2015-01-01

    Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death—through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection. PMID:26481155

  19. Accuracy of CT-based attenuation correction in PET/CT bone imaging

    NASA Astrophysics Data System (ADS)

    Abella, Monica; Alessio, Adam M.; Mankoff, David A.; MacDonald, Lawrence R.; Vaquero, Juan Jose; Desco, Manuel; Kinahan, Paul E.

    2012-05-01

    We evaluate the accuracy of scaling CT images for attenuation correction of PET data measured for bone. While the standard tri-linear approach has been well tested for soft tissues, the impact of CT-based attenuation correction on the accuracy of tracer uptake in bone has not been reported in detail. We measured the accuracy of attenuation coefficients of bovine femur segments and patient data using a tri-linear method applied to CT images obtained at different kVp settings. Attenuation values at 511 keV obtained with a 68Ga/68Ge transmission scan were used as a reference standard. The impact of inaccurate attenuation images on PET standardized uptake values (SUVs) was then evaluated using simulated emission images and emission images from five patients with elevated levels of FDG uptake in bone at disease sites. The CT-based linear attenuation images of the bovine femur segments underestimated the true values by 2.9 ± 0.3% for cancellous bone regardless of kVp. For compact bone the underestimation ranged from 1.3% at 140 kVp to 14.1% at 80 kVp. In the patient scans at 140 kVp the underestimation was approximately 2% averaged over all bony regions. The sensitivity analysis indicated that errors in PET SUVs in bone are approximately proportional to errors in the estimated attenuation coefficients for the same regions. The variability in SUV bias also increased approximately linearly with the error in linear attenuation coefficients. These results suggest that bias in bone uptake SUVs of PET tracers ranges from 2.4% to 5.9% when using CT scans at 140 and 120 kVp for attenuation correction. Lower kVp scans have the potential for considerably more error in dense bone. This bias is present in any PET tracer with bone uptake but may be clinically insignificant for many imaging tasks. However, errors from CT-based attenuation correction methods should be carefully evaluated if quantitation of tracer uptake in bone is important.

  20. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    PubMed

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  1. Use of bacteriophage to target bacterial surface structures required for virulence: a systematic search for antibiotic alternatives.

    PubMed

    Orndorff, Paul E

    2016-11-01

    Bacteriophages (phage) that infect pathogenic bacteria often attach to surface receptors that are coincidentally required for virulence. Receptor loss or modification through mutation renders mutants both attenuated and phage resistant. Such attenuated mutants frequently have no apparent laboratory growth defects, but in the host, they fail to exhibit properties needed to produce disease such as mucosal colonization or survival within professional phagocytic cells. The connection between attenuation and phage resistance has been exploited in experimental demonstrations of phage therapy. In such experiments, phage resistant mutants that arise naturally during therapy are inconsequential because of their attenuated status. A more contemporary approach to exploiting this connection involves identifying small effector molecules, identified in high-throughput screens, that inhibit one or more of the steps needed to produce a functioning phage receptor. Since such biosynthetic steps are unique to bacteria, inhibitors can be utilized therapeutically, in lieu of antibiotics. Also, since the inhibitor is specific to a particular bacterium or group of bacteria, no off-target resistance is generated in the host's commensal bacterial population. This brief review covers examples of how mutations that confer phage resistance produce attenuation, and how this coincidental relationship can be exploited in the search for the next generation of therapeutic agents for bacterial diseases.

  2. 2017 Scientific Sessions Sol Sherry Distinguished Lecture in Thrombosis: Factor XI as a Target for New Anticoagulants.

    PubMed

    Weitz, Jeffrey I; Fredenburgh, James C

    2018-02-01

    The goal of anticoagulant therapy is to attenuate thrombosis without compromising hemostasis. Although the direct oral anticoagulants are associated with less intracranial hemorrhage than vitamin K antagonists, bleeding remains their major side effect. Factor XI has emerged as a promising target for anticoagulants that may be safer than those currently available. The focus on factor XI stems from epidemiological evidence of its role in thrombosis, the observation of attenuated thrombosis in factor XI-deficient mice, identification of novel activators, and the fact that factor XI deficiency is associated with only a mild bleeding diathesis. Proof-of-concept comes from the demonstration that compared with enoxaparin, factor XI knockdown reduces venous thromboembolism without increasing bleeding after elective knee arthroplasty. This article rationalizes the selection of factor XI as a target for new anticoagulants, reviews the agents under development, and outlines a potential path forward for their development. © 2017 American Heart Association, Inc.

  3. Attenuation of radionuclide activity by metal-cup arthroplasties

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

    Rosenthall, L.; Rosenthall, S.

    1985-04-01

    The half-value layers of stainless steel, bone cement, and polyethylene were measured for /sup 99m/Tc, /sup 67/Ga, /sup 111/In, and /sup 201/TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in /sup 99m/Tc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. /sup 67/Ga, using the 184 and 300 keV peaks, and /sup 111/In have greater half-value layers than /sup 99m/Tc and are subject to less attenuation bymore » the metallic cup.« less

  4. Ultrasound guided fluorescence molecular tomography with improved quantification by an attenuation compensated born-normalization and in vivo preclinical study of cancer

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

    Li, Baoqiang; Berti, Romain; Abran, Maxime

    2014-05-15

    Ultrasound imaging, having the advantages of low-cost and non-invasiveness over MRI and X-ray CT, was reported by several studies as an adequate complement to fluorescence molecular tomography with the perspective of improving localization and quantification of fluorescent molecular targets in vivo. Based on the previous work, an improved dual-modality Fluorescence-Ultrasound imaging system was developed and then validated in imaging study with preclinical tumor model. Ultrasound imaging and a profilometer were used to obtain the anatomical prior information and 3D surface, separately, to precisely extract the tissue boundary on both sides of sample in order to achieve improved fluorescence reconstruction. Furthermore,more » a pattern-based fluorescence reconstruction on the detection side was incorporated to enable dimensional reduction of the dataset while keeping the useful information for reconstruction. Due to its putative role in the current imaging geometry and the chosen reconstruction technique, we developed an attenuation compensated Born-normalization method to reduce the attenuation effects and cancel off experimental factors when collecting quantitative fluorescence datasets over large area. Results of both simulation and phantom study demonstrated that fluorescent targets could be recovered accurately and quantitatively using this reconstruction mechanism. Finally, in vivo experiment confirms that the imaging system associated with the proposed image reconstruction approach was able to extract both functional and anatomical information, thereby improving quantification and localization of molecular targets.« less

  5. Implementation of Enhanced Attenuation at the DOE Mound Site OU-1 Landfill: Accelerating Progress and Reducing Costs

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

    Hooten, Gwendolyn; Cato, Rebecca; Looney, Brian

    At the US Department of Energy (DOE), Office of Legacy Management, Mound, Ohio, Site, chlorinated organic contaminants (cVOCs) originating from the former solid-waste landfill have impacted groundwater in Operable Unit 1 (OU-1). The baseline groundwater remedy was groundwater pump and treat (P&T). Since the source materials have been removed from the landfill, the Mound core team, which consists of DOE, US Environmental Protection Agency (US EPA), Ohio EPA, and other stakeholders, is assessing the feasibility of switching from the active P&T remedy to a passive attenuation-based remedy. Toward this end, an enhanced attenuation (EA) strategy based on the creation ofmore » structured geochemical zones was developed. This EA strategy addresses the residual areas of elevated cVOCs in soil and groundwater while minimizing the rebound of groundwater concentrations above regulatory targets (e.g., maximum contaminant levels [MCLs]) and avoiding plume expansion while the P&T system is turned off. The EA strategy has improved confidence and reduced risk on the OU-1 groundwater transition path to monitored natural attenuation (MNA). To better evaluate the EA strategy, DOE is conducting a field demonstration to evaluate the use of edible oils to enhance the natural attenuation processes. The field demonstration is designed to determine whether structured geochemical zones can be established that expedite the attenuation of cVOCs in the OU-1 groundwater. The EA approach at OU-1 was designed based on “structured geochemical zones” and relies on groundwater flow through a succession of anaerobic and aerobic zones. The anaerobic zones stimulate relatively rapid degradation of the original solvent source compounds (e.g., cVOCs such as tetrachloroethene [PCE] and trichloroethene [TCE]). The surrounding aerobic areas encourage relatively rapid degradation of daughter products (such as dichloroethene [DCE] and vinyl chloride [VC]) as well as enhanced cometabolism of TCE

  6. Radiometer calibration procedure and beacon attenuation estimation reference level

    NASA Technical Reports Server (NTRS)

    Crane, Robert K.

    1994-01-01

    The primary objectives are to compare radiometer attenuation with beacon attenuation and to compare sky temperature estimates with calculations using simultaneous meteorological data. Secondary objectives are: (1) noise diode and reference load measurements and (2) to adjust for outside temperature and component temperature changes.

  7. Anticipation of Monetary Reward Can Attenuate the Vigilance Decrement

    PubMed Central

    Grosso, Mallory; Liu, Guanyu; Mitko, Alex; Morris, Rachael; DeGutis, Joseph

    2016-01-01

    Motivation and reward can have differential effects on separate aspects of sustained attention. We previously demonstrated that continuous reward/punishment throughout a sustained attention task improves overall performance, but not vigilance decrements. One interpretation of these findings is that vigilance decrements are due to resource depletion, which is not overcome by increasing overall motivation. However, an alternative explanation is that as one performs a continuously rewarded task there are less potential gains/losses as the task progresses, which could decrease motivation over time, producing a vigilance decrement. This would predict that keeping future gains/losses consistent throughout the task would reduce the vigilance decrement. In the current study, we examined this possibility by comparing two versions (continuous-small loss vs. anticipate-large loss) of a 10-minute gradual onset continuous performance task (gradCPT), a challenging go/no-go sustained attention task. Participants began each task with the potential to keep $18. In the continuous-small-loss version, small monetary losses were accrued continuously throughout the task for each error. However, in the anticipate-large-loss version, participants lost all $18 if they erroneously responded to one target that always appeared toward the end of the vigil. Typical vigilance decrements were observed in the continuous-small-loss condition. In the anticipate-large-loss condition, vigilance decrements were reduced, particularly when the anticipate-large loss condition was completed second. This suggests that the looming possibility of a large loss can attenuate the vigilance decrement and that this attenuation may occur most consistently after sufficient task experience. We discuss these results in the context of current theories of sustained attention. PMID:27472785

  8. Evaluating Transport and Attenuation of Inorganic Contaminants in the Vadose Zone for Aqueous Waste Disposal Sites

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

    Truex, Michael J.; Oostrom, Martinus; Tartakovsky, Guzel D.

    An approach was developed for evaluating vadose zone transport and attenuation of aqueous wastes containing inorganic (non-volatile) contaminants that were disposed of at the land surface (i.e., directly to the ground in cribs, trenches, tile fields, etc.) and their effect on the underlying groundwater. The approach provides a structured method for estimating transport of contaminants through the vadose zone and the resulting temporal profile of groundwater contaminant concentrations. The intent of the approach is also to provide a means for presenting and explaining the results of the transport analysis in the context of the site-specific waste disposal conditions and sitemore » properties, including heterogeneities and other complexities. The document includes considerations related to identifying appropriate monitoring to verify the estimated contaminant transport and associated predictions of groundwater contaminant concentrations. While primarily intended for evaluating contaminant transport under natural attenuation conditions, the approach can also be applied to identify types of, and targets for, mitigation approaches in the vadose zone that would reduce the temporal profile of contaminant concentrations in groundwater, if needed.« less

  9. Principles underlying rational design of live attenuated influenza vaccines

    PubMed Central

    Jang, Yo Han

    2012-01-01

    Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

  10. Radar attenuation and temperature within the Greenland Ice Sheet

    USGS Publications Warehouse

    MacGregor, Joseph A; Li, Jilu; Paden, John D; Catania, Ginny A; Clow, Gary D.; Fahnestock, Mark A; Gogineni, Prasad S.; Grimm, Robert E.; Morlighem, Mathieu; Nandi, Soumyaroop; Seroussi, Helene; Stillman, David E

    2015-01-01

    The flow of ice is temperature-dependent, but direct measurements of englacial temperature are sparse. The dielectric attenuation of radio waves through ice is also temperature-dependent, and radar sounding of ice sheets is sensitive to this attenuation. Here we estimate depth-averaged radar-attenuation rates within the Greenland Ice Sheet from airborne radar-sounding data and its associated radiostratigraphy. Using existing empirical relationships between temperature, chemistry, and radar attenuation, we then infer the depth-averaged englacial temperature. The dated radiostratigraphy permits a correction for the confounding effect of spatially varying ice chemistry. Where radar transects intersect boreholes, radar-inferred temperature is consistently higher than that measured directly. We attribute this discrepancy to the poorly recognized frequency dependence of the radar-attenuation rate and correct for this effect empirically, resulting in a robust relationship between radar-inferred and borehole-measured depth-averaged temperature. Radar-inferred englacial temperature is often lower than modern surface temperature and that of a steady state ice-sheet model, particularly in southern Greenland. This pattern suggests that past changes in surface boundary conditions (temperature and accumulation rate) affect the ice sheet's present temperature structure over a much larger area than previously recognized. This radar-inferred temperature structure provides a new constraint for thermomechanical models of the Greenland Ice Sheet.

  11. Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

    PubMed

    Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

    2008-02-01

    Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

  12. Attenuation of p38-Mediated miR-1/133 Expression Facilitates Myoblast Proliferation during the Early Stage of Muscle Regeneration

    PubMed Central

    Zhang, Duo; Li, Xihua; Chen, Chuchu; Li, Yuyin; Zhao, Lei; Jing, Yanyan; Liu, Wei; Wang, Xiaoyun; Zhang, Ying; Xia, Hongfeng; Chang, Yaning; Gao, Xiang; Yan, Jun; Ying, Hao

    2012-01-01

    Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration. PMID:22911796

  13. Experimental wave attenuation study over flexible plants on a submerged slope

    NASA Astrophysics Data System (ADS)

    Yin, Zegao; Yang, Xiaoyu; Xu, Yuanzhao; Ding, Meiling; Lu, Haixiang

    2017-12-01

    Using plants is a kind of environmentally-friendly coastal protection to attenuate wave energy. In this paper, a set of experiments were conducted to investigate the wave attenuation performance using flexible grasses on a submerged slope, and the wave attenuation coefficient for these experiments was calculated for different still water depths, slope and grass configurations. It was found that the slope plays a significant role in wave attenuation. The wave attenuation coefficient increases with increasing relative row number and relative density. For a small relative row number, the two configurations from the slope top to its toe and from the slope toe to its top performed equally to a large extent. For a medium relative row number, the configuration from the slope toe to its top performed more poorly than that from the slope top to its toe; however, it performed better than that from the slope top to its toe for a high relative row number. With a single row of grasses close to the slope top from the slope toe, the wave attenuation coefficient shows double peaks. With increasing grass rows or still water depth, the grass location corresponding to the maximum wave attenuation coefficient is close to the slope top. The dimensional analysis and the least square method were used to derive an empirical equation of the wave attenuation coefficient considering the effect of relative density, the slope, the relative row number and the relative location of the middle row, and the equation was validated to experimental data.

  14. Prediction of aircraft sideline noise attenuation

    NASA Technical Reports Server (NTRS)

    Zorumski, W. E.

    1978-01-01

    A computational study is made using the recommended ground effect theory by Pao, Wenzel, and Oncley. It is shown that this theory adequately predicts the measured ground attenuation data by Parkin and Scholes, which is the only available large data set. It is also shown, however, that the ground effect theory does not predict the measured lateral attenuations from actual aircraft flyovers. There remain one or more important lateral effects on aircraft noise, such as sideline shielding of sources, which must be incorporated in the prediction methods. Experiments at low elevation angles (0 deg to 10 deg) and low-to-intermediate frequencies are recommended to further validate the ground effect theory.

  15. [Rubella virus genetic determinant of attenuation].

    PubMed

    Dmitriev, G V; Borisova, T K; Faizuloev, E B; Desiatskova, R G; Zverev, V V

    2014-01-01

    Vaccination is the most effective and available way to prevent Rubella. Presently, 9 vaccine strains were registered. Nevertheless, the molecular mechanisms of the attenuation were poorly elucidated for the rubella virus. However, the study of these mechanisms identifying genotypic and phenotypic markers of attenuation, which together with sequence analysis could be used for the genetic stability control of vaccine strains, is still of current interest. Common trends of genetic changes in the process of adaptation to cold were found due to comparison of nucleic acid and amino acid sequences of the Russian strain C-77 with corresponding positions of the known rubella virus strains and its wild type progenitors, if available.

  16. Sulfated Hexasaccharides Attenuate Metastasis by Inhibition of P-selectin and Heparanase1

    PubMed Central

    Borsig, Lubor; Vlodavsky, Israel; Ishai-Michaeli, Rivka; Torri, Giangiacomo; Vismara, Elena

    2011-01-01

    Development of compounds that target both heparanase and selectins is emerging as a promising approach for cancer therapy. Selectins are vascular cell adhesion molecules that mediate tumor cell interactions with platelets, leukocytes, and the vascular endothelium. Heparanase is an endoglycosidase that degrades heparan sulfate in the tumor microenvironment, cell surfaces, and vessel wall. Acting together, these molecules facilitate tumor cell arrest, extravasation, and metastasis. Here, we report the preparation of novel semisynthetic sulfated tri mannose C-C-linked dimers (STMCs) endowed with heparanase and selectin inhibitory activity. The P-selectin specificity of the STMC was defined by the anomeric linkage of the C-C bond. This STMC hexasaccharide is an effective inhibitor of P-selectin in vivo. We show that selective inhibition of heparanase attenuates metastasis in B16-BL6 melanoma cells, expressing high levels of this endoglycosidase, but has no effect on the metastasis of MC-38 carcinoma cells that express little or no heparanase activity. P-selectin-specific STMC attenuated metastasis in both animal models, indicating that inhibition of tumor cell interaction with the vascular endothelium is critical for cancer dissemination. Thus, the small size, the stability of the C-C bond, and the chemically defined structure of the newly generated STMCs make them superior to heparin derivatives and signify STMCs as valuable candidates for further evaluation. PMID:21532885

  17. Unusual Attenuation Recovery Process After Fiber Optic Cable Irradiation

    NASA Astrophysics Data System (ADS)

    Konečná, Z.; Plaček, V.; Havránek, P.

    2017-11-01

    At present, the number of optical cables in nuclear power plants has been increasing. Fiber optic cables are commonly used at nuclear power plants in instrumentation and control systems but they are usually used in environments without radiation. Nevertheless, currently, the number of applications in NPP containment with radiation is increasing. One of the most prevalent effects of radiation exposure is an increase of signal attenuation (signal loss). This is the result of fiber darkening due to radiation exposure and it is the main limitation factor in application of fiber optics in radiation environment. However, after the irradiation, the fiber optics go through a “recovery process” during which the optical properties improve again; i.e. attenuation decreases. However, we have found cable, where the expected healing process after few days changed its trend and the attenuation increased again to a value well above the attenuation just after the irradiation. This paper describes experiments that were carried out to explain this unusual recovery behaviour.

  18. Intercomparison of attenuation correction algorithms for single-polarized X-band radars

    NASA Astrophysics Data System (ADS)

    Lengfeld, K.; Berenguer, M.; Sempere Torres, D.

    2018-03-01

    Attenuation due to liquid water is one of the largest uncertainties in radar observations. The effects of attenuation are generally inversely proportional to the wavelength, i.e. observations from X-band radars are more affected by attenuation than those from C- or S-band systems. On the other hand, X-band radars can measure precipitation fields in higher temporal and spatial resolution and are more mobile and easier to install due to smaller antennas. A first algorithm for attenuation correction in single-polarized systems was proposed by Hitschfeld and Bordan (1954) (HB), but it gets unstable in case of small errors (e.g. in the radar calibration) and strong attenuation. Therefore, methods have been developed that restrict attenuation correction to keep the algorithm stable, using e.g. surface echoes (for space-borne radars) and mountain returns (for ground radars) as a final value (FV), or adjustment of the radar constant (C) or the coefficient α. In the absence of mountain returns, measurements from C- or S-band radars can be used to constrain the correction. All these methods are based on the statistical relation between reflectivity and specific attenuation. Another way to correct for attenuation in X-band radar observations is to use additional information from less attenuated radar systems, e.g. the ratio between X-band and C- or S-band radar measurements. Lengfeld et al. (2016) proposed such a method based isotonic regression of the ratio between X- and C-band radar observations along the radar beam. This study presents a comparison of the original HB algorithm and three algorithms based on the statistical relation between reflectivity and specific attenuation as well as two methods implementing additional information of C-band radar measurements. Their performance in two precipitation events (one mainly convective and the other one stratiform) shows that a restriction of the HB is necessary to avoid instabilities. A comparison with vertically pointing

  19. Image reconstruction from cone-beam projections with attenuation correction

    NASA Astrophysics Data System (ADS)

    Weng, Yi

    1997-07-01

    In single photon emission computered tomography (SPECT) imaging, photon attenuation within the body is a major factor contributing to the quantitative inaccuracy in measuring the distribution of radioactivity. Cone-beam SPECT provides improved sensitivity for imaging small organs. This thesis extends the results for 2D parallel- beam and fan-beam geometry to 3D parallel-beam and cone- beam geometries in order to derive filtered backprojection reconstruction algorithms for the 3D exponential parallel-beam transform and for the exponential cone-beam transform with sampling on a sphere. An exact inversion formula for the 3D exponential parallel-beam transform is obtained and is extended to the 3D exponential cone-beam transform. Sampling on a sphere is not useful clinically and current cone-beam tomography, with the focal point traversing a planar orbit, does not acquire sufficient data to give an accurate reconstruction. Thus a data acquisition method that obtains complete data for cone-beam SPECT by simultaneously rotating the gamma camera and translating the patient bed, so that cone-beam projections can be obtained with the focal point traversing a helix that surrounds the patient was developed. First, an implementation of Grangeat's algorithm for helical cone- beam projections was developed without attenuation correction. A fast new rebinning scheme was developed that uses all of the detected data to reconstruct the image and properly normalizes any multiply scanned data. In the case of attenuation no theorem analogous to Tuy's has been proven. We hypothesized that an artifact-free reconstruction could be obtained even if the cone-beam data are attenuated, provided the imaging orbit satisfies Tuy's condition and the exact attenuation map is known. Cone-beam emission data were acquired by using a circle- and-line and a helix orbit on a clinical SPECT system. An iterative conjugate gradient reconstruction algorithm was used to reconstruct projection data with a

  20. Seismic evidence for broad attenuation anomalies in the asthenosphere beneath the Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Adenis, Alice; Debayle, Eric; Ricard, Yanick

    2017-06-01

    We present QADR17, a global model of Rayleigh-wave attenuation based on a massive surface wave data set (372 629 frequency-dependent attenuation curves in the period range 50-260 s). We correct for focusing-defocusing effects and geometrical spreading, and perform a stringent selection to only keep robust observations. Then, data with close epicentres recorded at the same station are clustered, as they sample the same Earth's structure. After this pre-selection, our data set consists of about 35 000 curves that constrain the Rayleigh-wave intrinsic attenuation in the upper mantle. The logarithms of the attenuation along the individual rays are then inverted to obtain global maps of the logarithm of the local attenuation. After a first inversion, outliers are rejected and a second inversion yields a variance reduction of about 45 per cent. Our attenuation maps present strong agreement with surface tectonics at periods lower than 200 s, with low attenuation under continents and high attenuation under oceans. Over oceans, attenuation decreases with increasing crustal ages, but at periods sensitive to the uppermost 150 km, mid-ocean ridges are not characterized by a very localized anomaly, in contrast to what is commonly observed for seismic velocity models. Attenuation is rather well correlated with hotspots, especially in the Pacific ocean, where a strong attenuating anomaly is observed in the long wavelength component of our signal at periods sampling the oceanic asthenosphere. We suggest that this anomaly results from the horizontal spreading of several thermal plumes within the asthenosphere. Strong velocity reductions associated with high attenuation anomalies of moderate amplitudes beneath the East Pacific Rise, the Red Sea and the eastern part of Asia may require additional mechanisms, such as partial melting.

  1. Proteomic Analysis of Pathogenic and Attenuated Alcelaphine Herpesvirus 1▿

    PubMed Central

    Dry, Inga; Haig, David M.; Inglis, Neil F.; Imrie, Lisa; Stewart, James P.; Russell, George C.

    2008-01-01

    The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) causes malignant catarrhal fever in susceptible ungulates but infects its natural host, wildebeest, without obvious clinical signs. In tissue culture, AlHV-1 is initially predominantly cell associated and virulent but on extended culture becomes cell-free and attenuated. We wanted to determine what changes in protein composition had taken place during the transition from virulent to attenuated virus in culture. Purified virus preparations were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and proteins were analyzed by liquid chromatography-electrospray ionization-tandem mass spectrometry. Peptides were identified in serial gel slices by using MASCOT software to interrogate virus-specific and nonredundant sequence databases. Twenty-three AlHV-1-encoded proteins and six cellular proteins were identified in the attenuated and virulent viruses. Two polypeptides were detected in only the virulent virus preparations, while one other protein was found in only the attenuated virus. Two of these virus-specific proteins were identified by a single peptide, suggesting that these may be low-abundance virion proteins rather than markers of attenuation or pathogenesis. The results suggest that attenuation of AlHV-1 is not the result of gross changes in the composition of the virus particle but probably due to altered viral gene expression in the infected cell. PMID:18353942

  2. Attenuation Coefficient Estimation of the Healthy Human Thyroid In Vivo

    NASA Astrophysics Data System (ADS)

    Rouyer, J.; Cueva, T.; Portal, A.; Yamamoto, T.; Lavarello, R.

    Previous studies have demonstrated that attenuation coefficients can be useful towards characterizing thyroid tissues. In this work, ultrasonic attenuation coefficients were estimated from healthy human thyroids in vivo using a clinical scanner. The selected subjects were five young, healthy volunteers (age: 26 ± 6 years old, gender: three females, two males) with no reported history of thyroid diseases, no palpable thyroid nodules, no smoking habits, and body mass index less than 30 kg/m2. Echographic examinations were conducted by a trained sonographer using a SonixTouch system (Ultrasonix Medical Corporation, Richmond, BC) equipped with an L14-5 linear transducer array (nominal center frequency of 10 MHz, transducer footprint of 3.8 cm). Radiofrequency data corresponding to the collected echographic images in both transverse and longitudinal views were digitized at a sampling rate of 40 MHz and processed with Matlab codes (MathWorks, Natick, MA) to estimate attenuation coefficients using the spectral log difference method. The estimation was performed using an analysis bandwidth spanning from 4.0 to 9.0 MHz. The average value of the estimated ultrasonic attenuation coefficients was equal to 1.34 ± 0.15 dB/(cm.MHz). The standard deviation of the estimated average attenuation coefficient across different volunteers suggests a non-negligible inter-subject variability in the ultrasonic attenuation coefficient of the human thyroid.

  3. Ultrasonic attenuation in superconducting molybdenum-rhenium alloys.

    NASA Technical Reports Server (NTRS)

    Ashkin, M.; Deis, D. W.; Gottlieb, M.; Jones, C. K.

    1971-01-01

    Investigation of longitudinal sound attenuation in superconducting Mo-Re alloys as a function of temperature, magnetic field, and frequency. Evaporated thin film CdS transducers were used for the measurements at frequencies up to 3 GHz. The normal state attenuation coefficient was found to be proportional to the square of frequency over this frequency range. Measurements in zero magnetic field yielded a value of the energy gap parameter close to the threshold value of 3.56 kTc, appropriate to a weakly coupled dirty limit superconductor.

  4. Investigation of guided wave propagation and attenuation in pipe buried in sand

    NASA Astrophysics Data System (ADS)

    Leinov, Eli; Lowe, Michael J. S.; Cawley, Peter

    2015-07-01

    Long-range guided wave testing is a well-established method for detection of corrosion defects in pipelines. The method is currently used routinely for above ground pipelines in a variety of industries, e.g. petrochemical and energy. When the method is applied to pipes buried in soil, test ranges tend to be significantly compromised and unpredictable due to attenuation of the guided wave resulting from energy leakage into the embedding soil. The attenuation characteristics of guided wave propagation in an 8 in. pipe buried in sand are investigated using a laboratory full-scale experimental rig and model predictions. We report measurements of attenuation of the T(0,1) and L(0,2) guided wave modes over a range of sand conditions, including loose, compacted, mechanically compacted, water saturated and drained. Attenuation values are found to be in the range of 1.65-5.5 dB/m and 0.98-3.2 dB/m for the torsional and longitudinal modes, respectively, over the frequency of 11-34 kHz. The application of overburden pressure modifies the compaction of the sand and increases the attenuation. Mechanical compaction of the sand yields similar attenuation values to those obtained with applied overburden pressure. The attenuation decreases in the fully water-saturated sand, and increases in drained sand to values comparable with those obtained for compacted sand. Attenuation measurements are compared with Disperse software model predictions and confirm that the attenuation phenomenon in buried pipes is essentially governed by the bulk shear velocity in the sand. The attenuation behaviour of the torsional guided wave mode is found not to be captured by a uniform soil model; comparison with predictions obtained with the Disperse software suggest that this is likely to be due to a layer of sand adhering to the surface of the pipe.

