Sample records for attenuates sulindac sulfide-mediated

  1. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

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    Bai Han


    Full Text Available Abstract Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID, on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

  2. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

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    Christopher S. Williams


    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  3. Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells. (United States)

    Horinaka, Mano; Yoshida, Tatsushi; Tomosugi, Mitsuhiro; Yasuda, Shusuke; Sowa, Yoshihiro; Sakai, Toshiyuki


    A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of DR5 by sulindac sulfide. Sulindac sulfide induced the expression of DR5 at the protein and mRNA levels in colon cancer SW480 cells. Furthermore, sulindac sulfide increased DR5 promoter activity. We showed that sulindac sulfide stimulated DR5 promoter activity via the -301 to -253 region. This region contained a putative MZF1-binding site. Site-directed mutations in the site abrogated the enhancement in DR5 promoter activity by sulindac sulfide. MZF1 directly bound to the putative MZF1-binding site of the DR5 promoter and the binding was increased by sulindac sulfide. The expression of MZF1 was also increased by sulindac sulfide, and MZF1 siRNA attenuated the upregulation of DR5 by sulindac sulfide. These results indicate that sulindac sulfide induces the expression of DR5 by up-regulating MZF1.

  4. Compound list: sulindac [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available sulindac SUL 00100 ...

  5. Sulindac attenuates valproic acid-induced oxidative stress levels in primary cultured cortical neurons and ameliorates repetitive/stereotypic-like movement disorders in Wistar rats prenatally exposed to valproic acid. (United States)

    Zhang, Yinghua; Yang, Cailing; Yuan, Guoyan; Wang, Zhongping; Cui, Weigang; Li, Ruixi


    Accumulating evidence suggests that anti-inflammatory agents and antioxidants have neuroprotective properties and may be beneficial in the treatment of neurodevelopental disorders, such as autism. In the present study, the possible neuroprotective properties of sulindac, a non-steroidal anti-inflammatory drug (NSAID), were investigated in vitro using cultured cortical neurons with valproic acid (VPA)-induced neurotoxicity, as well as in vivo through the behavioral analysis of rats prenatally exposed to VPA as a model of autism. VPA induced 4-hydroxynonenal (4-HNE) expression, reactive oxygen species (ROS) generation and decreased cell viability in primary cultured cortical neurons established from timed-pregnant (embryonic day 18) Wistar rat pups. However, co-incubation of the neurons with VPA and sulindac reduced oxidative stress and increased cell viability. The rats were administered an intraperitoneal injection with one of the following: VPA, sulindac, VPA and sulindac, or physiological saline, and their offspring were subjected to the open field test. During the test trials, repetitive/stereotypic-like movements for each rat were recorded and analyzed. The results revealed that treatment with both sulindac and VPA reduced the VPA-induced repetitive/stereotypic-like activity and the sulindac and VPA-treated animals responded better in the open field test compared to the VPA-treated animals. The results from the present study demonstrate that the antioxidant properties of sulindac may prove to be beneficial in the treatment of autism, suggesting that the upregulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and facilitates susceptibility to autism.

  6. Sulindac has strong antifibrotic effects by suppressing STAT3-related miR-21. (United States)

    Zhou, Xue; Li, You-Jie; Gao, Shu-Yan; Wang, Xiao-Zhi; Wang, Ping-Yu; Yan, Yun-Fei; Xie, Shu-Yang; Lv, Chang-Jun


    Pulmonary fibrosis (PF) is a disease with an unknown cause and a poor prognosis. In this study, we aimed to explore the pathogenesis of PF and the mechanism of sulindac in attenuating bleomycin (BLM)-induced PF. The rat PF model was induced by BLM and verified through histological studies and hydroxyproline assay. The severity of BLM-induced PF in rats and other effects, such as the extent of the wet lung to bw ratios, thickening of alveolar interval or collagen deposition, was obviously ameliorated in sulindac-treated rat lungs compared with BLM-induced lungs. Sulindac also reversed the epithelial mesenchymal transition (EMT) and inhibited the PF process by restoring the levels of E-cadherin and α-smooth muscle actin (SMA) in A549 cells. Our results further demonstrated that the above effects of sulindac might be related to regulating of interferon gamma (IFN-γ) expression, which further affects signal transducers and activators of transcription 3 (STAT3) and phosphorylated STAT3 (p-STAT3) levels. Moreover, higher miR-21 levels with the decreased E-cadherin and increased α-SMA expressions were found in transforming growth factor-β1-treated A549 cells, which can be reversed by sulindac. Collectively, our results demonstrate that by decreasing IFN-γ-induced STAT3/p-STAT3 expression to down-regulate miR-21, sulindac could significantly reverse EMT in A549 cells and prevent BLM-induced PF.

  7. Sulindac and its metabolites: sulindac sulfide and sulindac sulfone enhance cytotoxic effects of arsenic trioxide on leukemic cell lines. (United States)

    Stępnik, Maciej; Ferlińska, Magdalena; Smok-Pieniążek, Anna; Gradecka-Meesters, Dobrosława; Arkusz, Joanna; Stańczyk, Małgorzata


    The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200 μM) with SS being the most cytotoxic (72 h WST-1 reduction test). The cytotoxicity of ATO was enhanced by combination with sulindacs. The combination of ATO (1 μM) with SS or SF at concentrations over 50 μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48 h to the combinations showed smaller decrease in viability. Measurements of Jurkat, HL-60 and K562 cells exposed to ATO (1 μM) and sulindacs (100 μM or 200 μM for K562 cells) indicated apoptosis as the main cell death mechanism. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.

  8. Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice. (United States)

    Bravi, Luca; Rudini, Noemi; Cuttano, Roberto; Giampietro, Costanza; Maddaluno, Luigi; Ferrarini, Luca; Adams, Ralf H; Corada, Monica; Boulday, Gwenola; Tournier-Lasserve, Elizabeth; Dejana, Elisabetta; Lampugnani, Maria Grazia


    Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences. At present, the only recommended treatment of CCM is surgical. Because surgery is often not applicable, pharmacological treatment would be highly desirable. We describe here a murine model of the disease that develops after endothelial-cell-selective ablation of the CCM3 gene. We report an early, cell-autonomous, Wnt-receptor-independent stimulation of β-catenin transcription activity in CCM3-deficient endothelial cells both in vitro and in vivo and a triggering of a β-catenin-driven transcription program that leads to endothelial-to-mesenchymal transition. TGF-β/BMP signaling is then required for the progression of the disease. We also found that the anti-inflammatory drugs sulindac sulfide and sulindac sulfone, which attenuate β-catenin transcription activity, reduce vascular malformations in endothelial CCM3-deficient mice. This study opens previously unidentified perspectives for an effective pharmacological therapy of intracranial vascular cavernomas.

  9. A novel sulindac derivative lacking cyclooxygenase-inhibitory activities suppresses carcinogenesis in the transgenic adenocarcinoma of mouse prostate model. (United States)

    Zhang, Yong; Zhang, Jinhui; Wang, Lei; Quealy, Emily; Gary, Bernard D; Reynolds, Robert C; Piazza, Gary A; Lü, Junxuan


    Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX)-inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX-independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N-dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G(1) arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis.

  10. Sulindac induces apoptosis and protects against colon carcinoma in mice

    Institute of Scientific and Technical Information of China (English)

    Bao-Cun Sun; Xiu-Lan Zhao; Shi-Wu Zhang; Yi-Xin Liu; Lan Wang; Xin Wang


    AIM: To study the effect of sulindac on colon cancer induction in mice.METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL)technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena.RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%,and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H= 33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet. CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.

  11. Topical sulindac therapy in diabetic senile cataracts : cataract IV

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    Sharma Y


    Full Text Available Sulindac, a non-steroidal anti-inflammatory drug has been found to be a potent inhibitor of enzyme aldose reductase. We used sulindac topically in diabetic senile cataract patients to note if it effects the progression of cataracts. More of sulindac treated eyes maintained initial vision and fewer eyes had visual loss of up to two lines or more as compared to control eyes. The extent and density of different opacities showed less progression in sulindac treated eyes but it was not statistically significant except that the ophthalmoscopically observed density of opacity showed statistically very significant lesser mean increase in sulindac treated eyes. We suggest that sulindac is a potential drug which should be further evaluated in large double blind photodocumented studies in diabetic senile cataracts.

  12. Sulindac Prevents Esophageal Adenocarcinomas Induced by Gastroduodenal Reflux in Rats


    Kim, Sung Wook; Jang, Tae Jung; Jung, Ki Hoon; Suh, Jung Il


    Purpose It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). Materials and Methods Fifty-one rats were divided into a control group (n = 27), a 500 ppm sulindac-treated group (n = 15) and 1000 ppm sulindac-treated group (n = 9). Randomly selected rats were...

  13. Aerosol administration of phospho-sulindac inhibits lung tumorigenesis. (United States)

    Cheng, Ka Wing; Wong, Chi C; Alston, Ninche; Mackenzie, Gerardo G; Huang, Liqun; Ouyang, Nengtai; Xie, Gang; Wiedmann, Timothy; Rigas, Basil


    Phospho-sulindac is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of phospho-sulindac might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of phospho-sulindac and evaluated the antitumor efficacy of inhaled phospho-sulindac in an orthotopic model of human non-small cell lung cancer (A549 cells). We found that administration by inhalation delivered high levels of phospho-sulindac to the lungs and minimized its hydrolysis to less active metabolites. Consequently, inhaled phospho-sulindac (6.5 mg/kg) was highly effective in inhibiting lung tumorigenesis (75%; P sulindac suppressed lung tumorigenesis by (i) inhibiting EGF receptor (EGFR) activation, leading to profound inhibition of Raf/MEK/ERK and PI3K/AKT/mTOR survival cascades; (ii) inducing oxidative stress, which provokes the collapse of mitochondrial membrane potential and mitochondria-dependent cell death; and (iii) inducing autophagic cell death. Our data establish that inhalation delivery of phospho-sulindac is an efficacious approach to the control of lung cancer, which merits further evaluation.

  14. Sulindac Sulfide Differentially Induces Apoptosis in Smac-Proficient and -Deficient Human Colon Cancer Cells


    Shi, Jingxue; He, Qin; An, Jie; Sun, Hong; Huang, Ying; Sheikh, M. Saeed


    Sulindac, the non-steroidal anti-inflammatory drug has shown promise in the prevention of colon cancer but the molecular mechanisms by which it mediates such effects remain to be elucidated. Sulindac sulfide is the major active metabolite of sulindac and believed to be responsible for mediating the effects of sulindac. Previously, our group and others have shown that sulindac sulfide induces apoptosis by engaging death receptor and mitochondrial pathways and that a cross-talk exists between t...

  15. Sulindac sulfide suppresses 5-lipoxygenase at clinically relevant concentrations. (United States)

    Steinbrink, Svenja D; Pergola, Carlo; Bühring, Ulrike; George, Sven; Metzner, Julia; Fischer, Astrid S; Häfner, Ann-Kathrin; Wisniewska, Joanna M; Geisslinger, Gerd; Werz, Oliver; Steinhilber, Dieter; Maier, Thorsten J


    Sulindac is a non-selective inhibitor of cyclooxygenases (COX) used to treat inflammation and pain. Additionally, non-COX targets may account for the drug's chemo-preventive efficacy against colorectal cancer and reduced gastrointestinal toxicity. Here, we demonstrate that the pharmacologically active metabolite of sulindac, sulindac sulfide (SSi), targets 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes (LTs). SSi inhibited 5-LO in ionophore A23187- and LPS/fMLP-stimulated human polymorphonuclear leukocytes (IC(50) approximately 8-10 microM). Importantly, SSi efficiently suppressed 5-LO in human whole blood at clinically relevant plasma levels (IC(50) = 18.7 microM). SSi was 5-LO-selective as no inhibition of related lipoxygenases (12-LO, 15-LO) was observed. The sulindac prodrug and the other metabolite, sulindac sulfone (SSo), failed to inhibit 5-LO. Mechanistic analysis demonstrated that SSi directly suppresses 5-LO with an IC(50) of 20 muM. Together, these findings may provide a novel molecular basis to explain the COX-independent pharmacological effects of sulindac under therapy.

  16. Sulindac sulfide inhibits colon cancer cell growth and downregulates specificity protein transcription factors


    Li, Xi; Pathi, Satya S.; Safe, Stephen


    Background Specificity protein (Sp) transcription factors play pivotal roles in maintaining the phenotypes of many cancers. We hypothesized that the antineoplastic effects of sulindac and its metabolites were due, in part, to targeting downregulation of Sp transcription factors. Methods The functional effects of sulindac, sulindac sulfone and sulindac sulfide on colon cancer cell proliferation were determined by cell counting. Effects of these compounds on expression of Sp1, Sp3, Sp4 and pro-...

  17. The role of NAG-1/GDF15 in the inhibition of intestinal polyps in APC/Min mice by sulindac. (United States)

    Wang, Xingya; Kingsley, Philip J; Marnett, Larry J; Eling, Thomas E


    The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its prodrug DM-sulindac] that do not inhibit COX-2 activity. Sulindac sulfide and DM-sulindac induced the expression of NAG-1/GDF15 in HCT116 cells as determined by quantitative real-time PCR and Western blot. We fed APC/Min mice with 320 ppm of sulindac and doses of DM-sulindac. Only sulindac significantly inhibited tumor formation inAPC/Min mice. To determine the pharmacokinetic properties of sulindac and DM-sulindac in vivo, wild-type C57/B6 mice were fed with sulindac and DM-sulindac at 80, 160, and 320 ppm. High-performance liquid chromatography analysis revealed that the conversion of DM-sulindac to DM-sulindac sulfide (active form) was less efficient than the conversion of sulindac to sulindac sulfide (active form) in the mice. Lower levels of DM-sulindac sulfide accumulated in intestinal and colon tissues in comparison with sulindac sulfide. In addition, NAG-1/GDF15 was induced in the liver of sulindac-fed mice but not in the DM-sulindac-fed mice. Collectively, our results suggest that the tumor-inhibitory effects of sulindac in APC/Min mice may be due to, in part, NAG-1/GDF15 induction in the liver. Our study also suggests that pharmacologic properties should be carefully evaluated when developing drug candidates.

  18. Sulindac metabolites inhibit epidermal growth factor receptor activation and expression

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    Pangburn Heather A


    Full Text Available Abstract Background Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs is associated with a decreased mortality from colorectal cancer (CRC. NSAIDs induce apoptotic cell death in colon cancer cells in vitro and inhibit growth of neoplastic colonic mucosa in vivo however, the biochemical mechanisms required for these growth inhibitory effects are not well defined. We previously reported that metabolites of the NSAID sulindac downregulate extracellular-signal regulated kinase 1/2 (ERK1/2 signaling and that this effect is both necessary and sufficient for the apoptotic effects of these drugs. The goal of this project was to specifically test the hypothesis that sulindac metabolites block activation and/or expression of the epidermal growth factor (EGF receptor (EGFR. Methods HT29 human colon cancer cells were treated with EGF, alone, or in the presence of sulindac sulfide or sulindac sulfone. Cells lysates were assayed by immunoblotting for phosphorylated EGFR (pEGFR, pY1068, total EGFR, phosphorylated ERK1/2 (pERK1/2, total ERK1/2, activated caspase-3, and α-tubulin. Results EGF treatment rapidly induced phosphorylation of both EGFR and ERK1/2 in HT29 colon cancer cells. Pretreatment with sulindac metabolites for 24 h blocked EGF-induced phosphorylation of both EGFR and ERK1/2 and decreased total EGFR protein expression. Under basal conditions, downregulation of pEGFR and total EGFR was detected as early as 12 h following sulindac sulfide treatment and persisted through at least 48 h. Sulindac sulfone induced downregulation of pEGFR and total EGFR was detected as early as 1 h and 24 h, respectively, following drug treatment, and persisted through at least 72 h. EGFR downregulation by sulindac metabolites was observed in three different CRC cell lines, occurred prior to the observed downregulation of pERK1/2 and induction of apoptosis by these drugs, and was not dependent of caspase activation. Conclusion These results suggest that

  19. Sulindac and Sulindac Metabolites in Nipple Aspirate Fluid and Effect on Drug Targets in a Phase I Trial


    Thompson, Patricia A.; Hsu, Chiu-Hsieh; Green, Sylvan; Stopeck, Alison T.; Johnson, Karen; Alberts, David S.; Chow, H.-H. Sherry


    Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of breast cancer. Sulindac, a non-selective NSAID with both cyclooxygenase 2 (COX2) dependent and independent activities, is a candidate for breast chemoprevention. We conducted a Phase Ib trial in 30 women at increased risk for breast cancer to evaluate the breast tissue distribution of sulindac at two dose levels (150 mg q.d. and 150 mg b.i.d. for 6 weeks), using nipple aspirate fluid (NAF) as...

  20. Population pharmacokinetic model for cancer chemoprevention with sulindac in healthy subjects. (United States)

    Berg, Alexander K; Mandrekar, Sumithra J; Ziegler, Katie L Allen; Carlson, Elsa C; Szabo, Eva; Ames, Mathew M; Boring, Daniel; Limburg, Paul J; Reid, Joel M


    Sulindac is a prescription-based non-steroidal anti-inflammatory drug (NSAID) that continues to be actively investigated as a candidate cancer chemoprevention agent. To further current understanding of sulindac bioavailability, metabolism, and disposition, we developed a population pharmacokinetic model for the parent compound and its active metabolites, sulindac sulfide, and exisulind. This analysis was based on data from 24 healthy subjects who participated in a bioequivalence study comparing two formulations of sulindac. The complex disposition of sulindac and its metabolites was described by a seven-compartment model featuring enterohepatic recirculation and is the first reported population pharmacokinetic model for sulindac. The derived model was used to explore effects of clinical variables on sulindac pharmacokinetics and revealed that body weight, creatinine clearance, and gender were significantly correlated with pharmacokinetic parameters. Moreover, the model quantifies the relative bioavailability of the sulindac formulations and illustrates the utility of population pharmacokinetics in bioequivalence assessment. This novel population pharmacokinetic model provides new insights regarding the factors that may affect the pharmacokinetics of sulindac and the exisulind and sulindac sulfide metabolites in generally healthy subjects, which have implications for future chemoprevention trial design for this widely available agent.