  5. Experiment evaluation of impact attenuator for a racing car under static load

    NASA Astrophysics Data System (ADS)

    Imanullah, Fahmi; Ubaidillah, Prasojo, Arfi Singgih; Wirawan, Adhe Aji

    2018-02-01

    The automotive world is a world where one of the factors that must be considered carefully is the safety aspect. In the formula student car one of the safety factor in the form of impact attenuator. Impact attenuator is used as anchoring when a collision occurs in front of the vehicle. In the rule of formula society of automotive engineer (FSAE) student, impact attenuator is required to absorb the energy must meet or exceed 7350 Joules with a slowdown in speed not exceeding 20 g average and peak of 40 g. The student formula participants are challenged to pass the boundaries so that in designing and making the impact attenuator must pay attention to the strength and use of the minimum material so that it can minimize the expenditure. In this work, an impact attenuator was fabricated and tested using static compression. The primary goal was evaluating the actual capability of the impact attenuator for impact energy absorption. The prototype was made of aluminum alloy in a prismatic shape, and the inside wall was filled with rooftop plastic slices and polyurethane hard foam. The compression test has successfully carried out, and the load versus displacement data could be used in calculating energy absorption capability. The result of the absorbent energy of the selected impact attenuator material. Impact attenuator full polyurethane absorbed energy reach 6380 Joule. For impact attenuator with aluminum polyurethane with a slashed rooftop material as section absorbed energy reach 6600 Joule. Impact attenuator with Aluminum Polyurethane with aluminum orange peel partitions absorbed energy reach 8800 Joule. From standard student formula, energy absorbed in this event must meet or exceed 7350 Joules that meet aluminum polyurethane with aluminum orange peel partitions with the ability to absorb 8800 Joule.

  6. MTBE, TBA, and TAME attenuation in diverse hyporheic zones.

    PubMed

    Landmeyer, James E; Bradley, Paul M; Trego, Donald A; Hale, Kevin G; Haas, Joseph E

    2010-01-01

    Groundwater contamination by fuel-related compounds such as the fuel oxygenates methyl tert-butyl ether (MTBE), tert-butyl alcohol (TBA), and tert-amyl methyl ether (TAME) presents a significant issue to managers and consumers of groundwater and surface water that receives groundwater discharge. Four sites were investigated on Long Island, New York, characterized by groundwater contaminated with gasoline and fuel oxygenates that ultimately discharge to fresh, brackish, or saline surface water. For each site, contaminated groundwater discharge zones were delineated using pore water geochemistry data from 15 feet (4.5 m) beneath the bottom of the surface water body in the hyporheic zone and seepage-meter tests were conducted to measure discharge rates. These data when combined indicate that MTBE, TBA, and TAME concentrations in groundwater discharge in a 5-foot (1.5-m) thick section of the hyporheic zone were attenuated between 34% and 95%, in contrast to immeasurable attenuation in the shallow aquifer during contaminant transport between 0.1 and 1.5 miles (0.1 to 2.4 km). The attenuation observed in the hyporheic zone occurred primarily by physical processes such as mixing of groundwater and surface water. Biodegradation also occurred as confirmed in laboratory microcosms by the mineralization of U- (14)C-MTBE and U-(14)C-TBA to (14)CO(2) and the novel biodegradation of U- (14)C-TAME to (14)CO(2) under oxic and anoxic conditions. The implication of fuel oxygenate attenuation observed in diverse hyporheic zones suggests an assessment of the hyporheic zone attenuation potential (HZAP) merits inclusion as part of site assessment strategies associated with monitored or engineered attenuation.

  7. MTBE, TBA, and TAME attenuation in diverse hyporheic zones

    USGS Publications Warehouse

    Landmeyer, J.E.; Bradley, P.M.; Trego, D.A.; Hale, K.G.; Haas, J.E.

    2010-01-01

    Groundwater contamination by fuel-related compounds such as the fuel oxygenates methyl tert-butyl ether (MTBE), tert-butyl alcohol (TBA), and tert-amyl methyl ether (TAME) presents a significant issue to managers and consumers of groundwater and surface water that receives groundwater discharge. Four sites were investigated on Long Island, New York, characterized by groundwater contaminated with gasoline and fuel oxygenates that ultimately discharge to fresh, brackish, or saline surface water. For each site, contaminated groundwater discharge zones were delineated using pore water geochemistry data from 15 feet (4.5 m) beneath the bottom of the surface water body in the hyporheic zone and seepage-meter tests were conducted to measure discharge rates. These data when combined indicate that MTBE, TBA, and TAME concentrations in groundwater discharge in a 5-foot (1.5-m) thick section of the hyporheic zone were attenuated between 34% and 95%, in contrast to immeasurable attenuation in the shallow aquifer during contaminant transport between 0.1 and 1.5 miles (0.1 to 2.4 km). The attenuation observed in the hyporheic zone occurred primarily by physical processes such as mixing of groundwater and surface water. Biodegradation also occurred as confirmed in laboratory microcosms by the mineralization of U- 14C-MTBE and U- 14C-TBA to 14CO2 and the novel biodegradation of U- 14C-TAME to 14CO2 under oxic and anoxic conditions. The implication of fuel oxygenate attenuation observed in diverse hyporheic zones suggests an assessment of the hyporheic zone attenuation potential (HZAP) merits inclusion as part of site assessment strategies associated with monitored or engineered attenuation. ?? 2009 National Ground Water Association.

  8. Monoclonal antibody to a cancer-specific and drug-responsive hydroquinone (NADH) oxidase from the sera of cancer patients

    NASA Technical Reports Server (NTRS)

    Cho, NaMi; Chueh, Pin-Ju; Kim, Chinpal; Caldwell, Sara; Morre, Dorothy M.; Morre, D. James

    2002-01-01

    Monoclonal antibodies were generated in mice to a 34-kDa circulating form of a drug-responsive hydroquinone (NADH) oxidase with a protein disulfide-thiol interchange activity specific to the surface of cancer cells and the sera of cancer patients. Screening used Western blots with purified 34-kDa tNOX from HeLa cells and the sera of cancer patients. Epitopes were sought that inhibited the drug-responsive oxidation of NADH with the sera of cancer patients, but which had no effect on NADH oxidation with the sera of healthy volunteers. Two such antisera were generated. One, designated monoclonal antibody (mAb) 12.1, was characterized extensively. The NADH oxidase activity inhibited by mAb 12.1 also was inhibited by the quinone site inhibitor capsaicin (8-methyl- N-vanillyl-6-noneamide). The inhibition was competitive for the drug-responsive protein disulfide-thiol interchange activity assayed either by restoration of activity to scrambled RNase or by cleavage of a dithiodipyridine substrate, and was uncompetitive for NADH oxidation. Both the mAb 12.1 and the postimmune antisera immunoprecipitated drug-responsive NOX activity and identified the same 34-kDa tNOX protein in the sera of cancer patients that was absent from sera of healthy volunteers, and was utilized as immunogen. Preimmune sera from the same mouse as the postimmune antisera was without effect. Both mouse ascites containing mAb 12.1 and postimmune sera (but not preimmune sera) slowed the growth of human cancer cell lines in culture, but did not affect the growth of non-cancerous cell lines. Immunocytochemical and histochemical findings showed that mAb 12.1 reacted with the surface membranes of human carcinoma cells and tissues.

  9. MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and β-arrestin 2.

    PubMed

    Zhou, Yu; Song, Yan; Shaikh, Zahir; Li, Hui; Zhang, Haiju; Caudle, Yi; Zheng, Shouhua; Yan, Hui; Hu, Dan; Stuart, Charles; Yin, Deling

    2017-07-18

    Cardiac dysfunction is correlated with detrimental prognosis of sepsis and contributes to a high risk of mortality. After an initial hyperinflammatory reaction, most patients enter a protracted state of immunosuppression (late sepsis) that alters both innate and adaptive immunity. The changes of cardiac function in late sepsis are not yet known. MicroRNA-155 (miR-155) is previously found to play important roles in both regulations of immune activation and cardiac function. In this study, C57BL/6 mice were operated to develop into early and late sepsis phases, and miR-155 mimic was injected through the tail vein 48 h after cecal ligation and puncture (CLP). The effect of miR-155 on CLP-induced cardiac dysfunction was explored in late sepsis. We found that increased expression of miR-155 in the myocardium protected against cardiac dysfunction in late sepsis evidenced by attenuating sepsis-reduced cardiac output and enhancing left ventricular systolic function. We also observed that miR-155 markedly reduced the infiltration of macrophages and neutrophils into the myocardium and attenuated the inflammatory response via suppression of JNK signaling pathway. Moreover, overexpression of β-arrestin 2 (Arrb2) exacerbated the mice mortality and immunosuppression in late sepsis. Furthermore, transfection of miR-155 mimic reduced Arrb2 expression, and then restored immunocompetence and improved survival in late septic mice. We conclude that increased miR-155 expression through systemic administration of miR-155 mimic attenuates cardiac dysfunction and improves late sepsis survival by targeting JNK associated inflammatory signaling and Arrb2 mediated immunosuppression.

  10. 40 CFR 211.206 - Methods for measurement of sound attenuation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Methods for measurement of sound attenuation. 211.206 Section 211.206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... measurement of sound attenuation. ...

  11. 40 CFR 211.206 - Methods for measurement of sound attenuation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Methods for measurement of sound attenuation. 211.206 Section 211.206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... measurement of sound attenuation. ...

  12. 40 CFR 211.206 - Methods for measurement of sound attenuation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Methods for measurement of sound attenuation. 211.206 Section 211.206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... measurement of sound attenuation. ...

  13. 40 CFR 211.206 - Methods for measurement of sound attenuation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Methods for measurement of sound attenuation. 211.206 Section 211.206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... measurement of sound attenuation. ...

  14. 40 CFR 211.206 - Methods for measurement of sound attenuation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Methods for measurement of sound attenuation. 211.206 Section 211.206 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... measurement of sound attenuation. ...

  15. The Study of Rain Specific Attenuation for the Prediction of Satellite Propagation in Malaysia

    NASA Astrophysics Data System (ADS)

    Mandeep, J. S.; Ng, Y. Y.; Abdullah, H.; Abdullah, M.

    2010-06-01

    Specific attenuation is the fundamental quantity in the calculation of rain attenuation for terrestrial path and slant paths representing as rain attenuation per unit distance (dB/km). Specific attenuation is an important element in developing the predicted rain attenuation model. This paper deals with the empirical determination of the power law coefficients which allow calculating the specific attenuation in dB/km from the knowledge of the rain rate in mm/h. The main purpose of the paper is to obtain the coefficients of k and α of power law relationship between specific attenuation. Three years (from 1st January 2006 until 31st December 2008) rain gauge and beacon data taken from USM, Nibong Tebal have been used to do the empirical procedure analysis of rain specific attenuation. The data presented are semi-empirical in nature. A year-to-year variation of the coefficients has been indicated and the empirical measured data was compared with ITU-R provided regression coefficient. The result indicated that the USM empirical measured data was significantly vary from ITU-R predicted value. Hence, ITU-R recommendation for regression coefficients of rain specific attenuation is not suitable for predicting rain attenuation at Malaysia.

  16. Parametric detection and measurement of perfusion defects in attenuated contrast echocardiographic images.

    PubMed

    Yoshifuku, Shiro; Chen, Shigao; McMahon, Eileen; Korinek, Josef; Yoshikawa, Akiko; Ochiai, Izuru; Sengupta, Partho P; Belohlavek, Marek

    2007-06-01

    Attenuation of radio frequency (RF) signals limits the use of contrast echocardiography. The harmonic-to-fundamental ratio (HFR) of the RF signals compensates for attenuation. We tested whether HFR analysis measures the left ventricular nonperfused area under simulated experimental attenuation. Radio frequency image data from short axis systolic projections were obtained from 11 open-chest dogs with left anterior descending or left circumflex coronary artery occlusion followed by left atrial bolus injection of a perflutren microbubble contrast agent. Clinical attenuation was simulated by calibrated silicone pads interposed between the epicardial surface and the transducer to induce mild (7-dB) and severe (14-dB) reduction of the backscattered RF signals. Harmonic-to-fundamental ratio values were calculated for each image pixel for 0-, 7-, and 14-dB attenuation conditions and reproducibly showed a "perfused area" and a "nonperfused area." A reference nonperfused area was obtained by manual delineation in high-quality contrast scans. Correlations of the HFR-detected and manually outlined perfusion defect areas were R = 0.92 for 0 dB, R = 0.94 for 7 dB, and R = 0.90 for 14 dB; the mean difference was less than 0.36 cm(2) (negligible) in all 3 attenuation settings. Conclusions. Attenuation compensation by our HFR method allows precise measurement of myocardial perfusion defect areas in contrast scans with simulated high level of attenuation.

  17. A New Approach for Quantitative Evaluation of Ultrasonic Wave Attenuation in Composites

    NASA Astrophysics Data System (ADS)

    Ni, Qing-Qing; Li, Ran; Xia, Hong

    2017-02-01

    When ultrasonic waves propagate in composite materials, the propagation behaviors result from the combination effects of various factors, such as material anisotropy and viscoelastic property, internal microstructure and defects, incident wave characteristics and interface condition between composite components. It is essential to make it clear how these factors affect the ultrasonic wave propagation and attenuation characteristics, and how they mutually interact on each other. In the present paper, based on a newly developed time-domain finite element analysis code, PZflex, a unique approach for clarifying the detailed influence mechanism of aforementioned factors is proposed, in which each attenuation component can be extracted from the overall attenuation and analyzed respectively. By taking into consideration the interrelation between each individual attenuation component, the variation behaviors of each component and internal dynamic stress distribution against material anisotropy and matrix viscosity are separately and quantitatively evaluated. From the detailed analysis results of each attenuation component, the energy dissipation at interface is a major component in ultrasonic wave attenuation characteristics, which can provide a maximum contribution rate of 68.2 % to the overall attenuation, and each attenuation component is closely related to the material anisotropy and viscoelasticity. The results clarify the correlation between ultrasonic wave propagation characteristics and material viscoelastic properties, which will be useful in the further development of ultrasonic technology in defect detection.

  18. Attenuation-emission alignment in cardiac PET∕CT based on consistency conditions

    PubMed Central

    Alessio, Adam M.; Kinahan, Paul E.; Champley, Kyle M.; Caldwell, James H.

    2010-01-01

    Purpose: In cardiac PET and PET∕CT imaging, misaligned transmission and emission images are a common problem due to respiratory and cardiac motion. This misalignment leads to erroneous attenuation correction and can cause errors in perfusion mapping and quantification. This study develops and tests a method for automated alignment of attenuation and emission data. Methods: The CT-based attenuation map is iteratively transformed until the attenuation corrected emission data minimize an objective function based on the Radon consistency conditions. The alignment process is derived from previous work by Welch et al. [“Attenuation correction in PET using consistency information,” IEEE Trans. Nucl. Sci. 45, 3134–3141 (1998)] for stand-alone PET imaging. The process was evaluated with the simulated data and measured patient data from multiple cardiac ammonia PET∕CT exams. The alignment procedure was applied to simulations of five different noise levels with three different initial attenuation maps. For the measured patient data, the alignment procedure was applied to eight attenuation-emission combinations with initially acceptable alignment and eight combinations with unacceptable alignment. The initially acceptable alignment studies were forced out of alignment a known amount and quantitatively evaluated for alignment and perfusion accuracy. The initially unacceptable studies were compared to the proposed aligned images in a blinded side-by-side review. Results: The proposed automatic alignment procedure reduced errors in the simulated data and iteratively approaches global minimum solutions with the patient data. In simulations, the alignment procedure reduced the root mean square error to less than 5 mm and reduces the axial translation error to less than 1 mm. In patient studies, the procedure reduced the translation error by >50% and resolved perfusion artifacts after a known misalignment for the eight initially acceptable patient combinations. The side

  19. Blockade of Endocannabinoid Hydrolytic Enzymes Attenuates Precipitated Opioid Withdrawal Symptoms in MiceS⃞

    PubMed Central

    Ramesh, Divya; Ross, Gracious R.; Schlosburg, Joel E.; Owens, Robert A.; Abdullah, Rehab A.; Kinsey, Steven G.; Long, Jonathan Z.; Nomura, Daniel K.; Sim-Selley, Laura J.; Cravatt, Benjamin F.; Akbarali, Hamid I.

    2011-01-01

    Δ9-Tetrahydrocannbinol (THC), the primary active constituent of Cannabis sativa, has long been known to reduce opioid withdrawal symptoms. Although THC produces most of its pharmacological actions through the activation of CB1 and CB2 cannabinoid receptors, the role these receptors play in reducing the variety of opioid withdrawal symptoms remains unknown. The endogenous cannabinoids, N-arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), activate both cannabinoid receptors but are rapidly metabolized by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. The objective of this study was to test whether increasing AEA or 2-AG, via inhibition of their respective hydrolytic enzymes, reduces naloxone-precipitated morphine withdrawal symptoms in in vivo and in vitro models of opioid dependence. Morphine-dependent mice challenged with naloxone reliably displayed a profound withdrawal syndrome, consisting of jumping, paw tremors, diarrhea, and weight loss. THC and the MAGL inhibitor 4-nitrophenyl 4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184) dose dependently reduced the intensity of most measures through the activation of CB1 receptors. JZL184 also attenuated spontaneous withdrawal signs in morphine-dependent mice. The FAAH inhibitor N-(pyridin-3-yl)-4-(3-(5-(trifluoromethyl)pyridin-2-yloxy)benzyl)-piperdine-1-carboxamide (PF-3845) reduced the intensity of naloxone-precipitated jumps and paw flutters through the activation of CB1 receptors but did not ameliorate incidence of diarrhea or weight loss. In the final series of experiments, we investigated whether JZL184 or PF-3845 would attenuate naloxone-precipitated contractions in morphine-dependent ilea. Both enzyme inhibitors attenuated the intensity of naloxone-induced contractions, although this model does not account mechanistically for the autonomic withdrawal responses (i.e., diarrhea) observed in vivo. These results indicate

  20. Stabilizing laser energy density on a target during pulsed laser deposition of thin films

    DOEpatents

    Dowden, Paul C.; Jia, Quanxi

    2016-05-31

    A process for stabilizing laser energy density on a target surface during pulsed laser deposition of thin films controls the focused laser spot on the target. The process involves imaging an image-aperture positioned in the beamline. This eliminates changes in the beam dimensions of the laser. A continuously variable attenuator located in between the output of the laser and the imaged image-aperture adjusts the energy to a desired level by running the laser in a "constant voltage" mode. The process provides reproducibility and controllability for deposition of electronic thin films by pulsed laser deposition.

  1. Acoustic attenuation design requirements established through EPNL parametric trades

    NASA Technical Reports Server (NTRS)

    Veldman, H. F.

    1972-01-01

    An optimization procedure for the provision of an acoustic lining configuration that is balanced with respect to engine performance losses and lining attenuation characteristics was established using a method which determined acoustic attenuation design requirements through parametric trade studies using the subjective noise unit of effective perceived noise level (EPNL).

  2. miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression.

    PubMed

    Zheng, Liduan; Jiao, Wanju; Song, Huajie; Qu, Hongxia; Li, Dan; Mei, Hong; Chen, Yajun; Yang, Feng; Li, Huanhuan; Huang, Kai; Tong, Qiangsong

    2016-09-29

    Previous studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines. In contrast, Smad4 suppressed the nascent transcription and expression of HPSE via directly binding to its promoter. Mechanistically, miR-558 recognized its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1-dependent manner. Ectopic expression or knockdown experiments indicated that miR-558 promoted the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cell lines via attenuating Smad4-mediated repression of HPSE expression. In clinical gastric cancer specimens, up-regulation of miR-558 and down-regulation of Smad4 were positively correlated with HPSE expression. Kaplan-Meier survival analysis revealed that miR-558 and Smad4 were associated with unfavourable and favourable outcome of gastric cancer patients, respectively. Therefore, these findings demonstrate that miR-558 facilitates the progression of gastric cancer through directly targeting the HPSE promoter to attenuate Smad4-mediated repression of HPSE expression.

  3. miRNA-558 promotes gastric cancer progression through attenuating Smad4-mediated repression of heparanase expression

    PubMed Central

    Zheng, Liduan; Jiao, Wanju; Song, Huajie; Qu, Hongxia; Li, Dan; Mei, Hong; Chen, Yajun; Yang, Feng; Li, Huanhuan; Huang, Kai; Tong, Qiangsong

    2016-01-01

    Previous studies have indicated that as the only mammalian endo-β-D-glucuronidase, heparanase (HPSE) is up-regulated and associated with poor prognosis in gastric cancer, while the underlying mechanisms still remain to be determined. Herein, through integrative analysis of public datasets, we found microRNA-558 (miR-558) and SMAD family member 4 (Smad4) as the crucial transcription regulators of HPSE expression in gastric cancer, with their adjacent target sites within the promoter of HPSE. We identified that endogenous miR-558 activated the transcription and expression of HPSE in gastric cancer cell lines. In contrast, Smad4 suppressed the nascent transcription and expression of HPSE via directly binding to its promoter. Mechanistically, miR-558 recognized its complementary site within HPSE promoter to decrease the binding of Smad4 in an Argonaute 1-dependent manner. Ectopic expression or knockdown experiments indicated that miR-558 promoted the in vitro and in vivo tumorigenesis and aggressiveness of gastric cancer cell lines via attenuating Smad4-mediated repression of HPSE expression. In clinical gastric cancer specimens, up-regulation of miR-558 and down-regulation of Smad4 were positively correlated with HPSE expression. Kaplan–Meier survival analysis revealed that miR-558 and Smad4 were associated with unfavourable and favourable outcome of gastric cancer patients, respectively. Therefore, these findings demonstrate that miR-558 facilitates the progression of gastric cancer through directly targeting the HPSE promoter to attenuate Smad4-mediated repression of HPSE expression. PMID:27685626

  4. A depolarization and attenuation experiment using the COMSTAR and CTS satellites

    NASA Technical Reports Server (NTRS)

    Bostian, C. W.; Babula, S. M.; Dent, J. R.; Dombroski, R. E.; Lane, S. O.; Manus, E. A.; Marshall, R. E.; Meadows, D. N.; Stutzman, W. L.; Wiley, P. H.

    1979-01-01

    Monthly and annual percent-of-time data on ground rain fall rate and attenuation on satellite downlinks at 11.7 GHz, 19.04 GHz, and 28.56 GHz is presented. Equal probability values of attenuation and rain rate are compared for monthly, quarterly, half-year periods and for the entire year. Regression equations relating cross polarization isolation to the logarithm of attenuation are also presented.

  5. Ultrasonic attenuation measurements determine onset, degree, and completion of recrystallization

    NASA Technical Reports Server (NTRS)

    Generazio, E. R.

    1988-01-01

    Ultrasonic attenuation was measured for cold worked Nickel 200 samples annealed at increasing temperatures. Localized dislocation density variations, crystalline order and volume percent of recrystallized phase were determined over the anneal temperature range using transmission electron microscopy, X-ray diffraction, and metallurgy. The exponent of the frequency dependence of the attenuation was found to be a key variable relating ultrasonic attenuation to the thermal kinetics of the recrystallization process. Identification of this key variable allows for the ultrasonic determination of onset, degree, and completion of recrystallization.

  6. SU-F-T-46: The Effect of Inter-Seed Attenuation and Tissue Composition in Prostate 125I Brachytherapy Dose Calculations

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

    Tamura, K; Araki, F; Ohno, T

    Purpose: To investigate the difference of dose distributions with/without the effect of inter-seed attenuation and tissue compositions in prostate {sup 125}I brachytherapy dose calculations, using Monte Carlo simulations of Particle and Heavy Ion Transport code System (PHITS). Methods: The dose distributions in {sup 125}I prostate brachytherapy were calculated using PHITS for non-simultaneous and simultaneous alignments of STM1251 sources in water or prostate phantom for six patients. The PHITS input file was created from DICOM-RT file which includes source coordinates and structures for clinical target volume (CTV) and organs at risk (OARs) of urethra and rectum, using in-house Matlab software. Photonmore » and electron cutoff energies were set to 1 keV and 100 MeV, respectively. The dose distributions were calculated with the kerma approximation and the voxel size of 1 × 1 × 1 mm{sup 3}. The number of incident photon was set to be the statistical uncertainty (1σ) of less than 1%. The effect of inter-seed attenuation and prostate tissue compositions was evaluated from dose volume histograms (DVHs) for each structure, by comparing to results of the AAPM TG-43 dose calculation (without the effect of inter-seed attenuation and prostate tissue compositions). Results: The dose reduction due to the inter-seed attenuation by source capsules was approximately 2% for CTV and OARs compared to those of TG-43. In additions, by considering prostate tissue composition, the D{sub 90} and V{sub 100} of CTV reduced by 6% and 1%, respectively. Conclusion: It needs to consider the dose reduction due to the inter-seed attenuation and tissue composition in prostate {sup 125}I brachytherapy dose calculations.« less

  7. The feature extraction of "cat-eye" targets based on bi-spectrum

    NASA Astrophysics Data System (ADS)

    Zhang, Tinghua; Fan, Guihua; Sun, Huayan

    2016-10-01

    In order to resolve the difficult problem of detection and identification of optical targets in complex background or in long-distance transmission, this paper mainly study the range profiles of "cat-eye" targets using bi-spectrum. For the problems of laser echo signal attenuation serious and low Signal-Noise Ratio (SNR), the multi-pulse laser signal echo signal detection algorithm which is based on high-order cumulant, filter processing and the accumulation of multi-pulse is proposed. This could improve the detection range effectively. In order to extract the stable characteristics of the one-dimensional range profile coming from the cat-eye targets, a method is proposed which extracts the bi-spectrum feature, and uses the singular value decomposition to simplify the calculation. Then, by extracting data samples of different distance, type and incidence angle, verify the stability of the eigenvector and effectiveness extracted by bi-spectrum.

  8. Subsurface Characterization To Support Evaluation Of Radionuclide Transport And Attenuation

    EPA Science Inventory

    Remediation of ground water contaminated with radionuclides may be achieved using attenuation-based technologies. These technologies may rely on engineered processes (e.g., bioremediation) or natural processes (e.g., monitored natural attenuation) within the subsurface. In gene...

  9. Mixture model based joint-MAP reconstruction of attenuation and activity maps in TOF-PET

    NASA Astrophysics Data System (ADS)

    Hemmati, H.; Kamali-Asl, A.; Ghafarian, P.; Ay, M. R.

    2018-06-01

    A challenge to have quantitative positron emission tomography (PET) images is to provide an accurate and patient-specific photon attenuation correction. In PET/MR scanners, the nature of MR signals and hardware limitations have led to a real challenge on the attenuation map extraction. Except for a constant factor, the activity and attenuation maps from emission data on TOF-PET system can be determined by the maximum likelihood reconstruction of attenuation and activity approach (MLAA) from emission data. The aim of the present study is to constrain the joint estimations of activity and attenuation approach for PET system using a mixture model prior based on the attenuation map histogram. This novel prior enforces non-negativity and its hyperparameters can be estimated using a mixture decomposition step from the current estimation of the attenuation map. The proposed method can also be helpful on the solving of scaling problem and is capable to assign the predefined regional attenuation coefficients with some degree of confidence to the attenuation map similar to segmentation-based attenuation correction approaches. The performance of the algorithm is studied with numerical and Monte Carlo simulations and a phantom experiment and was compared with MLAA algorithm with and without the smoothing prior. The results demonstrate that the proposed algorithm is capable of producing the cross-talk free activity and attenuation images from emission data. The proposed approach has potential to be a practical and competitive method for joint reconstruction of activity and attenuation maps from emission data on PET/MR and can be integrated on the other methods.

  10. Attenuating endogenous Fgfr2b ligands during bleomycin-induced lung fibrosis does not compromise murine lung repair

    PubMed Central

    MacKenzie, BreAnne; Henneke, Ingrid; Hezel, Stefanie; Al Alam, Denise; El Agha, Elie; Chao, Cho-Ming; Quantius, Jennifer; Wilhelm, Jochen; Jones, Matthew; Goth, Kerstin; Li, Xiaokun; Seeger, Werner; Königshoff, Melanie; Herold, Susanne; Rizvanov, Albert A.; Günther, Andreas

    2015-01-01

    Fibroblast growth factors (Fgfs) mediate organ repair. Lung epithelial cell overexpression of Fgf10 postbleomycin injury is both protective and therapeutic, characterized by increased survival and attenuated fibrosis. Exogenous administration of FGF7 (palifermin) also showed prophylactic survival benefits in mice. The role of endogenous Fgfr2b ligands on bleomycin-induced lung fibrosis is still elusive. This study reports the expression of endogenous Fgfr2b ligands, receptors, and signaling targets in wild-type mice following bleomycin lung injury. In addition, the impact of attenuating endogenous Fgfr2b-ligands following bleomycin-induced fibrosis was tested by using a doxycycline (dox)-based inducible, soluble, dominant-negative form of the Fgfr2b receptor. Double-transgenic (DTG) Rosa26rtTA/+;tet(O)solFgfr2b mice were validated for the expression and activity of soluble Fgfr2b (failure to regenerate maxillary incisors, attenuated recombinant FGF7 signal in the lung). As previously reported, no defects in lung morphometry were detected in DTG (+dox) mice exposed from postnatal days (PN) 1 through PN105. Female single-transgenic (STG) and DTG mice were subjected to various levels of bleomycin injury (1.0, 2.0, and 3.0 U/kg). Fgfr2b ligands were attenuated either throughout injury (days 0–11; days 0–28) or during later stages (days 6–28 and 14–28). No significant changes in survival, weight, lung function, confluent areas of fibrosis, or hydroxyproline deposition were detected in DTG mice. These results indicate that endogenous Fgfr2b ligands do not significantly protect against bleomycin injury, nor do they expedite the resolution of bleomycin-induced lung injury in mice. PMID:25820524

  11. Using Tectonic Tremor to Constrain Seismic-wave Attenuation in Cascadia

    NASA Astrophysics Data System (ADS)

    Littel, G.; Thomas, A.; Baltay, A.