  1. Sulindac treatment in hereditary non-pollyposis colorectal cancer

    NARCIS (Netherlands)

    Rijcken, Fleur E. M.; Hollema, Harry; van der Zee, Ate G. J.; van der Sluis, Tineke; Ek, Wytske Boersma-van; Kleibeuker, Jan H.


    Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively studied for chemoprevention in familial adenomatous polyposis, but not in hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in HNPCC using surrogate end-points for cancer risk. In a randomised dou

  2. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29. (United States)

    Guillen-Ahlers, Hector; Tan, Jiangning; Castellino, Francis J; Ploplis, Victoria A


    Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+) colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  3. Effect of sulindac sulfide on metallohydrolases in the human colon cancer cell line HT-29.

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    Hector Guillen-Ahlers

    Full Text Available Matrix metalloproteinase 7 (MMP7, a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+ colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.

  4. Studies on the Metabolism and Biological Activity of the Epimers of Sulindac


    Brunell, David; Sagher, Daphna; Kesaraju, Shailaja; Brot, Nathan; Weissbach, Herbert


    Sulindac is a nonsteroidal, anti-inflammatory drug (NSAID) that has also been studied for its anticancer activity. Recent studies suggest that sulindac and its metabolites act by sensitizing cancer cells to oxidizing agents and drugs that affect mitochondrial function, resulting in the production of reactive oxygen species and death by apoptosis. In contrast, normal cells are not killed under these conditions and, in some instances, are protected against oxidative stress. Sulindac has a methy...

  5. Structural analysis of sulindac as an inhibitor of aldose reductase and AKR1B10. (United States)

    Cousido-Siah, Alexandra; Ruiz, Francesc X; Crespo, Isidro; Porté, Sergio; Mitschler, André; Parés, Xavier; Podjarny, Alberto; Farrés, Jaume


    Aldose reductase (AR, AKR1B1) and AKR1B10 are enzymes implicated in important pathologies (diabetes and cancer) and therefore they have been proposed as suitable targets for drug development. Sulindac is the metabolic precursor of the potent non-steroidal anti-inflammatory drug (NSAID) sulindac sulfide, which suppresses prostaglandin production by inhibition of cyclooxygenases (COX). In addition, sulindac has been found to be one of the NSAIDs with higher antitumoral activity, presumably through COX inhibition. However, sulindac anticancer activity could be partially mediated through COX-independent mechanisms, including the participation of AR and AKR1B10. Previously, it had been shown that sulindac and sulindac sulfone were good AR inhibitors and the structure of the ternary complex with NADP(+) and sulindac was described (PDB ID 3U2C). In this work, we determined the three-dimensional structure of AKR1B10 with sulindac and established structure-activity relationships (SAR) of sulindac and their derivatives with AR and AKR1B10. The difference in the IC50 values for sulindac between AR (0.36 μM) and AKR1B10 (2.7 μM) might be explained by the different positioning and stacking interaction given by Phe122/Phe123, and by the presence of two buried and ordered water molecules in AKR1B10 but not in AR. Moreover, SAR analysis shows that the substitution of the sulfinyl group is structurally allowed in sulindac derivatives. Hence, sulindac and its derivatives emerge as lead compounds for the design of more potent and selective AR and AKR1B10 inhibitors.

  6. Population Pharmacokinetic Model for Cancer Chemoprevention With Sulindac in Healthy Subjects


    Berg, Alexander K.; Mandrekar, Sumithra J.; Ziegler, Katie L. Allen; Carlson, Elsa C.; Szabo, Eva; Ames, Mathew M.; Boring, Daniel; Limburg, Paul J.; Reid, Joel M.


    Sulindac is a prescription-based non-steroidal anti-inflammatory drug (NSAID) that continues to be actively investigated as a candidate cancer chemoprevention agent. To further current understanding of sulindac bioavailability, metabolism, and disposition, we developed a population pharmacokinetic model for the parent compound and its active metabolites, sulindac sulfide, and exisulind. This analysis was based on data from 24 healthy subjects who participated in a bioequivalence study compari...

  7. In Vivo Antineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model. (United States)

    Katoumas, Konstantinos; Nikitakis, Nikolaos; Perrea, Despina; Dontas, Ismene; Sklavounou, Alexandra


    The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n = 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression.

  8. Sulindac metabolites induce proteosomal and lysosomal degradation of the epidermal growth factor receptor. (United States)

    Pangburn, Heather A; Ahnen, Dennis J; Rice, Pamela L


    The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. In response to ligand, EGFR is internalized and degraded by the ubiquitin-proteasome/lysosome pathway. We previously reported that metabolites of the nonsteroidal anti-inflammatory drug sulindac downregulate the expression of EGFR and inhibit basal and EGF-induced EGFR signaling through extracellular signal-regulated kinase 1/2. We now have evaluated the mechanisms of sulindac metabolite-induced downregulation of EGFR. EGF-induced downregulation of EGFR occurs within 10 minutes and lasts for 24 hours. By contrast, downregulation of EGFR by sulindac sulfide and sulindac sulfone was first evident at 4 and 24 hours, respectively, with maximal downregulation at 72 hours. Pretreatment with either the lysosomal inhibitor chloroquine or the proteosomal inhibitor MG132 blocked sulindac metabolite-induced downregulation of EGFR. Sulindac metabolites also increased the ubiquitination of EGFR. Whereas sulindac metabolites inhibited phosphorylation of EGFR pY1068, they increased phosphorylation of EGFR pY1045, the docking site where c-Cbl binds, thereby enabling receptor ubiquitination and degradation. Immunofluorescence analysis of EGF and EGFR distribution confirmed the biochemical observations that sulindac metabolites alter EGFR localization and EGFR internalization in a manner similar to that seen with EGF treatment. Expression of ErbB family members HER2 and HER3 was also downregulated by sulindac metabolites. We conclude that downregulation of EGFR expression by sulindac metabolites is mediated via lysosomal and proteosomal degradation that may be due to drug-induced phosphorylation at pY1045 with resultant ubiquitination of EGFR. Thus, sulindac metabolite-induced downregulation of EGFR seems to be mediated through mechanism(s) similar, at least in part, to those involved in EGF-induced downregulation of EGFR.

  9. Studies on the metabolism and biological activity of the epimers of sulindac. (United States)

    Brunell, David; Sagher, Daphna; Kesaraju, Shailaja; Brot, Nathan; Weissbach, Herbert


    Sulindac is a nonsteroidal, anti-inflammatory drug (NSAID) that has also been studied for its anticancer activity. Recent studies suggest that sulindac and its metabolites act by sensitizing cancer cells to oxidizing agents and drugs that affect mitochondrial function, resulting in the production of reactive oxygen species and death by apoptosis. In contrast, normal cells are not killed under these conditions and, in some instances, are protected against oxidative stress. Sulindac has a methyl sulfoxide moiety with a chiral center and was used in all of the previous studies as a mixture of the R- and S-epimers. Because epimers of a compound can have very different chemical and biological properties, we have separated the R- and S-epimers of sulindac, studied their individual metabolism, and performed preliminary experiments on their effect on normal and lung cancer cells exposed to oxidative stress. Previous results had indicated that the reduction of (S)-sulindac to sulindac sulfide, the active NSAID, was catalyzed by methionine sulfoxide reductase (Msr) A. In the present study, we purified an enzyme that reduces (R)-sulindac and resembles MsrB in its substrate specificity. The oxidation of both epimers to sulindac sulfone is catalyzed primarily by the microsomal cytochrome P450 (P450) system, and the individual enzymes responsible have been identified. (S)-Sulindac increases the activity of the P450 system better than (R)-sulindac, but both epimers increase primarily the enzymes that oxidize (R)-sulindac. Both epimers can protect normal lung cells against oxidative damage and enhance the killing of lung cancer cells exposed to oxidative stress.

  10. A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy. (United States)

    Gurpinar, Evrim; Grizzle, William E; Shacka, John J; Mader, Burton J; Li, Nan; Piazza, Nicholas A; Russo, Suzanne; Keeton, Adam B; Piazza, Gary A


    Nonsteroidal anti-inflammatory drugs such as sulindac sulfide have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from COX inhibition limit their use in cancer therapy. We recently described a N,N-dimethylethyl amine derivative of sulindac sulfide, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth-inhibitory activity. Here, we studied the basis for the growth-inhibitory effects of SSA on human lung adenocarcinoma cell lines. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2 to 5 μmol/L compared with 44 to 52 μmol/L for sulindac sulfide. SSA also suppressed DNA synthesis and caused a G0-G1 cell-cycle arrest. SSA-induced cell death was associated with characteristics of autophagy, but significant caspase activation or PARP cleavage was not observed after treatment at its IC50 value. siRNA knockdown of Atg7 attenuated SSA-induced autophagy and cell death, whereas pan-caspase inhibitor ZVAD was not able to rescue viability. SSA treatment also inhibited Akt/mTOR signaling and the expression of downstream proteins that are regulated by this pathway. Overexpression of a constitutively active form of Akt was able to reduce autophagy markers and confer resistance to SSA-induced cell death. Our findings provide evidence that SSA inhibits lung tumor cell growth by a mechanism involving autophagy induction through the suppression of Akt/mTOR signaling. This unique mechanism of action, along with its increased potency and lack of COX inhibition, supports the development of SSA or related analogs for the prevention and/or treatment of lung cancer.

  11. Docosahexaenoic acid sensitizes colon cancer cells to sulindac sulfide-induced apoptosis. (United States)

    Lim, Soo-Jeong; Lee, Eunmyong; Lee, Eun-Hye; Kim, Soo-Yeon; Cha, Jun Hyung; Choi, Hwanho; Park, Wanseo; Choi, Hyeon Kyeom; Ko, Seong-Hee; Kim, So Hee


    Sulindac analogs represent one of the most efficacious groups of NSAIDs reducing the risk of colon cancer. Recent studies have shown that sulindac sulfide, a sulindac analog effective at lower doses compared to its parent compound, triggers the death receptor (DR)5-dependent extrinsic apoptotic pathway. Induction of apoptosis via activation of the DR-mediated pathway would be an ideal therapeutic strategy to eliminate cancer cells. In this study, we investigated the possibility that colon cancer cells are sensitized to sulindac sulfide-induced apoptosis by docosahexaenoic acid (DHA), via activation of the DR/extrinsic apoptotic pathway. Our data demonstrated that DHA combination sensitized colon cancer cells to sulindac sulfide-induced apoptosis, leading to enhanced growth suppression of human colon cancer xenografts. The combination effect was primarily attributed to increased cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8 activation. Moreover, pretreatment with z-IETD-FMK (caspase-8 inhibitor) or stable expression of dominant negative caspase-8 genes blocked DHA/sulindac sulfide cotreatment-induced apoptosis. In view of the finding that DR5 silencing abrogated the combination-stimulated apoptosis, we propose that apoptotic synergy induced by sulindac sulfide plus DHA is mediated via DR5. Our findings collectively support the utility of a combination of sulindac sulfide and DHA in the effective prevention and treatment of colon cancer.

  12. Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells. (United States)

    Jakubowska-Mućka, Anna; Sieńko, Jacek; Zapała, Łukasz; Wolny, Rafał; Lasek, Witold


    Sulindac, a non-steroidal anti-inflammatory drug, suppresses carcinogenesis and inhibits growth of tumor cells. Pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, has been also identified as a potential anti-neoplastic agent. We hypothesized that combination of sulindac and PDTC could result in augmentation of cytotoxicity against ovarian cancer cells. The effect of sulindac and PDTC was examined on several ovarian cancer lines. Tumor cell viability was assessed using the MTT assay. Annexin-V/PI staining was used to detect apoptosis, cell cycle distribution was analyzed in FACS, and expression of cellular proteins was detected by western blotting. Incubation of OVA-14, OVP-10 and CAOV-1 ovarian cancer cells with sulindac and PDTC resulted in significantly greater inhibition of cell viability compared to either compound alone. In a model of OVA-14 cells it was evident that this effect was not related to the expression of COX enzymes since both active (sulindac sulfide) and inactive (sulindac) in vitro compounds affected the growth of tumor cells to a similar extent and synergized in cytotoxicity with PDTC. Combination of sulindac and PDTC lead to G0 arrest and massive apoptosis in co-treated cultures. Western blotting analysis argued for induction of the mitochondrial apoptotic pathway. These data demonstrate the synergistic cytotoxic effect of sulindac and PDTC on ovarian cancer cells through apoptosis and cell cycle arrest and prompt to test the efficacy of this combination in animal models.

  13. The inhibition of Wnt/β-catenin signaling pathway in human colon cancer cells by sulindac. (United States)

    Tai, Wei-Ping; Hu, Pin-Jin; Wu, Jing; Lin, Xiang-Chun


    The aberrant activation of Wnt/β-catenin signaling plays important roles in the initial development of colon cancer. Sulindac is a commonly used non-steroidal anti-inflammatory drug. We demonstrated the effects of sulindac on growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. Sulindac significantly inhibited proliferation of HT-29 colon cancer cells in a dose- and time-dependent manner. Sulindac was found to induce the apoptosis of HT-29 cells and inhibit the Wnt/β-catenin pathway. The inhibition was further confirmed by the decreased protein levels of β-catenin. The results indicate that sulindac may play a beneficial role in the comprehensive treatment of colon cancer.

  14. Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice

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    Bi Xiuli


    Full Text Available Abstract Background Both selenium and non-steroidal anti-inflammatory drug (NSAID sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms. Results We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p Conclusions The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.

  15. Molecular alterations associated with sulindac-resistant colon tumors in ApcMin/+ mice. (United States)

    Greenspan, Emily J; Nichols, Frank C; Rosenberg, Daniel W


    Although nonsteroidal anti-inflammatory drugs (NSAID), including sulindac, have been used extensively as chemopreventive agents for colorectal cancer, results are not consistent. NSAIDs, most reportedly sulindac, often do not cause a complete regression of adenomas and some patients develop resistance to NSAID treatment. In this study, we evaluated the effect of sulindac on colon tumorigenesis in the Apc(Min/+) mouse model. Sulindac (180 ppm) given in drinking water for 9 weeks to Apc(Min/+) mice significantly reduced the size of colon tumors, but actually caused an increase in colon tumor multiplicity relative to untreated controls (average of 5.5 versus 1.6 tumors per mouse, respectively; P sulindac significantly reduced tumor size and multiplicity relative to untreated controls (average of 2.3 versus 42.0 tumors per mouse, respectively; P sulindac treatment. Sulindac is also known to exert its growth inhibitory effects through regulation of many noncyclooxygenase targets, including p21, beta-catenin, E-cadherin, mitochondrial apoptotic proteins, and peroxisome proliferator-activated receptor-gamma. We found that sulindac treatment protected against E-cadherin loss in colon tumors, with associated inhibition of nuclear beta-catenin accumulation. Importantly, p21(WAF1/cip1) and peroxisome proliferator-activated receptor-gamma expression were absent in colon tumors from sulindac-treated mice, suggesting that loss of these proteins is necessary for drug resistance. Together, these observations may be translatable to designing novel clinical therapies using combinations of agents that target multiple molecular pathways to overcome sulindac resistance.

  16. Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC(Min) mice fed suboptimal levels of sulindac. (United States)

    Bobe, Gerd; Wang, Bing; Seeram, Navindra P; Nair, Muraleedharan G; Bourquin, Leslie D


    A promising approach for cancer chemoprevention might be a combination therapy utilizing dietary phytochemicals and anticarcinogenic pharmaceuticals at a suboptimal dosage to minimize any potential adverse side effects. To test this hypothesis, various dosages of anthocyanin-rich tart cherry extract were fed in combination with suboptimal levels of the nonsteroidal anti-inflammatory drug sulindac to APCMin mice for 19 weeks. By the end of the feeding period, fewer mice that were fed the anthocyanin-rich extract in combination with sulindac lost more than 10% of body weight than mice fed sulindac alone. Mice that were fed anthocyanin-rich extract (at any dose) in combination with sulindac had fewer tumors and a smaller total tumor burden (total tumor area per mouse) in the small intestine when compared to mice fed sulindac alone. These results suggest that a dietary combination of tart cherry anthocyanins and sulindac is more protective against colon cancer than sulindac alone.

  17. Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoarthritis. (United States)

    Cangiano, J L; Figueroa, J; Palmer, R


    We assessed the effects of nabumetone, sulindac, and placebo on renal function and renal excretion of vasodilatory prostaglandins in older female patients (age >50 years) with osteoarthritis and normal renal function. Using a prospective, crossover design, we compared the effects of nabumetone 2000 mg/d and sulindac 400 mg/d with placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1alpha in 12 patients. Urinary excretion of vasodilatory prostaglandins was not decreased after 14 days of treatment with either nabumetone or sulindac. Likewise, treatment with nabumetone or sulindac did not significantly alter renal function compared with placebo. There were no differences in mean changes in GFR or RPF from baseline after treatment with nabumetone or sulindac compared with placebo. The mean (+/- SD) changes in GFR from baseline were 0%+/-8% in patients receiving nabumetone, -8%+/-15% in patients receiving sulindac, and -7%+/-15% in patients receiving placebo. The results of this study demonstrate that treatment with nabumetone or sulindac caused no deterioration in renal function in older female patients with osteoarthritis and normal renal function.