    2017-12-01

    In addition to fast, seismic slip, many subduction zones also host slow, largely aseismic slip, accompanied by a weak seismic signal known as tectonic tremor. Tremor is a small amplitude, low-frequency seismic signal that originates at the plate interface, down-dip of where large earthquakes typically occur. The Cascadia subduction zone has not seen a large megathrust earthquake since 1700, yet its recurrence interval of 350-500 years motivates heightened interest in understanding the seismic hazard of the region. Of great importance is to understand the degree to which waves are attenuated as they leave the plate interface and travel towards populated regions of interest. Ground motion prediction equations (GMPEs) relate ground motion to a number of parameters, including earthquake magnitude, depth, style of faulting, and anelastic attenuation, and are typically determined empirically from earthquake ground motion recordings. In Cascadia, however, earthquakes of the moderate size typically used to constrain GMPEs occur relatively infrequently compared to tectonic tremor events, which, in contrast, occur periodically approximately every 10-19 months. Studies have shown that the abundant tectonic tremor in Cascadia, despite its small amplitudes, can be used to constrain seismic wave attenuation in GMPEs. Here we quantify seismic wave attenuation and determine its spatial variations in Cascadia by performing an inversion using tremor ground motion amplitudes, taken as peak ground acceleration (PGA) and peak ground velocity (PGV) from 1 min window waveforms of each individual tremor event. We estimate the anelastic attenuation parameter for varying regional sections along the Cascadia margin. Changes in seismic-wave attenuation along the Cascadia Subduction Zone could result in significantly different ground motions in the event of a very large earthquake, hence quantifying attenuation may help to better estimate the severity of shaking in densely populated

  12. GLP-1-oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice.

    PubMed

    Schwenk, Robert W; Baumeier, Christian; Finan, Brian; Kluth, Oliver; Brauer, Christine; Joost, Hans-Georg; DiMarchi, Richard D; Tschöp, Matthias H; Schürmann, Annette

    2015-03-01

    Oestrogens have previously been shown to exert beta cell protective, glucose-lowering effects in mouse models. Therefore, the recent development of a glucagon-like peptide-1 (GLP-1)-oestrogen conjugate, which targets oestrogen into cells expressing GLP-1 receptors, offers an opportunity for a cell-specific and enhanced beta cell protection by oestrogen. The purpose of this study was to compare the effects of GLP-1 and GLP-1-oestrogen during beta cell failure under glucolipotoxic conditions. Male New Zealand obese (NZO) mice were treated with daily s.c. injections of GLP-1 and GLP-1-oestrogen, respectively. Subsequently, the effects on energy homeostasis and beta cell integrity were measured. In order to clarify the targeting of GLP-1-oestrogen, transcription analyses of oestrogen-responsive genes in distinct tissues as well as microarray analyses in pancreatic islets were performed. In contrast to GLP-1, GLP-1-oestrogen significantly decreased food intake resulting in a substantial weight reduction, preserved normoglycaemia, increased glucose tolerance and enhanced beta cell protection. Analysis of hypothalamic mRNA profiles revealed elevated expression of Pomc and Leprb. In livers from GLP-1-oestrogen-treated mice, expression of lipogenic genes was attenuated and hepatic triacylglycerol levels were decreased. In pancreatic islets, GLP-1-oestrogen altered the mRNA expression to a pattern that was similar to that of diabetes-resistant NZO females. However, conventional oestrogen-responsive genes were not different, indicating rather indirect protection of pancreatic beta cells. GLP-1-oestrogen efficiently protects NZO mice against carbohydrate-induced beta cell failure by attenuation of hyperphagia. In this regard, targeted delivery of oestrogen to the hypothalamus by far exceeds the anorexigenic capacity of GLP-1 alone.

  13. A model for attenuation and scattering in the Earth's crust

    NASA Astrophysics Data System (ADS)

    Toksöz, M. Nafi; Dainty, Anton M.; Reiter, Edmund; Wu, Ru-Shan

    1988-03-01

    The mechanisms contributing to the attenuation of earthquake ground motion in the distance range of 10 to 200 km are studied with the aid of laboratory data, coda waves Rg attenuation, strong motion attenuation measurements in the northeast United States and Canada, and theoretical models. The frequency range 1 10 Hz has been studied. The relative contributions to attenuation of anelasticity of crustal rocks (constant Q), fluid flow and scattering are evaluated. Scattering is found to be strong with an albedo B 0=0.8 0.9 and a scattering extinction length of 17 32 km. The albedo is defined as the ratio of the total extinction length to the scattering extinction length. The Rg results indicate that Q increases with depth in the upper kilometer or two of the crust, at least in New England. Coda Q appears to be equivalent to intrinsic (anelastic) Q and indicates that this Q increases with frequency as Q=Q o f n , where n is in the range of 0.2 0.9. The intrinsic attenuation in the crust can be explained by a high constant Q (500≤ Q o≤2000) and a frequency dependent mechanism most likely due to fluid effects in rocks and cracks. A fluid-flow attenuation model gives a frequency dependence ( Q≃ Q o f 0.5) similar to those determined from the analysis of coda waves of regional seismograms. Q is low near the surface and high in the body of the crust.

  14. Earplug rankings based on the protector-attenuation rating (P-AR).

    DOT National Transportation Integrated Search

    1975-01-01

    Forty-five attenuation spectra for earplugs were classified according to a simplified method designed to produce single-number ratings of noise reduction. The rating procedure was applied to the mean attenuation scores, to mean-minus-one-standard-dev...

  15. Urgent challenges in implementing live attenuated influenza vaccine.

    PubMed

    Singanayagam, Anika; Zambon, Maria; Lalvani, Ajit; Barclay, Wendy

    2018-01-01

    Conflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine. The live attenuated influenza vaccine appears to protect particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 viruses. During the 2015-16 influenza season, when pandemic H1N1 was the predominant virus, studies from the USA reported a complete lack of effectiveness of the live vaccine in children. This finding led to a crucial decision in the USA to recommend that the live vaccine not be used in 2016-17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada, and Finland, however, have continued to recommend the use of the live vaccine. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of the production capabilities of the live attenuated influenza vaccine for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of the live attenuated influenza vaccine and highlight the underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Determination of Dimensionless Attenuation Coefficient in Shaped Resonators

    NASA Technical Reports Server (NTRS)

    Daniels, C.; Steinetz, B.; Finkbeiner, J.; Raman, G.; Li, X.

    2003-01-01

    The value of dimensionless attenuation coefficient is an important factor when numerically predicting high-amplitude acoustic waves in shaped resonators. Both the magnitude of the pressure waveform and the quality factor rely heavily on this dimensionless parameter. Previous authors have stated the values used, but have not completely explained their methods. This work fully describes the methodology used to determine this important parameter. Over a range of frequencies encompassing the fundamental resonance, the pressure waves were experimentally measured at each end of the shaped resonators. At the corresponding dimensionless acceleration, the numerical code modeled the acoustic waveforms generated in the resonator using various dimensionless attenuation coefficients. The dimensionless attenuation coefficient that most closely matched the pressure amplitudes and quality factors of the experimental and numerical results was determined to be the value to be used in subsequent studies.

  17. Giardia duodenalis Infection Reduces Granulocyte Infiltration in an In Vivo Model of Bacterial Toxin-Induced Colitis and Attenuates Inflammation in Human Intestinal Tissue

    PubMed Central

    Cotton, James A.; Motta, Jean-Paul; Schenck, L. Patrick; Hirota, Simon A.; Beck, Paul L.; Buret, Andre G.

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn’s disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  18. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    PubMed

    Cotton, James A; Motta, Jean-Paul; Schenck, L Patrick; Hirota, Simon A; Beck, Paul L; Buret, Andre G

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  19. Attenuation - The Ugly Stepsister of Velocity in the Noise Correlation Family

    NASA Astrophysics Data System (ADS)

    Lawrence, J. F.; Prieto, G.; Denolle, M.; Seats, K. J.

    2012-12-01

    Noise correlation functions and noise transfer functions have shown in practice to preserve the relative amplitude information, despite the challenge to reliably resolve it compared to phase information. Yet amplitude contains important information about wavefield interactions with the subsurface structure, including focusing/defocusing and seismic attenuation. To focus on the anelastic effects, or attenuation, we measure amplitude decay with increased station separation (distance). We present numerical results showing that the noise correlation functions (NCFs) preserve the relative amplitude information and properly retrieve seismic attenuation for sufficient noise source distribution and appropriate processing. Attenuation is only preserved through the relative decay of distinct waves from multiple simultaneous source locations. With appropriate whitening (and no time domain normalization), the coherency preserves correlation amplitudes proportional to the relative decay expected with all the inter-station spacing. We present new attenuation results for the United States, and particularly the Yellowstone region that illustrate lateral variations that strongly correlate with known geological features such as sedimentary basins, crustal blocks and active volcanism.

  20. Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

    PubMed Central

    Vieira-Brock, Paula L.; McFadden, Lisa M.; Nielsen, Shannon M.; Smith, Misty D.; Hanson, Glen R.

    2015-01-01

    Background: Previous studies have demonstrated that methamphetamine abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors. The present study investigated whether nicotine attenuates methamphetamine-induced novel object recognition deficits in rats and explored potential underlying mechanisms. Methods: Adolescent or adult male Sprague-Dawley rats received either nicotine water (10–75 μg/mL) or tap water for several weeks. Methamphetamine (4×7.5mg/kg/injection) or saline was administered either before or after chronic nicotine exposure. Novel object recognition was evaluated 6 days after methamphetamine or saline. Serotonin transporter function and density and α4β2 nicotinic acetylcholine receptor density were assessed on the following day. Results: Chronic nicotine intake via drinking water beginning during either adolescence or adulthood attenuated the novel object recognition deficits caused by a high-dose methamphetamine administration. Similarly, nicotine attenuated methamphetamine-induced deficits in novel object recognition when administered after methamphetamine treatment. However, nicotine did not attenuate the serotonergic deficits caused by methamphetamine in adults. Conversely, nicotine attenuated methamphetamine-induced deficits in α4β2 nicotinic acetylcholine receptor density in the hippocampal CA1 region. Furthermore, nicotine increased α4β2 nicotinic acetylcholine receptor density in the hippocampal CA3, dentate gyrus and perirhinal cortex in both saline- and methamphetamine-treated rats. Conclusions: Overall, these findings suggest that nicotine-induced increases in α4β2 nicotinic acetylcholine receptors in the hippocampus and perirhinal cortex might be one mechanism by which

  1. The Physics Analysis of a Gas Attenuator with Argon as a Working Gas

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

    Ryutov,, D.D.

    2010-12-07

    A gas attenuator is an important element of the LCLS facility. The attenuator must operate in a broad range of x-ray energies, provide attenuation coefficient between 1 and 10{sup 4} with the accuracy of 1% and, at the same time, be reliable and allow for many months of un-interrupted operation. S. Shen has recently carried out a detailed design study of the attenuator based on the use of nitrogen as a working gas. In this note we assess the features of the attenuator based on the use of argon. We concentrate on the physics issues, not the design features.

  2. Comparison of OLYMPUS beacon and radiometric attenuation measurements at Blacksburg, Virginia

    NASA Technical Reports Server (NTRS)

    Snider, J. B.; Jacobson, M. D.; Beeler, R. H.; Hazen, D. A.

    1991-01-01

    Measurements of attenuation of the 20 and 30 GHz beacons onboard the OLYMPUS satellite are compared to simultaneous observations of atmospheric attenuation by a multichannel microwave radiometer along the same path. Departures from high correlation between the two measurements are believed to be related to differences in antenna beamwidths. Mean equivalent zenith attenuations derived from the slant path data are compared to zenith observations made at previous locations.

  3. Seismic Attenuation, Event Discrimination, Magnitude and Yield Estimation, and Capability Analysis

    DTIC Science & Technology

    2011-09-01

    waves are subject to path-dependent variations in amplitudes. We see geographic similarities between the crustal shear-wave attenuation and the...either Sn or Lg depending on tectonic region, distance, and frequency. Over the past year, we have made great progress on the calibration of surface...between the crustal shear-wave attenuation and the results from the coda attenuation. Calibration of coda in the Middle East and other areas is

  4. Coupled attenuation and multiscale damage model for composite structures

    NASA Astrophysics Data System (ADS)

    Moncada, Albert M.; Chattopadhyay, Aditi; Bednarcyk, Brett; Arnold, Steven M.

    2011-04-01

    Composite materials are widely used in many applications for their high strength, low weight, and tailorability for specific applications. However, the development of robust and reliable methodologies to detect micro level damage in composite structures has been challenging. For composite materials, attenuation of ultrasonic waves propagating through the media can be used to determine damage within the material. Currently available numerical solutions for attenuation induce arbitrary damage, such as fiber-matrix debonding or inclusions, to show variations between healthy and damaged states. This paper addresses this issue by integrating a micromechanics analysis to simulate damage in the form of a fiber-matrix crack and an analytical model for calculating the attenuation of the waves when they pass through the damaged region. The hybrid analysis is validated by comparison with experimental stress-strain curves and piezoelectric sensing results for attenuation measurement. The results showed good agreement between the experimental stress-strain curves and the results from the micromechanics analysis. Wave propagation analysis also showed good correlation between simulation and experiment for the tested frequency range.

  5. Thick-target transmission method for excitation functions of interaction cross sections

    NASA Astrophysics Data System (ADS)

    Aikawa, M.; Ebata, S.; Imai, S.

    2016-09-01

    We propose a method, called as thick-target transmission (T3) method, to obtain an excitation function of interaction cross sections. In an ordinal experiment to measure the excitation function of interaction cross sections by the transmission method, we need to change the beam energy for each cross section. In the T3 method, the excitation function is derived from the beam attenuations measured at the targets of different thicknesses without changing the beam energy. The advantage of the T3 method is the simplicity and availability for radioactive beams. To confirm the availability, we perform a simulation for the 12C + 27Al system with the PHITS code instead of actual experiments. Our results have large uncertainties but well reproduce the tendency of the experimental data.

  6. Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension

    PubMed Central

    Tang, Haiyang; Chen, Jiwang; Fraidenburg, Dustin R.; Song, Shanshan; Sysol, Justin R.; Drennan, Abigail R.; Offermanns, Stefan; Ye, Richard D.; Bonini, Marcelo G.; Minshall, Richard D.; Garcia, Joe G. N.; Machado, Roberto F.; Makino, Ayako

    2014-01-01

    Pulmonary vascular remodeling, mainly attributable to enhanced pulmonary arterial smooth muscle cell proliferation and migration, is a major cause for elevated pulmonary vascular resistance and pulmonary arterial pressure in patients with pulmonary hypertension. The signaling cascade through Akt, comprised of three isoforms (Akt1–3) with distinct but overlapping functions, is involved in regulating cell proliferation and migration. This study aims to investigate whether the Akt/mammalian target of rapamycin (mTOR) pathway, and particularly which Akt isoform, contributes to the development and progression of pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Compared with the wild-type littermates, Akt1−/− mice were protected against the development and progression of chronic HPH, whereas Akt2−/− mice did not demonstrate any significant protection against the development of HPH. Furthermore, pulmonary vascular remodeling was significantly attenuated in the Akt1−/− mice, with no significant effect noted in the Akt2−/− mice after chronic exposure to normobaric hypoxia (10% O2). Overexpression of the upstream repressor of Akt signaling, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), and conditional and inducible knockout of mTOR in smooth muscle cells were also shown to attenuate the rise in right ventricular systolic pressure and the development of right ventricular hypertrophy. In conclusion, Akt isoforms appear to have a unique function within the pulmonary vasculature, with the Akt1 isoform having a dominant role in pulmonary vascular remodeling associated with HPH. The PTEN/Akt1/mTOR signaling pathway will continue to be a critical area of study in the pathogenesis of pulmonary hypertension, and specific Akt isoforms may help specify therapeutic targets for the treatment of pulmonary hypertension. PMID:25416384

  7. Experimental measurements of seismic attenuation in microfracture sedimentary rock

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

    Peacock, S.; McCann, C.; Sothcott, J.

    1994-09-01

    In a previous paper (Peacock et al., 1994), the authors related ultrasonic velocities in water-saturated Carrara Marble to crack densities in polished sections to verify Hudson's (1980, 1981, 1986) theory for velocities in cracked rock. They describe the empirical relationships between attenuation and crack density that they established during these experiments in the hope of clarifying the mechanism of attenuation in rocks with fluid-filled cracks. Relating seismic velocity and attenuation to crack density is important in predicting the productivity of fractured petroleum reservoirs such as the North Sea Brent Field. It also allows cracks to be used as stress indicatorsmore » throughout the shallow crust (Crampin and Lovell, 1991).« less

  8. SENTRE and TREND attenuating systems

    DOT National Transportation Integrated Search

    1991-07-01

    The objective of this study was to construct SENTRE and TREND attenuator systems and evaluate their in-service performance as set forth in NCHRP-230 for a period of two years. The evaluation was conducted as part of ADOTs New Product Evaluation Progr...

  9. Attenuation Modified by DIG and Dust as Seen in M31

    NASA Astrophysics Data System (ADS)

    Tomičić, Neven; Kreckel, Kathryn; Groves, Brent; Schinnerer, Eva; Sandstrom, Karin; Kapala, Maria; Blanc, Guillermo A.; Leroy, Adam

    2017-08-01

    The spatial distribution of dust in galaxies affects the global attenuation, and hence inferred properties, of galaxies. We trace the spatial distribution of dust in five approximately kiloparsec fields of M31 by comparing optical attenuation with the total dust mass distribution. We measure the attenuation from the Balmer decrement using Integral Field Spectroscopy and the dust mass from Herschel far-IR observations. Our results show that M31's dust attenuation closely follows a foreground screen model, contrary to what was previously found in other nearby galaxies. By smoothing the M31 data, we find that spatial resolution is not the cause for this difference. Based on the emission-line ratios and two simple models, we conclude that previous models of dust/gas geometry need to include a weakly or non-attenuated diffuse ionized gas (DIG) component. Due to the variation of dust and DIG scale heights with galactic radius, we conclude that different locations in galaxies will have different vertical distributions of gas and dust and therefore different measured attenuation. The difference between our result in M31 with that found in other nearby galaxies can be explained by our fields in M31 lying at larger galactic radii than the previous studies that focused on the centers of galaxies.

  10. Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection

    PubMed Central

    Krishna, Benjamin A.; Poole, Emma L.; Smit, Martine J.; Wills, Mark R.

    2017-01-01

    ABSTRACT Reactivation of human cytomegalovirus (HCMV) latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR), which, during lytic infection, is a constitutive cell-signaling activator. Here we now show that in monocytes, which are recognized sites of HCMV latency in vivo, US28 attenuates multiple cell signaling pathways, including mitogen-activated protein (MAP) kinase and NF-κB, and that this is required to establish a latent infection; viruses deleted for US28 initiate a lytic infection in infected monocytes. We also show that these monocytes then become potent targets for the HCMV-specific host immune response and that latently infected cells treated with an inverse agonist of US28 also reactivate lytic infection and similarly become immune targets. Consequently, we suggest that the use of inhibitors of US28 could be a novel immunotherapeutic strategy to reactivate the latent viral reservoir, allowing it to be targeted by preexisting HCMV-specific T cells. PMID:29208743

  11. Seismic Full Waveform Modeling & Imaging in Attenuating Media

    NASA Astrophysics Data System (ADS)

    Guo, Peng

    Seismic attenuation strongly affects seismic waveforms by amplitude loss and velocity dispersion. Without proper inclusion of Q parameters, errors can be introduced for seismic full waveform modeling and imaging. Three different (Carcione's, Robertsson's, and the generalized Robertsson's) isotropic viscoelastic wave equations based on the generalized standard linear solid (GSLS) are evaluated. The second-order displacement equations are derived, and used to demonstrate that, with the same stress relaxation times, these viscoelastic formulations are equivalent. By introducing separate memory variables for P and S relaxation functions, Robertsson's formulation is generalized to allow different P and S wave stress relaxation times, which improves the physical consistency of the Qp and Qs modelled in the seismograms.The three formulations have comparable computational cost. 3D seismic finite-difference forward modeling is applied to anisotropic viscoelastic media. The viscoelastic T-matrix (a dynamic effective medium theory) relates frequency-dependent anisotropic attenuation and velocity to reservoir properties in fractured HTI media, based on the meso-scale fluid flow attenuation mechanism. The seismic signatures resulting from changing viscoelastic reservoir properties are easily visible. Analysis of 3D viscoelastic seismograms suggests that anisotropic attenuation is a potential tool for reservoir characterization. To compensate the Q effects during reverse-time migration (RTM) in viscoacoustic and viscoelastic media, amplitudes need to be compensated during wave propagation; the propagation velocity of the Q-compensated wavefield needs to be the same as in the attenuating wavefield, to restore the phase information. Both amplitude and phase can be compensated when the velocity dispersion and the amplitude loss are decoupled. For wave equations based on the GSLS, because Q effects are coupled in the memory variables, Q-compensated wavefield propagates faster than

  12. Variable photonic crystal fiber optical attenuator combining air hole reduction induced radiation and bending loss

    NASA Astrophysics Data System (ADS)

    Yokota, Hirohisa; Sano, Tomohiko; Imai, Yoh

    2018-06-01

    Recently, an optical attenuator has been important in fiber optic communication systems, because a transmission power in fiber has become higher due to a channel increment in wavelength division multiplexing transmission. A photonic crystal fiber (PCF) optical attenuator is fabricated by air hole diameter reduction in a part of PCF in which radiations are caused in the air hole diameter reduced part of PCF. A PCF optical attenuator has a high power resistance feature due to its radiation-induced operation of optical attenuation. In this paper, we proposed a variable PCF optical attenuator in which a bend was applied to the air hole diameter reduced part in PCF optical attenuator that was fabricated by CO2 laser irradiation. In PCF optical attenuator fabrication, the attenuation was adjusted by the reduced air hole diameter with laser irradiation time control. It was demonstrated that 10.6-13.5 dB of variable attenuation was obtained at 1550 nm-wavelength with 0°-90° bending angle applied to the air hole diameter reduced part in PCF optical attenuator.

  13. Variable photonic crystal fiber optical attenuator combining air hole reduction induced radiation and bending loss

    NASA Astrophysics Data System (ADS)

    Yokota, Hirohisa; Sano, Tomohiko; Imai, Yoh

    2018-02-01

    Recently, an optical attenuator has been important in fiber optic communication systems, because a transmission power in fiber has become higher due to a channel increment in wavelength division multiplexing transmission. A photonic crystal fiber (PCF) optical attenuator is fabricated by air hole diameter reduction in a part of PCF in which radiations are caused in the air hole diameter reduced part of PCF. A PCF optical attenuator has a high power resistance feature due to its radiation-induced operation of optical attenuation. In this paper, we proposed a variable PCF optical attenuator in which a bend was applied to the air hole diameter reduced part in PCF optical attenuator that was fabricated by CO2 laser irradiation. In PCF optical attenuator fabrication, the attenuation was adjusted by the reduced air hole diameter with laser irradiation time control. It was demonstrated that 10.6-13.5 dB of variable attenuation was obtained at 1550 nm-wavelength with 0°-90° bending angle applied to the air hole diameter reduced part in PCF optical attenuator.

  14. Variable optical attenuator and dynamic mode group equalizer for few mode fibers.

    PubMed

    Blau, Miri; Weiss, Israel; Gerufi, Jonathan; Sinefeld, David; Bin-Nun, Moran; Lingle, Robert; Grüner-Nielsen, Lars; Marom, Dan M

    2014-12-15

    Variable optical attenuation (VOA) for three-mode fiber is experimentally presented, utilizing an amplitude spatial light modulator (SLM), achieving up to -28dB uniform attenuation for all modes. Using the ability to spatially vary the attenuation distribution with the SLM, we also achieve up to 10dB differential attenuation between the fiber's two supported mode group (LP₀₁ and LP₁₁). The spatially selective attenuation serves as the basis of a dynamic mode-group equalizer (DME), potentially gain-balancing mode dependent optical amplification. We extend the experimental three mode DME functionality with a performance analysis of a fiber supporting 6 spatial modes in four mode groups. The spatial modes' distribution and overlap limit the available dynamic range and performance of the DME in the higher mode count case.

  15. Attenuation fluctuations and local dermal reflectivity are indicators of immune cell infiltrate and epidermal hyperplasia in skin inflammation

    NASA Astrophysics Data System (ADS)

    Phillips, Kevin G.; Wang, Yun; Choudhury, Niloy; Levitz, David; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven

    2012-02-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses responsible for skin homeostasis. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of psoriasis remains under investigated. To elucidate the spatial-temporal morphological evolution of psoriasis we undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to non-invasively document dermal alterations due to immune cell infiltration and epidermal hyperplasia in an Imiquimod (IMQ) induced model of psoriasis-like inflammation in DBA2/C57Bl6 hybrid mice. Quantitative appraisal of dermal architectural changes was achieved through a three parameter fit of OCT axial scans in the dermis of the form A(z) = ρ exp(-mu;z +ɛ(z)). Ensemble averaging of the fit parameters over 2000 axial scans per mouse in each treatment arm revealed that the local dermal reflectivity ρ, decreased significantly in response to 6 day IMQ treatment (p = 0.0001), as did the standard deviation of the attenuation fluctuation std(ɛ(z)), (p = 0.04), in comparison to cream controls and day 1 treatments. No significant changes were observed in the average dermal attenuation rate, μ. Our results suggest these label-free OCT-based metrics can be deployed to investigate new therapeutic targets in animal models as well as aid in clinical staging of psoriasis in conjunction with the psoriasis area and severity index.

  16. Ultrasonic Attenuation Results of Thermoplastic Resin Composites Undergoing Thermal and Fatigue Loading

    NASA Technical Reports Server (NTRS)

    Madaras, Eric I.

    1998-01-01

    As part of an effort to obtain the required information about new composites for aviation use, materials and NDE researchers at NASA are jointly performing mechanical and NDE measurements on new composite materials. The materials testing laboratory at NASA is equipped with environmental chambers mounted on load frames that can expose composite materials to thermal and loading cycles representative of flight protocols. Applying both temperature and load simultaneously will help to highlight temperature and load interactions during the aging of these composite materials. This report highlights our initial ultrasonic attenuation results from thermoplastic composite samples that have undergone over 4000 flight cycles to date. Ultrasonic attenuation measurements are a standard method used to assess the effects of material degradation. Recently, researchers have shown that they could obtain adequate contrast in the evaluation of thermal degradation in thermoplastic composites by using frequencies of ultrasound on the order of 24 MHz. In this study, we address the relationship of attenuation measured at lower frequencies in thermoplastic composites undergoing both thermal and mechanical loading. We also compare these thermoplastic results with some data from thermoset composites undergoing similar protocols. The composite s attenuation is reported as the slope of attenuation with respect to frequency, defined as b = Da(f)/Df. The slope of attenuation is an attractive parameter since it is quantitative, yet does not require interface corrections like conventional quantitative attenuation measurements. This latter feature is a consequence of the assumption that interface correction terms are frequency independent. Uncertainty in those correction terms can compromise the value of conventional quantitative attenuation data. Furthermore, the slope of the attenuation more directly utilizes the bandwidth information and in addition, the bandwidth can be adjusted in the post

  17. In vitro attenuation of impact shock in equine digits.

    PubMed

    Lanovaz, J L; Clayton, H M; Watson, L G

    1998-09-01

    This study was designed to test the impact characteristics of the equine digit in vitro with the objective of providing a better understanding of the role of the digital structures in the attenuation of impact shock. Uni-axial accelerometers were mounted on cadaver digits on the distolateral hoof wall, the proximolateral hoof wall, the dorsal surface of the second phalanx, and the mid-lateral first phalanx. The hoof-mounted accelerometers were aligned with the hoof tubules while the bone-mounted accelerometers were oriented along the longitudinal axis of the bone. Each digit was mounted in a test apparatus designed to simulate impact of the hoof with the ground during locomotion. The digits were subjected to 3 impact trials against a barrier at each of 3 vertical impact velocities that simulated a forward trotting velocity in the range of 2.67 to 4.46 m/s. The impact deceleration tended to increase with impact velocity. Attenuation of the impact shock by the digital tissues resulted in a reduction in impact decleration in the more proximal measuring locations. The interphalangeal joints appeared to play a larger role in amplitude attenuation than the hoof wall or the soft tissue structures within the hoof wall. The signal frequency data showed that the soft tissues within the hoof acted as a 'lowpass' filter, attenuating the higher deceleration frequencies. The hoof wall and the interphalangeal joints showed little frequency attenuation.

  18. Study of transmission line attenuation in broad band millimeter wave frequency range.

    PubMed

    Pandya, Hitesh Kumar B; Austin, M E; Ellis, R F

    2013-10-01

    Broad band millimeter wave transmission lines are used in fusion plasma diagnostics such as electron cyclotron emission (ECE), electron cyclotron absorption, reflectometry and interferometry systems. In particular, the ECE diagnostic for ITER will require efficient transmission over an ultra wide band, 100 to 1000 GHz. A circular corrugated waveguide transmission line is a prospective candidate to transmit such wide band with low attenuation. To evaluate this system, experiments of transmission line attenuation were performed and compared with theoretical loss calculations. A millimeter wave Michelson interferometer and a liquid nitrogen black body source are used to perform all the experiments. Atmospheric water vapor lines and continuum absorption within this band are reported. Ohmic attenuation in corrugated waveguide is very low; however, there is Bragg scattering and higher order mode conversion that can cause significant attenuation in this transmission line. The attenuation due to miter bends, gaps, joints, and curvature are estimated. The measured attenuation of 15 m length with seven miter bends and eighteen joints is 1 dB at low frequency (300 GHz) and 10 dB at high frequency (900 GHz), respectively.

  19. The ultraviolet attenuation law in backlit spiral galaxies

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

    Keel, William C.; Manning, Anna M.; Holwerda, Benne W.