  18. Sulindac Induces Apoptosis and Inhibits Tumor Growth In Vivo in Head and Neck Squamous Cell Carcinoma

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    Mark A. Scheper


    Full Text Available Sulindac has antineoplastic effects on various cancer cell lines; consequently, we assessed sulindac's effects on laryngeal squamous cell carcinoma (SCC cells in vitro and in vivo. In vitro, SCC (HEP-2 cells treated with various cyclooxygenase inhibitors or transfected with constitutively active signal transducer and activator of transcription 3 (Stat3 or survivin vectors were analyzed using Western blot analysis, annexin V assay, and cell proliferation assay. In parallel, nude mice injected subcutaneously with HEP-2 cells were either treated intraperitoneally with sulindac or left untreated, and analyzed for tumor weight, survivin expression, and tyrosine-phosphorylated Stat3 expression. In vitro studies confirmed the selective antiproliferative and proapoptotic effects of sulindac, which also downregulated Stat3 and survivin protein expression. Stat3 or survivin forced expression partially rescued the antiproliferative effects of sulindac. In vivo studies showed significant repression of HEP-2 xenograft growth in sulindactreated mice versus controls, with near-complete resolution at 10 days. Additionally, tumor specimens treated with sulindac showed downregulation of phosphorylated tyrosine-705 Stat3 and survivin expression. Taken together, our data suggest, for the first time, a specific inhibitory effect of sulindac on tumor growth and survivin expression in laryngeal cancer, both in vitro and in vivo, in a Stat3-dependent manner, suggesting a novel therapeutic approach to head and neck cancer.

  19. Combination of sulindac and dichloroacetate kills cancer cells via oxidative damage. (United States)

    Ayyanathan, Kasirajan; Kesaraju, Shailaja; Dawson-Scully, Ken; Weissbach, Herbert


    Sulindac is an FDA-approved non-steroidal anti-inflammatory drug with documented anticancer activities. Our recent studies showed that sulindac selectively enhanced the killing of cancer cells exposed to oxidizing agents via production of reactive oxygen species (ROS) resulting in mitochondrial dysfunction. This effect of sulindac and oxidative stress on cancer cells could be related to the defect in respiration in cancer cells, first described by Warburg 50 years ago, known as the Warburg effect. We postulated that sulindac might enhance the selective killing of cancer cells when combined with any compound that alters mitochondrial respiration. To test this hypothesis we have used dichloroacetate (DCA), which is known to shift pyruvate metabolism away from lactic acid formation to respiration. One might expect that DCA, since it stimulates aerobic metabolism, could stress mitochondrial respiration in cancer cells, which would result in enhanced killing in the presence of sulindac. In this study, we have shown that the combination of sulindac and DCA enhances the selective killing of A549 and SCC25 cancer cells under the conditions used. As predicted, the mechanism of killing involves ROS production, mitochondrial dysfunction, JNK signaling and death by apoptosis. Our results suggest that the sulindac-DCA drug combination may provide an effective cancer therapy.

  20. Combination of sulindac and dichloroacetate kills cancer cells via oxidative damage.

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    Kasirajan Ayyanathan

    Full Text Available Sulindac is an FDA-approved non-steroidal anti-inflammatory drug with documented anticancer activities. Our recent studies showed that sulindac selectively enhanced the killing of cancer cells exposed to oxidizing agents via production of reactive oxygen species (ROS resulting in mitochondrial dysfunction. This effect of sulindac and oxidative stress on cancer cells could be related to the defect in respiration in cancer cells, first described by Warburg 50 years ago, known as the Warburg effect. We postulated that sulindac might enhance the selective killing of cancer cells when combined with any compound that alters mitochondrial respiration. To test this hypothesis we have used dichloroacetate (DCA, which is known to shift pyruvate metabolism away from lactic acid formation to respiration. One might expect that DCA, since it stimulates aerobic metabolism, could stress mitochondrial respiration in cancer cells, which would result in enhanced killing in the presence of sulindac. In this study, we have shown that the combination of sulindac and DCA enhances the selective killing of A549 and SCC25 cancer cells under the conditions used. As predicted, the mechanism of killing involves ROS production, mitochondrial dysfunction, JNK signaling and death by apoptosis. Our results suggest that the sulindac-DCA drug combination may provide an effective cancer therapy.

  1. Acute kidney injury, hyperbilirubinemia, and ischemic skin necrosis due to massive sulindac overdose. (United States)

    Vaughn, John L; Shah, Kejal V; Ghossein, Maroun M; Meyer, William L; Kirkpatrick, Robert B


    Sulindac is a long-acting nonsteroidal anti-inflammatory drug (NSAID) widely used for the management of osteoarthritis, rheumatoid arthritis, ankylosing sponydlitis, and acute gouty arthritis. Reports of sulindac toxicity in the literature are rare. We report the case of a 22-year old male with a history of bipolar disorder who was brought to the emergency department after ingesting approximately 15 g of sulindac in a suicide attempt. He was found to have acute kidney injury and hyperbilirubinemia. Despite aggressive fluid resuscitation, his renal function progressively worsened requiring the initiation of hemodialysis. Ten days following ingestion of sulindac, he began to develop ischemic skin changes with a gangrenous appearance in his hands and feet. He continued to receive supportive treatment, and his acute kidney injury, hyperbillirubinemia, and ischemic skin necrosis eventually resolved. Clinicians should be aware of this long-acting NSAID and its ability to cause prolonged multisystem organ dysfunction.

  2. Effects of sulindac and naproxen in patients with chronic glomerular disease

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Christensen, P;


    Eight patients with chronic glomerulonephritis were treated with either naproxen or sulindac in an open randomized study to observe their effects on the urinary excretion of prostaglandins and renal function. Both drugs were given for 7 days. Naproxen caused a decrease (p less than 0.01) of 80......% in prostaglandin PGE2 and decrease (p less than 0.01) of 55% in prostaglandin PGF2 alpha. Sulindac caused a decrease (p = 0.01) of 37% in PGE2 and a decrease (p less than 0.05) in PGF2 alpha of 13%. The decrease in urinary excretion of prostaglandins were greater (p less than 0.05) during the naproxen treatment....... Sulindac did not change any of these parameters significantly. In conclusion, sulindac affects renal prostaglandin synthesis to a significantly minor degree than naproxen and contrary to naproxen it does not influence the renal function in patients with chronic glomerular disease....

  3. Sulindac and its metabolites inhibit multiple transport proteins in rat and human hepatocytes. (United States)

    Lee, Jin Kyung; Paine, Mary F; Brouwer, Kim L R


    Sulindac is a commonly used nonsteroidal anti-inflammatory drug. This study tested the hypothesis that sulindac-mediated drug-drug interactions and/or hepatotoxicity may be caused, in part, by inhibition of proteins responsible for the hepatic transport of drugs and/or bile acids by sulindac and/or sulindac metabolites [sulindac sulfone (S-sulfone) and sulindac sulfide (S-sulfide)]. The uptake and excretion of model substrates, [(3)H]taurocholate (TC), [(3)H]estradiol 17-beta-glucuronide (E217G), and nitrofurantoin (NF), were investigated in rat and human suspended and sandwich-cultured hepatocytes (SCH). In suspended rat hepatocytes, S-sulfone and S-sulfide inhibited Na(+)-dependent TC initial uptake (IC(50) of 24.9 +/- 6.4 and 12.5 +/- 1.8 microM, respectively) and Na(+)-independent E217G initial uptake (IC(50) of 12.1 +/- 1.6 and 6.3 +/- 0.3 microM, respectively). In rat SCH, sulindac metabolites (100 microM) decreased the in vitro biliary clearance (Cl(biliary)) of TC, E217G, and NF by 38 to 83%, 81 to 97%, and 33 to 57%, respectively; S-sulfone and S-sulfide also decreased the TC and NF biliary excretion index by 39 to 55%. In suspended human hepatocytes, S-sulfone and S-sulfide inhibited Na(+)-dependent TC initial uptake (IC(50) of 42.2 and 3.1 microM, respectively); S-sulfide also inhibited the TC Cl(biliary) in human SCH. Sulindac/metabolites markedly inhibited hepatic uptake and biliary excretion of E217G by 51 to 100% in human SCH. In conclusion, sulindac and metabolites are potent inhibitors of the uptake and biliary clearance of bile acids in rat and human hepatocytes and also inhibit substrates of rat breast cancer resistance protein, rat and human organic anion-transporting polypeptides, and human multidrug resistance-associated protein 2. Inhibition of multiple hepatic transport proteins by sulindac/metabolites may play an important role in clinically significant sulindac-mediated drug-drug interactions and/or liver injury.

  4. Exploring the mechanism of interaction between sulindac and human serum albumin: Spectroscopic and molecular modeling methods

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    Zhang, Xiao-Ping; Hou, Ya-He [Department of Material Engineering, Xuzhou College of Industrial Technology, Xuzhou, Jiangsu 221140 (China); Wang, Li [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); Zhang, Ye-Zhong, E-mail: [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); Liu, Yi, E-mail: [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); College of Chemistry and Molecular Sciences and State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)


    In the present study, a combination of fluorescence, molecular modeling and circular dichroism (CD) approaches had been employed to investigate the interaction between sulindac and human serum albumin (HSA). Results of mechanism discussion demonstrated that the fluorescence quenching of HSA by sulindac was a static quenching procedure. Binding parameters calculated from the modified Stern–Volmer equation showed that sulindac bound to HSA with the binding affinities in the order of 10{sup 5} L mol{sup −1}. The thermodynamic parameters (ΔH=−18.58 kJ mol{sup −1}; ΔS=37.26 J mol{sup −1} K{sup −1}) obtained by the van′t Hoff equation revealed that hydrophobic forces played a leading role in the formation of sulindac–HSA complex, but hydrogen bonds could not be omitted. Site marker competitive experiments revealed a displacement of warfarin by sulindac, which indicated that the binding site of sulindac to HSA located in the sub-domain IIA (Sudlow′s site I). The molecular docking study confirmed the specific binding mode and binding site obtained by fluorescence and site marker competitive experiments. CD and three-dimensional fluorescence spectroscopy were used to investigate the changes of HSA secondary structure and microenvironment in the presence of sulindac. Alterations of HSA conformation were observed with the reduction of α-helix from 60.1% (free HSA) to 57.3%, manifesting a slight unfolding of the polypeptides of protein. -- Highlights: ► The quenching mechanism between sulindac and HSA is a static process. ► The binding of sulindac to HSA takes place in sub-domain IIA (Sudlow′s site I). ► The binding is spontaneous and hydrophobic force plays major role in stabilizing the complex. ► CD and 3-D fluorescence spectra prove the change of the microenvironment and conformation of HSA.

  5. Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system. (United States)

    Minagawa, Keiji; Berber, Mohamed R; Hafez, Inas H; Mori, Takeshi; Tanaka, Masami


    Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of ~50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230° C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration.

  6. Evaluating the inhibitory potential of sulindac against the bleomycin-induced pulmonary fibrosis in wistar rats. (United States)

    Verma, Ramesh; Brahmankar, Mahesh; Kushwah, Lokendra; Suresh, Balakrishnan


    The present study examined the protective effect of sulindac on bleomycin-induced lung fibrosis in rats. Animals were divided into saline group, bleomycin group (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally from day 1 to day 20). Bleomycin administration reduced the body weight, altered antioxidant status (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione) while it increased the lung weight, hydroxyproline content, collagen deposition and lipid peroxidation. However, simultaneous administration of sulindac improved the body weight, antioxidant status and decreased the collagen deposition in lungs. Moreover, the levels of inflammatory cytokine tumour necrosis factor-α increased in bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour necrosis factor-α were found reduced. Finally, histological evidence also supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The results of the present study indicate that sulindac can be used as an agent against bleomycin-induced pulmonary fibrosis.

  7. Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α. (United States)

    Sur, Arunodoy; Kesaraju, Shailaja; Prentice, Howard; Ayyanathan, Kasirajan; Baronas-Lowell, Diane; Zhu, Danhong; Hinton, David R; Blanks, Janet; Weissbach, Herbert


    The retinal pigmented epithelial (RPE) layer is one of the major ocular tissues affected by oxidative stress and is known to play an important role in the etiology of age-related macular degeneration (AMD), the major cause of blinding in the elderly. In the present study, sulindac, a nonsteroidal antiinflammatory drug (NSAID), was tested for protection against oxidative stress-induced damage in an established RPE cell line (ARPE-19). Besides its established antiinflammatory activity, sulindac has previously been shown to protect cardiac tissue against ischemia/reperfusion damage, although the exact mechanism was not elucidated. As shown here, sulindac can also protect RPE cells from chemical oxidative damage or UV light by initiating a protective mechanism similar to what is observed in ischemic preconditioning (IPC) response. The mechanism of protection appears to be triggered by reactive oxygen species (ROS) and involves known IPC signaling components such as PKG and PKC epsilon in addition to the mitochondrial ATP-sensitive K(+) channel. Sulindac induced iNOS and Hsp70, late-phase IPC markers in the RPE cells. A unique feature of the sulindac protective response is that it involves activation of the peroxisome proliferator-activated receptor alpha (PPAR-α). We have also used low-passage human fetal RPE and polarized primary fetal RPE cells to validate the basic observation that sulindac can protect retinal cells against oxidative stress. These findings indicate a mechanism for preventing oxidative stress in RPE cells and suggest that sulindac could be used therapeutically for slowing the progression of AMD.

  8. Sulindac, a non-steroidal anti-inflammatory drug, mediates breast cancer inhibition as an immune modulator. (United States)

    Yin, Tao; Wang, Guoping; Ye, Tinghong; Wang, Yongsheng


    The cooperation of adaptive immunity with pharmacologic therapy influences cancer progression. Though non-steroidal anti-inflammatory drugs (NSAIDs) have a long history of cancer prevention, it is unclear whether adaptive immune system affects the action of those drugs. In present study, we revealed a novel immunological mechanism of sulindac. Our data showed that sulindac had substantial efficacy as a single agent against 4T1 murine breast cancer and prolonged the survival of tumor-bearing mice. However, in the athymic nude mice, sulindac treatment was ineffective. Further in vivo T cell subsets depletion experiments showed that CD8+ T lymphocytes deficiency reversed the anti-tumor effect of sulindac. In addition, sulindac significantly reduced M2 macrophages recruitment, cancer-related inflammation and tumor angiogenesis. Our results advance our understanding of the mechanisms of NSAIDs, and more importantly, this will provide insight into rational drug design or antitumor immunotherapy.

  9. Sulindac reversal of 15-PGDH-mediated resistance to colon tumor chemoprevention with NSAIDs. (United States)

    Fink, Stephen P; Dawson, Dawn M; Zhang, Yongyou; Kresak, Adam; Lawrence, Earl G; Yang, Peiying; Chen, Yanwen; Barnholtz-Sloan, Jill S; Willis, Joseph E; Kopelovich, Levy; Markowitz, Sanford D


    Non-steroidal anti-inflammatory drugs prevent colorectal cancer by inhibiting cyclooxygenase (COX) enzymes that synthesize tumor-promoting prostaglandins. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a tumor suppressor that degrades tumor-promoting prostaglandins. Murine knockout of 15-PGDH increases susceptibility to azoxymethane-induced colon tumors. It also renders these mice resistant to celecoxib, a selective inhibitor of inducible COX-2 during colon neoplasia. Similarly, humans with low colonic 15-PGDH are also resistant to colon adenoma prevention with celecoxib. Here, we used aspirin and sulindac, which inhibit both COX-1 and COX-2, in order to determine if these broader COX inhibitors can prevent colon tumors in 15-PGDH knockout (KO) mice. Unlike celecoxib, sulindac proved highly effective in colon tumor prevention of 15-PGDH KO mice. Significantly, however, aspirin demonstrated no effect on colon tumor incidence in either 15-PGDH wild-type or KO mice, despite a comparable reduction in colonic mucosal Prostaglandin E₂ (PGE₂) levels by both sulindac and aspirin. Notably, colon tumor prevention activity by sulindac was accompanied by a marked induction of lymphoid aggregates and proximal colonic inflammatory mass lesions, a side effect seen to a lesser degree with celecoxib, but not with aspirin. These findings suggest that sulindac may be the most effective agent for colon cancer prevention in humans with low 15-PGDH, but its use may also be associated with inflammatory lesions in the colon.

  10. Phospho-sulindac (OXT-328) combined with difluoromethylornithine prevents colon cancer in mice. (United States)

    Mackenzie, Gerardo G; Ouyang, Nengtai; Xie, Gang; Vrankova, Kvetoslava; Huang, Liqun; Sun, Yu; Komninou, Despina; Kopelovich, Levy; Rigas, Basil


    The nonsteroidal anti-inflammatory drug (NSAID) sulindac and the ornithine decarboxylase (ODC) antagonist difluoromethylornithine (DFMO), individually and together, are effective inhibitors of colon carcinogenesis. However, chronic use of sulindac is associated with significant side effects. We evaluated the chemopreventive efficacy of phospho-sulindac (P-S, OXT-328), an apparently safe derivative of sulindac, together with DFMO, in HT-29 human colon cancer xenografts. Nude mice were divided into four groups as follows: group 1 received vehicle (corn oil); group 2 received P-S (100 mg/kg/d) by oral gavage; group 3 received DFMO (2% in drinking water); and group 4 received P-S (100 mg/kg/d) by gavage plus DFMO (2% in drinking water; P-S/DFMO). Eighteen days after implantation, compared with controls, tumor volume was inhibited 65.9% by P-S, 52.9% by DFMO, and 70.9% by P-S/DFMO (P sulindac. P-S/DFMO has an intricate mechanism of action extending beyond polyamines and including the thioredoxin system, an emerging regulator of chemoprevention. P-S/DFMO merits further evaluation.

  11. Crystallization of micro particles of sulindac using rapid expansion of supercritical solution (United States)

    Zeinolabedini Hezave, Ali; Esmaeilzadeh, Feridun


    In pharmaceutical industry, many drugs exhibit poor solubility in biological fluid. Solubility of drugs affects on the rate of dissolution and bioavailability in biological fluids. The bioavailability of drugs can be enhanced by decreasing the drug particle size. In this study, sulindac was micronized via rapid expansion of supercritical solution (RESS) where CO2 was used as a solvent. The experiments were conducted to investigate the effect of the extraction pressure and temperature (140-230 bar and 40-60 °C), collection distance (1-10 cm), effective nozzle diameter (450-1700 μm) and nozzle length (2-15 mm) on the size and morphology of the sulindac particles. The size and morphology of the precipitated particles were monitored by scanning electron microscopy (SEM). The particle size of intact sulindac particles was about 33.03 μm, while the average particle size of the micronized sulindac particles was between 0.76 and 8.02 μm based on different experimental conditions. Additionally, the different morphology of the micronized particles was observed like needle, rectangular, quasi spherical and irregular form while the morphology of the intact particles of sulindac was rectangular and irregular.

  12. Sulindac enhances the killing of cancer cells exposed to oxidative stress.

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    Maria Marchetti

    Full Text Available BACKGROUND: Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID that affects prostaglandin production by inhibiting cyclooxygenases (COX 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer. PRINCIPAL FINDINGS: Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP or hydrogen peroxide. This effect does not involve cyclooxygenase (COX inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells. SIGNIFICANCE: These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

  13. Effect of sulindac on improving autistic behaviors in rats%舒林酸对孤独症模型大鼠病症行为的改善作用

    Institute of Scientific and Technical Information of China (English)

    秦利燕; 戴旭芳


    Objective To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms. Methods Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin and phosphorylated Gsk3βin the brain tissues were investigated by Western blotting. Results Compared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3βdownregulation andβ-catenin upregulation in the prefrontal lobe, seahorse and cerebellum. Conclusion Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.%目的 探讨舒林酸对孤独症模型大鼠病症行为的改善作用.方法 在大鼠怀孕12.5 d后采用一次性腹腔注射丙戊酸钠(VPA)制备孤独症大鼠模型.针对舒林酸处理组,于VPA注射后每天给大鼠口服20 mg/kg舒林酸直至断奶.将出生幼鼠分为4组:对照组,VPA处理组,舒林酸处理组及VPA联合舒林酸处理组.出生后35 d对幼鼠进行社会交往行为检测、敞箱焦虑样行为检测,并分离提取脑组织蛋白利用Western blot分析Wnt信号通路关键蛋白β-catenin与Gsk3β表达情况.结果 成功制备孤独症大鼠模型.与对照组相比,VPA处理组社会交往能力下降、在中央区活动时间增加、

  14. Sulindac-derived RXRα modulators inhibit cancer cell growth by binding to a novel site. (United States)

    Chen, Liqun; Wang, Zhi-Gang; Aleshin, Alexander E; Chen, Fan; Chen, Jiebo; Jiang, Fuquan; Alitongbieke, Gulimiran; Zeng, Zhiping; Ma, Yue; Huang, Mingfeng; Zhou, Hu; Cadwell, Gregory; Zheng, Jian-Feng; Huang, Pei-Qiang; Liddington, Robert C; Zhang, Xiao-kun; Su, Ying


    Retinoid X receptor-alpha (RXRα), an intriguing and unique drug target, can serve as an intracellular target mediating the anticancer effects of certain nonsteroidal anti-inflammatory drugs (NSAIDs), including sulindac. We report the synthesis and characterization of two sulindac analogs, K-8008 and K-8012, which exert improved anticancer activities over sulindac in a RXRα-dependent manner. The analogs inhibit the interaction of the N-terminally truncated RXRα (tRXRα) with the p85α subunit of PI3K, leading to suppression of AKT activation and induction of apoptosis. Crystal structures of the RXRα ligand-binding domain (LBD) with K-8008 or K-8012 reveal that both compounds bind to tetrameric RXRα LBD at a site different from the classical ligand-binding pocket. Thus, these results identify K-8008 and K-8012 as tRXRα modulators and define a binding mechanism for regulating the nongenomic action of tRXRα.

  15. NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. (United States)

    Zhou, Hu; Liu, Wen; Su, Ying; Wei, Zhen; Liu, Jie; Kolluri, Siva Kumar; Wu, Hua; Cao, Yu; Chen, Jiebo; Wu, Yin; Yan, Tingdong; Cao, Xihua; Gao, Weiwei; Molotkov, Andrei; Jiang, Fuquan; Li, Wen-Gang; Lin, Bingzhen; Zhang, Hai-Ping; Yu, Jinghua; Luo, Shi-Peng; Zeng, Jin-Zhang; Duester, Gregg; Huang, Pei-Qiang; Zhang, Xiao-Kun


    Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-alpha (RXRalpha). We identified an N-terminally truncated RXRalpha (tRXRalpha) in several cancer cell lines and primary tumors, which interacted with the p85alpha subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-alpha (TNFalpha) promoted tRXRalpha interaction with the p85alpha, activating PI3K/AKT signaling. When combined with TNFalpha, Sulindac inhibited TNFalpha-induced tRXRalpha/p85alpha interaction, leading to activation of the death receptor-mediated apoptotic pathway. We designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXRalpha but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXRalpha-dependent AKT activation and tRXRalpha tumor growth in animals.

  16. Synthesis and biological evaluation of nitric oxide-donating analogues of sulindac for prostate cancer treatment. (United States)

    Nortcliffe, Andrew; Ekstrom, Alexander G; Black, James R; Ross, James A; Habib, Fouad K; Botting, Nigel P; O'Hagan, David


    A series of analogues of the non-steroidal anti-inflammatory drug (NSAID) sulindac 1 were synthesised tethered to nitric oxide (NO) donating functional groups. Sulindac shows antiproliterative effects against immortal PC3 cell lines. It was previously demonstrated that the effect can be enhanced when tethered to NO releasing groups such as nitrate esters, furoxans and sydnonimines. To explore this approach further, a total of fifty-six sulindac-NO analogues were prepared and they were evaluated as NO-releasing cytotoxic agents against prostate cancer (PCa) cell lines. Compounds 1k and 1n exhibited significant cytotoxic with IC50 values of 6.1±4.1 and 12.1±3.2μM, respectively, coupled with observed nitric oxide release.

  17. Preparation and characterization of a sulindac sensor based on PVC/TOA-SUL membrane. (United States)

    Lenik, Joanna


    A potentiometric sulindac sensitive sensor based on tetraoctylammonium (Z)-5-fluoro-2-methyl-1-[[p-(methylsulfinyl)phenyl]methylene]-1H-indene-3-acetate (TOA-SUL) was described. The electrode responded with sensitivity of 57.5±1.6mV decade(-1) over the linear range 5×10(-5)-1×10(-2)mol L(-1) at pH6.0-9.0. It had the limit of detection 1.4×10(-5)mol L(-1), a fast response time of 13s and showed clear discrimination of sulindac ions from several inorganic and organic compounds and also amino acids. This electrode did not contain any inner solutions, so it was easy and comfortable to use. The proposed sensor was used to determine sulindac in clear solution and in urine sample solution.

  18. Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Yong-Le Xie; Yi Yu; Qiu-Ning Zhang


    AIM: To investigate the effects of mitomycin (MMC)combined with sulindac on cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2)in gastric cancer SGC-7901cells.METHODS: Human gastric cancer SGC-7901 cells were divided into three treatment groups,namely sulindac treatment group, MMC treatment group and combined sulindac with MMC treatment group. After being treated with drugs, cell viability was examined by MTr assay.Flow cytometry was used to evaluate the cell cycle distribution and apoptotic rates. Morphology of the cells was observed under light microscope and interactive laser microscope. Expression of COX-2 and Bcl-2 was determined by immunocytochemical method.RESULTS: After exposure for 12 h to three kinds of drugs,gastric cancer SGC-7901 cells presented some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Growth inhibition was more obvious in combined sulindac with MMC treatment group and sulindac treatment group than in MMC treatment group. The apoptotic rates in co-treated cells and MMC-treated cells 24 h after treatment were 12.0% and 7.2%, respectively.After exposure for 24 h to MMC, the expression of COX-2and Bcl-2 protein was up-regulated, COX-2 levels were down-regulated but Bcl-2 gene expression was not changed significantly in combined treatment group.CONCLUSION: MMC-induced apoptosis is reduced by up-regulating the expression of COX-2 and Bcl-2 genes.MMC combined with sulindac can suppress the growth of gastric cancer cells through induction of apoptosis mediated by down-regulation of apoptosis-related Bcl-2and COX-2 gene.

  19. Nutrient Availability Alters the Effect of Autophagy on Sulindac Sulfide-Induced Colon Cancer Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Shiun-Kwei Chiou


    Full Text Available Autophagy is a catabolic process by which a cell degrades its intracellular materials to replenish itself. Induction of autophagy under various cellular stress stimuli can lead to either cell survival or cell death via apoptotic and/or autophagic (nonapoptotic pathways. The NSAID sulindac sulfide induces apoptosis in colon cancer cells. Here, we show that inhibition of autophagy under serum-deprived conditions resulted in significant reductions of sulindac sulfide-induced apoptosis in HT-29 colon cancer cells. In contrast, inhibition of autophagy under conditions where serum is available significantly increased sulindac sulfide-induced apoptosis in HT-29 cells. We previously showed that the apoptosis inhibitor, survivin, plays a role in regulating NSAID-induced apoptosis and autophagic cell death. Here, we show that survivin protein half-life is increased in the presence of autophagy inhibitors under serum-deprived conditions, but not under conditions when serum is available. Thus, the increased levels of survivin may be a factor contributing to inhibition of sulindac sulfide-induced apoptosis under serum-deprived conditions. These results suggest that whether a cell lives or dies due to autophagy induction depends on the balance of factors that regulate both autophagic and apoptotic processes.

  20. CXCR2 inhibition enhances sulindac-mediated suppression of colon cancer development. (United States)

    Lee, Yong Suk; Choi, Dongwon; Kim, Nam Yoon; Yang, Sara; Jung, Eunson; Hong, Mingu; Yang, Dongyun; Lenz, Heinz-Josef; Hong, Young-Kwon


    Small chemical compound sulindac has been approved as a preventive approach against colon cancer for its effectiveness in treatment of precancerous adenoma. Due to its severe toxicities in the cardiovascular, gastrointestinal and renal systems, however, a combination of low-dose sulindac with other chemopreventive agents has been sought after as an alternative therapeutic strategy that could increase its effectiveness, while minimizing its adverse effects. To identify the promising alternative approach, we investigated the therapeutic potential of targeting the interleukin (IL)-8/CXCR2 pathway in colon cancer treatment using both loss-of-function (CXCR2 knockout) and gain-of-function (IL-8 overexpression) mouse models, as the IL-8/CXCR2 pathway has been shown to be activated in intestinal tumors of both human and experimental animals. We found that deletion of CXCR2 gene and ectopic expression of IL-8 suppresses and enhances, respectively, intestinal tumor development caused by a mutation in the APC gene. Moreover, a single copy deletion of CXCR2 gene resulted in abrogation of COX-2 and Gro-α upregulation in intestinal tumors caused by the APC mutation. Moreover, a single copy (heterozygote) deletion of CXCR2 gene was sufficient to synergize with a low-dose sulindac treatment in suppressing APCmin-induced intestinal polyposis. Together, our study provides a therapeutic justification of combined inhibition of CXCR2 and sulindac treatment in colon cancer prevention.

  1. Sulindac modulates secreted protein expression from LIM1215 colon carcinoma cells prior to apoptosis. (United States)

    Greening, David W; Ji, Hong; Kapp, Eugene A; Simpson, Richard J


    Colorectal cancer (CRC) is a major cause of mortality in Western populations. Growing evidence from human and rodent studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) cause regression of existing colon tumors and act as effective chemopreventive agents in sporadic colon tumor formation. Although much is known about the action of the NSAID sulindac, especially its role in inducing apoptosis, mechanisms underlying these effects is poorly understood. In previous secretome-based proteomic studies using 2D-DIGE/MS and cytokine arrays we identified over 150 proteins released from the CRC cell line LIM1215 whose expression levels were dysregulated by treatment with 1mM sulindac over 16h; many of these proteins are implicated in molecular and cellular functions such as cell proliferation, differentiation, adhesion, angiogenesis and apoptosis (Ji et al., Proteomics Clin. Appl. 2009, 3, 433-451). We have extended these studies and describe here an improved protein/peptide separation strategy that facilitated the identification of 987 proteins and peptides released from LIM1215 cells following 1mM sulindac treatment for 8h preceding the onset of apoptosis. This peptidome separation strategy involved fractional centrifugal ultrafiltration of concentrated cell culture media (CM) using nominal molecular weight membrane filters (NMWL 30K, 3K and 1K). Proteins isolated in the >30K and 3-30K fractions were electrophoretically separated by SDS-PAGE and endogenous peptides in the 1-3K membrane filter were fractioned by RP-HPLC; isolated proteins and peptides were identified by nanoLC-MS-MS. Collectively, our data show that LIM1215 cells treated with 1mM sulindac for 8h secrete decreased levels of proteins associated with extracellular matrix remodeling (e.g., collagens, perlecan, syndecans, filamins, dyneins, metalloproteinases and endopeptidases), cell adhesion (e.g., cadherins, integrins, laminins) and mucosal maintenance (e.g., glycoprotein 340 and mucins 5AC, 6

  2. Therapeutic potential of sulindac hydroxamic acid against human pancreatic and colonic cancer cells. (United States)

    Fogli, Stefano; Banti, Irene; Stefanelli, Fabio; Picchianti, Luca; Digiacomo, Maria; Macchia, Marco; Breschi, Maria Cristina; Lapucci, Annalina


    The non-steroidal anti-inflammatory drug (NSAID) sulindac exhibits cyclooxygenase (COX)-dependent and COX-independent chemopreventive properties in human cancer. The present study was aimed at investigating whether the hydroxamic acid substitution for the carboxylic acid group could enhance the in vitro antitumor and antiangiogenic activities of sulindac. Characterization tools used on this study included analyses of cell viability, caspase 3/7 induction, DNA fragmentation, and gene expression. Our findings demonstrate that the newly synthesized hydroxamic acid derivative of sulindac and its sulfone and sulfide metabolites were characterized by a good anticancer activity on human pancreatic and colon cancer cells, both in terms of potency (IC(50) mean values from 6 ± 1.1 μM to 64 ± 1.1 μM) and efficacy (E(max) of ∼100%). Hydroxamic acid derivatives trigger a higher degree of apoptosis than carboxylic acid counterparts, increase bax/bcl-2 expression ratio and induce caspase 3/7 activation. Most notably, these compounds significantly inhibit proangiogenic growth factor-stimulated proliferation of vascular endothelial cell (HUVEC) at sub-micromolar concentrations. Our data also provide evidence that the COX-active metabolite of sulindac hydroxamic acid were the most active of the series and selective inhibition of COX-1 but not COX-2 can mimic its effects, suggesting that COX inhibition could only play a partial role in the mechanism of compound action. In conclusion, these data demonstrate that substitution of the carboxylic acid group with the hydroxamic acid moiety enhances in vitro antiproliferative, proapoptotic and antiangiogenic properties of sulindac, therefore increasing the therapeutic potential of this drug.

  3. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)


    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO-sulindac

  4. Genotoxicity of the cyclo-oxygenase-inhibitor sulindac sulfide in the filamentous fungus Aspergillus nidulans Genotoxicidade de sulfeto de sulindaco em Aspergillus nidulans


    Claudinéia Conationi da Silva Franco; Claudia Tiemi Miyamoto; Juliane Rocha de Sant'Anna; Marialba Avezum Alves Castro-Prado


    Sulindac sulfide is a non-steroidal anti-inflammatory drug (NSAID) with chemopreventive effect on human cancer cells. Due to the involvement of the somatic recombination in the carcinogenic process, sulindac sulfide's recombinogenic potential was evaluated by the Homozygotization Index (HI) in the filamentous fungus Aspergillus nidulans. The drug's recombinogenic potential was evaluated by its capacity to induce homozygosis of recessive genes from heterozygous diploid cells. Sulindac sulfide ...

  5. Intervening in β-Catenin Signaling by Sulindac Inhibits S100A4-Dependent Colon Cancer Metastasis

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    Ulrike Stein


    Full Text Available Colon cancer metastasis is often associated with activation of the Wnt/β-catenin signaling pathway and high expression of the metastasis mediator S100A4. We previously demonstrated the transcriptional regulation of S100A4 by β-catenin and the importance of the interconnection of these cellular programs for metastasis. Here we probe the hypothesis that the nonsteroidal anti-inflammatory drug sulindac sulfide can inhibit colon cancer metastasis by intervening in β-catenin signaling and thereby interdicting S100A4. We treated colon cancer cell lines heterozygous for gain-of-function and wild-type β-catenin with sulindac. We analyzed sulindac's effects on β-catenin expression and subcellular localization, β-catenin binding to the T-cell factor (TCF/S100A4 promoter complex, S100A4 promoter activity, S100A4 expression, cell motility, and proliferation. Mice intrasplenically transplanted with S100A4-overexpressing colon cancer cells were treated with sulindac. Tumor growth and metastasis, and their β-catenin and S100A4 expressions, were determined. We report the expression knockdown of β-catenin by sulindac, leading to its reduced nuclear accumulation. The binding of β-catenin to TCF was clearly lowered, resulting in reduced S100A4 promoter activity and expression. This correlated well with the inhibition of cell migration and invasion, which could be rescued by ectopic S100A4 expression. In mice, sulindac treatment resulted in reduced tumor growth in the spleen (P = .014 and decreased liver metastasis in a human colon cancer xenograft model (P = .025. Splenic tumors and liver metastases of sulindac-treated mice showed lowered β-catenin and S100A4 levels. These results suggest that modulators of β-catenin signaling such as sulindac offer potential as antimetastatic agents by interdicting S100A4 expression.