    The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet (UV) regime is well known only for actively star-forming objects and combines effects of the grain properties, fine structure in the dust distribution, and relative distributions of stars and dust. We use Galaxy Evolution Explorer, XMM Optical Monitor, and Hubble Space Telescope (HST) data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with the candidate list of pairs provided by Galaxy Zoo participants. New optical images help to constrain the geometry and structure of the targetmore » galaxies. Our analysis incorporates galaxy symmetry, using non-overlapping regions of each galaxy to derive error estimates on the attenuation measurements. The entire sample has an attenuation law across the optical and UV that is close to the Calzetti et al. form; the UV slope for the overall sample is substantially shallower than found by Wild et al., which is a reasonable match to the more distant galaxies in our sample but not to the weighted combination including NGC 2207. The nearby, bright spiral NGC 2207 alone gives an accuracy almost equal to the rest of our sample, and its outer arms have a very low level of foreground starlight. Thus, this widespread, fairly 'gray' law can be produced from the distribution of dust alone, without a necessary contribution from differential escape of stars from dense clouds. Our results indicate that the extrapolation needed to compare attenuation between backlit galaxies at moderate redshifts from HST data, and local systems from Sloan Digital Sky Survey and similar data, is mild enough to allow the use of galaxy overlaps to trace the cosmic history of dust in galaxies. For NGC 2207, HST data in the near-UV F336W band show that the covering factor of clouds with small optical attenuation becomes a dominant factor farther into the UV, which opens the possibility that

  20. Chinese Herbal Medicines Attenuate Acute Pancreatitis: Pharmacological Activities and Mechanisms

    PubMed Central

    Xiang, Hong; Zhang, Qingkai; Qi, Bing; Tao, Xufeng; Xia, Shilin; Song, Huiyi; Qu, Jialin; Shang, Dong

    2017-01-01

    Acute pancreatitis (AP) is a commonly occurring gastrointestinal disorder. An increase in the annual incidence of AP has been observed, and it causes acute hospitalization and high mortality. The diagnosis and treatment guidelines for AP recommend conservative medical treatments focused on reducing pancreatic secretion and secondary injury, as a primary therapeutic approach. Unfortunately, the existing treatment options have limited impact on the incidence and severity of AP due to the complex and multifaceted pathological process of this disease. In recent decades, Chinese herbal medicines (CHMs) have been used as efficient therapeutic agents to attenuate AP in Asian countries. Despite early cell culture, animal models, and clinical trials, CHMs are capable of interacting with numerous molecular targets participating in the pathogenesis of AP; however, comprehensive, up-to-date communication in this field is not yet available. This review focuses on the pharmacological activities of CHMs against AP in vitro and in vivo and the underlying mechanisms. A computational prediction of few selected and promising plant-derived molecules (emodin, baicalin, resveratrol, curcumin, ligustrazine, and honokiol) to target numerous proteins or networks involved in AP was initially established based on a network pharmacology simulation. Moreover, we also summarized some potential toxic natural products for pancreas in order to more safe and reasonable medication. These breakthrough findings may have important implications for innovative drug research and the future development of treatments for AP. PMID:28487653

  1. Functional food addressing heart health: do we have to target the gut microbiota?

    PubMed

    Ryan, Paul M; Ross, Reynolds Paul; Fitzgerald, Gerald F; Caplice, Noel M; Stanton, Catherine

    2015-11-01

    Health promoting functional food ingredients for cardiovascular health are generally aimed at modulating lipid metabolism in consumers. However, significant advances have furthered our understanding of the mechanisms involved in development, progression, and treatment of cardiovascular disease. In parallel, a central role of the gut microbiota, both in accelerating and attenuating cardiovascular disease, has emerged. Modulation of the gut microbiota, by use of prebiotics and probiotics, has recently shown promise in cardiovascular disease prevention. Certain prebiotics can promote a short chain fatty acid profile that alters hormone secretion and attenuates cholesterol synthesis, whereas bile salt hydrolase and exopolysaccharide-producing probiotics have been shown to actively correct hypercholesterolemia. Furthermore, specific microbial genera have been identified as potential cardiovascular disease risk factors. This effect is attributed to the ability of certain members of the gut microbiota to convert dietary quaternary amines to trimethylamine, the primary substrate of the putatively atherosclerosis-promoting compound trimethylamine-N-oxide. In this respect, current research is indicating trimethylamine-depleting Achaea - termed Archeabiotics as a potential novel dietary strategy for promoting heart health. The microbiota offers a modifiable target, which has the potential to progress or prevent cardiovascular disease development. Whereas host-targeted interventions remain the standard, current research implicates microbiota-mediated therapies as an effective means of modulating cardiovascular health.

  2. Wild type measles virus attenuation independent of type I IFN.

    PubMed

    Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

    2008-02-03

    Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the alpha/beta IFN system.

  3. Wild type measles virus attenuation independent of type I IFN

    PubMed Central

    Druelle, Johan; Sellin, Caroline I; Waku-Kouomou, Diane; Horvat, Branka; Wild, Fabian T

    2008-01-01

    Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt). Results The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system. PMID:18241351

  4. Screening attenuation of coaxial cables determined in GTEM-cells

    NASA Astrophysics Data System (ADS)

    Knobloch, A.; Garbe, H.

    2004-05-01

    This paper describes the determination of the screening attenuation with a GTEM cell. An analytical part gives the link between the voltage at the cell port and the total radiated power. The next section investigates the optimal cable setup in the cell. With a measurement of the common mode current on the cable and a simulation of the radiation resistance the loop antenna characteristic of the cable setup could be verified. It is shown that the use of ferrit cores decrease the difference between the maximum and the minimum screening attenuation. The determination of great screening attenuation could be improved with the use of N-type measurement cables. A comparison between this GTEM cell method and the standard methods shows a good agreement.

  5. The attenuation of sound by turbulence in internal flows.

    PubMed

    Weng, Chenyang; Boij, Susann; Hanifi, Ardeshir

    2013-06-01

    The attenuation of sound waves due to interaction with low Mach number turbulent boundary layers in internal flows (channel or pipe flow) is examined. Dynamic equations for the turbulent Reynolds stress on the sound wave are derived, and the analytical solution to the equation provides a frequency dependent eddy viscosity model. This model is used to predict the attenuation of sound propagating in fully developed turbulent pipe flow. The predictions are shown to compare well with the experimental data. The proposed dynamic equation shows that the turbulence behaves like a viscoelastic fluid in the interaction process, and that the ratio of turbulent relaxation time near the wall and the sound wave period is the parameter that controls the characteristics of the attenuation induced by the turbulent flow.

  6. Numerical simulation of several impact attenuator design for a formula student car

    NASA Astrophysics Data System (ADS)

    Sinaga, Farlian Rizky; Ubaidillah, Kurniawan, Krishna Eka; Fadhil, Muhamad Ivan; Cahyono, Sukmaji Indro; Idris, Muhamad Hafiz

    2018-02-01

    In the Formula Society of Automotive Engineer (SAE), safety is a vigorous factor. One of the safety components in the Formula SAE car is the impact attenuator. The purpose of this study is to get the impact attenuator design with the best ability to absorb kinetic energy from several existing designs, through numerical approaches, for estimating conditions against dynamic impacts. Material of impact attenuator use combination of aluminum and Zirconium G350. The simulation was caried out by crashing the impact with the rigid wall, to find the deformation that occurs and the energies are absorbed. The impact attenuator design to be simulated should be optimized to meet some parameters in the SAE Formula. The result of impact attenuator simulation should be able to absorb energy of 7350 joules at move 7 m/s and deformation at bulkhead less than 25.4 mm.

  7. Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute2

    PubMed Central

    De, Nabanita; Young, Lisa; Lau, Pick-Wei; Meisner, Nicole-Claudia; Morrissey, David V.; MacRae, Ian J.

    2013-01-01

    SUMMARY Argonaute proteins use small RNAs to guide the silencing of complementary target RNAs in many eukaryotes. Although small RNA biogenesis pathways are well studied, mechanisms for removal of guide RNAs from Argonaute are poorly understood. Here we show that the Argonaute2 (Ago2) guide RNA complex is extremely stable, with a half-life on the order of days. However, highly complementary target RNAs destabilize the complex and significantly accelerate release of the guide RNA from Ago2. This “unloading” activity can be enhanced by mismatches between the target and the guide 5′ end and attenuated by mismatches to the guide 3′ end. The introduction of 3′ mismatches leads to more potent silencing of abundant mRNAs in mammalian cells. These findings help to explain why the 3′ ends of mammalian microRNAs (miRNAs) rarely match their targets, suggest a mechanism for sequence-specific small RNA turnover, and offer insights for controlling small RNAs in mammalian cells. PMID:23664376

  8. Characterizing light attenuation within Northwest Florida ...

    EPA Pesticide Factsheets

    Water Quality (WQ) condition is based on ecosystem stressor indicators (e.g. water clarity) which are biogeochemically important and critical when considering the Deepwater Horizon oil spill restoration efforts under the 2012 RESTORE Act. Nearly all of the proposed RESTORE projects list restoring WC as a goal, but 90% neglect water clarity. Here, dynamics of optical constituents impacting clarity are presented from a 2009-2011 study within Pensacola, Choctawhatchee, St. Andrew and St. Joseph estuaries (targeted RESTORE sites) in Northwest Florida. Phytoplankton were the smallest contribution to total absorption (at-wPAR) at 412 nm (5-11%), whereas colored dissolved organic matter was the largest (61-79%). Estuarine at-wPAR was significantly related to light attenuation (KdPAR), where individual contributors to clarity and the influence of climatic events were discerned. Provided are conversion equations demonstrating interoperability of clarity indicators between traditional State-measured WQ measures (e.g. secchi disc), optical constituents, and even satellite remote sensing for obtaining baseline assessments. This paper arose from efforts under SSWR and SHC to utilize water quality data as baseline measures for RESTORE Act monitoring in Florida estuaries. This paper aims to (1) describe dynamics of optical constituents that impact water clarity in four NW Florida estuaries, and (2) make a case for the total absorption coefficient (at-wPAR) as a valuable

  9. Results of the VPI&SU Comstar experiment. [depolarization and attenuation due to rain

    NASA Technical Reports Server (NTRS)

    Andrews, J. H.; Ozbay, C.; Pratt, T.; Bostian, C. W.; Manus, E. A.; Gaines, J. M.; Marshall, R. E.; Stutzman, W. L.; Wiley, P. H.

    1982-01-01

    This paper summarizes annual and cumulative attenuation data, depolarization data, and associated local rain rate distributions obtained with the Comstar family of 19.04- and 28.56-GHz satellite beacons during the years 1977-1981. It discusses the relationships between attenuation and rain rate and between attenuation and depolarization, compares measured data on the joint distribution of attenuation and depolarization, and examines the limitations that propagation effects will impose on future 20/30-GHz satellite communications systems.

  10. Loss of Matrix Metalloproteinase-13 Attenuates Murine Radiation-Induced Pulmonary Fibrosis

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

    Flechsig, Paul; Hartenstein, Bettina; Teurich, Sybille

    2010-06-01

    Purpose: Pulmonary fibrosis is a disorder of the lungs with limited treatment options. Matrix metalloproteinases (MMPs) constitute a family of proteases that degrade extracellular matrix with roles in fibrosis. Here we studied the role of MMP13 in a radiation-induced lung fibrosis model using a MMP13 knockout mouse. Methods and Materials: We investigated the role of MMP13 in lung fibrosis by investigating the effects of MMP13 deficiency in C57Bl/6 mice after 20-Gy thoracic irradiation (6-MV Linac). The morphologic results in histology were correlated with qualitative and quantitative results of volume computed tomography (VCT), magnetic resonance imaging (MRI), and clinical outcome. Results:more » We found that MMP13 deficient mice developed less pulmonary fibrosis than their wildtype counterparts, showed attenuated acute pulmonary inflammation (days after irradiation), and a reduction of inflammation during the later fibrogenic phase (5-6 months after irradiation). The reduced fibrosis in MMP13 deficient mice was evident in histology with reduced thickening of alveolar septi and reduced remodeling of the lung architecture in good correlation with reduced features of lung fibrosis in qualitative and quantitative VCT and MRI studies. The partial resistance of MMP13-deficient mice to fibrosis was associated with a tendency towards a prolonged mouse survival. Conclusions: Our data indicate that MMP13 has a role in the development of radiation-induced pulmonary fibrosis. Further, our findings suggest that MMP13 constitutes a potential drug target to attenuate radiation-induced lung fibrosis.« less

  11. Immunization with Eimeria ninakohlyakimovae-live attenuated oocysts protect goat kids from clinical coccidiosis.

    PubMed

    Ruiz, Antonio; Muñoz, María Carmen; Molina, José Manuel; Hermosilla, Carlos; Andrada, Marisa; Lara, Pedro; Bordón, Elisa; Pérez, Davinia; López, Adassa María; Matos, Lorena; Guedes, Aránzazu Carmen; Falcón, Soraya; Falcón, Yaiza; Martín, Sergio; Taubert, Anja

    2014-01-17

    Caprine coccidiosis, affecting mainly young goat kids around the weaning period, is worldwide the most important disease in the goat industry. Control of caprine coccidiosis is increasingly hampered by resistances developed against coccidiostatic drugs leading to an enhanced need for anticoccidial vaccines. In the current study we conducted an oral immunization trial with live attenuated sporulated Eimeria ninakohlyakimovae oocysts. Sporulated E. ninakohlyakimovae oocysts were attenuated by X-irradiation technique. The experimental design included a total of 18 goat kids divided into the following groups: (i) animals immunized with attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-irradiated homologous oocysts (group 1); (ii) animals infected with non-attenuated E. ninakohlyakimovae oocysts at 5 weeks of age and challenged 3 weeks later with non-attenuated homologous oocysts (group 2); (iii) animals primary-infected with untreated E. ninakohlyakimovae oocysts at 8 weeks of age (control of the challenge infection, group 3); (iv) non-infected control animals (group 4). Goat kids immunized with live attenuated E. ninakohlyakimovae oocysts (group 1) excreted significantly less oocysts in the faeces (95.3% reduction) than kids infected with non-attenuated ones (group 2). Furthermore, immunization with live but attenuated oocysts resulted in ameliorated clinical coccidiosis compared to goat kids infected with untreated oocysts (group 2) and resulted in equally reduced signs of coccidiosis after challenge infection compared to acquired immunity driven by non-attenuated oocysts. Overall, the present study demonstrates for the first time that live attenuated E. ninakohlyakimovae oocysts orally administered showed almost no pathogenicity but enough immunogenicity in terms of immunoprotection. Importantly, vaccinated animals still shed low amounts of oocysts, guaranteeing environmental contamination and consecutive booster

  12. An Attenuated CRISPR-Cas System in Enterococcus faecalis Permits DNA Acquisition

    PubMed Central

    Hullahalli, Karthik; Rodrigues, Marinelle; Nguyen, Uyen Thy

    2018-01-01

    ABSTRACT Antibiotic-resistant bacteria are critical public health concerns. Among the prime causative factors for the spread of antibiotic resistance is horizontal gene transfer (HGT). A useful model organism for investigating the relationship between HGT and antibiotic resistance is the opportunistic pathogen Enterococcus faecalis, since the species possesses highly conjugative plasmids that readily disseminate antibiotic resistance genes and virulence factors in nature. Unlike many commensal E. faecalis strains, the genomes of multidrug-resistant (MDR) E. faecalis clinical isolates are enriched for mobile genetic elements (MGEs) and lack clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) genome defense systems. CRISPR-Cas systems cleave foreign DNA in a programmable, sequence-specific manner and are disadvantageous for MGE-derived genome expansion. An unexplored facet of CRISPR biology in E. faecalis is that MGEs that are targeted by native CRISPR-Cas systems can be maintained transiently. Here, we investigate the basis for this “CRISPR tolerance.” We observe that E. faecalis can maintain self-targeting constructs that direct Cas9 to cleave the chromosome, but at a fitness cost. Interestingly, DNA repair genes were not upregulated during self-targeting, but integrated prophages were strongly induced. We determined that low cas9 expression contributes to this transient nonlethality and used this knowledge to develop a robust CRISPR-assisted genome-editing scheme. Our results suggest that E. faecalis has maximized the potential for DNA acquisition by attenuating its CRISPR machinery, thereby facilitating the acquisition of potentially beneficial MGEs that may otherwise be restricted by genome defense. PMID:29717009

  13. Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

    PubMed

    Maldjian, P D; Chen, T

    2016-11-01

    To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism.

    PubMed

    Yo, Kikuo; Yu, Yong-Ming; Zhao, Gaofeng; Bonab, Ali A; Aikawa, Naoki; Tompkins, Ronald G; Fischman, Alan J

    2013-02-15

    Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1.

  15. Comparative proteomic analysis of virulent and rifampicin attenuated Flavobacterium psychrophilum

    USDA-ARS?s Scientific Manuscript database

    Flavobacterium psychrophilum is the etiologic agent of bacterial coldwater disease and rainbow trout fry syndrome. In this study we compared a wild-type strain (CSF 259.93) with a rifampicin resistant and virulence attenuated strain of F. psychrophilum (CSF 259.93B.17). The attenuated strain harbour...

  16. Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells

    PubMed Central

    Zhang, Feng; Zhang, Zili; Chen, Li; Kong, Desong; Zhang, Xiaoping; Lu, Chunfeng; Lu, Yin; Zheng, Shizhong

    2014-01-01

    Hepatic fibrosis is concomitant with sinusoidal pathological angiogenesis, which has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. Our prior studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of a number of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells and rat aortic ring angiogenesis were not impaired by curcumin. These results indicated that hepatic stellate cells (HSCs) that are characterized as liver-specific pericytes could be potential target cells for curcumin. Further investigations showed that curcumin inhibited VEGF expression in HSCs associated with disrupting platelet-derived growth factor-β receptor (PDGF-βR)/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin associated with blocking PDGF-βR/focal adhesion kinase/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPAR-γ activation-dependent mechanism. PPAR-γ could be a target molecule for reducing pathological angiogenesis during liver fibrosis. PMID:24779927

  17. [Herpes simplex virus-mediated RNA interference targeting vesicular glutamate transporter 3 attenuates tactile allodynia in mice].

    PubMed

    Liu, Jie-Qiong; Li, Chen-Hong; Luo, Qiong; Yin, Ping-Ping; Lei, Tao; Luo, Fang

    2016-11-20

    To construct a replication-deficient herpes simplex virus (HSV-1) for delivering a short hairpin RNA (shRNA) targeting vesicular glutamate transporter 3 (VGLUT3) and observe its effect in alleviating allodynia in mice. The recombinant HSV-1 vector carrying the shRNA targeting Vglut3 (HSV-1-shvglut3) was constructed and inoculated in the sciatic nerve in a mouse model of mechanical allodynia to test its analgesia effect. Mechanical allodynia and heat hypersensitivity of the mice were tested by von Frey filaments and Hargreaves' test, respectively. VGLUT3 expression in the dorsal root ganglion (DRG) was evaluated by immunohistochemistry and Western blotting. Following inoculation in the sciatic nerve, the HSV vector HSV-1-shvglut3 was retrogradely transported to the DRG. Mechanical withdraw thresholds of the mouse models receiving HSV-1-shvglut3 inoculation were reversed to nearly the baseline level, and VGLUT3 expression in the DRG was down-regulated 2 weeks after vector inoculation. The analgesic effect lasted for over 2 weeks in these mice without obvious systematic side effects or changes in heat hypersensitivity threshold. Vglut3 in the DRG is a promising therapeutic target for alleviating mechanical allodynia, and HSV-1 vector-mediated RNA interference is safe and efficient for inducing long-lasting analgesia after peripheral inoculation of the vector.

  18. Phase Aberration and Attenuation Effects on Acoustic Radiation Force-Based Shear Wave Generation.

    PubMed

    Carrascal, Carolina Amador; Aristizabal, Sara; Greenleaf, James F; Urban, Matthew W

    2016-02-01

    Elasticity is measured by shear wave elasticity imaging (SWEI) methods using acoustic radiation force to create the shear waves. Phase aberration and tissue attenuation can hamper the generation of shear waves for in vivo applications. In this study, the effects of phase aberration and attenuation in ultrasound focusing for creating shear waves were explored. This includes the effects of phase shifts and amplitude attenuation on shear wave characteristics such as shear wave amplitude, shear wave speed, shear wave center frequency, and bandwidth. Two samples of swine belly tissue were used to create phase aberration and attenuation experimentally. To explore the phase aberration and attenuation effects individually, tissue experiments were complemented with ultrasound beam simulations using fast object-oriented C++ ultrasound simulator (FOCUS) and shear wave simulations using finite-element-model (FEM) analysis. The ultrasound frequency used to generate shear waves was varied from 3.0 to 4.5 MHz. Results: The measured acoustic pressure and resulting shear wave amplitude decreased approximately 40%-90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, and the resulting Pearson's correlation coefficients were 0.99 and 0.97. Analysis of shear wave generation with tissue samples (phase aberration and attenuation case), measured phase screen, (only phase aberration case), and FOCUS/FEM model (only attenuation case) showed that tissue attenuation affected the shear wave generation more than tissue aberration. Decreasing the ultrasound frequency helped maintain a focused beam for creation of shear waves in the presence of both phase aberration and attenuation.

  19. Hydrogen sulfide attenuates carbon tetrachloride-induced hepatotoxicity, liver cirrhosis and portal hypertension in rats.

    PubMed

    Tan, Gang; Pan, Shangha; Li, Jie; Dong, Xuesong; Kang, Kai; Zhao, Mingyan; Jiang, Xian; Kanwar, Jagat R; Qiao, Haiquan; Jiang, Hongchi; Sun, Xueying

    2011-01-01

    Hydrogen sulfide (H(2)S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H(2)S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H(2)S in carbon tetrachloride (CCl(4))-induced hepatotoxicity, cirrhosis and portal hypertension. Sodium hydrosulfide (NaHS), a donor of H(2)S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine γ-lyase (CSE), were applied to the rats to investigate the effects of H(2)S on CCl(4)-induced acute hepatotoxicity, cirrhosis and portal hypertension by measuring serum levels of H(2)S, hepatic H(2)S producing activity and CSE expression, liver function, activity of cytochrome P450 (CYP) 2E1, oxidative and inflammatory parameters, liver fibrosis and portal pressure. CCl(4) significantly reduced serum levels of H(2)S, hepatic H(2)S production and CSE expression. NaHS attenuated CCl(4)-induced acute hepatotoxicity by supplementing exogenous H(2)S, which displayed anti-oxidative activities and inhibited the CYP2E1 activity. NaHS protected liver function, attenuated liver fibrosis, inhibited inflammation, and reduced the portal pressure, evidenced by the alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), albumin, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and soluble intercellular adhesion molecule (ICAM)-1, liver histology, hepatic hydroxyproline content and α-smooth muscle actin (SMA) expression. PAG showed opposing effects to NaHS on most of the above parameters. Exogenous H(2)S attenuates CCl(4)-induced hepatotoxicity, liver cirrhosis and portal hypertension by its multiple functions including anti-oxidation, anti-inflammation, cytoprotection and anti-fibrosis, indicating that targeting H(2)S may present a promising approach, particularly for its prophylactic effects, against liver cirrhosis and portal hypertension.

  20. Secreted Klotho Attenuates Inflammation-Associated Aortic Valve Fibrosis in Senescence-Accelerated Mice P1.

    PubMed

    Chen, Jianglei; Fan, Jun; Wang, Shirley; Sun, Zhongjie

    2018-05-01

    Senescence-accelerated mice P1 (SAMP1) is an aging model characterized by shortened lifespan and early signs of senescence. Klotho is an aging-suppressor gene. The purpose of this study is to investigate whether in vivo expression of secreted klotho ( Skl ) gene attenuates aortic valve fibrosis in SAMP1 mice. SAMP1 mice and age-matched (AKR/J) control mice were used. SAMP1 mice developed obvious fibrosis in aortic valves, namely fibrotic aortic valve disease. Serum level of Skl was decreased drastically in SAMP1 mice. Expression of MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), F4/80, and CD68 was increased in aortic valves of SAMP1 mice, indicating inflammation. An increase in expression of α-smooth muscle actin (myofibroblast marker), transforming growth factorβ-1, and scleraxis (a transcription factor of collagen synthesis) was also found in aortic valves of SAMP1 mice, suggesting that accelerated aging is associated with myofibroblast transition and collagen gene activation. We constructed adeno-associated virus 2 carrying mouse Skl cDNA for in vivo expression of Skl. Skl gene delivery effectively increased serum Skl of SAMP1 mice to the control level. Skl gene delivery inhibited inflammation and myofibroblastic transition in aortic valves and attenuated fibrotic aortic valve disease in SAMP1 mice. It is concluded that senescence-related fibrotic aortic valve disease in SAMP1 mice is associated with a decrease in serum klotho leading to inflammation, including macrophage infiltration and transforming growth factorβ-1/scleraxis-driven myofibroblast differentiation in aortic valves. Restoration of serum Skl levels by adeno-associated virus 2 carrying mouse Skl cDNA effectively suppresses inflammation and myofibroblastic transition and attenuates aortic valve fibrosis. Skl may be a potential therapeutic target for fibrotic aortic valve disease. © 2018 American Heart Association, Inc.

  1. Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

    PubMed

    Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

    2016-07-01

    To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

  2. Post-Retrieval Extinction Attenuates Cocaine Memories

    PubMed Central

    Sartor, Gregory C; Aston-Jones, Gary

    2014-01-01

    Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine-related memories by using the post-retrieval extinction paradigm in male Sprague Dawley rats. Results revealed that starting extinction training 1 h after cocaine contextual memory was retrieved significantly attenuated cocaine-primed reinstatement of conditioned place preference (CPP) and relapse of cocaine CPP (drug-free and cocaine-primed) following 30 days of abstinence. However, animals that did not retrieve the contextual cocaine memory before extinction training, or animals that began extinction training 24 h after retrieval (outside of the reconsolidation window), demonstrated normal cocaine CPP. Conversely, animals that received additional CPP conditioning, rather than extinction training, 1 h after reactivation of cocaine memory showed enhanced cocaine CPP compared with animals that did not reactivate the cocaine memory before conditioning. These results reveal that a behavioral manipulation that takes advantage of reconsolidation and extinction of drug memories may be useful in decreasing preference for, and abuse of, cocaine. PMID:24257156

  3. Attenuation Modified by DIG and Dust as Seen in M31

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

    Tomičić, Neven; Kreckel, Kathryn; Schinnerer, Eva

    The spatial distribution of dust in galaxies affects the global attenuation, and hence inferred properties, of galaxies. We trace the spatial distribution of dust in five approximately kiloparsec fields of M31 by comparing optical attenuation with the total dust mass distribution. We measure the attenuation from the Balmer decrement using Integral Field Spectroscopy and the dust mass from Herschel far-IR observations. Our results show that M31's dust attenuation closely follows a foreground screen model, contrary to what was previously found in other nearby galaxies. By smoothing the M31 data, we find that spatial resolution is not the cause for thismore » difference. Based on the emission-line ratios and two simple models, we conclude that previous models of dust/gas geometry need to include a weakly or non-attenuated diffuse ionized gas (DIG) component. Due to the variation of dust and DIG scale heights with galactic radius, we conclude that different locations in galaxies will have different vertical distributions of gas and dust and therefore different measured attenuation. The difference between our result in M31 with that found in other nearby galaxies can be explained by our fields in M31 lying at larger galactic radii than the previous studies that focused on the centers of galaxies.« less

  4. Seismic attenuation structure beneath Nazca Plate subduction zone in southern Peru

    NASA Astrophysics Data System (ADS)

    Jang, H.; Kim, Y.; Clayton, R. W.

    2017-12-01

    We estimate seismic attenuation in terms of quality factors, QP and QS using P and S phases, respectively, beneath Nazca Plate subduction zone between 10°S and 18.5°S latitude in southern Peru. We first relocate 298 earthquakes with magnitude ranges of 4.0-6.5 and depth ranges of 20-280 km. We measure t*, which is an integrated attenuation through the seismic raypath between the regional earthquakes and stations. The measured t* are inverted to construct three-dimensional attenuation structures of southern Peru. Checkerboard test results for both QP and QS structures ensure good resolution in the slab-dip transition zone between flat and normal slab subduction down to a depth of 200 km. Both QP and QS results show higher attenuation continued down to a depth of 50 km beneath volcanic arc and also beneath the Quimsachata volcano, the northernmost young volcano, located far east of the main volcanic front. We also observe high attenuation in mantle wedge especially beneath the normal subduction region in both QP and QS (100-130 in QP and 100-125 in QS) and slightly higher QP and QS beneath the flat-subduction and slab-dip transition regions. We plan to relate measured attenuation in the mantle wedge to material properties such as viscosity to understand the subduction zone dynamics.

  5. Enhanced Attenuation: Chlorinated Organics

    DTIC Science & Technology

    2008-04-01

    attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it...plumes that include chlorinated organics. The flux of organic-rich leachate to underlying aquifers can create favorable conditions for the natural

  6. Radar attenuation tomography using the centroid frequency downshift method

    USGS Publications Warehouse

    Liu, L.; Lane, J.W.; Quan, Y.

    1998-01-01

    A method for tomographically estimating electromagnetic (EM) wave attenuation based on analysis of centroid frequency downshift (CFDS) of impulse radar signals is described and applied to cross-hole radar data. The method is based on a constant-Q model, which assumes a linear frequency dependence of attenuation for EM wave propagation above the transition frequency. The method uses the CFDS to construct the projection function. In comparison with other methods for estimating attenuation, the CFDS method is relatively insensitive to the effects of geometric spreading, instrument response, and antenna coupling and radiation pattern, but requires the data to be broadband so that the frequency shift and variance can be easily measured. The method is well-suited for difference tomography experiments using electrically conductive tracers. The CFDS method was tested using cross-hole radar data collected at the U.S. Geological Survey Fractured Rock Research Site at Mirror Lake, New Hampshire (NH) during a saline-tracer injection experiment. The attenuation-difference tomogram created with the CFDS method outlines the spatial distribution of saline tracer within the tomography plane. ?? 1998 Elsevier Science B.V. All rights reserved.

  7. Measurement of attenuation coefficients of the fundamental and second harmonic waves in water

    NASA Astrophysics Data System (ADS)

    Zhang, Shuzeng; Jeong, Hyunjo; Cho, Sungjong; Li, Xiongbing

    2016-02-01

    Attenuation corrections in nonlinear acoustics play an important role in the study of nonlinear fluids, biomedical imaging, or solid material characterization. The measurement of attenuation coefficients in a nonlinear regime is not easy because they depend on the source pressure and requires accurate diffraction corrections. In this work, the attenuation coefficients of the fundamental and second harmonic waves which come from the absorption of water are measured in nonlinear ultrasonic experiments. Based on the quasilinear theory of the KZK equation, the nonlinear sound field equations are derived and the diffraction correction terms are extracted. The measured sound pressure amplitudes are adjusted first for diffraction corrections in order to reduce the impact on the measurement of attenuation coefficients from diffractions. The attenuation coefficients of the fundamental and second harmonics are calculated precisely from a nonlinear least squares curve-fitting process of the experiment data. The results show that attenuation coefficients in a nonlinear condition depend on both frequency and source pressure, which are much different from a linear regime. In a relatively lower drive pressure, the attenuation coefficients increase linearly with frequency. However, they present the characteristic of nonlinear growth in a high drive pressure. As the diffraction corrections are obtained based on the quasilinear theory, it is important to use an appropriate source pressure for accurate attenuation measurements.

  8. DOTAM derivatives as active cartilage-targeting drug carriers for the treatment of osteoarthritis.

    PubMed

    Hu, Hai-Yu; Lim, Ngee-Han; Ding-Pfennigdorff, Danping; Saas, Joachim; Wendt, K Ulrich; Ritzeler, Olaf; Nagase, Hideaki; Plettenburg, Oliver; Schultz, Carsten; Nazare, Marc

    2015-03-18

    Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.

  9. Attenuation tomography of the main volcanic regions of the Campanian Plain.

    NASA Astrophysics Data System (ADS)

    de Siena, Luca; Del Pezzo, Edoardo; Bianco, Francesca

    2010-05-01

    Passive, high resolution attenuation tomography is used to image the geological structure in the first upper 4 km of shallow crust beneath the Campanian Plain. Images were produced by two separate attenuation tomography studies of the main volcanic regions of the Campanian Plain, Southern Italy, Mt. Vesuvius volcano and Campi Flegrei caldera. The three-dimensional S wave attenuation tomography of Mt. Vesuvius has been obtained with multiple measurements of coda-normalized S-wave spectra of local small magnitude earthquakes. P-wave attenuation tomography was performed using classical spectral methods. The images were obtained inverting the spectral data with a multiple resolution approach expressively designed for attenuation tomography. This allowed to obtain a robust attenuation image of the volumes under the central cone at a maximum resolution of 300 m. The same approach was applied to a data set recorded in the Campi Flegrei area during the 1982-1984 seismic crisis. Inversion ensures a minimum cell size resolution of 500 meters in the zones with sufficient ray coverage, and 1000 meters outside these zones. The study of the resolution matrix as well as the synthetic tests guarantee an optimal reproduction of the input anomalies in the center of the caldera, between 0 and 3.5 km in depth. Results allowed an unprecedented view of several features of the medium, like the residual part of solidified magma from the last eruption, under the central cone of Mt. Vesuvius, and the feeding systems and top of the carbonate basement, 3 km depth below both volcanic areas. Vertical Q contrast image important fault zones, such as the La Starza fault, as well as high attenuation structures that correspond to gas or fluid reservoirs, and reveal the upper part of gas bearing conduits connecting these high attenuation volumes with the magma sill revealed at about 7 km in depth by passive travel-time tomography under the whole Campanian Plain.

  10. Implication of seismic attenuation for gas hydrate resource characterization, Mallik, Mackenzie Delta, Canada

    NASA Astrophysics Data System (ADS)

    Bellefleur, G.; Riedel, M.; Brent, T.; Wright, F.; Dallimore, S. R.

    2007-10-01

    Wave attenuation is an important physical property of hydrate-bearing sediments that is rarely taken into account in site characterization with seismic data. We present a field example showing improved images of hydrate-bearing sediments on seismic data after compensation of attenuation effects. Compressional quality factors estimated from zero-offset Vertical Seismic Profiling data acquired at Mallik, Northwest Territories, Canada, demonstrate significant wave attenuation for hydrate-bearing sediments. These results are in agreement with previous attenuation estimates obtained from sonic logs and crosshole data at different frequency intervals. The application of an inverse Q-filter to compensate attenuation effects of permafrost and hydrate-bearing sediments improved the resolution of surface 3D seismic data and its correlation with log data, particularly for the shallowest gas hydrate interval. Compensation of the attenuation effects of the permafrost likely explains most of the improvements for the shallow gas hydrate zone. Our results show that characterization of the Mallik gas hydrates with seismic data not corrected for attenuation would tend to overestimate thicknesses and lateral extent of hydrate-bearing strata and hence, the volume of hydrates in place.

  11. Frequency dependent Lg attenuation in south-central Alaska

    USGS Publications Warehouse

    McNamara, D.E.

    2000-01-01

    The characteristics of seismic energy attenuation are determined using high frequency Lg waves from 27 crustal earthquakes, in south-central Alaska. Lg time-domain amplitudes are measured in five pass-bands and inverted to determine a frequency-dependent quality factor, Q(f), model for south-central Alaska. The inversion in this study yields the frequency-dependent quality factor, in the form of a power law: Q(f) = Q0fη = 220(±30) f0.66(±0.09) (0.75≤f≤12Hz). The results from this study are remarkably consistent with frequency dependent quality factor estimates, using local S-wave coda, in south-central Alaska. The consistency between S-coda Q(f) and Lg Q(f) enables constraints to be placed on the mechanism of crustal attenuation in south-central Alaska. For the range of frequencies considered in this study both scattering and intrinsic attenuation mechanisms likely play an equal role.

  12. Plasmodium yoelii: induction of attenuated mutants by irradiation

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

    Waki, S.; Yonome, I.; Suzuki, M.

    When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number ofmore » blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method.« less

  13. Backscatter and attenuation properties of mammalian brain tissues

    NASA Astrophysics Data System (ADS)

    Wijekularatne, Pushpani Vihara

    Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

  14. An electromechanical attenuator/actuator for Space Station docking

    NASA Technical Reports Server (NTRS)

    Stokes, Lebarian; Glenn, Dean; Carroll, Monty B.

    1987-01-01

    The development of a docking system for aerospace vehicles has identified the need for reusable and variably controlled attenuators/actuators for energy absorption and compliance. One approach to providing both the attenuator and the actuator functions is by way of an electromechanical attenuator/actuator (EMAA) as opposed to a hydraulic system. The use of the electromechanical devices is considered to be more suitable for a space environment because of the absence of contamination from hydraulic fluid leaks and because of the cost effectiveness of maintenance. A smart EMAA that uses range/rate/attitude sensor information to preadjust a docking interface to eliminate misalignments and to minimize contact and stroking forces is described. A prototype EMAA was fabricated and is being tested and evaluated. Results of preliminary testing and analysis already performed have established confidence that this concept is feasible and will provide the desired reliability and low maintenance for repetitive long term operation typical of Space Station requirements.

  15. Acetazolamide Attenuates Lithium–Induced Nephrogenic Diabetes Insipidus

    PubMed Central

    de Groot, Theun; Sinke, Anne P.; Kortenoeven, Marleen L.A.; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F.

    2016-01-01

    To reduce lithium–induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA–specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects. PMID:26574046

  16. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.

    PubMed

    de Groot, Theun; Sinke, Anne P; Kortenoeven, Marleen L A; Alsady, Mohammad; Baumgarten, Ruben; Devuyst, Olivier; Loffing, Johannes; Wetzels, Jack F; Deen, Peter M T

    2016-07-01

    To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI. In collecting duct (mpkCCD) cells, acetazolamide reduced the cellular lithium content and attenuated lithium-induced downregulation of aquaporin-2 through a mechanism different from that of amiloride. Treatment of lithium-NDI mice with acetazolamide or thiazide/amiloride induced similar antidiuresis and increased urine osmolality and aquaporin-2 abundance. Thiazide/amiloride-treated mice showed hyponatremia, hyperkalemia, hypercalcemia, metabolic acidosis, and increased serum lithium concentrations, adverse effects previously observed in patients but not in acetazolamide-treated mice in this study. Furthermore, acetazolamide treatment reduced inulin clearance and cortical expression of sodium/hydrogen exchanger 3 and attenuated the increased expression of urinary PGE2 observed in lithium-NDI mice. These results show that the antidiuresis with acetazolamide was partially caused by a tubular-glomerular feedback response and reduced GFR. The tubular-glomerular feedback response and/or direct effect on collecting duct principal or intercalated cells may underlie the reduced urinary PGE2 levels with acetazolamide, thereby contributing to the attenuation of lithium-NDI. In conclusion, CA activity contributes to lithium-NDI development, and acetazolamide attenuates lithium-NDI development in mice similar to thiazide/amiloride but with fewer adverse effects. Copyright © 2016 by the American Society of Nephrology.

  17. Radar attenuation in Europa's ice shell: obstacles and opportunities for constraining shell thickness and thermal structure

    NASA Astrophysics Data System (ADS)

    Kalousova, Klara; Schroeder, Dustin M.; Soderlund, Krista M.; Sotin, Christophe

    2016-10-01

    With its strikingly young surface and possibly recent endogenic activity, Europa is one of the most exciting bodies within our Solar System and a primary target for spacecraft exploration. Future missions to Europa are expected to carry ice penetrating radar instruments which are powerful tools to investigate the subsurface thermophysical structure of its ice shell.Several authors have addressed the 'penetration depth' of radar sounders at icy moons, however, the concept and calculation of a single value penetration depth is a potentially misleading simplification since it ignores the thermal and attenuation structure complexity of a realistic ice shell. Here we move beyond the concept of a single penetration depth by exploring the variation in two-way radar attenuation for a variety of potential thermal structures of Europa's ice shell as well as for a low loss and high loss temperature-dependent attenuation model. The possibility to detect brines is also investigated.Our results indicate that: (i) for all ice shell thicknesses investigated (5-30 km), a nominal satellite-borne radar sounder will penetrate between 15% and 100% of the total thickness, (ii) the maximum penetration depth strongly varies laterally with the deepest penetration possible through the cold downwellings, (iii) the direct detection of the ice/ocean interface might be possible for shells of up to 15 km if the radar signal travels through the cold downwelling, (iv) even if the ice/ocean interface is not detected, the penetration through most of the shell could constrain the deep shell structure through the loss of signal, and (v) for all plausible ice shells the two-way attenuation to the eutectic point is ≤30 dB which shows a robust potential for longitudinal investigation of the ice shell's shallow structure.Part of this work has been performed at the Jet Propulsion Laboratory, California Institute of Technology, under contract to NASA. K.K. acknowledges support by the Grant Agency of the

  18. Strong Lg-wave attenuation in the Middle East continental collision orogenic belt

    NASA Astrophysics Data System (ADS)

    Zhao, Lian-Feng; Xie, Xiao-Bi

    2016-04-01

    Using Lg-wave Q tomography, we construct a broadband crustal attenuation model for the Middle East. The QLg images reveal a relationship between attenuation and geological structures. Strong attenuation is found in the continental collision orogenic belt that extends from the Turkish and Iranian plateau to the Pamir plateau. We investigate the frequency dependence of QLg in different geologic formations. The results illustrate that QLg values generally increase with increasing frequency but exhibit complex relationships both with frequency and between regions. An average QLg value between 0.2 and 2.0 Hz, QLg (0.2-2.0 Hz), may be a critical index for crustal attenuation and is used to infer the regional geology. Low-QLg anomalies are present in the eastern Turkish plateau and correlate well with low Pn-velocities and Cenozoic volcanic activity, thus indicating possible partial melting within the crust in this region. Very strong attenuation is also observed in central Iran, the Afghanistan block, and the southern Caspian Sea. This in line with the previously observed high crustal temperature, high-conductivity layers, and thick marine sediments in these areas, suggests the high Lg attenuation is caused by abnormally high tectonic and thermal activities.

  19. Study of transmission line attenuation in broad band millimeter wave frequency range

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

    Pandya, Hitesh Kumar B.; Austin, M. E.; Ellis, R. F.

    2013-10-15

    Broad band millimeter wave transmission lines are used in fusion plasma diagnostics such as electron cyclotron emission (ECE), electron cyclotron absorption, reflectometry and interferometry systems. In particular, the ECE diagnostic for ITER will require efficient transmission over an ultra wide band, 100 to 1000 GHz. A circular corrugated waveguide transmission line is a prospective candidate to transmit such wide band with low attenuation. To evaluate this system, experiments of transmission line attenuation were performed and compared with theoretical loss calculations. A millimeter wave Michelson interferometer and a liquid nitrogen black body source are used to perform all the experiments. Atmosphericmore » water vapor lines and continuum absorption within this band are reported. Ohmic attenuation in corrugated waveguide is very low; however, there is Bragg scattering and higher order mode conversion that can cause significant attenuation in this transmission line. The attenuation due to miter bends, gaps, joints, and curvature are estimated. The measured attenuation of 15 m length with seven miter bends and eighteen joints is 1 dB at low frequency (300 GHz) and 10 dB at high frequency (900 GHz), respectively.« less

  20. Sulforaphane attenuates EGFR signaling in NSCLC cells.

    PubMed

    Chen, Chi-Yuan; Yu, Zhu-Yun; Chuang, Yen-Shu; Huang, Rui-Mei; Wang, Tzu-Chien V

    2015-06-03

    EGFR, a receptor tyrosine kinase (RTK), is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of many cancers, including NSCLC. However, intrinsic and acquired resistance to TKI remains a common obstacle. One strategy that may help overcome EGFR-TKI resistance is to target EGFR for degradation. As EGFR is a client protein of heat-shock protein 90 (HSP90) and sulforaphane is known to functionally regulate HSP90, we hypothesized that sulforaphane could attenuate EGFR-related signaling and potentially be used to treat NSCLC. Our study revealed that sulforaphane displayed antitumor activity against NSCLC cells both in vitro and in vivo. The sensitivity of NSCLC cells to sulforaphane appeared to positively correlate with the inhibition of EGFR-related signaling, which was attributed to the increased proteasomal degradation of EGFR. Combined treatment of NSCLC cells with sulforaphane plus another HSP90 inhibitor (17-AAG) enhanced the inhibition of EGFR-related signaling both in vitro and in vivo. We have shown that sulforaphane is a novel inhibitory modulator of EGFR expression and is effective in inhibiting the tumor growth of EGFR-TKI-resistant NSCLC cells. Our findings suggest that sulforaphane should be further explored for its potential clinical applications against NSCLC.

  1. Sound attenuation of fiberglass lined ventilation ducts

    NASA Astrophysics Data System (ADS)

    Albright, Jacob

    Sound attenuation is a crucial part of designing any HVAC system. Most ventilation systems are designed to be in areas occupied by one or more persons. If these systems do not adequately attenuate the sound of the supply fan, compressor, or any other source of sound, the affected area could be subject to an array of problems ranging from an annoying hum to a deafening howl. The goals of this project are to quantify the sound attenuation properties of fiberglass duct liner and to perform a regression analysis to develop equations to predict insertion loss values for both rectangular and round duct liners. The first goal was accomplished via insertion loss testing. The tests performed conformed to the ASTM E477 standard. Using the insertion loss test data, regression equations were developed to predict insertion loss values for rectangular ducts ranging in size from 12-in x 18-in to 48-in x 48-in in lengths ranging from 3ft to 30ft. Regression equations were also developed to predict insertion loss values for round ducts ranging in diameters from 12-in to 48-in in lengths ranging from 3ft to 30ft.

  2. 8-Nitro-cGMP Attenuates the Interaction between SNARE Complex and Complexin through S-Guanylation of SNAP-25.

    PubMed

    Kishimoto, Yusuke; Kunieda, Kohei; Kitamura, Atsushi; Kakihana, Yuki; Akaike, Takaaki; Ihara, Hideshi

    2018-02-21

    8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is the second messenger in nitric oxide/reactive oxygen species redox signaling. This molecule covalently binds to protein thiol groups, called S-guanylation, and exerts various biological functions. Recently, we have identified synaptosomal-associated protein 25 (SNAP-25) as a target of S-guanylation, and demonstrated that S-guanylation of SNAP25 enhanced SNARE complex formation. In this study, we have examined the effects of S-guanylation of SNAP-25 on the interaction between the SNARE complex and complexin (cplx), which binds to the SNARE complex with a high affinity. Pull-down assays and coimmunoprecipitation experiments have revealed that S-guanylation of Cys90 in SNAP-25 attenuates the interaction between the SNARE complex and cplx. In addition, blue native-PAGE followed by Western blot analysis revealed that the amount of cplx detected at a high molecular weight decreased upon 8-nitro-cGMP treatment in SH-SY5Y cells. These results demonstrated for the first time that S-guanylation of SNAP-25 attenuates the interaction between the SNARE complex and cplx.

  3. Guided wave attenuation in coated pipes buried in sand

    NASA Astrophysics Data System (ADS)

    Leinov, Eli; Cawley, Peter; Lowe, Michael J. S.

    2016-02-01

    Long-range guided wave testing (GWT) is routinely used for the monitoring and detection of corrosion defects in above ground pipelines in various industries. The GWT test range in buried, coated pipelines is greatly reduced compared to aboveground pipelines due to energy leakage into the embedding soil. In this study, we aim to increase test ranges for buried pipelines. The effect of pipe coatings on the T(0,1) and L(0,2) guided wave attenuation is investigated using a full-scale experimental apparatus and model predictions. Tests are performed on a fusion-bonded epoxy (FBE)-coated 8" pipe, buried in loose and compacted sand over a frequency range of 10-35 kHz. The application of a low impedance coating is shown to effectively decouple the influence of the sand on the ultrasound leakage from the buried pipe. We demonstrate ultrasonic isolation of a buried pipe by coating the pipe with a Polyethylene (PE)-foam layer that has a smaller impedance than both pipe and sand and the ability to withstand the overburden load from the sand. The measured attenuation in the buried PE-foam-FBE-coated pipe is substantially reduced, in the range of 0.3-1.2 dBm-1 for loose and compacted sand conditions, compared to buried FBE-coated pipe without the PE-foam, where the measured attenuation is in the range of 1.7-4.7 dBm-1. The acoustic properties of the PE-foam are measured independently using ultrasonic interferometry technique and used in model predictions of guided wave propagation in a buried coated pipe. Good agreement is found between the attenuation measurements and model predictions. The attenuation exhibits periodic peaks in the frequency domain corresponding to the through-thickness resonance frequencies of the coating layer. The large reduction in guided wave attenuation for PE-coated pipes would lead to greatly increased GWT test ranges, so such coatings would be attractive for new pipeline installations.

  4. Seismic wave attenuation and velocity dispersion in UAE carbonates

    NASA Astrophysics Data System (ADS)

    Ogunsami, Abdulwaheed Remi

    Interpreting the seismic property of fluids in hydrocarbon reservoirs at low frequency scale has been a cherished goal of petroleum geophysics research for decades. Lately, there has been tremendous interest in understanding attenuation as a result of fluid flow in porous media. Although interesting, the emerging experimental and theoretical information still remain ambiguous and are practically not utilized for reasons not too obscure. Attenuation is frequency dependent and hard to measure in the laboratory at low frequency. This thesis describes and reports the results of an experimental study of low frequency attenuation and velocity dispersion on a selected carbonate reservoir samples in the United Arab Emirates (UAE). For the low frequency measurements, stress-strain method was used to measure the moduli from which the velocity is derived. Attenuation was measured as the phase difference between the applied stress and the strain. For the ultrasonic component, the pulse propagation method was employed. To study the fluid effect especially at reservoir in situ conditions, the measurements were made dry and saturated with liquid butane and brine at differential pressures of up to 5000 psi with pore pressure held constant at 500 psi. Similarly to what has been documented in the literatures for sandstone, attenuation of the bulk compressibility mode dominates the losses in these dry and somewhat partially saturated carbonate samples with butane and brine. Overall, the observed attenuation cannot be simply said to be frequency dependent within this low seismic band. While attenuation seems to be practically constant in the low frequency band for sample 3H, such conclusion cannot be made for sample 7H. For the velocities, significant dispersion is observed and Gassmann generally fails to match the measured velocities. Only the squirt model fairly fits the velocities, but not at all pressures. Although the observed dispersion is larger than Biot's prediction, the fact

  5. Pulse transducer with artifact signal attenuator. [heart rate sensors

    NASA Technical Reports Server (NTRS)

    Cash, W. H., Jr.; Polhemus, J. T. (Inventor)

    1980-01-01

    An artifact signal attenuator for a pulse rate sensor is described. The circuit for attenuating background noise signals is connected with a pulse rate transducer which has a light source and a detector for light reflected from blood vessels of a living body. The heart signal provided consists of a modulated dc signal voltage indicative of pulse rate. The artifact signal resulting from light reflected from the skin of the body comprises both a constant dc signal voltage and a modulated dc signal voltage. The amplitude of the artifact signal is greater and the frequency less than that of the heart signal. The signal attenuator circuit includes an operational amplifier for canceling the artifact signal from the output signal of the transducer and has the capability of meeting packaging requirements for wrist-watch-size packages.

  6. Markers of angiogenesis associated with surgical attenuation of congenital portosystemic shunts in dogs.

    PubMed

    Tivers, M S; House, A K; Smith, K C; Wheeler-Jones, C P D; Lipscomb, V J

    2014-01-01

    Dogs with congenital portosystemic shunts (CPSS) have hypoplasia of the intrahepatic portal veins. Surgical CPSS attenuation results in the development of the intrahepatic portal vasculature, the precise mechanism for which is unknown, although new vessel formation by angiogenesis is suspected. That the degree of portal vascular development and the increase in portal vascularization after CPSS attenuation is significantly associated with hepatic vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) gene expression and serum VEGF concentration. Client-owned dogs with CPSS undergoing surgical treatment. Forty-nine dogs were included in the gene expression data and 35 in the serum VEGF data. Dogs surgically treated by partial or complete CPSS attenuation were prospectively recruited. Relative gene expression of VEGF and VEGFR2 was measured in liver biopsy samples taken at initial and follow-up surgery using quantitative polymerase chain reaction. Serum VEGF concentration was measured before and after CPSS attenuation using a canine specific ELISA. Statistical significance was set at the 5% level (P ≤ .05). There was a significant increase in the mRNA expression of VEGFR2 after partial attenuation (P = .006). Dogs that could tolerate complete attenuation had significantly greater VEGFR2 mRNA expression than those that only tolerated partial attenuation (P = .037). Serum VEGF concentration was significantly increased at 24 (P < .001) and 48 (P = .003) hours after attenuation. These findings suggest that intrahepatic angiogenesis is likely to occur after the surgical attenuation of CPSS in dogs, and contributes to the development of the intrahepatic vasculature postoperatively. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  7. Study of rain attenuation in Ka band for satellite communication in South Korea

    NASA Astrophysics Data System (ADS)

    Shrestha, Sujan; Choi, Dong-You

    2016-10-01

    The important factor to be considered in the link budget estimation for satellite communication systems, operating at frequencies above 10 GHz is the rain attenuation. Scattering and absorption are the main concern for system designers at these frequency bands. This has resulted in the need for suitable prediction models that can best provide estimates of attenuation due to rain with available information of rain attenuation data. Researchers have developed models that can be used to estimate 1-min rainfall attenuation distribution for earth space link but there is still some confusion with regard to choosing the right model to predict attenuation for the location of interest. In this context, the existing prediction models need to be tested against the measured results. This paper presents studies on rain attenuation at 19.8 GHz, which specifies the performance parameters for Ka-Band under earth space communication system. It presents the experimental result of rain rates and rain-induced attenuation in 19.8 and 20.73 GHz for vertical and circular polarization respectively. The received signal data for rain attenuation and rain rate were collected at 10 s intervals over a three year periods from 2013 to 2015. The data highlights the impact of clear air variation and rain fade loss. Rain rate data was measured through OTT Parsivel. During the observation period, rain rates of about 50 mm/h and attenuation values of 11.6 dB for 0.01% of the time were noted. The experimental link was set up at Korea Radio Promotion Association, Mokdong, Seoul. Out of several models, this paper present discussion and comparison of ITU-R P.618-12, Unified Method, Dissanayake Allnutt and Haidara (DAH), Simple Attenuation (SAM), Crane Global and Ramachandran and Kumar models. The relative error margin of 27.51, 89.84,72.46% and 67.24, 130.84, 166.48% are obtained for 0.1%, 0.01% and 0.001% of the time for 19.8 and 20.73 GHz under vertical and circular polarization respectively from ITU

  8. Radar attenuation in Europa's ice shell: Obstacles and opportunities for constraining the shell thickness and its thermal structure

    NASA Astrophysics Data System (ADS)

    Kalousová, Klára; Schroeder, Dustin M.; Soderlund, Krista M.

    2017-03-01

    Young surface and possible recent endogenic activity make Europa one of the most exciting solar system bodies and a primary target for spacecraft exploration. Future Europa missions are expected to carry ice-penetrating radar instruments designed to investigate its subsurface thermophysical structure. Several authors have addressed the radar sounders' performance at icy moons, often ignoring the complex structure of a realistic ice shell. Here we explore the variation in two-way radar attenuation for a variety of potential thermal structures of Europa's shell (determined by reference viscosity, activation energy, tidal heating, surface temperature, and shell thickness) as well as for low and high loss temperature-dependent attenuation model. We found that (i) for all investigated ice shell thicknesses (5-30 km), the radar sounder will penetrate between 15% and 100% of the total thickness, (ii) the maximum penetration depth varies laterally, with deepest penetration possible through cold downwellings, (iii) direct ocean detection might be possible for shells of up to 15 km thick if the signal travels through cold downwelling ice or the shell is conductive, (iv) even if the ice/ocean interface is not directly detected, penetration through most of the shell could constrain the deep shell structure through returns from deep non-ocean interfaces or the loss of signal itself, and (v) for all plausible ice shells, the two-way attenuation to the eutectic point is ≲30 dB which shows a robust potential for longitudinal investigation of the ice shell's shallow thermophysical structure.

  9. Monitored Natural Attenuation For Inorganic Contaminants In Ground Water - Technical Issues

    EPA Science Inventory

    Remediation of ground water contaminated with radionuclides may be achieved using attenuation-based technologies. These technologies may rely on engineered processes (e.g., bioremediation) or natural processes (e.g., monitored natural attenuation) within the subsurface. In gene...

  10. Targeting Interleukin-13 with Tralokinumab Attenuates Lung Fibrosis and Epithelial Damage in a Humanized SCID Idiopathic Pulmonary Fibrosis Model

    PubMed Central

    Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.

    2014-01-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475

  11. Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress.

    PubMed

    Hosoi, Toru; Yamaguchi, Rie; Noji, Kikuko; Matsuo, Suguru; Baba, Sachiko; Toyoda, Keisuke; Suezawa, Takahiro; Kayano, Takaaki; Tanaka, Shinpei; Ozawa, Koichiro

    2014-03-01

    Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded proteins, is involved in the development of obesity. We demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited chaperone activity, which reduced protein aggregation and alleviated ER stress-induced leptin resistance, characterized by insensitivity to the actions of the anti-obesity hormone leptin. This result was further supported by flurbiprofen attenuating high-fat diet-induced obesity in mice. The other NSAIDs tested did not exhibit such effects, which suggested that this anti-obesity action is mediated independent of NSAIDs. Using ferriteglycidyl methacrylate beads, we identified aldehyde dehydrogenase as the target of flurbiprofen, but not of the other NSAIDs. These results suggest that flurbiprofen may have unique pharmacological properties that reduce the accumulation of unfolded proteins and may represent a new class of drug for the fundamental treatment of obesity.

  12. Computational Modeling of Micro-Crack Induced Attenuation in CFRP Composites

    NASA Technical Reports Server (NTRS)

    Roberts, R. A.; Leckey, C. A. C.

    2012-01-01

    A computational study is performed to determine the contribution to ultrasound attenuation in carbon fiber reinforced polymer composite laminates of linear elastic scattering by matrix micro-cracking. Multiple scattering approximations are benchmarked against exact computational approaches. Results support linear scattering as the source of observed increased attenuation in the presence of micro-cracking.

  13. Ketoconazole attenuates radiation-induction of tumor necrosis factor

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

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2more » inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.« less

  14. Measurement of breast-tissue x-ray attenuation by spectral mammography: solid lesions

    NASA Astrophysics Data System (ADS)

    Fredenberg, Erik; Kilburn-Toppin, Fleur; Willsher, Paula; Moa, Elin; Danielsson, Mats; Dance, David R.; Young, Kenneth C.; Wallis, Matthew G.

    2016-04-01

    Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to distinguish between cysts and solid tumours at mammography screening would be highly desirable to reduce recalls, but the development requires knowledge of the x-ray attenuation for cysts and tumours. We have previously measured the attenuation of cyst fluid using photon-counting spectral mammography. Data on x-ray attenuation for solid breast lesions are available in the literature, but cover a relatively wide range, likely caused by natural spread between samples, random measurement errors, and different experimental conditions. In this study, we have adapted a previously developed spectral method to measure the linear attenuation of solid breast lesions. A total of 56 malignant and 5 benign lesions were included in the study. The samples were placed in a holder that allowed for thickness measurement. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The spread in equivalent material thicknesses was relatively large between samples, which is likely to be caused mainly by natural variation and only to a minor extent by random measurement errors and sample inhomogeneity. No significant difference in attenuation was found between benign and malignant solid lesions. The separation between cyst-fluid and tumour attenuation was, however, significant, which suggests it may be possible to distinguish cystic from solid breast lesions, and the results lay the groundwork for a clinical trial. In addition, the study adds a relatively large sample set to the published data and may contribute to a reduction in the overall uncertainty in the literature.

  15. Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence

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

    Zheng, H.; Crowley, J.J.; Chan, J.C.

    Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents thatmore » attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.« less

  16. A rack-mounted precision waveguide-below-cutoff attenuator with an absolute electronic readout

    NASA Technical Reports Server (NTRS)

    Cook, C. C.

    1974-01-01

    A coaxial precision waveguide-below-cutoff attenuator is described which uses an absolute (unambiguous) electronic digital readout of displacement in inches in addition to the usual gear driven mechanical counter-dial readout in decibels. The attenuator is rack-mountable and has the input and output RF connectors in a fixed position. The attenuation rate for 55, 50, and 30 MHz operation is given along with a discussion of sources of errors. In addition, information is included to aid the user in making adjustments on the attenuator should it be damaged or disassembled for any reason.

  17. Energy release, beam attenuation radiation damage, gas production and accumulation of long-lived activity in Pb, Pb-Bi and Hg targets

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

    Shubin, Yu.N.

    1996-06-01

    The calculation and analysis of the nuclei concentrations and long-lived residual radioactivity accumulated in Pb, Pb-Bi and Hg targets irradiated by 800 MeV, 30 mA proton beam have been performed. The dominating components to the total radioactivity of radionuclides resulting from fission and spallation reactions and radiative capture by both target nuclei and accumulated radioactive nuclei for various irradiation and cooling times were analyzed. The estimations of spectral component contributions of neutron and proton fluxes to the accumulated activity were carried out. The contributions of fission products to the targets activity and partial activities of main long-lived fission products tomore » the targets activity and partial activities of main long-lived fission products were evaluated. The accumulation of Po isotopes due to reactions induced by secondary alpha-particles were found to be important for the Pb target as compared with two-step radiative capture. The production of Tritium in the targets and its contribution to the total targets activity was considered in detail. It is found that total activities of both targets are close to one another.« less

  18. Polymeric PLC-type thermo-optic optical attenuator fabricated by UV imprint technique

    NASA Astrophysics Data System (ADS)

    Kim, Jin Tae; Choi, Choon-Gi

    2006-01-01

    A planar lightwave circuit-type polymer thermo-optic optical attenuator was fabricated via a UV imprint technique. In order to reduce the step for filling of cores and minimize the detrimental residual slab waveguide, convex ridge-type micro cores for guidance of light were defined with an accuracy of ±0.5 μm on the under-clad by a single step of imprinting. The voltage-controlled polymer optical attenuator showed 30-dB attenuation with 80-mW electrical input power at a wavelength of 1.55 μm. The rise and fall times are less than 5 ms. It displays about 0.2- and 1-dB polarization dependence at 0- and 10-dB attenuations, respectively.

  19. Attenuation properties of diagnostic x-ray shielding materials.

    PubMed

    Archer, B R; Fewell, T R; Conway, B J; Quinn, P W

    1994-09-01

    Single- and three-phase broad-beam x-ray attenuation data have been obtained using lead, steel, plate glass, gypsum wallboard, lead acrylic, and wood. Tube voltages of 50, 70, 100, 125, and 150 kVp were employed and the resulting curves were compared to transmission data found in the literature. To simplify computation of barrier requirements, all data sets were parametrized by nonlinear least-squares fit to a previously described mathematical model. High attenuation half value layers and the lead equivalence of the alternate materials were also determined.

  20. Hybrid modelling of a high-power X-ray attenuator plasma.

    PubMed

    Martín Ortega, Álvaro; Lacoste, Ana; Minea, Tiberiu

    2018-05-01

    X-ray gas attenuators act as stress-free high-pass filters for synchrotron and free-electron laser beamlines to reduce the heat load in downstream optical elements without affecting other properties of the X-ray beam. The absorption of the X-ray beam triggers a cascade of processes that ionize and heat up the gas locally, changing its density and therefore the X-ray absorption. Aiming to understand and predict the behaviour of the gas attenuator in terms of efficiency versus gas pressure, a hybrid model has been developed, combining three approaches: an analytical description of the X-ray absorption; Monte Carlo for the electron thermalization; and a fluid treatment for the electron diffusion, recombination and excited-states relaxation. The model was applied to an argon-filled attenuator prototype built and tested at the European Synchrotron Radiation Facility, at a pressure of 200 mbar and assuming stationary conditions. The results of the model showed that the electron population thermalizes within a few nanoseconds after the X-ray pulse arrival and it occurs just around the X-ray beam path, recombining in the bulk of the gas rather than diffusing to the attenuator walls. The gas temperature along the beam path reached 850 K for 770 W of incident power and 182 W m -1 of absorbed power. Around 70% of the absorbed power is released as visible and UV radiation rather than as heat to the gas. Comparison of the power absorption with the experiment showed an overall agreement both with the plasma radial profile and power absorption trend, the latter within an error smaller than 20%. This model can be used for the design and operation of synchrotron gas attenuators and as a base for a time-dependent model for free-electron laser attenuators.

  1. Crustal attenuation characteristics in western Turkey

    NASA Astrophysics Data System (ADS)

    Kurtulmuş, Tevfik Özgür; Akyol, Nihal

    2013-11-01

    We analysed 1764 records produced by 322 micro- and moderate-size local earthquakes in western Turkey to estimate crustal attenuation characteristics in the frequency range of 1.0 ≤ f ≤ 10 Hz. In the first step, we obtained non-parametric attenuation functions and they show that seismic recordings of transverse and radial S waves exhibit different characteristics at short and long hypocentral distances. Applying a two-step inversion, we parametrized Q( f ) and geometrical spreading exponent b( f ) for the entire distance range between 10 and 200 km and then we estimated separately Q and b values for short (10-70 km) and large (120-200 km) distance ranges. We could not observe significant frequency dependencies of b for short distance range, whereas the significant frequency dependence of b was observed for large distances. Low Q0 values (˜60) with strong frequency dependence of Q (˜1.4) for short distances suggest that scattering might be an important factor contributing to the attenuation of body waves in the region, which could be associated to a high degree of fracturing, fluid filled cracks, young volcanism and geothermal activity in the crust. Weak Q frequency dependence and higher Q0 values for large distances manifest more homogenous medium because of increasing pressure and enhanced healing of cracks with increasing temperature and depth. Q anisotropy was also observed for large hypocentral distance ranges.

  2. Low-energy gamma ray attenuation characteristics of aviation fuels

    NASA Technical Reports Server (NTRS)

    Singh, Jag J.; Shen, Chih-Ping; Sprinkle, Danny R.

    1990-01-01

    Am241 (59.5 keV) gamma ray attenuation characteristics were investigated in 270 aviation fuel (Jet A and Jet A-1) samples from 76 airports around the world as a part of world wide study to measure the variability of aviation fuel properties as a function of season and geographical origin. All measurements were made at room temperature which varied from 20 to 27 C. Fuel densities (rho) were measured concurrently with their linear attenuation coefficients (mu), thus providing a measure of mass attenuation coefficient (mu/rho) for the test samples. In 43 fuel samples, rho and mu values were measured at more than one room temperature, thus providing mu/rho values for them at several temperatures. The results were found to be independent of the temperature at which mu and rho values were measured. It is noted that whereas the individual mu and rho values vary considerably from airport to airport as well as season to season, the mu/rho values for all samples are constant at 0.1843 + or - 0.0013 cu cm/gm. This constancy of mu/rho value for aviation fuels is significant since a nuclear fuel quantity gauging system based on low energy gamma ray attenuation will be viable throughout the world.

  3. New Technologies in Using Recombinant Attenuated Salmonella Vaccine Vectors

    PubMed Central

    Curtiss, Roy; Xin, Wei; Li, Yuhua; Kong, Wei; Wanda, Soo-Young; Gunn, Bronwyn; Wang, Shifeng

    2014-01-01

    Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as “factories” to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization. PMID:20370633

  4. Tomography using monochromatic thermal neutrons with attenuation and phase contrast

    NASA Astrophysics Data System (ADS)

    Dubus, Francois; Bonse, Ulrich; Biermann, Theodor; Baron, Matthias; Beckmann, Felix; Zawisky, Michael

    2002-01-01

    Attenuation-contrast tomography with monochromatic thermal neutrons was developed and operated at guide station S18 of the institute Laue-Langevin in Grenoble. From the S18 spectrum the neutron wavelength (lambda) equals 0.18 nm was selected by employing a fore crystal with the silicon 220 reflection at a Bragg angle (Theta) equals 30 degrees. Projections were registered by a position sensitive detector (PSD) consisting of a neutron-to-visible-light converter coupled to a CCD detector. Neutron tomography and its comparison with X-ray tomography is studied. This is of special interest since the cross section for neutron attenuation ((sigma) atom) and the cross section for neutron phase shift (bc) are isotope specific and, in addition, by no means mostly monotonous functions of atomic number Z as are attenuation coefficient ((mu) x) and atomic scattering amplitude (f) in the case of X-rays. Results obtained with n-attenuation tomography will be presented. Possibilities and the setup of an instrument for neutron phase-contrast tomography based on single-crystal neutron interferometry will be described.

  5. Attenuation of sound in sand sediments due to porosity fluctuations.

    PubMed

    Hefner, Brian T; Jackson, Darrell R

    2014-08-01

    At high frequencies, the attenuation measured in sand sediments is larger than that predicted by Biot theory. To account for this discrepancy, perturbation theory is used to incorporate losses due to scattering by porosity variations into both Biot's poroelastic equations and the effective density fluid model. While previous results showed that fluctuations in the bulk frame modulus were insufficient to produce significant attenuation in a sand sediment, modest levels of fluctuations in the porosity produce significant scattering loss. By using the sediment parameters and the heterogeneity power spectrum measured during the Sediment Acoustics Experiment in 2004, the perturbation theory result shows good agreement with the sound speed and attenuation data without any free parameters.

  6. Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis.

    PubMed

    Shah, Meera; Stebbins, John L; Dewing, Antimone; Qi, Jianfei; Pellecchia, Maurizio; Ronai, Ze'ev A

    2009-12-01

    The E3 ubiquitin ligase Siah2 has been implicated in the regulation of the hypoxia response, as well as in the control of Ras, JNK/p38/NF-kappaB signaling pathways. Both Ras/mitogen-activated protein kinase (MAPK) and hypoxia pathways are important for melanoma development and progression, pointing to the possible use of Siah2 as target for treatment of this tumor type. In the present study, we have established a high-throughput electro-chemiluninescent-based assay in order to screen and identify inhibitors of Siah2 ubiquitin ligase activity. Of 1840 compounds screened, we identified and characterized menadione (MEN) as a specific inhibitor of Siah2 ligase activity. MEN attenuated Siah2 self-ubiquitination, and increased expression of its substrates PHD3 and Sprouty2, with concomitant decrease in levels of HIF-1alpha and pERK, the respective downstream effectors. MEN treatment no longer affected PHD3 or Sprouty2 in Siah-KO cells, pointing to its Siah-dependent effects. Further, MEN inhibition of Siah2 was not attenuated by free radical scavenger, suggesting it is ROS-independent. Significantly, growth of xenograft melanoma tumors was inhibited following the administration of MEN or its derivative. These findings reveal an efficient platform for the identification of Siah inhibitors while identifying and characterizing MEN as Siah inhibitor that attenuates hypoxia and MAPK signaling, and inhibits melanoma tumorigenesis.

  7. Therapeutic targeting of SPINK1-positive prostate cancer.

    PubMed

    Ateeq, Bushra; Tomlins, Scott A; Laxman, Bharathi; Asangani, Irfan A; Cao, Qi; Cao, Xuhong; Li, Yong; Wang, Xiaoju; Feng, Felix Y; Pienta, Kenneth J; Varambally, Sooryanarayana; Chinnaiyan, Arul M

    2011-03-02

    Gene fusions involving ETS (erythroblastosis virus E26 transformation-specific) family transcription factors are found in ~50% of prostate cancers and as such can be used as a basis for the molecular subclassification of prostate cancer. Previously, we showed that marked overexpression of SPINK1 (serine peptidase inhibitor, Kazal type 1), which encodes a secreted serine protease inhibitor, defines an aggressive molecular subtype of ETS fusion-negative prostate cancers (SPINK1+/ETS⁻, ~10% of all prostate cancers). Here, we examined the potential of SPINK1 as an extracellular therapeutic target in prostate cancer. Recombinant SPINK1 protein (rSPINK1) stimulated cell proliferation in benign RWPE as well as cancerous prostate cells. Indeed, RWPE cells treated with either rSPINK1 or conditioned medium from 22RV1 prostate cancer cells (SPINK1+/ETS⁻) significantly increased cell invasion and intravasation when compared with untreated cells. In contrast, knockdown of SPINK1 in 22RV1 cells inhibited cell proliferation, cell invasion, and tumor growth in xenograft assays. 22RV1 cell proliferation, invasion, and intravasation were attenuated by a monoclonal antibody (mAb) to SPINK1 as well. We also demonstrated that SPINK1 partially mediated its neoplastic effects through interaction with the epidermal growth factor receptor (EGFR). Administration of antibodies to SPINK1 or EGFR (cetuximab) in mice bearing 22RV1 xenografts attenuated tumor growth by more than 60 and 40%, respectively, or ~75% when combined, without affecting PC3 xenograft (SPINK1⁻/ETS⁻) growth. Thus, this study suggests that SPINK1 may be a therapeutic target in a subset of patients with SPINK1+/ETS⁻ prostate cancer. Our results provide a rationale for both the development of humanized mAbs to SPINK1 and evaluation of EGFR inhibition in SPINK1+/ETS⁻ prostate cancers.

  8. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

    PubMed

    Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

    2017-08-01

    Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D pol ) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D pol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A 24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F HF ) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I LF ) and W237L LF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D pol mutations that affect polymerase

  9. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity

    PubMed Central

    Rai, Devendra K.; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A.; Kloc, Anna; de los Santos, Teresa; Peersen, Olve

    2017-01-01

    ABSTRACT Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3Dpol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3Dpol mutations that affect polymerase fidelity

  10. Evolution of Natural Attenuation Evaluation Protocols

    EPA Science Inventory

    Traditionally the evaluation of the efficacy of natural attenuation was based on changes in contaminant concentrations and mass reduction. Statistical tools and models such as Bioscreen provided evaluation protocols which now are being approached via other vehicles including m...

  11. Detailed study of seismic wave attenuation from four oilfields in Abu Dhabi, United Arab Emirates

    NASA Astrophysics Data System (ADS)

    Bouchaala, F.; Ali, M. Y.; Matsushima, J.

    2018-02-01

    In the present study, we provide a detailed study of seismic wave attenuation obtained from four oilfields. The reservoir zones of these oilfields are complicated due to complex fracture networks, the presence of tar mat and high heterogeneity of carbonate rocks of which the subsurface of Abu Dhabi is mainly composed. These complexities decrease signal-to-noise ratio and make attenuation estimation difficult. We obtained high-resolution attenuation profiles from vertical seismic profiling (VSP) and sonic waveform data. The VSP data were recorded in all four oilfields and the sonic data were acquired in the reservoir zones of oilfields I and IV. We found that the VSP scattering attenuation ({Q}{{S}{{c}}{{a}}{{t}}}-1) varies from -0.080 to 0.180 over a depth range of 400-3500 m. We attributed this significant scattering to the high heterogeneity of carbonate rocks. The scattering profiles seem to be sensitive to fractures, lithology heterogeneity and tar mat, but their effect is superimposed. The VSP intrinsic attenuation varies from -0.15 to 0.246 with high variation within each formation. Since intrinsic attenuation is closely related to fluids, we assumed that this variation is due to the non-uniform distribution of fluids caused by the complex porosity network of the subsurface. The sonic monopole attenuation ({Q}{{M}{{f}}}-1) in the reservoir zones ranges between 0.033-0.094 and dipole inline attenuation ({Q}{{I}{{n}}{{l}}}-1) ranges from 0.040-0.138. The sonic attenuation appears to be sensitive to the presence of fluid and type of fractures, where it shows high attenuation for open fractures and low attenuation for resistive fractures. The zones with high clay content display high sonic intrinsic attenuation in the reservoir of oilfield II. We explain this by the frictional movement between the clay and carbonates due to the elasticity contrast of these two materials. Therefore, the solid grain friction may be the dominant attenuation mechanism in those zones.

  12. Effects of adaptation of vestibulo-ocular reflex function on manual target localization

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Merkle, L. A.; Barry, S. R.; Huebner, W. P.; Cohen, H. S.; Mueller, S. A.; Fordice, J.

    2000-01-01

    The goal of the present study was to determine if adaptive modulation of vestibulo-ocular reflex (VOR) function is associated with commensurate alterations in manual target localization. To measure the effects of adapted VOR on manual responses we developed the Vestibular-Contingent Pointing Test (VCP). In the VCP test, subjects pointed to a remembered target following passive whole body rotation in the dark. In the first experiment, subjects performed VCP before and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR gain. Results showed that adaptive reduction in horizontal VOR gain was accompanied by a commensurate change in VCP performance. In the second experiment, bilaterally labyrinthine deficient (LD) subjects were tested to confirm that vestibular cues were central to the spatial coding of both eye and hand movements during VCP. LD subjects performed significantly worse than normal subjects. These results demonstrate that adaptive change in VOR can lead to alterations in manual target localization.

  13. Characterizing ultraviolet and infrared observational properties for galaxies. II. Features of attenuation law

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

    Mao, Ye-Wei; Kong, Xu; Lin, Lin, E-mail: ywmao@pmo.ac.cn, E-mail: xkong@ustc.edu.cn, E-mail: linlin@shao.ac.cn

    Variations in the attenuation law have a significant impact on observed spectral energy distributions for galaxies. As one important observational property for galaxies at ultraviolet and infrared wavelength bands, the correlation between infrared-to-ultraviolet luminosity ratio and ultraviolet color index (or ultraviolet spectral slope), i.e., the IRX-UV relation (or IRX-β relation), offered a widely used formula for correcting dust attenuation in galaxies, but the usability appears to be in doubt now because of considerable dispersion in this relation found by many studies. In this paper, on the basis of spectral synthesis modeling and spatially resolved measurements of four nearby spiral galaxies,more » we provide an interpretation of the deviation in the IRX-UV relation with variations in the attenuation law. From both theoretical and observational viewpoints, two components in the attenuation curve, the linear background and the 2175 Å bump, are suggested to be the parameters in addition to the stellar population age (addressed in the first paper of this series) in the IRX-UV function; different features in the attenuation curve are diagnosed for the galaxies in our sample. Nevertheless, it is often difficult to ascertain the attenuation law for galaxies in actual observations. Possible reasons for preventing the successful detection of the parameters in the attenuation curve are also discussed in this paper, including the degeneracy of the linear background and the 2175 Å bump in observational channels, the requirement for young and dust-rich systems to study, and the difficulty in accurate estimates of dust attenuations at different wavelength bands.« less

  14. Characterizing Ultraviolet and Infrared Observational Properties for Galaxies. II. Features of Attenuation Law

    NASA Astrophysics Data System (ADS)

    Mao, Ye-Wei; Kong, Xu; Lin, Lin

    2014-07-01

    Variations in the attenuation law have a significant impact on observed spectral energy distributions for galaxies. As one important observational property for galaxies at ultraviolet and infrared wavelength bands, the correlation between infrared-to-ultraviolet luminosity ratio and ultraviolet color index (or ultraviolet spectral slope), i.e., the IRX-UV relation (or IRX-β relation), offered a widely used formula for correcting dust attenuation in galaxies, but the usability appears to be in doubt now because of considerable dispersion in this relation found by many studies. In this paper, on the basis of spectral synthesis modeling and spatially resolved measurements of four nearby spiral galaxies, we provide an interpretation of the deviation in the IRX-UV relation with variations in the attenuation law. From both theoretical and observational viewpoints, two components in the attenuation curve, the linear background and the 2175 Å bump, are suggested to be the parameters in addition to the stellar population age (addressed in the first paper of this series) in the IRX-UV function; different features in the attenuation curve are diagnosed for the galaxies in our sample. Nevertheless, it is often difficult to ascertain the attenuation law for galaxies in actual observations. Possible reasons for preventing the successful detection of the parameters in the attenuation curve are also discussed in this paper, including the degeneracy of the linear background and the 2175 Å bump in observational channels, the requirement for young and dust-rich systems to study, and the difficulty in accurate estimates of dust attenuations at different wavelength bands.

  15. Tickle me, I think I might be dreaming! Sensory attenuation, self-other distinction, and predictive processing in lucid dreams

    PubMed Central

    Windt, Jennifer M.; Harkness, Dominic L.; Lenggenhager, Bigna

    2014-01-01

    The contrast between self- and other-produced tickles, as a special case of sensory attenuation for self-produced actions, has long been a target of empirical research. While in standard wake states it is nearly impossible to tickle oneself, there are interesting exceptions. Notably, participants awakened from REM (rapid eye movement-) sleep dreams are able to tickle themselves. So far, however, the question of whether it is possible to tickle oneself and be tickled by another in the dream state has not been investigated empirically or addressed from a theoretical perspective. Here, we report the results of an explorative web-based study in which participants were asked to rate their sensations during self-tickling and being tickled during wakefulness, imagination, and lucid dreaming. Our results, though highly preliminary, indicate that in the special case of lucid control dreams, the difference between self-tickling and being tickled by another is obliterated, with both self- and other produced tickles receiving similar ratings as self-tickling during wakefulness. This leads us to the speculative conclusion that in lucid control dreams, sensory attenuation for self-produced tickles spreads to those produced by non-self dream characters. These preliminary results provide the backdrop for a more general theoretical and metatheoretical discussion of tickling in lucid dreams in a predictive processing framework. We argue that the primary value of our study lies not so much in our results, which are subject to important limitations, but rather in the fact that they enable a new theoretical perspective on the relationship between sensory attenuation, the self-other distinction and agency, as well as suggest new questions for future research. In particular, the example of tickling during lucid dreaming raises the question of whether sensory attenuation and the self-other distinction can be simulated largely independently of external sensory input. PMID:25278861

  16. Tickle me, I think I might be dreaming! Sensory attenuation, self-other distinction, and predictive processing in lucid dreams.

    PubMed

    Windt, Jennifer M; Harkness, Dominic L; Lenggenhager, Bigna

    2014-01-01

    The contrast between self- and other-produced tickles, as a special case of sensory attenuation for self-produced actions, has long been a target of empirical research. While in standard wake states it is nearly impossible to tickle oneself, there are interesting exceptions. Notably, participants awakened from REM (rapid eye movement-) sleep dreams are able to tickle themselves. So far, however, the question of whether it is possible to tickle oneself and be tickled by another in the dream state has not been investigated empirically or addressed from a theoretical perspective. Here, we report the results of an explorative web-based study in which participants were asked to rate their sensations during self-tickling and being tickled during wakefulness, imagination, and lucid dreaming. Our results, though highly preliminary, indicate that in the special case of lucid control dreams, the difference between self-tickling and being tickled by another is obliterated, with both self- and other produced tickles receiving similar ratings as self-tickling during wakefulness. This leads us to the speculative conclusion that in lucid control dreams, sensory attenuation for self-produced tickles spreads to those produced by non-self dream characters. These preliminary results provide the backdrop for a more general theoretical and metatheoretical discussion of tickling in lucid dreams in a predictive processing framework. We argue that the primary value of our study lies not so much in our results, which are subject to important limitations, but rather in the fact that they enable a new theoretical perspective on the relationship between sensory attenuation, the self-other distinction and agency, as well as suggest new questions for future research. In particular, the example of tickling during lucid dreaming raises the question of whether sensory attenuation and the self-other distinction can be simulated largely independently of external sensory input.

  17. Interferon beta overexpression attenuates adipose tissue inflammation and high-fat diet-induced obesity and maintains glucose homeostasis.

    PubMed

    Alsaggar, M; Mills, M; Liu, D

    2017-01-01

    The worldwide prevalence of obesity is increasing, raising health concerns regarding obesity-related complications. Chronic inflammation has been characterized as a major contributor to the development of obesity and obesity-associated metabolic disorders. The purpose of the current study is to assess whether the overexpression of interferon beta (IFNβ1), an immune-modulating cytokine, will attenuate high-fat diet-induced adipose inflammation and protect animals against obesity development. Using hydrodynamic gene transfer to elevate and sustain blood concentration of IFNβ1 in mice fed a high-fat diet, we showed that the overexpression of Ifnβ1 gene markedly suppressed immune cell infiltration into adipose tissue, and attenuated production of pro-inflammatory cytokines. Systemically, IFNβ1 blocked adipose tissue expansion and body weight gain, independent of food intake. Possible browning of white adipose tissue might also contribute to blockade of weight gain. More importantly, IFNβ1 improved insulin sensitivity and glucose homeostasis. These results suggest that targeting inflammation represents a practical strategy to block the development of obesity and its related pathologies. In addition, IFNβ1-based therapies have promising potential for clinical applications for the prevention and treatment of various inflammation-driven pathologies.

  18. The caenorhabditis elegans CDT-2 ubiquitin ligase is required for attenuation of EGFR signalling in vulva precursor cells

    PubMed Central

    2010-01-01

    Background Attenuation of the EGFR (Epidermal Growth Factor Receptor) signalling cascade is crucial to control cell fate during development. A candidate-based RNAi approach in C. elegans identified CDT-2 as an attenuator of LET-23 (EGFR) signalling. Human CDT2 is a component of the conserved CDT2/CUL4/DDB1 ubiquitin ligase complex that plays a critical role in DNA replication and G2/M checkpoint. Within this complex, CDT2 is responsible for substrate recognition. This ubiquitin ligase complex has been shown in various organisms, including C. elegans, to target the replication-licensing factor CDT1, and the CDK inhibitor p21. However, no previous link to EGFR signalling has been identified. Results We have characterised CDT-2's role during vulva development and found that it is a novel attenuator of LET-23 signalling. CDT-2 acts redundantly with negative modulators of LET-23 signalling and CDT-2 or CUL-4 downregulation causes persistent expression of the egl-17::cfp transgene, a marker of LET-23 signalling during vulva development. In addition, we show that CDT-2 physically interacts with SEM-5 (GRB2), a known negative modulator of LET-23 signalling that directly binds LET-23, and provide genetic evidence consistent with CDT-2 functioning at or downstream of LET-23. Interestingly, both SEM-5 and CDT-2 were identified independently in a screen for genes involved in receptor-mediated endocytosis in oocytes, suggesting that attenuation of LET-23 by CDT-2 might be through regulation of endocytosis. Conclusions In this study, we have shown that CDT-2 and CUL-4, members of the CUL-4/DDB-1/CDT-2 E3 ubiquitin ligase complex attenuate LET-23 signalling in vulval precursor cells. In future, it will be interesting to investigate the potential link to endocytosis and to determine whether other signalling pathways dependent on endocytosis, e.g. LIN-12 (Notch) could be regulated by this ubiquitin ligase complex. This work has uncovered a novel function for the CUL-4/DDB-1/CDT-2 E

  19. Diffuse characteristics study of laser target board using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Yang, Pengling; Wu, Yong; Wang, Zhenbao; Tao, Mengmeng; Wu, Junjie; Wang, Ping; Yan, Yan; Zhang, Lei; Feng, Gang; Zhu, Jinghui; Feng, Guobin

    2013-05-01

    In this paper, Torrance-Sparrow and Oren-Nayar model is adopt to study diffuse characteristics of laser target board. The model which based on geometric optics, assumes that rough surfaces are made up of a series of symmetric V-groove cavities with different slopes at microscopic level. The distribution of the slopes of the V-grooves are modeled as beckman distribution function, and every microfacet of the V-groove cavity is assumed to behave like a perfect mirror, which means the reflected ray follows Fresnel law at the microfacet. The masking and shadowing effects of rough surface are also taken into account through geometric attenuation factor. Monte Carlo method is used to simulate the diffuse reflectance distribution of the laser target board with different materials and processing technology, and all the calculated results are verified by experiment. It is shown that the profile of bidirectional reflectance distribution curve is lobe-shaped with the maximum lies along the mirror reflection direction. The width of the profile is narrower for a lower roughness value, and broader for a higher roughness value. The refractive index of target material will also influence the intensity and distribution of diffuse reflectance of laser target surface.

  20. Targeting host factors to treat West Nile and dengue viral infections.

    PubMed

    Krishnan, Manoj N; Garcia-Blanco, Mariano A

    2014-02-10

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans.

  1. Targeting Host Factors to Treat West Nile and Dengue Viral Infections

    PubMed Central

    Krishnan, Manoj N.; Garcia-Blanco, Mariano A.

    2014-01-01

    West Nile (WNV) and Dengue (DENV) viruses are major arboviral human pathogens belonging to the genus Flavivirus. At the current time, there are no approved prophylactics (e.g., vaccines) or specific therapeutics available to prevent or treat human infections by these pathogens. Due to their minimal genome, these viruses require many host molecules for their replication and this offers a therapeutic avenue wherein host factors can be exploited as treatment targets. Since several host factors appear to be shared by many flaviviruses the strategy may result in pan-flaviviral inhibitors and may also attenuate the rapid emergence of drug resistant mutant viruses. The scope of this strategy is greatly enhanced by the recent en masse identification of host factors impacting on WNV and DENV infection. Excellent proof-of-principle experimental demonstrations for host-targeted control of infection and infection-induced pathogenesis have been reported for both WNV and DENV. These include exploiting not only those host factors supporting infection, but also targeting host processes contributing to pathogenesis and innate immune responses. While these early studies validated the host-targeting approach, extensive future investigations spanning a range of aspects are needed for a successful deployment in humans. PMID:24517970

  2. Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

    PubMed

    Duann, Pu; Lianos, Elias A

    2011-10-01

    Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. Copyright © 2011. Published by Mosby, Inc.