  6. Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. (United States)

    Stein, Ulrike; Arlt, Franziska; Smith, Janice; Sack, Ulrike; Herrmann, Pia; Walther, Wolfgang; Lemm, Margit; Fichtner, Iduna; Shoemaker, Robert H; Schlag, Peter M


    Colon cancer metastasis is often associated with activation of the Wnt/β-catenin signaling pathway and high expression of the metastasis mediator S100A4. We previously demonstrated the transcriptional regulation of S100A4 by β-catenin and the importance of the interconnection of these cellular programs for metastasis. Here we probe the hypothesis that the nonsteroidal anti-inflammatory drug sulindac sulfide can inhibit colon cancer metastasis by intervening in β-catenin signaling and thereby interdicting S100A4. We treated colon cancer cell lines heterozygous for gain-of-function and wild-type β-catenin with sulindac. We analyzed sulindac's effects on β-catenin expression and subcellular localization, β-catenin binding to the T-cell factor (TCF)/S100A4 promoter complex, S100A4 promoter activity, S100A4 expression, cell motility, and proliferation. Mice intrasplenically transplanted with S100A4-overexpressing colon cancer cells were treated with sulindac. Tumor growth and metastasis, and their β-catenin and S100A4 expressions, were determined. We report the expression knockdown of β-catenin by sulindac, leading to its reduced nuclear accumulation. The binding of β-catenin to TCF was clearly lowered, resulting in reduced S100A4 promoter activity and expression. This correlated well with the inhibition of cell migration and invasion, which could be rescued by ectopic S100A4 expression. In mice, sulindac treatment resulted in reduced tumor growth in the spleen (P = .014) and decreased liver metastasis in a human colon cancer xenograft model (P = .025). Splenic tumors and liver metastases of sulindac-treated mice showed lowered β-catenin and S100A4 levels. These results suggest that modulators of β-catenin signaling such as sulindac offer potential as antimetastatic agents by interdicting S100A4 expression.

  7. Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells


    Mano Horinaka; Tatsushi Yoshida; Mitsuhiro Tomosugi; Shusuke Yasuda; Yoshihiro Sowa; Toshiyuki Sakai


    A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of...

  8. Synergistic induction of apoptosis by sulindac and simvastatin in A549 human lung cancer cells via reactive oxygen species-dependent mitochondrial dysfunction. (United States)

    Hwang, Ki-Eun; Park, Chul; Kwon, Su-Jin; Kim, Young-Suk; Park, Do-Sim; Lee, Mi-Kyung; Kim, Byoung-Ryun; Park, Seong-Hoon; Yoon, Kwon-Ha; Jeong, Eun-Taik; Kim, Hak-Ryul


    Prevention of lung cancer is more feasible and holds greater promise when different agents are used in combination to target multiple processes during carcinogenesis. The mechanisms by which non-steroidal anti-inflammatory drugs and statins inhibit cancer cell growth and induce apoptosis are not fully understood. This study was designed to investigate lung cancer chemoprevention through a mechanism-based approach using sulindac at low doses in combination with simvastatin. We found that sulindac-induced cytotoxicity was significantly enhanced in the presence of simvastatin. The combination of sulindac and simvastatin induced more extensive caspase-dependent apoptosis in A549 cells compared to that induced with either drug alone. The combination of sulindac and simvastatin also increased the loss of mitochondrial transmembrane potential (∆Ψm) and the cytosolic release of cytochrome c. In addition, ROS generation in cells treated with both sulindac and simvastatin was markedly increased compared to cells treated with either sulindac or simvastatin alone. The enhancement of ROS generation by sulindac and simvastatin was abrogated by pretreatment with NAC, which also prevented apoptosis and mitochondrial dysfunction induced by sulindac and simvastatin. These results suggest that sulindac and simvastatin-induced ROS generation in A549 lung cancer cells causes their accumulation in mitochondria, triggering the release of apoptogenic molecules from the mitochondria to the cytosol, and thus leading to caspase activation and cell death.

  9. Assessment of the involvement of oxidative stress and Mitogen-Activated Protein Kinase signaling pathways in the cytotoxic effects of arsenic trioxide and its combination with sulindac or its metabolites: sulindac sulfide and sulindac sulfone on human leukemic cell lines. (United States)

    Stępnik, M; Ferlińska, M; Smok-Pieniążek, A; Gradecka-Meesters, D; Arkusz, J; Stańczyk, M


    The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using L: -buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 μM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 μM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 μM) and DPI (0.0025-0.1 μM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

  10. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties


    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder


    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6 h post-adm...

  11. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis. (United States)

    Chaudhary, Sandeep C; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A; Kopelovich, Levy; Athar, Mohammad


    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (psulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial-mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways.

  12. Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yun-Lin Wu; Bo Sun; Xue-Jun Zhang; Sheng-Nian Wang; Heng-Yi He; Min-Min Qiao; Jie Zhong; Jia-Yu Xu


    AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC)cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG2and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX(2) and Bcl-2 were detected by Westem dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG2 and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG2 cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24hours incubation with sulindac at 2mmol. L-1 and 4mmol.L-1, the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG2 cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater then that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

  13. COX inhibitors Indomethacin and Sulindac derivatives as antiproliferative agents: synthesis, biological evaluation, and mechanism investigation. (United States)

    Chennamaneni, Snigdha; Zhong, Bo; Lama, Rati; Su, Bin


    Cyclooxygenase (COX) inhibitors Indomethacin and its structural analogs Sulindac exhibit cell growth inhibition and apoptosis inducing activities in various cancer cell lines via COX independent mechanisms. In this study, the molecular structures of Indomethacin and Sulindac were used as starting scaffolds to design novel analogs and their effects on the proliferation of human cancer cells were evaluated. Compared to Indomethacin and Sulindac inhibiting cancer cell proliferation with IC(50)s of more than 1 mM, the derivatives displayed significantly increased activities. Especially, one of the Indomethacin analogs inhibited the growth of a series of cancer cell lines with IC(50)s around 0.5 μM-3 μM. Mechanistic investigation revealed that the new analog was in fact a tubulin inhibitor, although the parental compound Indomethacin did not show any tubulin inhibitory activity. Tubulin polymerization assay indicated this compound inhibited tubulin assembly at high concentrations, but promoted this process at low concentrations which is a very unique mechanism. The binding mode of this compound in tubulin was predicted using the molecular docking simulation.

  14. Effects of intervention with sulindac and inulin/VSL#3 on mucosal and luminal factors in the pouch of patients with familial adenomatous polyposis

    NARCIS (Netherlands)

    Friederich, P.; Verschuur, J.; Heumen, B.W. van; Schaap-Roelofs, H.M.J.; Berkhout, M.; Nagtegaal, I.D.; Oijen, M.G.H. van; Krieken, J.H. van; Peters, W.H.M.; Nagengast, F.M.


    BACKGROUND/AIM: In order to define future chemoprevention strategies for adenomas or carcinomas in the pouch of patients with familial adenomatous polyposis (FAP), a 4-weeks intervention with (1) sulindac, (2) inulin/VSL#3, and (3) sulindac/inulin/VSL#3 was performed on 17 patients with FAP in a sin

  15. Effects of single-nucleotide polymorphisms of FMO3 and FMO6 genes on pharmacokinetic characteristics of sulindac sulfide in premature labor. (United States)

    Park, Sunny; Lee, Na Ra; Lee, Kyung Eun; Park, Jin Young; Kim, Young Ju; Gwak, Hye Sun


    This study aimed to investigate the effects of polymorphisms of the flavin-containing mono-oxygenase 3 (FMO3) and flavin-containing mono-oxygenase 6 (FMO6) genes on the pharmacokinetics of sulindac sulfide, the active metabolite of sulindac, in patients with preterm labor. Ten single-nucleotide polymorphisms (SNPs) were genotyped, and plasma sulindac sulfide concentrations were measured at 0, 1.5, 4, and 10 hours after drug administration. The area under the curve from time 0 to the last sampling time point (AUC(last)) for sulindac sulfide was obtained. The AUC(last) of sulindac sulfide was significantly higher in patients with variant-type homozygotes of FMO3 (rs909530) than those with ancestral alleles or heterozygotes. FMO3 (rs2266780) was in complete linkage disequilibrium with FMO6 (rs7885012), and there was marginal significance between the genotypes (P = 0.049). From multiple linear regression models, FMO3 (rs909530) was found to have significant influence on the AUClast of sulindac sulfide after adjusting for gestational age, weight, and all studied SNPs. The predictive contribution of rs909530 to the variability of sulindac sulfide AUC(last) was 27.0%. In conclusion, the results of this study could help clinicians predict the efficacies and side effects of sulindac in the development of individualized treatment of patients with preterm labor.

  16. The Role of NAG-1/GDF15 in the Inhibition of Intestinal Polyps in APC/Min Mice by Sulindac


    Wang, Xingya; Kingsley, Philip J.; Marnett, Larry J.; Thomas E Eling


    The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon carcinogenesis by NSAIDs, we evaluated several sulindac derivatives [des-methyl (DM)-sulindac sulfide and its ...

  17. Sulindac sulfide induces autophagic death in gastric epithelial cells via survivin down-regulation: a mechanism of NSAIDs-induced gastric injury. (United States)

    Chiou, Shiun-Kwei; Hoa, Neil; Hodges, Amy


    Sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID), has anti-tumorigenic and anti-inflammatory activities, but causes gastric mucosal damage. NSAIDs cause gastric injury in part by down-regulation of Survivin, an apoptosis inhibitor, resulting in apoptosis induction. Autophagy is a process that promotes cellular health by destroying unwanted cellular materials. Excessive autophagy induction could lead to a non-apoptotic cell death (autophagic cell death). The present study showed that sulindac sulfide at a physiological concentration also induces autophagic death in human gastric epithelial AGS and rat gastric epithelial RGM-1 cells, and that Survivin down-regulation is a mechanism involved: Sulindac sulfide treatment increased LC3b-II and APG7 levels and cytosolic vacuole formation, indications of autophagy induction, in AGS and RGM-1 cells. Sulindac sulfide treatment induced AGS and RGM-1 cell death, which was significantly reduced by pretreatment with the autophagy inhibitors 3-methyladenine and chloroquine, indicating that sulindac sulfide induced autophagic cell death. Stable overexpression of Survivin in RGM-1 cells did not inhibit the induction of LC3b-II levels or vacuole formation by sulindac sulfide, but significantly reduced the resulting cell death, suggesting that Survivin may inhibit autophagic cell death downstream of LC3b-II induction and vacuole formation. Indeed, siRNA depletion of LC3b in AGS cells inhibited the down-regulation of Survivin levels and the induction of cell death by sulindac sulfide, confirming that down-regulation of Survivin occurs in the autophagy pathway downstream of LC3b-II induction by sulindac sulfide. Induction of Survivin-dependent autophagic cell death is a novel mechanism by which sulindac sulfide induces gastric mucosal injury.

  18. The in vitro metabolism of phospho-sulindac amide, a novel potential anticancer agent. (United States)

    Xie, Gang; Cheng, Ka-Wing; Huang, Liqun; Rigas, Basil


    Phospho-sulindac amide (PSA) is a novel potential anti-cancer and anti-inflammatory agent. Here we report the metabolism of PSA in vitro. PSA was rapidly hydroxylated at its butane-phosphate moiety to form two di-hydroxyl-PSA and four mono-hydroxyl-PSA metabolites in mouse and human liver microsomes. PSA also can be oxidized or reduced at its sulindac moiety to form PSA sulfone and PSA sulfide, respectively. PSA was mono-hydroxylated and cleared more rapidly in mouse liver microsomes than in human liver microsomes. Of eight major human cytochrome P450s (CYPs), CYP3A4 and CYP2D6 exclusively catalyzed the hydroxylation and sulfoxidation reactions of PSA, respectively. We also examined the metabolism of PSA by three major human flavin monooxygenases (FMOs). FMO1, FMO3 and FMO5 were all capable of catalyzing the sulfoxidation (but not hydroxylation) of PSA, with FMO1 being by far the most active isoform. PSA was predominantly sulfoxidized in human kidney microsomes because FMO1 is the dominant isoform in human kidney. PSA (versus sulindac) is a preferred substrate of both CYPs and FMOs, likely because of its greater lipophilicity and masked-COOH group. Ketoconazole (a CYP3A4 inhibitor) and alkaline pH strongly inhibited the hydroxylation of PSA, but moderately suppressed its sulfoxidation in liver microsomes. Together, our results establish the metabolic pathways of PSA, identify the major enzymes mediating its biotransformations and reveal significant inter-species and inter-tissue differences in its metabolism.

  19. Diallyl trisulfide protects against ethanol-induced oxidative stress and apoptosis via a hydrogen sulfide-mediated mechanism. (United States)

    Chen, Lian-Yun; Chen, Qin; Zhu, Xiao-Jing; Kong, De-Song; Wu, Li; Shao, Jiang-Juan; Zheng, Shi-Zhong


    Garlic is one natural source of organic sulfur containing compounds and has shown promise in the treatment of chronic liver disease. Dietary garlic consumption is inversely correlated with the progression of alcoholic fatty liver (AFL), although the exact underlying mechanisms are not clear. Our previous studies also have shown that diallyl trisulfide (DATS), the primary organosulfur compound from Allium sativum L, displayed anti-lipid deposition and antioxidant properties in AFL. The aim of the present study was to clarify the underlying mechanisms. In the present study, we used the intragastric infusion model of alcohol administration and human normal liver cell line LO2 cultured with suitable ethanol to mimic the pathological condition of AFL. We showed that accumulation of intracellular reactive oxygen species (ROS) was lowered significantly by the administration of DATS, but antioxidant capacity was increased by DATS. Additionally, DATS inhibited hepatocyte apoptosis via down-regulating Bax expression and up-regulating Bcl-2 expression, and attenuated alcohol-induced caspase-dependent apoptosis. More importantly, using iodoacetamide (IAM) to block hydrogen sulfide (H2S) production from DATS, we noted that IAM abolished all the above effects of DATS in ethanol-treated LO2 cells. Lastly, we found DATS could increase the expressions of cystathionine gamma-lyase (CSE) and cystathionine beta-synthase (CBS), the major H2S-producing enzymes. These results demonstrate that DATS protect against alcohol-induced fatty liver via a H2S-mediated mechanism. Therefore, targeting H2S may play a therapeutic role for AFL.

  20. The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase. (United States)

    Zheng, Xuehua; Zhang, Liping; Zhai, Jing; Chen, Yunyun; Luo, Haibin; Hu, Xiaopeng


    Sulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that π-π stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo.

  1. NOSH-sulindac (AVT-18A) is a novel nitric oxide- and hydrogen sulfide-releasing hybrid that is gastrointestinal safe and has potent anti-inflammatory, analgesic, antipyretic, anti-platelet, and anti-cancer properties. (United States)

    Kashfi, Khosrow; Chattopadhyay, Mitali; Kodela, Ravinder


    Sulindac is chemopreventive and has utility in patients with familial adenomatous polyposis; however, side effects preclude its long-term use. NOSH-sulindac (AVT-18A) releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, anti-pyretic, anti-platelet, and anti-cancer properties of sulindac and NOSH-sulindac administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, number/size of hemorrhagic lesions in stomachs were counted. Tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Anti-cancer: We examined the effects of NOSH-sulindac on the growth properties of 12 human cancer cell lines of six different tissue origins. Both agents reduced PGE2 levels in stomach tissue; however, NOSH-sulindac did not cause any stomach ulcers, whereas sulindac caused significant bleeding. Lipid peroxidation induced by sulindac was higher than that from NOSH-sulindac. SOD activity was significantly lowered by sulindac but increased by NOSH-sulindac. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Sulindac increased plasma TNFα whereas this rise was lower in the NOSH-sulindac-treated animals. NOSH-sulindac inhibited the growth of all cancer cell lines studied, with potencies of 1000- to 9000-fold greater than that of sulindac. NOSH-sulindac inhibited cell proliferation, induced apoptosis, and caused G2/M cell

  2. Multistage vector delivery of sulindac and silymarin for prevention of colon cancer. (United States)

    Scavo, Maria Principia; Gentile, Emanuela; Wolfram, Joy; Gu, Jianhua; Barone, Michele; Evangelopoulos, Michael; Martinez, Jonathan O; Liu, Xuewu; Celia, Christian; Tasciotti, Ennio; Vilar, Eduardo; Shen, Haifa


    Familial adenomatous polyposis (FAP) is an inherited condition secondary to germline mutations in the APC gene, thus resulting in the formation of hundreds of colonic adenomas that eventually progress into colon cancer. Surgical removal of the colon remains the only treatment option to avoid malignancy, as long-term exposure to chemopreventive agents such as sulindac (a non-steroidal anti-inflammatory drug) and silymarin (phytoestrogen) is not feasible. Here, we have developed a multistage silicon-based drug delivery platform for sulindac and silymarin that preferentially interacts with colon cancer cells as opposed to normal intestinal mucosa. Preferential binding and internalization of these drugs into colon cancer cells was obtained using a targeting strategy against the protein meprin A, which we demonstrate is overexpressed in human colon cancer cells and in the small intestine of Apc(Min/+) mice. We propose that this delivery system could potentially be used to reduce drug-induced side effects in FAP patients, thus enabling long-term prevention of adenoma formation.

  3. Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect. (United States)

    Huang, Liqun; Zhu, Caihua; Sun, Yu; Xie, Gang; Mackenzie, Gerardo G; Qiao, George; Komninou, Despina; Rigas, Basil


    Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy. Here, we evaluated the effect of a new sulindac derivative, phospho-sulindac or OXT-922, on the growth of human cancer cell lines and its mechanism of action. OXT-922 inhibited the growth of human cancer cell lines originating from colon, pancreas and breast ~11- to 30-fold more potently than sulindac. This effect was mediated by a strong cytokinetic effect. Compared with control, OXT-922 inhibited cell proliferation by up to 67%, induced apoptosis 4.1-fold over control and blocked the G(1) to S cell cycle phase transition. OXT-922 suppressed the levels of cell cycle regulating proteins, including cyclins D(1) and D(3) and Cyclin-dependent kinases (CDK) 4 and 6. The levels of intracellular reactive oxygen species (ROS), especially those of mitochondrial O₂ⁱ⁻, were markedly elevated (5.5-fold) in response to OXT-922. ROS collapsed the mitochondrial membrane potential and triggered apoptosis, which was largely abrogated by antioxidants. OXT-922 suppressed nuclear factor-kappaB activation and downregulated thioredoxin-1 expression. It also suppressed the production of prostaglandin E(2) and decreased cyclooxygenase-1 expression. Similar to sulindac, OXT-922 enhanced spermidine/spermine N(1)-acetyltransferase activity, reduced the cellular polyamine content and synergized with difluoromethylornithine to inhibit cancer cell proliferation and induce apoptosis. Our results suggest that OXT-922 possesses promising anticancer properties and deserves further evaluation.