  3. The Violent Content in Attenuated Psychotic Symptoms.

    PubMed

    Marshall, Catherine; Deighton, Stephanie; Cadenhead, Kristin S; Cannon, Tyrone D; Cornblatt, Barbara A; McGlashan, Thomas H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Bearden, Carrie E; Mathalon, Daniel; Addington, Jean

    2016-08-30

    The relationship between psychosis and violence has typically focused on factors likely to predict who will commit violent acts. One unexplored area is violence in the content of subthreshold positive symptoms. The current aim was to conduct an exploratory analysis of violent content in the attenuated psychotic symptoms (APS) of those at clinical high risk of psychosis (CHR) who met criteria for attenuated psychotic symptom syndrome (APSS). The APS of 442 CHR individuals, determined by the Structured Interview for Prodromal Syndromes, were described in comprehensive vignettes. The content of these symptoms were coded using the Content of Attenuated Positive Symptoms Codebook. Other measures included clinical symptoms, functioning, beliefs and trauma. Individuals with violent content had significantly higher APS, greater negative beliefs about the self and others, and increased bullying. The same findings and higher ratings on anxiety symptoms were present when participants with self-directed violence were compared to participants with no violent content. Individuals reporting violent content differ in their clinical presentation compared to those who do not experience violent content. Adverse life events, like bullying, may impact the presence of violent content in APS symptoms. Future studies should explore violent content in relation to actual behavior. Copyright © 2016. Published by Elsevier Ireland Ltd.

  4. GROUND WATER ISSUE - CALCULATION AND USE OF FIRST-ORDER RATE CONSTANTS FOR MONITORED NATURAL ATTENUATION STUDIES

    EPA Science Inventory

    This issue paper explains when and how to apply first-order attenuation rate constant calculations in monitored natural attenuation (MNA) studies. First-order attenuation rate constant calculations can be an important tool for evaluating natural attenuation processes at ground-wa...

  5. Contaminant Attenuation Processes at Mining Sites

    EPA Science Inventory

    Monitored natural attenuation is sometimes used in combination with active treatment technologies to achieve site-specific remediation objectives. The global imprint of acid drainage problems at mining sites, however, is a clear reminder that in most cases natural processes are ...

  6. ATTENUATION OF MULTI-TARGETED PROLIFERATION-LINKED SIGNALING BY 3,3′-DIINDOLYLMETHANE (DIM): FROM BENCH TO CLINIC

    PubMed Central

    Banerjee, Sanjeev; Kong, Dejuan; Wang, Zhiwei; Bao, Bin; Hillman, Gilda G; Sarkar, Fazlul H

    2013-01-01

    Emerging evidence provide credible support in favor of the potential role of bioactive products derived from ingesting cruciferous vegetables such as broccoli, brussel sprouts, cauliflower and cabbage. Among many compounds, 3,3′-Diindolylmethane (DIM) is generated in the acidic environment of the stomach following dimerization of Indole-3-Carbinol (I3C) monomers present in these classes of vegetables. Both I3C and DIM have been investigated for their use in preventing, inhibiting, and reversing the progression of cancer- as a chemopreventive agent. In this review, we summarize an updated, wide-ranging pleiotropic anti-tumor and biological effects elicited by DIM against tumor cells. It is unfeasible to point one single target as basis of cellular target of action of DIM. We emphasize key cellular and molecular events that are effectively modulated in the direction of inducing apoptosis and suppressing cell proliferation. Collectively, DIM orchestrates signaling through Ah receptor, NF-κB/Wnt/Akt/mTOR pathways impinging on cell cycle arrest, modulation of key cytochrome P450 enzymes, altering angiogenesis, invasion, metastasis and epigenetic behaviors of cancer cells. The ability of DIM to selectively induce tumor cells to undergo apoptosis has been observed in preclinical models, and thus it has been speculated in improving the therapeutic efficacy of other anticancer agents that have diverse molecular targets. Consequently, DIM has moved through preclinical development into phase-I clinical trials, thereby suggesting that DIM could be a promising and novel agent either alone or as an adjunct to conventional therapeutics such as chemo-radio therapy, and targeted therapies. An important development has been the availability of DIM formulation with superior bioavailability for humans. Therefore, DIM appears to be a promising chemopreventive agent or chemo-radio-sensitizer for the prevention of tumor recurrence and/or for the treatment of human malignancies. PMID

  7. Seismic‐wave attenuation determined from tectonic tremor in multiple subduction zones

    USGS Publications Warehouse

    Yabe, Suguru; Baltay, Annemarie S.; Ide, Satoshi; Beroza, Gregory C.

    2014-01-01

    Tectonic tremor provides a new source of observations that can be used to constrain the seismic attenuation parameter for ground‐motion prediction and hazard mapping. Traditionally, recorded earthquakes of magnitude ∼3–8 are used to develop ground‐motion prediction equations; however, typical earthquake records may be sparse in areas of high hazard. In this study, we constrain the distance decay of seismic waves using measurements of the amplitude decay of tectonic tremor, which is plentiful in some regions. Tectonic tremor occurs in the frequency band of interest for ground‐motion prediction (i.e., ∼2–8  Hz) and is located on the subducting plate interface, at the lower boundary of where future large earthquakes are expected. We empirically fit the distance decay of peak ground velocity from tremor to determine the attenuation parameter in four subduction zones: Nankai, Japan; Cascadia, United States–Canada; Jalisco, Mexico; and southern Chile. With the large amount of data available from tremor, we show that in the upper plate, the lower crust is less attenuating than the upper crust. We apply the same analysis to intraslab events in Nankai and show the possibility that waves traveling from deeper intraslab events experience more attenuation than those from the shallower tremor due to ray paths that pass through the subducting and highly attenuating oceanic crust. This suggests that high pore‐fluid pressure is present in the tremor source region. These differences imply that the attenuation parameter determined from intraslab earthquakes may underestimate ground motion for future large earthquakes on the plate interface.

  8. Development and applications of a radar-attenuation model for polar ice sheets

    NASA Astrophysics Data System (ADS)

    MacGregor, Joseph A.

    Modern ice sheets are currently responding to significant climatic forcings and undergoing ice-dynamics changes that are not yet well understood. Ice-penetrating radar surveys are often used to infer their basal condition (e.g., is the bed wet or dry?) and internal properties. However, such inferences typically require a model of the electromagnetic attenuation through the ice sheet. Here I first develop and test a radar-attenuation model that is based on a synthesis of existing laboratory measurements of the dielectric properties of ice. This synthesis shows that radar attenuation in polar ice has a strong non-linear temperature dependence and a weaker linear dependence on the concentrations of acid and sea-salt chloride. This model was tested at Siple Dome, West Antarctica, using ice-core-chemistry and borehole-temperature data, and the model agreed well with an existing radar-attenuation measurement. I then use this model to investigate the nature of radar detection of accreted ice over Lake Vostok, East Antarctica. My analysis of ice-core and radar data found that the observed reflection is likely due to a fabric contrast near the boundary between the dirty and clean accreted ices. This reflection mechanism is also consistent with the spatial pattern of detection of the reflection. In anticipation of the requirements of a thermomechanical ice-sheet model to predict the spatial variation of attenuation over Lake Vostok, I develop an accumulation-rate map for the Lake Vostok region using radar data, a steady-state flow-band model, and inverse methods. I found that accumulation rates there are not inversely correlated with surface elevation, that there is a broad maximum above the lake's northwestern corner, and a minimum above most of its eastern shoreline. Finally, I investigate the spatial variability of attenuation in an ice sheet, using the flowline that crosses through the Vostok ice core as an example. I use radar layers and ice-velocity and temperature

  9. Monitored Natural Attenuation of ino9rganic Contaminants Treatability Study Final Report

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

    Crapse, K

    2004-05-19

    The identification and quantification of key natural attenuation processes for inorganic contaminants at D-Area is detailed herein. Two overarching goals of this evaluation of monitored natural attenuation (MNA) as a remediation strategy were (1) to better define the availability of inorganic contaminants as potential sources for transport to groundwater and uptake by environmental receptors and (2) to understand the site-specific mechanisms controlling attenuation of these inorganic contaminants through tandem geochemical and biological characterization. Data collected in this study provides input for more appropriate site groundwater transport models. Significant natural attenuation is occurring at D-Area as evidenced by relatively low aqueousmore » concentrations of constituents of concern (COCs) (Be, Ni, U, and As) at all locations characterized and the decrease in groundwater concentrations with increasing distance from the source. The observed magnitude of decrease in groundwater concentrations of COCs with distance from the D-Area Coal Pile Runoff Basin (DCPRB) could not be accounted for by the modeled physical attenuation processes of dilution/dispersion. This additional attenuation, i.e., the observed difference between the groundwater concentrations of COCs and the modeled physical attenuation, is due to biogeochemical processes occurring at the D-Area. In tandem geochemical and microbiological characterization studies designed to evaluate the mechanisms contributing to natural attenuation, pH was the single parameter found to be most predictive of contaminant attenuation. The increasing pH with distance from the source is likely responsible for increased sorption of COCs to soil surfaces within the aquifer at D-Area. Importantly, because the sediments appear to have a high buffering capacity, the acid emanating from the DCPRB has been neutralized by the soil, and these conditions have led to large Kd values at the site. Two major types of soils are

  10. Markerless attenuation correction for carotid MRI surface receiver coils in combined PET/MR imaging

    NASA Astrophysics Data System (ADS)

    Eldib, Mootaz; Bini, Jason; Robson, Philip M.; Calcagno, Claudia; Faul, David D.; Tsoumpas, Charalampos; Fayad, Zahi A.

    2015-06-01

    The purpose of the study was to evaluate the effect of attenuation of MR coils on quantitative carotid PET/MR exams. Additionally, an automated attenuation correction method for flexible carotid MR coils was developed and evaluated. The attenuation of the carotid coil was measured by imaging a uniform water phantom injected with 37 MBq of 18F-FDG in a combined PET/MR scanner for 24 min with and without the coil. In the same session, an ultra-short echo time (UTE) image of the coil on top of the phantom was acquired. Using a combination of rigid and non-rigid registration, a CT-based attenuation map was registered to the UTE image of the coil for attenuation and scatter correction. After phantom validation, the effect of the carotid coil attenuation and the attenuation correction method were evaluated in five subjects. Phantom studies indicated that the overall loss of PET counts due to the coil was 6.3% with local region-of-interest (ROI) errors reaching up to 18.8%. Our registration method to correct for attenuation from the coil decreased the global error and local error (ROI) to 0.8% and 3.8%, respectively. The proposed registration method accurately captured the location and shape of the coil with a maximum spatial error of 2.6 mm. Quantitative analysis in human studies correlated with the phantom findings, but was dependent on the size of the ROI used in the analysis. MR coils result in significant error in PET quantification and thus attenuation correction is needed. The proposed strategy provides an operator-free method for attenuation and scatter correction for a flexible MRI carotid surface coil for routine clinical use.

  11. Neutron attenuation characteristics of polyethylene, polyvinyl chloride, and heavy aggregate concrete and mortars.

    PubMed

    Abdul-Majid, S; Othman, F

    1994-03-01

    Polyethylene and polyvinyl chloride pellets were introduced into concrete to improve its neutron attenuation characteristics while several types of heavy coarse aggregates were used to improve its gamma ray attenuation properties. Neutron and gamma ray attenuation were studied in concrete samples containing coarse aggregates of barite, pyrite, basalt, hematite, and marble as well as polyethylene and polyvinyl chloride pellets in narrow-beam geometry. The highest neutron attenuation was shown by polyethylene mortar, followed by polyvinyl chloride mortar; barite and pyrite concrete showed higher gamma ray attenuation than ordinary concrete. Broad-beam and continuous (infinite) medium geometries were used to study the neutron attenuation of samples containing polymers at different concentrations with and without heavy aggregates, the fitting equations were established, and from these the neutron removal coefficients were deduced. In a radiation field of neutrons and gamma rays, the appropriate concentration of polymer and heavy aggregate can be selected to give the optimum total dose attenuation depending on the relative intensities of each type of radiation. This would give much better design flexibility over ordinary concrete. The compressive strength tests performed on mortar and concrete samples showed that their value, in general, decreases as polymer concentration increases and that the polyvinyl chloride mortar showed higher values than the polyethylene mortar. For general construction purposes, the compression strength was considered acceptable in these samples.

  12. Separating intrinsic and scattering attenuation in full waveform sonic logging with radiative transfer theory

    NASA Astrophysics Data System (ADS)

    Durán, Evert L.; van Wijk, Kasper; Adam, Ludmila; Wallis, Irene C.

    2018-05-01

    Fitting the intensity of ensembles of sonic log waveforms with a radiative transfer model allows us to separate scattering from intrinsic attenuation in two wells of the Ngatamariki geothermal field, New Zealand. Independent estimates of scattering and intrinsic attenuation add to the geologic interpretation based on other well log data. Particularly, our estimates of the intrinsic attenuation confirm or refine inferences on fluid mobility in the subsurface. Zones of strong intrinsic attenuation in Well 1 correlate with identified feed zones in three of the six cases, and hint at permeability just above two of the other three zones. In Well 2, intrinsic attenuation estimates help identify all three identified permeable intervals, including a washout.

  13. Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.

    PubMed

    Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D

    2016-06-01

    Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans.

  14. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury.

    PubMed

    Sen, Chandan K; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

    2017-03-01

    The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT - ) or RAMT + groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT + increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT - controls. Furthermore, RAMT + rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury. © FASEB.

  15. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury

    PubMed Central

    Sen, Chandan K.; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

    2017-01-01

    The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to researchers for systematic preclinical testing. This work represents a maiden effort to develop a robot-assisted mechanical therapy (RAMT) device to objectively address the significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were subjected to right hemisphere middle-cerebral artery occlusion and reperfusion. After 24 h, rats were split into control (RAMT−) or RAMT+ groups (30 min daily RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d 14. RAMT+ increased perfusion 1.5-fold in stroke-affected gastrocnemius as compared to RAMT− controls. Furthermore, RAMT+ rats demonstrated improved poststroke track width (11% wider), stride length (21% longer), and travel distance (61% greater), as objectively measured using software-automated testing platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain-derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke-induced increase in myostatin and increased BDNF expression in skeletal muscle. Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP-10/CXCL10) were identified from a cytokine array. Taken together, outcomes suggest stroke acutely influences signal transduction in hindlimb skeletal muscle. Regimens based on mechanical therapy have the clear potential to protect hindlimb function from such adverse influence.—Sen, C. K., Khanna, S., Harris, H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C. Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle injury. PMID:27895105

  16. Wavelength tunable and broadband variable fiber-optic attenuators using liquid crystals

    NASA Astrophysics Data System (ADS)

    Khan, Sajjad A.; Riza, Nabeel A.

    2005-05-01

    Fiber-Optic Variable Optical Attenuators (VOAs) are demonstrated using Liquid Crystals (LC) for broadband as well as wavelength tunable applications. Attenuation is achieved by using a beam spoiling approach implemented via electrically reconfigurable non-pixelated no moving parts Nematic LC deflectors. The VOAs feature in-line architecture and polarization insensitive design without the use of bulky polarization splitting and combining optics. The proof-of-concept VOAs in the 1550 nm band demonstrate >30 dB attenuation ranges, low polarization dependent losses and low power consumption. Applications for these VOAs include agile wavelength tunable secure data communications networks and RF sensor systems.

  17. Methods of Attenuation Correction for Dual-Wavelength and Dual-Polarization Weather Radar Data

    NASA Technical Reports Server (NTRS)

    Meneghini, R.; Liao, L.

    2007-01-01

    In writing the integral equations for the median mass diameter and number concentration, or comparable parameters of the raindrop size distribution, it is apparent that the forms of the equations for dual-polarization and dual-wavelength radar data are identical when attenuation effects are included. The differential backscattering and extinction coefficients appear in both sets of equations: for the dual-polarization equations, the differences are taken with respect to polarization at a fixed frequency while for the dual-wavelength equations, the differences are taken with respect to frequency at a fixed polarization. An alternative to the integral equation formulation is that based on the k-Z (attenuation coefficient-radar reflectivity factor) parameterization. This-technique was originally developed for attenuating single-wavelength radars, a variation of which has been applied to the TRMM Precipitation Radar data (PR). Extensions of this method have also been applied to dual-polarization data. In fact, it is not difficult to show that nearly identical equations are applicable as well to dualwavelength radar data. In this case, the equations for median mass diameter and number concentration take the form of coupled, but non-integral equations. Differences between this and the integral equation formulation are a consequence of the different ways in which attenuation correction is performed under the two formulations. For both techniques, the equations can be solved either forward from the radar outward or backward from the final range gate toward the radar. Although the forward-going solutions tend to be unstable as the attenuation out to the range of interest becomes large in some sense, an independent estimate of path attenuation is not required. This is analogous to the case of an attenuating single-wavelength radar where the forward solution to the Hitschfeld-Bordan equation becomes unstable as the attenuation increases. To circumvent this problem, the

  18. Flexural wave attenuation in a sandwich beam with viscoelastic periodic cores

    NASA Astrophysics Data System (ADS)

    Guo, Zhiwei; Sheng, Meiping; Pan, Jie

    2017-07-01

    The flexural-wave attenuation performance of traditional constraint-layer damping in a sandwich beam is improved by using periodic constrained-layer damping (PCLD), where the monolithic viscoelastic core is replaced with two periodically alternating viscoelastic cores. Closed-form solutions of the wave propagation constants of the infinite periodic sandwich beam and the forced response of the corresponding finite sandwich structure are theoretically derived, providing computational support on the analysis of attenuation characteristics. In a sandwich beam with PCLD, the flexural waves can be attenuated by both Bragg scattering effect and damping effect, where the attenuation level is mainly dominated by Bragg scattering in the band-gaps and by damping in the pass-bands. Affected by these two effects, when the parameters of periodic cores are properly selected, a sandwich beam with PCLD can effectively reduce vibrations of much lower frequencies than that with traditional constrained-layer damping. The effects of the parameters of viscoelastic periodic cores on band-gap properties are also discussed, showing that the average attenuation in the desired frequency band can be maximized by tuning the length ratio and core thickness to proper values. The research in this paper could possibly provide useful information for the researches and engineers to design damping structures.

  19. Wave attenuation in the marginal ice zone during LIMEX

    NASA Technical Reports Server (NTRS)

    Liu, Antony K.; Peng, Chih Y.; Vachon, Paris W.

    1991-01-01

    During LIMEX'87 and '89, the CCRS CV-580 aircraft collected SAR (synthetic aperture radar) data over the marginal ice zone off the coast of Newfoundland. Based upon the wavenumber spectra from SAR data, the wave attenuation rate is estimated and compared with a model. The model-data comparisons are reasonably good for the ice conditions during LIMEX (Labrador Ice Margin Experiment). Both model and SAR-derived wave attenuation rates show a roll-over at high wavenumbers.

  20. Live Attenuated Influenza Vaccines by Computer-Aided Rational Design

    PubMed Central

    Mueller, Steffen; Coleman, J. Robert; Papamichail, Dimitris; Ward, Charles B.; Nimnual, Anjaruwee; Futcher, Bruce; Skiena, Steven; Wimmer, Eckard

    2010-01-01

    Influenza claims 250,000 - 500,000 lives annually worldwide. Despite existing vaccines and enormous efforts in biomedical research, these staggering numbers have not changed significantly over the last two decades1, motivating the search for new, more effective, vaccines that can be rapidly designed and easily produced. Using influenza virus strain A/PR/8/34, we describe a systematic, rational approach, termed Synthetic Attenuated Virus Engineering (SAVE), to develop new, efficacious live attenuated influenza virus vaccine candidates through genome-scale changes in codon pair bias. Attenuation is based on many hundreds of nucleotide changes across the viral genome, offering high genetic stability and a wide margin of safety. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is significant for dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza. PMID:20543832

  1. Attenuation of X and Gamma Rays in Personal Radiation Shielding Protective Clothing.

    PubMed

    Kozlovska, Michaela; Cerny, Radek; Otahal, Petr

    2015-11-01

    A collection of personal radiation shielding protective clothing, suitable for use in case of accidents in nuclear facilities or radiological emergency situations involving radioactive agents, was gathered and tested at the Nuclear Protection Department of the National Institute for Nuclear, Chemical and Biological Protection, Czech Republic. Attenuating qualities of shielding layers in individual protective clothing were tested via spectra measurement of x and gamma rays, penetrating them. The rays originated from different radionuclide point sources, the gamma ray energies of which cover a broad energy range. The spectra were measured by handheld spectrometers, both scintillation and High Purity Germanium. Different narrow beam geometries were adjusted using a special testing bench and a set of various collimators. The main experimentally determined quantity for individual samples of personal radiation shielding protective clothing was x and gamma rays attenuation for significant energies of the spectra. The attenuation was assessed comparing net peak areas (after background subtraction) in spectra, where a tested sample was placed between the source and the detector, and corresponding net peak areas in spectra, measured without the sample. Mass attenuation coefficients, which describe attenuating qualities of shielding layers materials in individual samples, together with corresponding lead equivalents, were determined as well. Experimentally assessed mass attenuation coefficients of the samples were compared to the referred ones for individual heavy metals.

  2. Determination of intrinsic attenuation in the oceanic lithosphere-asthenosphere system

    NASA Astrophysics Data System (ADS)

    Takeuchi, Nozomu; Kawakatsu, Hitoshi; Shiobara, Hajime; Isse, Takehi; Sugioka, Hiroko; Ito, Aki; Utada, Hisashi

    2017-12-01

    We recorded P and S waves traveling through the oceanic lithosphere-asthenosphere system (LAS) using broadband ocean-bottom seismometers in the northwest Pacific, and we quantitatively separated the intrinsic (anelastic) and extrinsic (scattering) attenuation effects on seismic wave propagation to directly infer the thermomechanical properties of the oceanic LAS. The strong intrinsic attenuation in the asthenosphere obtained at higher frequency (~3 hertz) is comparable to that constrained at lower frequency (~100 seconds) by surface waves and suggests frequency-independent anelasticity, whereas the intrinsic attenuation in the lithosphere is frequency dependent. This difference in frequency dependence indicates that the strong and broad peak dissipation recently observed in the laboratory exists only in the asthenosphere and provides new insight into what distinguishes the asthenosphere from the lithosphere.

  3. Monitored Natural Attenuation Case Study Evaluations

    EPA Science Inventory

    Monitored natural attenuation (MNA) has been selected as a component of groundwater remedies at several sites with metals and/or radionuclide contamination. An overview of the site characterization effort and remedy performance will be provided for several sites where MNA was se...

  4. Note: Attenuation motion of acoustically levitated spherical rotor

    NASA Astrophysics Data System (ADS)

    Lü, P.; Hong, Z. Y.; Yin, J. F.; Yan, N.; Zhai, W.; Wang, H. P.

    2016-11-01

    Here we observe the attenuation motion of spherical rotors levitated by near-field acoustic radiation force and analyze the factors that affect the duration time of free rotation. It is found that the rotating speed of freely rotating rotor decreases exponentially with respect to time. The time constant of exponential attenuation motion depends mainly on the levitation height, the mass of rotor, and the depth of concave ultrasound emitter. Large levitation height, large mass of rotor, and small depth of concave emitter are beneficial to increase the time constant and hence extend the duration time of free rotation.

  5. Note: Attenuation motion of acoustically levitated spherical rotor.

    PubMed

    Lü, P; Hong, Z Y; Yin, J F; Yan, N; Zhai, W; Wang, H P

    2016-11-01

    Here we observe the attenuation motion of spherical rotors levitated by near-field acoustic radiation force and analyze the factors that affect the duration time of free rotation. It is found that the rotating speed of freely rotating rotor decreases exponentially with respect to time. The time constant of exponential attenuation motion depends mainly on the levitation height, the mass of rotor, and the depth of concave ultrasound emitter. Large levitation height, large mass of rotor, and small depth of concave emitter are beneficial to increase the time constant and hence extend the duration time of free rotation.

  6. MONITORED NATURAL ATTENUATION AND RISK MANAGEMENT OF MTBE IN GROUND WATER

    EPA Science Inventory

    Monitored natural attenuation (as U.S. EPA defines the term) is a remedy, where natural processes bring the concentration of MTBE to an acceptable level in a reasonable period of time. The longevity of the plume is its critical property. The rate of attenuation is typically con...

  7. Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus

    PubMed Central

    Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

    2017-01-01

    Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

  8. Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus.

    PubMed

    Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

    2017-12-01

    Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

  9. MR-Consistent Simultaneous Reconstruction of Attenuation and Activity for Non-TOF PET/MR

    NASA Astrophysics Data System (ADS)

    Heußer, Thorsten; Rank, Christopher M.; Freitag, Martin T.; Dimitrakopoulou-Strauss, Antonia; Schlemmer, Heinz-Peter; Beyer, Thomas; Kachelrieß, Marc

    2016-10-01

    Attenuation correction (AC) is required for accurate quantification of the reconstructed activity distribution in positron emission tomography (PET). For simultaneous PET/magnetic resonance (MR), however, AC is challenging, since the MR images do not provide direct information on the attenuating properties of the underlying tissue. Standard MR-based AC does not account for the presence of bone and thus leads to an underestimation of the activity distribution. To improve quantification for non-time-of-flight PET/MR, we propose an algorithm which simultaneously reconstructs activity and attenuation distribution from the PET emission data using available MR images as anatomical prior information. The MR information is used to derive voxel-dependent expectations on the attenuation coefficients. The expectations are modeled using Gaussian-like probability functions. An iterative reconstruction scheme incorporating the prior information on the attenuation coefficients is used to update attenuation and activity distribution in an alternating manner. We tested and evaluated the proposed algorithm for simulated 3D PET data of the head and the pelvis region. Activity deviations were below 5% in soft tissue and lesions compared to the ground truth whereas standard MR-based AC resulted in activity underestimation values of up to 12%.

  10. Optical Attenuation Coefficient Meter

    DTIC Science & Technology

    2016-06-22

    detector 43 is measured and recorded at the Pico Scope 80 to validate the laser pulse strength (which is proportional to the output and time wave shape ...unusable. [0004] As such, there is a need for a meter, recognizing back scattering by a pulsed laser source, that would allow a propagation path which...an attenuation meter with a transmitter and receiver is provided in which the transmitter produces a laser pulse of a duration and water

  11. A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

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

    Akram, Muhammad

    Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPDmore » 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.« less

  12. Seismic-wave attenuation associated with crustal faults in the New Madrid seismic zone

    USGS Publications Warehouse

    Hamilton, R.M.; Mooney, W.D.

    1990-01-01

    The attenuation of upper crustal seismic waves that are refracted with a velocity of about 6 kilometers per second varies greatly among profiles in the area of the New Madrid seismic zone in the central Mississippi Valley. The waves that have the strongest attenuation pass through the seismic trend along the axis of the Reelfoot rift in the area of the Blytheville arch. Defocusing of the waves in a low-velocity zone and/ or seismic scattering and absorption could cause the attenuation; these effects are most likely associated with the highly deformed rocks along the arch. Consequently, strong seismic-wave attenuation may be a useful criterion for identifying seismogenic fault zones.

  13. Wave attenuation and mode dispersion in a waveguide coated with lossy dielectric material

    NASA Technical Reports Server (NTRS)

    Lee, C. S.; Chuang, S. L.; Lee, S. W.; Lo, Y. T.

    1984-01-01

    The modal attenuation constants in a cylindrical waveguide coated with a lossy dielectric material are studied as functions of frequency, dielectric constant, and thickness of the dielectric layer. A dielectric material best suited for a large attenuation is suggested. Using Kirchhoff's approximation, the field attenuation in a coated waveguide which is illuminated by a normally incident plane wave is also studied. For a circular guide which has a diameter of two wavelengths and is coated with a thin lossy dielectric layer (omega sub r = 9.1 - j2.3, thickness = 3% of the radius), a 3 dB attenuation is achieved within 16 diameters.

  14. Contaminant Attenuation and Transport Characterization of 200-UP-1 Operable Unit Sediment Samples

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

    Lee, Brady D.; Szecsody, James E.; Qafoku, Nikolla

    Contaminants disposed of at the land surface migrate through the vadose zone, forming plumes in groundwater. Processes that occur in the groundwater can attenuate contaminant concentrations during transport through the aquifer. For this reason, quantifying contaminant attenuation and contaminant transport processes in the aquifer, in support of the conceptual site model (CSM) and fate and transport modeling, are important for assessing the need for, and type of, remediation in the groundwater, including monitored natural attenuation (MNA). The framework to characterize attenuation and transport processes provided in U.S. Environmental Protection Agency (EPA) guidance documents was used to guide the laboratory effortmore » reported herein.« less

  15. Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

    PubMed

    Masillo, Alice; Brandizzi, M; Valmaggia, L R; Saba, R; Lo Cascio, N; Lindau, J F; Telesforo, L; Venturini, P; Montanaro, D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

    2018-03-01

    Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

  16. Research on the underwater target imaging based on the streak tube laser lidar

    NASA Astrophysics Data System (ADS)

    Cui, Zihao; Tian, Zhaoshuo; Zhang, Yanchao; Bi, Zongjie; Yang, Gang; Gu, Erdan

    2018-03-01

    A high frame rate streak tube imaging lidar (STIL) for real-time 3D imaging of underwater targets is presented in this paper. The system uses 532nm pulse laser as the light source, the maximum repetition rate is 120Hz, and the pulse width is 8ns. LabVIEW platform is used in the system, the system control, synchronous image acquisition, 3D data processing and display are realized through PC. 3D imaging experiment of underwater target is carried out in a flume with attenuation coefficient of 0.2, and the images of different depth and different material targets are obtained, the imaging frame rate is 100Hz, and the maximum detection depth is 31m. For an underwater target with a distance of 22m, the high resolution 3D image real-time acquisition is realized with range resolution of 1cm and space resolution of 0.3cm, the spatial relationship of the targets can be clearly identified by the image. The experimental results show that STIL has a good application prospect in underwater terrain detection, underwater search and rescue, and other fields.

  17. Flurbiprofen ameliorated obesity by attenuating leptin resistance induced by endoplasmic reticulum stress

    PubMed Central

    Hosoi, Toru; Yamaguchi, Rie; Noji, Kikuko; Matsuo, Suguru; Baba, Sachiko; Toyoda, Keisuke; Suezawa, Takahiro; Kayano, Takaaki; Tanaka, Shinpei; Ozawa, Koichiro

    2014-01-01

    Endoplasmic reticulum (ER) stress, caused by the accumulation of unfolded proteins, is involved in the development of obesity. We demonstrated that flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), exhibited chaperone activity, which reduced protein aggregation and alleviated ER stress-induced leptin resistance, characterized by insensitivity to the actions of the anti-obesity hormone leptin. This result was further supported by flurbiprofen attenuating high-fat diet-induced obesity in mice. The other NSAIDs tested did not exhibit such effects, which suggested that this anti-obesity action is mediated independent of NSAIDs. Using ferriteglycidyl methacrylate beads, we identified aldehyde dehydrogenase as the target of flurbiprofen, but not of the other NSAIDs. These results suggest that flurbiprofen may have unique pharmacological properties that reduce the accumulation of unfolded proteins and may represent a new class of drug for the fundamental treatment of obesity. Subject Categories Metabolism; Pharmacology & Drug Discovery PMID:24421337

  18. Inferring global upper-mantle shear attenuation structure by waveform tomography using the spectral element method

    NASA Astrophysics Data System (ADS)

    Karaoǧlu, Haydar; Romanowicz, Barbara

    2018-06-01

    We present a global upper-mantle shear wave attenuation model that is built through a hybrid full-waveform inversion algorithm applied to long-period waveforms, using the spectral element method for wavefield computations. Our inversion strategy is based on an iterative approach that involves the inversion for successive updates in the attenuation parameter (δ Q^{-1}_μ) and elastic parameters (isotropic velocity VS, and radial anisotropy parameter ξ) through a Gauss-Newton-type optimization scheme that employs envelope- and waveform-type misfit functionals for the two steps, respectively. We also include source and receiver terms in the inversion steps for attenuation structure. We conducted a total of eight iterations (six for attenuation and two for elastic structure), and one inversion for updates to source parameters. The starting model included the elastic part of the relatively high-resolution 3-D whole mantle seismic velocity model, SEMUCB-WM1, which served to account for elastic focusing effects. The data set is a subset of the three-component surface waveform data set, filtered between 400 and 60 s, that contributed to the construction of the whole-mantle tomographic model SEMUCB-WM1. We applied strict selection criteria to this data set for the attenuation iteration steps, and investigated the effect of attenuation crustal structure on the retrieved mantle attenuation structure. While a constant 1-D Qμ model with a constant value of 165 throughout the upper mantle was used as starting model for attenuation inversion, we were able to recover, in depth extent and strength, the high-attenuation zone present in the depth range 80-200 km. The final 3-D model, SEMUCB-UMQ, shows strong correlation with tectonic features down to 200-250 km depth, with low attenuation beneath the cratons, stable parts of continents and regions of old oceanic crust, and high attenuation along mid-ocean ridges and backarcs. Below 250 km, we observe strong attenuation in the

  19. Uncovering the genetic basis of attenuation in Marek’s disease virus

    USDA-ARS?s Scientific Manuscript database

    While in vitro serial passage of Marek’s disease virus (MDV) is a proven method to attenuate MDV strains, the underlying genetic changes responsible for attenuation remains unknown. To identify candidate genes and mutations, a virulent MDV generated from an Md5-containing BAC clone was serially pass...

  20. Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry.

    PubMed

    Kimura, Takeshi; Morimoto, Takeshi; Nakagawa, Yoshihisa; Kawai, Kazuya; Miyazaki, Shunichi; Muramatsu, Toshiya; Shiode, Nobuo; Namura, Masanobu; Sone, Takahito; Oshima, Shigeru; Nishikawa, Hideo; Hiasa, Yoshikazu; Hayashi, Yasuhiko; Nobuyoshi, Masakiyo; Mitudo, Kazuaki

    2012-01-31

    There is a scarcity of long-term data from large-scale drug-eluting stent registries with a large enough sample to evaluate low-frequency events such as stent thrombosis (ST). Five-year outcomes were evaluated in 12 812 consecutive patients undergoing sirolimus-eluting stent (SES) implantation in the j-Cypher registry. Cumulative incidence of definite ST was low (30 day, 0.3%; 1 year, 0.6%; and 5 years, 1.6%). However, late and very late ST continued to occur without attenuation up to 5 years after sirolimus-eluting stent implantation (0.26%/y). Cumulative incidence of target lesion revascularization within the first year was low (7.3%). However, late target lesion revascularization beyond 1 year also continued to occur without attenuation up to 5 years (2.2%/y). Independent risk factors of ST were completely different according to the timing of ST onset, suggesting the presence of different pathophysiological mechanisms of ST according to the timing of ST onset: acute coronary syndrome and target of proximal left anterior descending coronary artery for early ST; side-branch stenting, diabetes mellitus, and end-stage renal disease with or without hemodialysis for late ST; and current smoking and total stent length >28 mm for very late ST. Independent risk factors of late target lesion revascularization beyond 1 year were generally similar to those risk factors identified for early target lesion revascularization. Late adverse events such as very late ST and late target lesion revascularization are continuous hazards, lasting at least up to 5 years after implantation of the first-generation drug-eluting stents (sirolimus-eluting stents), which should be the targets for developing improved coronary stents.

  1. Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism

    PubMed Central

    Yo, Kikuo; Yu, Yong-Ming; Zhao, Gaofeng; Bonab, Ali A.; Aikawa, Naoki; Tompkins, Ronald G.

    2013-01-01

    Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1. PMID:23169784

  2. Crustal Seismic Attenuation in Germany Measured with Acoustic Radiative Transfer Theory

    NASA Astrophysics Data System (ADS)

    Gaebler, Peter J.; Eulenfeld, Tom; Wegler, Ulrich

    2017-04-01

    This work is carried out in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT). As part of this treaty a verification regime was introduced to detect, locate and characterize nuclear explosion testings. The study of seismology can provide essential information in the form of broadband waveform recordings for the identification and verification of these critical events. A profound knowledge of the Earth's subsurface between source and receiver is required for a detailed description of the seismic wave field. In addition to underground parameters such as seismic velocity or anisotropy, information about seismic attenuation values of the medium are required. Goal of this study is the creation of a comprehensive model of crustal seismic attenuation in Germany and adjacent areas. Over 20 years of earthquake data from the German Central Seismological Observatory data archive is used to estimate the spatial dependent distribution of seismic intrinsic and scattering attenuation of S-waves for frequencies between 0.5 and 20 Hz. The attenuation models are estimated by fitting synthetic seismogram envelopes calculated with acoustic radiative transfer theory to observed seismogram envelopes. This theory describes the propagation of seismic S-energy under the assumption of multiple isotropic scattering, the crustal structure of the scattering medium is hereby represented by a half-space model. We present preliminary results of the spatial distribution of intrinsic attenuation represented by the absorption path length, as well as of scattering attenuation in terms of the mean free path and compare the outcomes to results from previous studies. Furthermore catalog magnitudes are compared to moment magnitudes estimated during the inversion process. Additionally site amplification factors of the stations are presented.

  3. Neuromodulation targets intrinsic cardiac neurons to attenuate neuronally mediated atrial arrhythmias.

    PubMed

    Gibbons, David D; Southerland, E Marie; Hoover, Donald B; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L

    2012-02-01

    Our objective was to determine whether atrial fibrillation (AF) results from excessive activation of intrinsic cardiac neurons (ICNs) and, if so, whether select subpopulations of neurons therein represent therapeutic targets for suppression of this arrhythmogenic potential. Trains of five electrical stimuli (0.3-1.2 mA, 1 ms) were delivered during the atrial refractory period to mediastinal nerves (MSN) on the superior vena cava to evoke AF. Neuroanatomical studies were performed by injecting the neuronal tracer DiI into MSN sites that induced AF. Functional studies involved recording of neuronal activity in situ from the right atrial ganglionated plexus (RAGP) in response to MSN stimulation (MSNS) prior to and following neuromodulation involving either preemptive spinal cord stimulation (SCS; T(1)-T(3), 50 Hz, 200-ms duration) or ganglionic blockade (hexamethonium, 5 mg/kg). The tetramethylindocarbocyanine perchlorate (DiI) neuronal tracer labeled a subset (13.2%) of RAGP neurons, which also colocalized with cholinergic or adrenergic markers. A subset of DiI-labeled RAGP neurons were noncholinergic/nonadrenergic. MSNS evoked an ∼4-fold increase in RAGP neuronal activity from baseline, which SCS reduced by 43%. Hexamethonium blocked MSNS-evoked increases in neuronal activity. MSNS evoked AF in 78% of right-sided MSN sites, which SCS reduced to 33% and hexamethonium reduced to 7%. MSNS-induced bradycardia was maintained with SCS but was mitigated by hexamethonium. We conclude that MSNS activates subpopulations of intrinsic cardiac neurons, thereby resulting in the formation of atrial arrhythmias leading to atrial fibrillation. Stabilization of ICN local circuit neurons by SCS or the local circuit and autonomic efferent neurons with hexamethonium reduces the arrhythmogenic potential.

  4. Premature terminator analysis sheds light on a hidden world of bacterial transcriptional attenuation.

    PubMed

    Naville, Magali; Gautheret, Daniel

    2010-01-01

    Bacterial transcription attenuation occurs through a variety of cis-regulatory elements that control gene expression in response to a wide range of signals. The signal-sensing structures in attenuators are so diverse and rapidly evolving that only a small fraction have been properly annotated and characterized to date. Here we apply a broad-spectrum detection tool in order to achieve a more complete view of the transcriptional attenuation complement of key bacterial species. Our protocol seeks gene families with an unusual frequency of 5' terminators found across multiple species. Many of the detected attenuators are part of annotated elements, such as riboswitches or T-boxes, which often operate through transcriptional attenuation. However, a significant fraction of candidates were not previously characterized in spite of their unmistakable footprint. We further characterized some of these new elements using sequence and secondary structure analysis. We also present elements that may control the expression of several non-homologous genes, suggesting co-transcription and response to common signals. An important class of such elements, which we called mobile attenuators, is provided by 3' terminators of insertion sequences or prophages that may be exapted as 5' regulators when inserted directly upstream of a cellular gene. We show here that attenuators involve a complex landscape of signal-detection structures spanning the entire bacterial domain. We discuss possible scenarios through which these diverse 5' regulatory structures may arise or evolve.

  5. Physical and biogeochemical controls on light attenuation in a eutrophic, back-barrier estuary

    USGS Publications Warehouse

    Ganju, Neil K.; Miselis, Jennifer L.; Aretxabaleta, Alfredo L.

    2014-01-01

    Light attenuation is a critical parameter governing the ecological function of shallow estuaries. In these systems primary production is often dominated by benthic macroalgae and seagrass; thus light penetration to the bed is of primary importance. We quantified light attenuation in three seagrass meadows in Barnegat Bay, New Jersey, a shallow eutrophic back-barrier estuary; two of the sites were located within designated Ecologically Sensitive Areas (ESAs). We sequentially deployed instrumentation measuring photosynthetically active radiation, chlorophyll-a (chl-a) fluorescence, dissolved organic matter fluorescence (fDOM; a proxy for colored DOM absorbance), turbidity, pressure, and water velocity at 10 min intervals over three week periods at each site. At the southernmost site, where sediment availability was highest, light attenuation was highest and dominated by turbidity and to a lesser extent chl-a and CDOM. At the central site, chl-a dominated followed by turbidity and CDOM, and at the northernmost site turbidity and CDOM contributed equally to light attenuation. At a given site, the temporal variability of light attenuation exceeded the difference in median light attenuation at the three sites, indicating the need for continuous high-temporal resolution measurements. Vessel wakes, anecdotally implicated in increasing sediment resuspension, did not contribute to local resuspension within the seagrass beds, though frequent vessel wakes were observed in the channels. With regards to light attenuation and water clarity, physical and biogeochemical variables appear to outweigh any regulation of boat traffic within the ESAs.

  6. Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity

    PubMed Central

    Khan, Md. Abdul Hye; Liu, Jing; Kumar, Ganesh; Skapek, Stephen X.; Falck, John R.; Imig, John D.

    2013-01-01

    Nephrotoxicity severely limits the use of the anticancer drug cisplatin. Oxidative stress, inflammation, and endoplasmic reticulum (ER) stress contribute to cisplatin-induced nephrotoxicity. We developed novel orally active epoxyeicosatrienoic acid (EET) analogs and investigated their prophylactic effect in cisplatin-induced nephrotoxicity in rats. Cisplatin-induced nephrotoxicity was manifested by increases in blood urea nitrogen, plasma creatinine, urinary N-acetyl-β-(d)-glucosaminidase activity, kidney injury molecule 1, and histopathology. EET analogs (10 mg/kg/d) attenuated cisplatin-induced nephrotoxicity by reducing these renal injury markers by 40–80% along with a 50–70% reduction in renal tubular cast formation. This attenuated renal injury is associated with reduced oxidative stress, inflammation, and ER stress evident from reduction in related biomarkers and in the renal expression of genes involved in these pathways. Moreover, we demonstrated that the attenuated nephrotoxicity correlated with decreased apoptosis that is associated with 50–90% reduction in Bcl-2 protein family mediated proapoptotic signaling, reduced renal caspase-12 expression, and a 50% reduction in renal caspase-3 activity. We further demonstrated in vitro that the protective activity of EET analogs does not compromise the anticancer effects of cisplatin. Collectively, our data provide evidence that EET analogs attenuate cisplatin-induced nephrotoxicity by reducing oxidative stress, inflammation, ER stress, and apoptosis without affecting the chemotherapeutic effects of cisplatin.—Khan, Md. A. H., Liu, J., Kumar, G., Skapek, S. X., Falck, J. R., Imig, J. D. Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity. PMID:23603837

  7. Characterization of Rain Attenuation and Depolarization at W/V Bands

    DTIC Science & Technology

    2017-03-22

    attenuation and research into antennas that operate at these frequencies are in relative infancy compared to the more commonly used bands. This effort...atmospheric attenuation and research into antennas that operate at these frequencies are in relative infancy compared to the more commonly used bands...UNLIMITED. AIR FORCE RESEARCH LABORATORY Space Vehicles Directorate 3550 Aberdeen Ave SE AIR FORCE MATERIEL COMMAND KIRTLAND AIR FORCE BASE, NM 87117

  8. Remediation by Natural Attenuation Treatability Study for Operable Unit 5

    DTIC Science & Technology

    1997-12-01

    remaining as a result of all attenuation processes is equivalent to the fraction of contaminant remaining as a result of non - destructive attenuation...Alternative 1-- RNA Combined with LTM, Institutional Controls , Air Sparging Along Main Street, and Groundwater Extraction and Treatment Near Well Pair MW137...MW138 .............................. 6-4 6.3.2 Alternative 2 -- RNA, LTM, Institutional Controls , Air Sparging along Main Street, Groundwater

  9. Attenuation of Cisplatin-Induced Renal Injury by Inhibition of Soluble Epoxide Hydrolase Involves Nuclear Factor κB Signaling

    PubMed Central

    Liu, Yingmei; Webb, Heather K.; Fukushima, Hisayo; Micheli, Janine; Markova, Svetlana; Olson, Jean L.

    2012-01-01

    Acute kidney injury is associated with a significant inflammatory response that has been the target of renoprotection strategies. Epoxyeicosatrienoic acids (EETs) are anti-inflammatory cytochrome P450-derived eicosanoids that are abundantly produced in the kidney and metabolized by soluble epoxide hydrolase (sEH; Ephx2) to less active dihydroxyeicosatrienoic acids. Genetic disruption of Ephx2 and chemical inhibition of sEH were used to test whether the anti-inflammatory effects of EETs, and other lipid epoxide substrates of sEH, afford protection against cisplatin-induced nephrotoxicity. EET hydrolysis was significantly reduced in Ephx2(−/−) mice and was associated with an attenuation of cisplatin-induced increases in serum urea nitrogen and creatinine levels. Histological evidence of renal tubular damage and neutrophil infiltration was also reduced in the Ephx2(−/−) mice. Likewise, cisplatin had no effect on renal function, neutrophil infiltration, or tubular structure and integrity in mice treated with the potent sEH inhibitor 1-adamantan-1-yl-3-(1-methylsulfonyl-piperidin-4-yl-urea) (AR9273). Consistent with the ability of EETs to interfere with nuclear factor-κB (NF-κB) signaling, the observed renoprotection was associated with attenuation of renal NF-κB activity and corresponding decreases in the expression of tumor necrosis factor (TNF) α, TNF receptor (TNFR) 1, TNFR2, and intercellular adhesive molecule-1 before the detection of tubular injury. These data suggest that EETs or other fatty acid epoxides can attenuate cisplatin-induced kidney injury and sEH inhibition is a novel renoprotective strategy. PMID:22414856

  10. A Global Upper-Mantle Tomographic Model of Shear Attenuation

    NASA Astrophysics Data System (ADS)

    Karaoglu, H.; Romanowicz, B. A.

    2016-12-01

    Mapping anelastic 3D structure within the earth's mantle is key to understanding present day mantle dynamics, as it provides complementary constraints to those obtained from elastic structure, with the potential to distinguish between thermal and compositional heterogeneity. For this, we need to measure seismic wave amplitudes, which are sensitive to both elastic (through focusing and scattering) and anelastic structure. The elastic effects are less pronounced at long periods, so previous global upper-mantle attenuation models are based on teleseismic surface wave data, sometimes including overtones. In these studies, elastic effects are considered either indirectly, by eliminating data strongly contaminated by them (e.g. Romanowicz, 1995; Gung and Romanowicz, 2004), or by correcting for elastic focusing effects using an approximate linear approach (Dalton et al., 2008). Additionally, in these studies, the elastic structure is held fixed when inverting for intrinsic attenuation . The importance of (1) having a good starting elastic model, (2) accurate modeling of the seismic wavefield and (3) joint inversion for elastic and anelastic structure, becomes more evident as the targeted resolution level increases. Also, velocity dispersion effects due to anelasticity need to be taken into account. Here, we employ a hybrid full waveform inversion method, inverting jointly for global elastic and anelastic upper mantle structure, starting from the latest global 3D shear velocity model built by our group (French and Romanowicz, 2014), using the spectral element method for the forward waveform modeling (Capdeville et al., 2003), and normal-mode perturbation theory (NACT - Li and Romanowicz, 1995) for kernel computations. We present a 3D upper-mantle anelastic model built by using three component fundamental and overtone surface waveforms down to 60 s as well as long period body waveforms down to 30 s. We also include source and site effects to first order as frequency

  11. An investigation of hydraulic-line resonance and its attenuation

    NASA Technical Reports Server (NTRS)

    Sewall, J. L.; Wineman, D. A.; Herr, R. W.

    1973-01-01

    An investigation of fluid resonance in high-pressure hydraulic lines has been made with two types of fluid dampers (or filters) installed in the line. One type involved the use of one or more closed-end tubes branching at right angles from a main line, and the other type was a fluid muffler installed in-line. These devices were evaluated in forced vibration tests with oscillatory disturbances over a 1000-Hz range applied to one end of the line and with oscillatory pressures measured at various stations along the main pipe. Limited applications of acoustic-wave theory to the branched systems are also included. Results show varying attenuations of pressure perturbations, depending on the number and location of branches and the type of muffler. Up to three branches were used in the branch-resonator study, and the largest frequency range with maximum attenuation was obtained for a three-branch configuration. The widest frequency ranges with significant attenuations were obtained with two types of fluid mufflers.

  12. Wave attenuation in the marginal ice zone during LIMEX

    NASA Technical Reports Server (NTRS)

    Liu, Antony K.; Vachon, Paris W.; Peng, Chih Y.; Bhogal, A. S.

    1992-01-01

    The effect of ice cover on ocean-wave attenuation is investigated for waves under flexure in the marginal ice zone (MIZ) with SAR image spectra and the results of models. Directional wavenumber spectra are taken from the SAR image data, and the wave-attenuation rate is evaluated with SAR image spectra and by means of the model by Liu and Mollo-Christensen (1988). Eddy viscosity is described by means of dimensional analysis as a function of ice roughness and wave-induced velocity, and comparisons are made with the remotely sensed data. The model corrects the open-water model by introducing the effects of a continuous ice sheet, and turbulent eddy viscosity is shown to depend on ice thickness, floe sizes, significant wave height, and wave period. SAR and wave-buoy data support the trends described in the model results, and a characteristic rollover is noted in the model and experimental wave-attenuation rates at high wavenumbers.

  13. Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain

    PubMed Central

    Li, Zhe; Tseng, Pang-Yen; Tiwari, Vinod; Xu, Qian; He, Shao-Qiu; Wang, Yan; Zheng, Qin; Han, Liang; Wu, Zhiping; Blobaum, Anna L.; Cui, Yiyuan; Tiwari, Vineeta; Sun, Shuohao; Cheng, Yingying; Huang-Lionnet, Julie H. Y.; Geng, Yixun; Xiao, Bo; Peng, Junmin; Hopkins, Corey; Raja, Srinivasa N.; Guan, Yun; Dong, Xinzhong

    2017-01-01

    Human Mas-related G protein-coupled receptor X1 (MRGPRX1) is a promising target for pain inhibition, mainly because of its restricted expression in nociceptors within the peripheral nervous system. However, constrained by species differences across Mrgprs, drug candidates that activate MRGPRX1 do not activate rodent receptors, leaving no responsive animal model to test the effect on pain in vivo. Here, we generated a transgenic mouse line in which we replaced mouse Mrgprs with human MrgprX1. This humanized mouse allowed us to characterize an agonist [bovine adrenal medulla 8–22 (BAM8–22)] and a positive allosteric modulator (PAM), ML382, of MRGPRX1. Cellular studies suggested that ML382 enhances the ability of BAM8–22 to inhibit high-voltage-activated Ca2+ channels and attenuate spinal nociceptive transmission. Importantly, both BAM8–22 and ML382 effectively attenuated evoked, persistent, and spontaneous pain without causing obvious side effects. Notably, ML382 by itself attenuated both evoked pain hypersensitivity and spontaneous pain in MrgprX1 mice after nerve injury without acquiring coadministration of an exogenous agonist. Our findings suggest that humanized MrgprX1 mice provide a promising preclinical model and that activating MRGPRX1 is an effective way to treat persistent pain. PMID:28223516

  14. Comparison of RNFL thickness and RPE-normalized RNFL attenuation coefficient for glaucoma diagnosis

    NASA Astrophysics Data System (ADS)

    Vermeer, K. A.; van der Schoot, J.; Lemij, H. G.; de Boer, J. F.

    2013-03-01

    Recently, a method to determine the retinal nerve fiber layer (RNFL) attenuation coefficient, based on normalization on the retinal pigment epithelium, was introduced. In contrast to conventional RNFL thickness measures, this novel measure represents a scattering property of the RNFL tissue. In this paper, we compare the RNFL thickness and the RNFL attenuation coefficient on 10 normal and 8 glaucomatous eyes by analyzing the correlation coefficient and the receiver operator curves (ROCs). The thickness and attenuation coefficient showed moderate correlation (r=0.82). Smaller correlation coefficients were found within normal (r=0.55) and glaucomatous (r=0.48) eyes. The full separation between normal and glaucomatous eyes based on the RNFL attenuation coefficient yielded an area under the ROC (AROC) of 1.0. The AROC for the RNFL thickness was 0.9875. No statistically significant difference between the two measures was found by comparing the AROC. RNFL attenuation coefficients may thus replace current RNFL thickness measurements or be combined with it to improve glaucoma diagnosis.

  15. Simultaneous source and attenuation reconstruction in SPECT using ballistic and single scattering data

    NASA Astrophysics Data System (ADS)

    Courdurier, M.; Monard, F.; Osses, A.; Romero, F.

    2015-09-01

    In medical single-photon emission computed tomography (SPECT) imaging, we seek to simultaneously obtain the internal radioactive sources and the attenuation map using not only ballistic measurements but also first-order scattering measurements and assuming a very specific scattering regime. The problem is modeled using the radiative transfer equation by means of an explicit non-linear operator that gives the ballistic and scattering measurements as a function of the radioactive source and attenuation distributions. First, by differentiating this non-linear operator we obtain a linearized inverse problem. Then, under regularity hypothesis for the source distribution and attenuation map and considering small attenuations, we rigorously prove that the linear operator is invertible and we compute its inverse explicitly. This allows proof of local uniqueness for the non-linear inverse problem. Finally, using the previous inversion result for the linear operator, we propose a new type of iterative algorithm for simultaneous source and attenuation recovery for SPECT based on the Neumann series and a Newton-Raphson algorithm.

  16. Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.

    PubMed

    Bex, Axel; Fournier, Laure; Lassau, Nathalie; Mulders, Peter; Nathan, Paul; Oyen, Wim J G; Powles, Thomas

    2014-04-01

    The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects

  17. Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils.

    PubMed

    Zhou, J; Zhang, H Y; Tang, X C

    2001-11-09

    The protective effects of huperzine A on transient global ischemia in gerbils were investigated. Five min of global ischemia in gerbils results in working memory impairments shown by increased escape latency in a water maze and reduced time spent in the target quadrant. These signs of dysfunction are accompanied by delayed degeneration of pyramidal hippocampal CA1 neurons and by decrease in acetylcholinesterase activity in the hippocampus. Subchronic oral administration of huperzine A (0.1 mg/kg, twice per day for 14 days) after ischemia significantly reduced the memory impairment, reduced neuronal degeneration in the CA1 region, and partially restored hippocampal choline acetyltransferase activity. The ability of huperzine A to attenuate memory deficits and neuronal damage after ischemia might be beneficial in cerebrovascular type dementia.

  18. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect?

    PubMed

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

    2017-06-01

    There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with less severe symptoms and better psychosocial functioning than presentation in childhood or younger adolescence. Ninety-four CAD (age 9-18) meeting Attenuated Psychosis Syndrome criteria participated in the study. The sample was divided and compared according to the age of presentation of Attenuated Psychosis Syndrome (9-14 vs 15-18 years). The predictive value of age of Attenuated Psychosis Syndrome presentation was investigated using receiver operating characteristic (ROC)-curve calculations. The two Attenuated Psychosis Syndrome groups were homogeneous in terms of gender distribution, IQ scores and comorbid diagnoses. Older Attenuated Psychosis Syndrome patients showed better functioning and lower depressive scores. ROC curves revealed that severity of functional impairment was best predicted using an age of presentation cut-off of 14.9 years for social functioning and 15.9 years for role functioning. This study partially confirmed our hypothesis; older age at presentation of Attenuated Psychosis Syndrome was associated with less functional impairment, but age was not associated with psychotic symptoms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Intensity, magnitude, location and attenuation in India for felt earthquakes since 1762

    USGS Publications Warehouse

    Szeliga, Walter; Hough, Susan; Martin, Stacey; Bilham, Roger

    2010-01-01

    A comprehensive, consistently interpreted new catalog of felt intensities for India (Martin and Szeliga, 2010, this issue) includes intensities for 570 earthquakes; instrumental magnitudes and locations are available for 100 of these events. We use the intensity values for 29 of the instrumentally recorded events to develop new intensity versus attenuation relations for the Indian subcontinent and the Himalayan region. We then use these relations to determine the locations and magnitudes of 234 historical events, using the method of Bakun and Wentworth (1997). For the remaining 336 events, intensity distributions are too sparse to determine magnitude or location. We evaluate magnitude and location accuracy of newly located events by comparing the instrumental- with the intensity-derived location for 29 calibration events, for which more than 15 intensity observations are available. With few exceptions, most intensity-derived locations lie within a fault length of the instrumentally determined location. For events in which the azimuthal distribution of intensities is limited, we conclude that the formal error bounds from the regression of Bakun and Wentworth (1997) do not reflect the true uncertainties. We also find that the regression underestimates the uncertainties of the location and magnitude of the 1819 Allah Bund earthquake, for which a location has been inferred from mapped surface deformation. Comparing our inferred attenuation relations to those developed for other regions, we find that attenuation for Himalayan events is comparable to intensity attenuation in California (Bakun and Wentworth, 1997), while intensity attenuation for cratonic events is higher than intensity attenuation reported for central/eastern North America (Bakun et al., 2003). Further, we present evidence that intensities of intraplate earthquakes have a nonlinear dependence on magnitude such that attenuation relations based largely on small-to-moderate earthquakes may significantly

  20. Intensity, magnitude, location, and attenuation in India for felt earthquakes since 1762

    USGS Publications Warehouse

    Szeliga, W.; Hough, S.; Martin, S.; Bilham, R.

    2010-01-01

    A comprehensive, consistently interpreted new catalog of felt intensities for India (Martin and Szeliga, 2010, this issue) includes intensities for 570 earth-quakes; instrumental magnitudes and locations are available for 100 of these events. We use the intensity values for 29 of the instrumentally recorded events to develop new intensity versus attenuation relations for the Indian subcontinent and the Himalayan region. We then use these relations to determine the locations and magnitudes of 234 historical events, using the method of Bakun and Wentworth (1997). For the remaining 336 events, intensity distributions are too sparse to determine magnitude or location. We evaluate magnitude and location accuracy of newly located events by comparing the instrumental-with the intensity-derived location for 29 calibration events, for which more than 15 intensity observations are available. With few exceptions, most intensity-derived locations lie within a fault length of the instrumentally determined location. For events in which the azimuthal distribution of intensities is limited, we conclude that the formal error bounds from the regression of Bakun and Wentworth (1997) do not reflect the true uncertainties. We also find that the regression underestimates the uncertainties of the location and magnitude of the 1819 Allah Bund earthquake, for which a location has been inferred from mapped surface deformation. Comparing our inferred attenuation relations to those developed for other regions, we find that attenuation for Himalayan events is comparable to intensity attenuation in California (Bakun and Wentworth, 1997), while intensity attenuation for cratonic events is higher than intensity attenuation reported for central/eastern North America (Bakun et al., 2003). Further, we present evidence that intensities of intraplate earth-quakes have a nonlinear dependence on magnitude such that attenuation relations based largely on small-to-moderate earthquakes may significantly