  4. Sulindac inhibits beta-catenin expression in normal-appearing colon of hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis patients

    NARCIS (Netherlands)

    Koornstra, JJ; Rijcken, FEM; Oldenhuis, CNAM; Zwart, N; van der Sluis, T; Hollema, H; deVries, EGE; Keller, JJ; Offerhaus, JA; Giardiello, FM; Kleibeuker, JH


    Sulindac reduces colorectal cancer risk in genetically susceptible humans and animals. The molecular mechanisms underlying these effects are incompletely understood. Many studies suggest an important role for induction of apoptosis involving the mitochondrial pathway and the death receptor pathway.

  5. Sulindac Sulfide Induces the Formation of Large Oligomeric Aggregates of the Alzheimer's Disease Amyloid-β Peptide Which Exhibit Reduced Neurotoxicity. (United States)

    Prade, Elke; Barucker, Christian; Sarkar, Riddhiman; Althoff-Ospelt, Gerhard; Lopez del Amo, Juan Miguel; Hossain, Shireen; Zhong, Yifei; Multhaup, Gerd; Reif, Bernd


    Alzheimer's disease is characterized by deposition of the amyloid β-peptide (Aβ) in brain tissue of affected individuals. In recent years, many potential lead structures have been suggested that can potentially be used for diagnosis and therapy. However, the mode of action of these compounds is so far not understood. Among these small molecules, the nonsteroidal anti-inflammatory drug (NSAID) sulindac sulfide received a lot of attention. In this manuscript, we characterize the interaction between the monomeric Aβ peptide and the NSAID sulindac sulfide. We find that sulindac sulfide efficiently depletes the pool of toxic oligomers by enhancing the rate of fibril formation. In vitro, sulindac sulfide forms colloidal particles which catalyze the formation of fibrils. Aggregation is immediate, presumably by perturbing the supersaturated Aβ solution. We find that sulindac sulfide induced Aβ aggregates are structurally homogeneous. The C-terminal part of the peptide adopts a β-sheet structure, whereas the N-terminus is disordered. The salt bridge between D23 and K28 is present, similar as in wild type fibril structures. (13)C-(19)F transferred echo double resonance experiments suggest that sulindac sulfide colocalizes with the Aβ peptide in the aggregate.

  6. Curcumin enhances the lung cancer chemopreventive efficacy of phospho-sulindac by improving its pharmacokinetics. (United States)

    Cheng, Ka-Wing; Wong, Chi C; Mattheolabakis, George; Xie, Gang; Huang, Liqun; Rigas, Basil


    Phospho-sulindac (PS) is a safe sulindac derivative with promising anticancer efficacy in colon cancer. We evaluated whether its combination with curcumin could enhance the efficacy in the treatment of lung cancer. Curcumin, the principal bioactive component in turmeric, has demonstrated versatile capabilities to modify the therapeutic efficacy of a wide range of anticancer agents. Here, we evaluated the effect of co-administration of curcumin on the anticancer activity of PS in a mouse xenograft model of human lung cancer. Curcumin enhanced the cellular uptake of PS in human lung and colon cancer cell lines. To assess the potential synergism between curcumin and PS in vivo, curcumin was suspended in 10% Tween-80 or formulated in micellar nanoparticles and given to mice by oral gavage prior to the administration of PS. Both formulations of curcumin significantly improved the pharmacokinetic profiles of PS, with the 10% Tween-80 suspension being much more effective than the nanoparticle formation. However, curcumin did not exhibit any significant modification of the metabolite profile of PS. Furthermore, in a mouse subcutaneous xenograft model of human lung cancer, PS (200 mg/kg) in combination with curcumin (500 mg/kg) suspended in 10% Tween-80 (51% inhibition, p<0.05) was significantly more efficacious than PS plus micelle curcumin (30%) or PS (25%) or curcumin alone (no effect). Consistent with the improved pharmacokinetics, the combination treatment group had higher levels of PS and its metabolites in the xenografts compared to PS alone. Our results show that curcumin substantially improves the pharmacokinetics of PS leading to synergistic inhibition of the growth of human lung cancer xenografts, representing a promising drug combination.

  7. Optimisation and validation of a fast HPLC method for the quantification of sulindac and its related impurities. (United States)

    Krier, Fabrice; Brion, Michaël; Debrus, Benjamin; Lebrun, Pierre; Driesen, Aurélie; Ziemons, Eric; Evrard, Brigitte; Hubert, Philippe


    The European Pharmacopoeia describes a liquid chromatography (LC) method for the quantification of sulindac, using a quaternary mobile phase including chloroform and with a rather long run time. In the present study, a new method using a short sub-2 μm column, which can be used on a classical HPLC system, was developed. The new LC conditions (without chloroform) were optimised by means of a new methodology based on design of experiments in order to obtain an optimal separation. Four factors were studied: the duration of the initial isocratic step, the percentage of organic modifier at the beginning of the gradient, the percentage of organic modifier at the end of the gradient and the gradient time. The optimal condition allows the separation of sulindac and of its 3 related impurities in 6 min instead of 18 min. Finally, the method was successfully validated using an accuracy profile approach in order to demonstrate its ability to accurately quantify these compounds.

  8. Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer. (United States)

    Cheng, Ka Wing; Mattheolabakis, George; Wong, Chi C; Ouyang, Nengtai; Huang, Liqun; Constantinides, Panayiotis P; Rigas, Basil


    Phospho-sulindac (P-S, OXT-328), a novel sulindac derivative, has shown superior anticancer efficacy and safety compared to sulindac. In this study, we investigated the efficacy of topical P-S hydrogel in the treatment of non-melanoma skin cancer in preclinical models. P-S is a potent inhibitor of A431 epidermoid carcinoma in vitro and achieves this effect by inhibiting cell proliferation and inducing apoptosis. The anticancer efficacy of topical and oral P-S was further evaluated in mice bearing A431 intradermal xenografts. Compared to the controls, topical P-S hydrogel inhibited the A431 xenografts by 70.5% (p500 nmol/g tumor tissue) of intact P-S in the tumors, accounting for 92.5% of the total metabolites in the A431 xenografts. This local delivery of high levels of intact P-S to the A431 xenografts is an important contributor to the potent activity of topical P-S and no local or systemic side effects were noted in the treatment group. Thus, topical P-S is a promising treatment modality against non-melanoma skin cancer and merits further evaluation.

  9. The influence of sulindac on diabetic cardiomyopathy: a non-invasive evaluation by Doppler echocardiography in streptozotocin-induced diabetic rats. (United States)

    Krishna, Kota M; Gopal, Gopisetty S; Chalam, Chitrapu R V; Madan, Kalagara; Kumar, Veeravalli K; Prakash, Gomedhikam J; Annapurna, Akula


    The aim of the present study was to investigate the cardioprotective activity of sulindac as an aldose reductase inhibitor in the development of cardiomyopathy by non-invasive techniques; M-mode and Doppler echocardiography. Diabetes was induced by streptozotocin (45 mg/kg, iv) in the Sprague-Dawley rats. Echocardiography, biochemical and histological studies were carried out in normal control, diabetic untreated, diabetic vehicle (sodium carboxy methyl cellulose, 1%, po) and sulindac (6 mg/kg and 20 mg/kg, po) treated animals at varying time intervals. In the diabetic untreated and vehicle treated rats at 12 weeks after induction of diabetes, there was a significant decrease in the E-wave, an increase in the A-wave and corresponding decrease in the E/A ratio was observed. Significant decrease in the Eat was found after 12 weeks (P rats (P rats, whereas in the sulindac (6 mg/kg) treated rats, minimal necrosis was found, with no evidence of necrosis in sulindac (20 mg/kg) group. Our results show for the first time that sulindac has a cardioprotective activity as this agent prevented the development of left ventricular dysfunction in STZ-induced diabetic rats in the 12-week chronic study.

  10. Sulindac compounds facilitate the cytotoxicity of β-lapachone by up-regulation of NAD(P)H quinone oxidoreductase in human lung cancer cells. (United States)

    Kung, Hsiu-Ni; Weng, Tsai-Yun; Liu, Yu-Lin; Lu, Kuo-Shyan; Chau, Yat-Pang


    β-lapachone, a major component in an ethanol extract of Tabebuia avellanedae bark, is a promising potential therapeutic drug for various tumors, including lung cancer, the leading cause of cancer-related deaths worldwide. In the first part of this study, we found that apoptotic cell death induced in lung cancer cells by high concentrations of β-lapachone was mediated by increased activation of the pro-apoptotic factor JNK and decreased activation of the cell survival/proliferation factors PI3K, AKT, and ERK. In addition, β-lapachone toxicity was positively correlated with the expression and activity of NAD(P)H quinone oxidoreductase 1 (NQO1) in the tumor cells. In the second part, we found that the FDA-approved non-steroidal anti-inflammatory drug sulindac and its metabolites, sulindac sulfide and sulindac sulfone, increased NQO1 expression and activity in the lung adenocarcinoma cell lines CL1-1 and CL1-5, which have lower NQO1 levels and lower sensitivity to β-lapachone treatment than the A549 cell lines, and that inhibition of NQO1 by either dicoumarol treatment or NQO1 siRNA knockdown inhibited this sulindac-induced increase in β-lapachone cytotoxicity. In conclusion, sulindac and its metabolites synergistically increase the anticancer effects of β-lapachone primarily by increasing NQO1 activity and expression, and these two drugs may provide a novel combination therapy for lung cancers.

  11. Sulindac compounds facilitate the cytotoxicity of β-lapachone by up-regulation of NAD(PH quinone oxidoreductase in human lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Hsiu-Ni Kung

    Full Text Available β-lapachone, a major component in an ethanol extract of Tabebuia avellanedae bark, is a promising potential therapeutic drug for various tumors, including lung cancer, the leading cause of cancer-related deaths worldwide. In the first part of this study, we found that apoptotic cell death induced in lung cancer cells by high concentrations of β-lapachone was mediated by increased activation of the pro-apoptotic factor JNK and decreased activation of the cell survival/proliferation factors PI3K, AKT, and ERK. In addition, β-lapachone toxicity was positively correlated with the expression and activity of NAD(PH quinone oxidoreductase 1 (NQO1 in the tumor cells. In the second part, we found that the FDA-approved non-steroidal anti-inflammatory drug sulindac and its metabolites, sulindac sulfide and sulindac sulfone, increased NQO1 expression and activity in the lung adenocarcinoma cell lines CL1-1 and CL1-5, which have lower NQO1 levels and lower sensitivity to β-lapachone treatment than the A549 cell lines, and that inhibition of NQO1 by either dicoumarol treatment or NQO1 siRNA knockdown inhibited this sulindac-induced increase in β-lapachone cytotoxicity. In conclusion, sulindac and its metabolites synergistically increase the anticancer effects of β-lapachone primarily by increasing NQO1 activity and expression, and these two drugs may provide a novel combination therapy for lung cancers.

  12. Sulindac derivatives inhibit cell growth and induce apoptosis in primary cells from malignant peripheral nerve sheath tumors of NF1-patients

    Directory of Open Access Journals (Sweden)

    Friedrich Reinhard E


    Full Text Available Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs are neoplasms leading to death in most cases. Patients with Neurofibromatosis type 1 have an increased risk of developing this malignancy. The metabolites of the inactive prodrug Sulindac, Sulindac Sulfide and Sulindac Sulfone (Exisulind are new chemopreventive agents that show promising results in the treatment of different cancer types. In this study we examined the antineoplastic effect of these compounds on primary cells derived from two MPNSTs of Neurofibromatosis type 1 patients. Results Exisulind and Sulindac Sulfide showed a dramatic time- and dose-dependent growth inhibitory effect with IC50-values of 120 μM and 63 μM, respectively. The decrease in viability of the tested cells correlated with induction of apoptosis. Treatment with 500 μM Exisulind and 125 μM Sulindac Sulfide for a period of 2 days increased the rate of apoptosis 21-27-fold compared to untreated cells. Reduced expression of RAS-GTP and phosphorylated ERK1/2 was detected in treated MPNST cells. Moreover, elevated levels of phosphorylated SAPK/JNK were found after drug treatment, and low activation of cleaved caspase-3 was seen. Conclusions Our results suggest that this class of compounds may be of therapeutic benefit for Neurofibromatosis type 1 patients with MPNST.

  13. Sulindac inhibits pancreatic carcinogenesis in LSL-KrasG12D-LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10). (United States)

    Li, Haonan; Yang, Allison L; Chung, Yeon Tae; Zhang, Wanying; Liao, Jie; Yang, Guang-Yu


    Sulindac has been identified as a competitive inhibitor of aldo-keto reductase 1B10 (AKR1B10), an enzyme that plays a key role in carcinogenesis. AKR1B10 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl. There have been no studies though showing that the inhibition of PDAC by sulindac is via inhibition of AKR1B10, particularly the metabolism of farnesyl/geranylgeranyl and Kras protein prenylation. To determine the chemopreventive effects of sulindac on pancreatic carcinogenesis, 5-week-old LSL-Kras(G12D)-LSL-Trp53(R172H)-Pdx-1-Cre mice (Pan(kras/p53) mice) were fed an AIN93M diet with or without 200 p.p.m. sulindac (n = 20/group). Kaplan-Meier survival analysis showed that average animal survival in Pan(kras/p53) mice was 143.7 ± 8.8 days, and average survival with sulindac was increased to 168.0 ± 8.8 days (P sulindac, the incidence of PDAC was reduced to 56% (P sulindac significantly decreased Ki-67-labeled cell proliferation and markedly reduced the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Raf and mitogen-activated protein kinase kinase 1 and 2. In in vitro experiments with PDAC cells from Pan(kras/p53) mice, sulindac exhibited dose-dependent inhibition of AKR1B10 activity. By silencing AKR1B10 expression through small interfering RNA or by sulindac treatment, these in vitro models showed a reduction in Kras and human DNA-J homolog 2 protein prenylation, and downregulation of phosphorylated C-raf, ERK1/2 and MEK1/2 expression. Our results demonstrate that sulindac inhibits pancreatic carcinogenesis by the inhibition of Kras protein prenylation by targeting AKR1B10.

  14. Inhibitory effect of herbal remedy PERVIVO and anti-inflammatory drug sulindac on L-1 sarcoma tumor growth and tumor angiogenesis in Balb/c mice. (United States)

    Skopiński, P; Bałan, B J; Kocik, J; Zdanowski, R; Lewicki, S; Niemcewicz, M; Gawrychowski, K; Skopińska-Różewska, E; Stankiewicz, W


    Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combined in vivo effect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

  15. Suppression of growth arrest and DNA damage-inducible 45alpha expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury. (United States)

    Chiou, Shiun-Kwei; Hodges, Amy; Hoa, Neil


    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin are a major cause of gastric erosions and ulcers. Induction of apoptosis by NSAIDs is an important mechanism involved. Understanding how NSAIDs affect genes that regulate apoptosis is useful for designing therapeutic or preventive strategies and for evaluating the efficacy of safer drugs being developed. We investigated whether growth arrest and DNA damage-inducible 45alpha (GADD45alpha), a stress signal response gene involved in regulation of DNA repair and induction of apoptosis, plays a part in NSAID-induced gastric mucosal injury and apoptosis in vivo in mice and in vitro in cultured human AGS and rat RGM-1 gastric epithelial cells. Intraperitoneal administration of sulindac and indomethacin both resulted in up-regulation of GADD45alpha expression and induction of significant injury and apoptosis in gastric mucosa of wild-type mice. GADD45alpha(-/-) mice were markedly more resistant to both sulindac- and indomethacin-induced gastric mucosal injury and apoptosis than wild-type mice. Sulindac sulfide and indomethacin treatments also concentration-dependently increased GADD45alpha expression and apoptosis in AGS and RGM-1 cells. Antisense suppression of GADD45alpha expression significantly reduced sulindac and indomethacin-induced activation of caspase-9 and apoptosis in AGS cells. Pretreatments with exogenous prostaglandins and small interfering RNA suppression of cyclooxygenase (COX)-1 and -2 did not affect up-regulation of GADD45alpha by sulindac sulfide and indomethacin in AGS cells. These findings indicate that GADD45alpha up-regulation is a COX-independent mechanism that is required for induction of severe gastric mucosal apoptosis and injury by NSAIDs, probably via a capase-9-dependent pathway of programmed cell death.

  16. Combination of atorvastatin with sulindac or naproxen profoundly inhibits colonic adenocarcinomas by suppressing the p65/β-catenin/cyclin D1 signaling pathway in rats. (United States)

    Suh, Nanjoo; Reddy, Bandaru S; DeCastro, Andrew; Paul, Shiby; Lee, Hong Jin; Smolarek, Amanda K; So, Jae Young; Simi, Barbara; Wang, Chung Xiou; Janakiram, Naveena B; Steele, Vernon; Rao, Chinthalapally V


    Evidence supports the protective role of nonsteroidal anti-inflammatory drugs (NSAID) and statins against colon cancer. Experiments were designed to evaluate the efficacies atorvastatin and NSAIDs administered individually and in combination against colon tumor formation. F344 rats were fed AIN-76A diet, and colon tumors were induced with azoxymethane. One week after the second azoxymethane treatment, groups of rats were fed diets containing atorvastatin (200 ppm), sulindac (100 ppm), naproxen (150 ppm), or their combinations with low-dose atorvastatin (100 ppm) for 45 weeks. Administration of atorvastatin at 200 ppm significantly suppressed both adenocarcinoma incidence (52% reduction, P = 0.005) and multiplicity (58% reduction, P = 0.008). Most importantly, colon tumor multiplicities were profoundly decreased (80%-85% reduction, P sulindac or naproxen. Also, a significant inhibition of colon tumor incidence was observed when given a low-dose atorvastatin with either sulindac (P = 0.001) or naproxen (P = 0.0005). Proliferation markers, proliferating cell nuclear antigen, cyclin D1, and β-catenin in tumors of rats exposed to sulindac, naproxen, atorvastatin, and/or combinations showed a significant suppression. Importantly, colon adenocarcinomas from atorvastatin and NSAIDs fed animals showed reduced key inflammatory markers, inducible nitric oxide synthase and COX-2, phospho-p65, as well as inflammatory cytokines, TNF-α, interleukin (IL)-1β, and IL-4. Overall, this is the first report on the combination treatment using low-dose atorvastatin with either low-dose sulindac or naproxen, which greatly suppress the colon adenocarcinoma incidence and multiplicity. Our results suggest that low-dose atorvastatin with sulindac or naproxen might potentially be useful combinations for colon cancer prevention in humans.

  17. Cyclooxygenase-1-selective inhibitors based on the (E)-2'-des-methyl-sulindac sulfide scaffold. (United States)

    Liedtke, Andy J; Crews, Brenda C; Daniel, Cristina M; Blobaum, Anna L; Kingsley, Philip J; Ghebreselasie, Kebreab; Marnett, Lawrence J


    Prostaglandins (PGs) are powerful lipid mediators in many physiological and pathophysiological responses. They are produced by oxidation of arachidonic acid (AA) by cyclooxygenases (COX-1 and COX-2) followed by metabolism of endoperoxide intermediates by terminal PG synthases. PG biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). Specific inhibition of COX-2 has been extensively investigated, but relatively few COX-1-selective inhibitors have been described. Recent reports of a possible contribution of COX-1 in analgesia, neuroinflammation, or carcinogenesis suggest that COX-1 is a potential therapeutic target. We designed, synthesized, and evaluated a series of (E)-2'-des-methyl-sulindac sulfide (E-DMSS) analogues for inhibition of COX-1. Several potent and selective inhibitors were discovered, and the most promising compounds were active against COX-1 in intact ovarian carcinoma cells (OVCAR-3). The compounds inhibited tumor cell proliferation but only at concentrations >100-fold higher than the concentrations that inhibit COX-1 activity. E-DMSS analogues may be useful probes of COX-1 biology in vivo and promising leads for COX-1-targeted therapeutic agents.

  18. New Form Discovery for the Analgesics Flurbiprofen and Sulindac Facilitated by Polymer-Induced Heteronucleation (United States)



    The selection and discovery of new crystalline forms is a longstanding issue in solid-state chemistry of critical importance because of the effect molecular packing arrangement exerts on materials properties. Polymer-induced heteronucleation has recently been developed as a powerful approach to discover and control the production of crystal modifications based on the insoluble polymer heteronucleant added to the crystallization solution. The selective nucleation and discovery of new crystal forms of the well-studied pharmaceuticals flurbiprofen (FBP) and sulindac (SUL) has been achieved utilizing this approach. For the first time, FBP form III was produced in bulk quantities and its crystal structure was also determined. Furthermore, a novel 3:2 FBP:H2O phase was discovered that nucleates selectively from only a few polymers. Crystallization of SUL in the presence of insoluble polymers facilitated the growth of form I single crystals suitable for structure determination. Additionally, a new SUL polymorph (form IV) was discovered by this method. The crystal forms of FBP and SUL are characterized by Raman and FTIR spectroscopies, X-ray diffraction, and differential scanning calorimetry. PMID:17567888

  19. Sulindac selectively inhibits colon tumor cell growth by activating the cGMP/PKG pathway to suppress Wnt/β-catenin signaling. (United States)

    Li, Nan; Xi, Yaguang; Tinsley, Heather N; Gurpinar, Evrim; Gary, Bernard D; Zhu, Bing; Li, Yonghe; Chen, Xi; Keeton, Adam B; Abadi, Ashraf H; Moyer, Mary P; Grizzle, William E; Chang, Wen-Chi; Clapper, Margie L; Piazza, Gary A


    Nonsteroidal anti-inflammatory drugs (NSAID) display promising antineoplastic activity for colorectal and other cancers, but toxicity from COX inhibition limits their long-term use for chemoprevention. Previous studies have concluded that the basis for their tumor cell growth inhibitory activity does not require COX inhibition, although the underlying mechanism is poorly understood. Here, we report that the NSAID sulindac sulfide inhibits cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE) activity to increase intracellular cGMP levels and activate cGMP-dependent protein kinase (PKG) at concentrations that inhibit proliferation and induce apoptosis of colon tumor cells. Sulindac sulfide did not activate the cGMP/PKG pathway, nor affect proliferation or apoptosis in normal colonocytes. Knockdown of the cGMP-specific PDE5 isozyme by siRNA and PDE5-specific inhibitors tadalafil and sildenafil also selectively inhibited the growth of colon tumor cells that expressed high levels of PDE5 compared with colonocytes. The mechanism by which sulindac sulfide and the cGMP/PKG pathway inhibits colon tumor cell growth involves the transcriptional suppression of β-catenin to inhibit Wnt/β-catenin T-cell factor transcriptional activity, leading to downregulation of cyclin D1 and survivin. These observations suggest that safer and more efficacious sulindac derivatives can be developed for colorectal cancer chemoprevention by targeting PDE5 and possibly other cGMP-degrading isozymes.

  20. Phospho-sulindac inhibits pancreatic cancer growth: NFATc1 as a drug resistance candidate. (United States)

    Murray, Onika T; Wong, Chi C; Vrankova, Kvetoslava; Rigas, Basil


    Phospho-sulindac (P-S), a promising anticancer agent, is efficacious in pre-clinical models of human cancer and is apparently safe. Here, we studied the effect of P-S on pancreatic cancer growth. We found that P-S strongly inhibits the growth of human pancreatic cancer cells in vitro, is efficacious in inhibiting the growth of pancreatic xenografts in nude mice, and has an excellent safety profile. Microarray analysis revealed that P-S induced the expression of nuclear factor of activated T-cells, isoform c1 (NFATc1) gene. NFATc1, a calcineurin-responsive transcription factor associated with aggressive pancreatic cancer. The role of increased NFATc1 expression on the growth inhibitory effect of P-S on cancer growth was evaluated by silencing or by overexpressing it both in vitro and in vivo. We found that when the expression of NFATc1 was abrogated by RNAi, pancreatic cancer cells were more responsive to treatment with P-S. Conversely, overexpressing the NFATc1 gene made the pancreatic cancer cells less responsive to treatment with P-S. NFATc1 likely mediates drug resistance to P-S and is an unfavorable prognostic factor that predicts poor tumor response. We also demonstrated that NFATc1-mediated resistance can be overcome by cyclosporin A (CsA), an NFAT inhibitor, and that the combination of P-S and CsA synergistically inhibited pancreatic cancer cell growth. In conclusion, our preclinical data establish P-S as an efficacious drug for pancreatic cancer in preclinical models, which merits further evaluation.

  1. Garcinia benzophenones inhibit the growth of human colon cancer cells and synergize with sulindac sulfide and turmeric. (United States)

    Einbond, Linda Saxe; Mighty, Jason; Kashiwazaki, Ryota; Figueroa, Mario; Jalees, Filza; Acuna, Ulyana Munoz; Le Gendre, Onica; Foster, David A; Kennelly, Edward J


    Previous studies indicate that extracts and purified components from Garcinia species inhibit the growth of human colon cancer cells. Garcinia benzophenones activate the expression of genes in the endoplasmic reticulum and cellular energy stress (mTOR) pathways. This study examines the growth inhibitory and synergistic effects of Garcinia benzophenones, alone or combined with chemopreventive agents, on human colon cancer cells. To find optimal combination treatments, HT29 colon cancer cells were treated with benzophenones alone, or combined with chemopreventive agents, and cell growth measured using the MTT assay. To reveal effects on signaling pathways, we assessed effects of the MEK inhibitor U0126 and the ER IP3 receptor antagonist heparin, as well as effects on the phosphorylation of 4E-BP-1 (mTOR pathway), using Western blot analysis. New and known benzophenones from Garcinia intermedia inhibited the growth of human colon cancer cells; an alcohol extract of Garcinia xanthochymus, as well as purified guttiferones (guttiferone E and xanthochymol), preferentially inhibited the growth of colon cancer versus nonmalignant intestinal epithelial cells. Guttiferone E exhibited synergy with the NSAID sulindac sulfide and xanthochymol, with the spice turmeric. Guttiferone A did not alter phosphorylation of 4E-BP-1, indicating that the mTORC1 pathway is not involved in its action. The effects of xanthochymol were enhanced by U0126, at low doses, and were blocked by heparin, indicating that the MEK pathway is involved, while the ER IP3 receptor is critical for its action. These studies indicate the potential of benzophenones, alone or combined with sulindac sulfide or turmeric, to prevent and treat colon cancer.

  2. Suppression of angiogenic activity of sera from diabetic patients with non-proliferative retinopathy by compounds of herbal origin and sulindac sulfone. (United States)

    Skopinski, Piotr; Szaflik, Jerzy; Duda-Król, Barbara; Nartowska, Jadwiga; Sommer, Ewa; Chorostowska-Wynimko, Joanna; Demkow, Urszula; Skopinska-Rózewska, Ewa


    Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathological processes including diabetic retinopathy. The physiological control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 micro g/ml, as well as for the low-dosage concomitant treatment with 2 micro g/ml of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 micro g/ml) or lowest doses of tested compounds. The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis experimental model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive anti-angiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.

  3. Sulindac sulfide reverses aberrant self-renewal of progenitor cells induced by the AML-associated fusion proteins PML/RARα and PLZF/RARα. (United States)

    Steinert, Gunnar; Oancea, Claudia; Roos, Jessica; Hagemeyer, Heike; Maier, Thorsten; Ruthardt, Martin; Puccetti, Elena


    Chromosomal translocations can lead to the formation of chimeric genes encoding fusion proteins such as PML/RARα, PLZF/RARα, and AML-1/ETO, which are able to induce and maintain acute myeloid leukemia (AML). One key mechanism in leukemogenesis is increased self renewal of leukemic stem cells via aberrant activation of the Wnt signaling pathway. Either X-RAR, PML/RARα and PLZF/RARα or AML-1/ETO activate Wnt signaling by upregulating γ-catenin and β-catenin. In a prospective study, a lower risk of leukemia was observed with aspirin use, which is consistent with numerous studies reporting an inverse association of aspirin with other cancers. Furthermore, a reduction in leukemia risk was associated with use of non-steroidal anti-inflammatory drug (NSAID), where the effects on AML risk was FAB subtype-specific. To better investigate whether NSAID treatment is effective, we used Sulindac Sulfide in X-RARα-positive progenitor cell models. Sulindac Sulfide (SSi) is a derivative of Sulindac, a NSAID known to inactivate Wnt signaling. We found that SSi downregulated both β-catenin and γ-catenin in X-RARα-expressing cells and reversed the leukemic phenotype by reducing stem cell capacity and increasing differentiation potential in X-RARα-positive HSCs. The data presented herein show that SSi inhibits the leukemic cell growth as well as hematopoietic progenitors cells (HPCs) expressing PML/RARα, and it indicates that Sulindac is a valid molecular therapeutic approach that should be further validated using in vivo leukemia models and in clinical settings.

  4. Sulindac sulfide reverses aberrant self-renewal of progenitor cells induced by the AML-associated fusion proteins PML/RARα and PLZF/RARα.

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    Gunnar Steinert

    Full Text Available Chromosomal translocations can lead to the formation of chimeric genes encoding fusion proteins such as PML/RARα, PLZF/RARα, and AML-1/ETO, which are able to induce and maintain acute myeloid leukemia (AML. One key mechanism in leukemogenesis is increased self renewal of leukemic stem cells via aberrant activation of the Wnt signaling pathway. Either X-RAR, PML/RARα and PLZF/RARα or AML-1/ETO activate Wnt signaling by upregulating γ-catenin and β-catenin. In a prospective study, a lower risk of leukemia was observed with aspirin use, which is consistent with numerous studies reporting an inverse association of aspirin with other cancers. Furthermore, a reduction in leukemia risk was associated with use of non-steroidal anti-inflammatory drug (NSAID, where the effects on AML risk was FAB subtype-specific. To better investigate whether NSAID treatment is effective, we used Sulindac Sulfide in X-RARα-positive progenitor cell models. Sulindac Sulfide (SSi is a derivative of Sulindac, a NSAID known to inactivate Wnt signaling. We found that SSi downregulated both β-catenin and γ-catenin in X-RARα-expressing cells and reversed the leukemic phenotype by reducing stem cell capacity and increasing differentiation potential in X-RARα-positive HSCs. The data presented herein show that SSi inhibits the leukemic cell growth as well as hematopoietic progenitors cells (HPCs expressing PML/RARα, and it indicates that Sulindac is a valid molecular therapeutic approach that should be further validated using in vivo leukemia models and in clinical settings.

  5. Genotoxicity of the cyclo-oxygenase-inhibitor sulindac sulfide in the filamentous fungus Aspergillus nidulans Genotoxicidade de sulfeto de sulindaco em Aspergillus nidulans

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    Claudinéia Conationi da Silva Franco


    Full Text Available Sulindac sulfide is a non-steroidal anti-inflammatory drug (NSAID with chemopreventive effect on human cancer cells. Due to the involvement of the somatic recombination in the carcinogenic process, sulindac sulfide's recombinogenic potential was evaluated by the Homozygotization Index (HI in the filamentous fungus Aspergillus nidulans. The drug's recombinogenic potential was evaluated by its capacity to induce homozygosis of recessive genes from heterozygous diploid cells. Sulindac sulfide at 175 and 350 µM concentrations induced mitotic recombination in A. nidulans diploid cells, with HI values for genetic markers higher than 2.0, and significantly different from control HI values. The recombinogenic effect of NSAID was related to the induction of DNA strand breaks and cell cycle alterations. Sulindac sulfide's carcinogenic potential was also discussed.Sulfeto de sulindaco é um antiinflamatório não-esteroidal com efeitos quimiopreventivos em cânceres humanos. O presente estudo teve como objetivo avaliar o potencial recombinagênico do sulfeto de sulindaco em células diplóides de Aspergillus nidulans. O efeito recombinagênico da droga foi demonstrado através da homozigotização de genes recessivos, previamente presentes em heterozigose. Os valores de HI (Índice de Homozigotização para diferentes marcadores genéticos apresentaram-se maiores do que 2,0 e significativamente diferentes dos valores obtidos em sulfeto de sulindaco ausência da droga (controle. O potencial recombinagênico do sulfeto de sulindaco foi associado à indução de quebras na molécula do DNA e a alterações no ciclo celular. O potencial carcinogênico do sulfeto de sulindaco foi discutido no presente trabalho.

  6. Structural Mechanism of the Interaction of Alzheimer Disease Aβ Fibrils with the Non-steroidal Anti-inflammatory Drug (NSAID) Sulindac Sulfide. (United States)

    Prade, Elke; Bittner, Heiko J; Sarkar, Riddhiman; Lopez Del Amo, Juan Miguel; Althoff-Ospelt, Gerhard; Multhaup, Gerd; Hildebrand, Peter W; Reif, Bernd


    Alzheimer disease is the most severe neurodegenerative disease worldwide. In the past years, a plethora of small molecules interfering with amyloid-β (Aβ) aggregation has been reported. However, their mode of interaction with amyloid fibers is not understood. Non-steroidal anti-inflammatory drugs (NSAIDs) are known γ-secretase modulators; they influence Aβ populations. It has been suggested that NSAIDs are pleiotrophic and can interact with more than one pathomechanism. Here we present a magic angle spinning solid-state NMR study demonstrating that the NSAID sulindac sulfide interacts specifically with Alzheimer disease Aβ fibrils. We find that sulindac sulfide does not induce drastic architectural changes in the fibrillar structure but intercalates between the two β-strands of the amyloid fibril and binds to hydrophobic cavities, which are found consistently in all analyzed structures. The characteristic Asp(23)-Lys(28) salt bridge is not affected upon interacting with sulindac sulfide. The primary binding site is located in the vicinity of residue Gly(33), a residue involved in Met(35) oxidation. The results presented here will assist the search for pharmacologically active molecules that can potentially be employed as lead structures to guide the design of small molecules for the treatment of Alzheimer disease.

  7. Inhibition of breast cancer cell motility with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFβ/miR-21 signaling. (United States)

    Yi, Bin; Chang, Hong; Ma, Ruixia; Feng, Xiangling; Li, Wei; Piazza, Gary A; Xi, Yaguang


    Compelling efficacy on intervention of tumorigenesis by nonsteroidal anti-inflammatory drugs (NSAIDs) has been documented intensively. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for human cancer chemoprevention. A novel derivative of the NSAID sulindac sulfide (SS), referred as sulindac sulfide amide (SSA), was recently developed, which lacks COX inhibitory activity, yet shows greater suppressive effect than SS on growth of various cancer cells. In this study, we focus on the inhibitory activity of SSA on breast tumor cell motility, which has not been studied previously. Our results show that SSA treatment at non-cytotoxic concentrations can specifically reduce breast tumor cell motility without influencing tumor cell growth, and the mechanism of action involves the suppression of TGFβ signaling by directly blocking Smad2/3 phosphorylation. Moreover, miR-21, a well-documented oncogenic miRNA for promoting tumor cell metastasis, was also found to be involved in inhibitory activity of SSA in breast tumor cell motility through the modulation of TGFβ pathway. In conclusion, we demonstrate that a non-COX inhibitory derivative of sulindac can inhibit breast tumor metastasis by a mechanism involving the TGFβ/miR-21 signaling axis.

  8. Inhibitory Effect of Herbal Remedy PERVIVO and Anti-Inflammatory Drug Sulindac on L-1 Sarcoma Tumor Growth and Tumor Angiogenesis in Balb/c Mice

    Directory of Open Access Journals (Sweden)

    P. Skopiński


    Full Text Available Anticancer activity of many herbs was observed for hundreds of years. They act as modifiers of biologic response, and their effectiveness may be increased by combining multiple herbal extracts . PERVIVO, traditional digestive herbal remedy, contains some of them, and we previously described its antiangiogenic activity. Numerous studies documented anticancer effects of nonsteroidal anti-inflammatory drugs. We were the first to show that sulindac and its metabolites inhibit angiogenesis. In the present paper the combined in vivo effect of multicomponent herbal remedy PERVIVO and nonsteroidal anti-inflammatory drug sulindac on tumor growth, tumor angiogenesis, and tumor volume in Balb/c mice was studied. These effects were checked after grafting cells collected from syngeneic sarcoma L-1 tumors into mice skin. The strongest inhibitory effect was observed in experimental groups treated with PERVIVO and sulindac together. The results of our investigation showed that combined effect of examined drugs may be the best way to get the strongest antiangiogenic and antitumor effect.

  9. Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells. (United States)

    Gong, Eun-Yeung; Shin, Yu Jin; Hwang, Ih-Yeon; Kim, Jeong Hee; Kim, Seung-Mi; Moon, Jai-Hee; Shin, Jae-Sik; Lee, Dae-Hee; Hur, Dae Young; Jin, Dong-Hoon; Hong, Seung-Woo; Lee, Won Keun; Lee, Wang-Jae


    Sulindac has anti-neoplastic properties against colorectal cancers; however, its use as a chemopreventive agent has been limited due to toxicity and efficacy concerns. Combinatorial treatment of colorectal cancers has been attempted to maximize anti-cancer efficacy with minimal side effects by administrating NSAIDs in combination with other inhibitory compounds or drugs such as l-ascorbic acid (vitamin C), which is known to exhibit cytotoxicity towards various cancer cells at high concentrations. In this study, we evaluated a combinatorial strategy utilizing sulindac and vitamin C. The death of HCT116 cells upon combination therapy occurred via a p53-mediated mechanism. The combination therapeutic resistance developed in isogenic p53 null HCT116 cells and siRNA-mediated p53 knockdown HCT116 cells, but the exogenous expression of p53 in p53 null isogenic cells resulted in the induction of cell death. In addition, we investigated an increased level of intracellular ROS (reactive oxygen species), which was preceded by p53 activation. The expression level of PUMA (p53-upregulated modulator of apoptosis), but not Bim, was significantly increased in HCT116 cells in response to the combination treatment. Taken together, our results demonstrate that combination therapy with sulindac and vitamin C could be a novel anti-cancer therapeutic strategy for p53 wild type colon cancers.

  10. 舒林酸对丙戊酸孤独症动物模型大鼠氧化应激变化的影响%Effects of sulindac on oxidative stress in an autistic model induced by pre-natal exposure to valproic acid

    Institute of Scientific and Technical Information of China (English)

    张应花; 杨彩玲; 崔卫刚; 王中平; 小军; 李瑞锡


    [ ABSTRACT] AIM:To investigate the effects of sulindac on oxidative stress in autism.METHODS:With an au-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of canonical Wnt pathway in the prefrontal cortex ( PFC) and hippocampus ( HC) of autistic rats treated with sulindac.The protein expression levels of glycogen synthase kinase 3β(GSK-3β), β-catenin and 4-hydroxynonenal (4-HNE) were ob-served by Western blotting.The mRNA expression of thioredoxin(Trx)1 and Trx2 was assessed by semi-quantitative RT-PCR.RESULTS:The protein level of GSK-3βand mRNA levels of Trx1 and Trx2 were lower, whereas the protein expres-sion levels ofβ-catenin and 4-HNE were higher in VPA group than those in control group.In contrast, the protein levels of GSK-3βwere significantly higher in the animals treated with both VPA and sulindac than those in VPA group, while the lev-els ofβ-catenin and 4-HNE were decreased.CONCLUSION:Sulindac attenuates oxidative stress in the pathogenesis of au-tism, suggesting the up-regulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and further facili-tates susceptibility to autism.%目的:探讨舒林酸对孤独症发生过程中氧化应激变化的影响。方法:利用丙戊酸( VPA)孤独症动物模型,检测经典Wnt信号通路特异性抑制剂舒林酸处理后经典Wnt信号通路及氧化应激标志物在孤独症模型大鼠前额叶皮质及海马脑区的表达变化。 Western blotting法检测糖原合成激酶3β( GSK-3β)、β-catenin和4-羟基壬烯醛(4-HNE)表达,半定量RT-PCR法检测硫氧还蛋白(Trx)1和Trx2 mRNA表达。结果:与对照组相比,在前额叶皮质及海马脑区VPA组GSK-3β蛋白表达减少, Trx1和Trx mRNA 表达减少,β-catenin与4-HNE的表达增加;而与VPA组相比,VPA与舒林酸同时处理组GSK-3β的表达显著增加,β-catenin和4-HNE的表达显著减少

  11. A novel COX-independent mechanism of sulindac sulfide involves cleavage of epithelial cell adhesion molecule protein. (United States)

    Liggett, Jason L; Min, Kyung-Won; Smolensky, Dmitriy; Baek, Seung Joon


    Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.

  12. Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation to induce apoptosis during initial stages of experimental colorectal cancer. (United States)

    Vaish, Vivek; Rana, Chandan; Piplani, Honit; Vaiphei, Kim; Sanyal, Sankar Nath


    In the present study we have elaborated the putative mechanisms could be followed by the non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and Celecoxib in the regulation of cell cycle checkpoints along with tumor suppressor proteins to achieve their chemopreventive effects in the initial stages of experimental colorectal cancer. Male Sprague-Dawley rats were administered with 1,2-dimethylhydrazine dihydrochloride (DMH) to produce early stages of colorectal carcinogenesis. The mRNA expression profiles of various target genes were analyzed by RT-PCR and validated by quantitative real-time PCR, whereas protein expression was analyzed by Western blotting. Nuclear localization of transcription factors or other nuclear proteins was analyzed by electrophoretic mobility shift assay and immunofluorescence. Flowcytometry was performed to analyze the differential apoptotic events and cell cycle regulation. Molecular docking studies with different target proteins were also performed to deduce the various putative mechanisms of action followed by Sulindac and Celecoxib. We observed that DMH administration has abruptly increased the proliferation of colonic cells which is macroscopically visible in the form of multiple plaque lesions and co-relates with the disturbed molecular mechanisms of cell cycle regulation. However, co-administration of NSAIDs has shown regulatory effects on cell cycle checkpoints via induction of various tumor suppressor proteins. We may conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated regulation of cell proliferation, where down regulation of NF-κB signaling and activation of PPARγ might serve as important additional events in vivo.

  13. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo; Beom; Eom; Hokyung; Kim; Jinchae; Kim; Un-Chul; Paek; Byeong; Ha; Lee


    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  14. Tracer attenuation in groundwater (United States)

    Cvetkovic, Vladimir


    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.

  15. Effect of Sulindac Binary System on In Vitro and In Vivo Release Profiles: An Assessment of Polymer Type and Its Ratio (United States)


    The bioavailability of sulindac (SDC), a nonsteroidal anti-inflammatory drug, is low due to poor aqueous solubility and poor dissolution rate. For this reason it is necessary to enhance the solubility and enhance dissolution of the drug by dispersing SDC in polyethylene glycols 6000 (PEG 6000) and polyvinyl pyrrolidone 40000 (PVP 40000) matrices using the coevaporation technique. Studying the influence of SDC to polymer ratio on drug content, percent yield, particle size, and in vitro release was performed. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize any change in crystal habit of SDC in the prepared formulae. The anti-inflammatory effect of SDC was studied using the hind paw edema model. It was found that incorporation of SDC in PEG 6000 and PVP 40000 matrices resulted in improving the dissolution rate, which was found to depend on the polymer and its weight ratio of the drug. It is clearly obvious that the dissolution rate was remarkably improved in drug PVP 40000 molecular dispersions when compared to drug PEG 6000 systems. Solid dispersion of SDC in PEG and PVP improved the anti-inflammatory effect of SDC and it was found that formula SDV5 exhibited a more pronounced inhibition of swelling than other formulae. PMID:27840824

  16. Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: relevant similarities to and important differences from celecoxib. (United States)

    White, M C; Johnson, G G; Zhang, W; Hobrath, J V; Piazza, G A; Grimaldi, M


    Malignant gliomas have low survival expectations regardless of current treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) prevent cell transformation and slow cancer cell growth by mechanisms independent of cyclooxygenase (COX) inhibition. Certain NSAIDs trigger the endoplasmic reticulum stress response (ERSR), as revealed by upregulation of molecular chaperones such as GRP78 and C/EBP homologous protein (CHOP). Although celecoxib (CELE) inhibits the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), an effect known to induce ERSR, sulindac sulfide (SS) has not been reported to affect SERCA. Here, we investigated these two drugs for their effects on Ca(2+) homeostasis, ERSR, and glioma cell survival. Our findings indicate that SS is a reversible inhibitor of SERCA and that both SS and CELE bind SERCA at its cyclopiazonic acid binding site. Furthermore, CELE releases additional Ca(2+) from the mitochondria. In glioma cells, both NSAIDS upregulate GRP78 and activate ER-associated caspase-4 and caspase-3. Although only CELE upregulates the expression of CHOP, it appears that CHOP induction could be associated with mitochondrial poisoning. In addition, CHOP induction appears to be uncorrelated with the gliotoxicity of these NSAIDS in our experiments. Our data suggest that activation of ERSR is primarily responsible for the gliotoxic effect of these NSAIDS. Because SS has good brain bioavailability, has lower COX-2 inhibition, and has no mitochondrial effects, it represents a more appealing molecular candidate than CELE to achieve gliotoxicity via activation of ERSR.

  17. Effect of Sulindac Binary System on In Vitro and In Vivo Release Profiles: An Assessment of Polymer Type and Its Ratio

    Directory of Open Access Journals (Sweden)

    Gamal A. Shazly


    Full Text Available The bioavailability of sulindac (SDC, a nonsteroidal anti-inflammatory drug, is low due to poor aqueous solubility and poor dissolution rate. For this reason it is necessary to enhance the solubility and enhance dissolution of the drug by dispersing SDC in polyethylene glycols 6000 (PEG 6000 and polyvinyl pyrrolidone 40000 (PVP 40000 matrices using the coevaporation technique. Studying the influence of SDC to polymer ratio on drug content, percent yield, particle size, and in vitro release was performed. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize any change in crystal habit of SDC in the prepared formulae. The anti-inflammatory effect of SDC was studied using the hind paw edema model. It was found that incorporation of SDC in PEG 6000 and PVP 40000 matrices resulted in improving the dissolution rate, which was found to depend on the polymer and its weight ratio of the drug. It is clearly obvious that the dissolution rate was remarkably improved in drug PVP 40000 molecular dispersions when compared to drug PEG 6000 systems. Solid dispersion of SDC in PEG and PVP improved the anti-inflammatory effect of SDC and it was found that formula SDV5 exhibited a more pronounced inhibition of swelling than other formulae.

  18. Landing gear noise attenuation (United States)

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


    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.

  19. Planetary Ices Attenuation Properties (United States)

    McCarthy, Christine; Castillo-Rogez, Julie C.

    In this chapter, we review the topic of energy dissipation in the context of icy satellites experiencing tidal forcing. We describe the physics of mechanical dissipation, also known as attenuation, in polycrystalline ice and discuss the history of laboratory methods used to measure and understand it. Because many factors - such as microstructure, composition and defect state - can influence rheological behavior, we review what is known about the mechanisms responsible for attenuation in ice and what can be inferred from the properties of rocks, metals and ceramics. Since attenuation measured in the laboratory must be carefully scaled to geologic time and to planetary conditions in order to provide realistic extrapolation, we discuss various mechanical models that have been used, with varying degrees of success, to describe attenuation as a function of forcing frequency and temperature. We review the literature in which these models have been used to describe dissipation in the moons of Jupiter and Saturn. Finally, we address gaps in our present knowledge of planetary ice attenuation and provide suggestions for future inquiry.

  20. Frequency Dependent Attenuation Revisited

    CERN Document Server

    Richard, Kowar; Xavier, Bonnefond


    The work is inspired by thermo-and photoacoustic imaging, where recent efforts are devoted to take into account attenuation and varying wave speed parameters. In this paper we study causal equations describing propagation of attenuated pressure waves. We review standard models like frequency power laws and and the thermo-viscous equation. The lack of causality of standard models in the parameter range relevant for photoacoustic imaging requires to derive novel equations. The main ingredients for deriving causal equations are the Kramers-Kronig relation and the mathematical concept of linear system theory. The theoretical results of this work are underpined by numerical experiments.

  1. The inhibitory effect of Sulindac on human pancreatic cancer cells' proliferation by targeting survivin/ Aurora B pathway%舒林酸经survivin/Aurora B途径对人胰腺癌细胞分裂的阻断效应

    Institute of Scientific and Technical Information of China (English)

    范学科; 廖宇圣; 张翠芳; 陈芬; 高慧涛; 覃华; 李德民; 赵秋


    Objective To observe the expression of survivin and Aurora B in human pancreatic cancer BXPC3 cells after the treatment of sulindac and to explore the potential mechanism. Methods MTr assay was used to determine the effect of sulindac on the proliferation of the BXPC3 cells. RT-PCR was used to detect the expression of mRNA level of survivin and Aurora B, western blot was used to detect protein expression of survivin and Aurora B Thr-232. Cell cycle and apoptosis were detected by flow eytometry (FCM). Results The BXPC3 cells were inhibited by sulindac in a dose and time-dependent manner; the expression of mRNA of survivin and Aurora B were both significantly decreased from 1.5644 and 0.6554 to 0. 4372 and 0.1132 (P< 0.01), the expression of survivin protein and the phosphorylation of Aurora B Thr-232 were also decreased from 1.2735 and 0.4680 to 0.2126 and 0.2546 (P<0.01); the proportion of cells in the G0/G1 phase was increased from (56.65±1.93)% to (70.58±3.21)% (P<0.01). Conclusions Sulindac had inhibitory effects on the growth of BXPC3 cells, the possible mechanism was via decreasing the expression of survivin which depressed the activity of Aurora B, then the CPC was influenced. The most of the cells were blocked in the G0/G1 phase, and the cells' mitosis was inhibited.%目的 观察舒林酸处理胰腺癌细胞BxPC3后对survivin、Aurora B表达及细胞周期和增殖的影响,探讨舒林酸的作用机制.方法 应用MTT法检测舒林酸对BxPC3细胞的增殖抑制作用,RT-PCR法检测survivin mRNA、Aurora B mRNA的表达,Western blot法检测survivin蛋白表达及Aurora BThr-232磷酸化水平,流式细胞仪检测细胞周期变化.结果 舒林酸呈时间和剂量依赖性抑制BxPC3细胞增殖.经500μmoL/L舒林酸作用细胞48 h后,survivin mRNA和Aurora B mRNA表达量分别从1.56和0.66下降到0.44和0.11(P<0.01);survivin蛋白表达从1.27下降到0.21(P<0.01),Aurora BThr-232磷酸化水平从0.47下降到0.25(P<0.01);G0/G1

  2. Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: a single-center long-term observational study in 134 patients. (United States)

    Quast, Daniel Robert; Schneider, Ralph; Burdzik, Emanuel; Hoppe, Steffen; Möslein, Gabriela


    Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen.

  3. Ultrasonic attenuation in pearlitic steel. (United States)

    Du, Hualong; Turner, Joseph A


    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.

  4. Semiactive control for vibration attenuation

    Energy Technology Data Exchange (ETDEWEB)

    Leitmann, G. [Univ. of California, Berkeley, CA (United States). Coll. of Engineering


    With the advent of materials, such as electrorheological fluids, whose material properties can be altered rapidly by means of external stimuli, employing such materials as actuators for the controlled attenuation of undesirable vibrations is now possible. Such control schemes are dubbed semiactive in that they attenuate vibrations whether applied actively or passively. The author investigates various such control schemes, allowing for both separate and joint control of the stiffness and damping characteristics of the material.

  5. Photoacoustic Imaging Taking into Account Attenuation

    CERN Document Server

    Kowar, Richard


    First, we review existing attenuation models and discuss their causality properties, which we believe to be essential for algorithms for inversion with attenuated data. Then, we survey causality properties of common attenuation models. We also derive integro-differential equations which the attenuated waves are satisfying. In addition we discuss the ill--conditionness of the inverse problem for calculating the unattenuated wave from the attenuated one.

  6. Attenuation in Superconducting Circular Waveguides

    Directory of Open Access Journals (Sweden)

    K. H. Yeap


    Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

  7. X-Ray Attenuation Cell

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D.; Toor, A.


    To minimize the pulse-to-pulse variation, the LCLS FEL must operate at saturation, i.e. 10 orders of magnitude brighter spectral brilliance than 3rd-generation light sources. At this intensity, ultra-high vacuums and windowless transport are required. Many of the experiments, however, will need to be conducted at a much lower intensity thereby requiring a reliable means to reduce the x-ray intensity by many orders of magnitude without increasing the pulse-to-pulse variation. In this report we consider a possible solution for controlled attenuation of the LCLS x-ray radiation. We suggest using for this purpose a windowless gas-filled cell with the differential pumping. Although this scheme is easily realizable in principle, it has to be demonstrated that the attenuator can be made short enough to be practical and that the gas loads delivered to the vacuum line of sight (LOS) are acceptable. We are not going to present a final, optimized design. Instead, we will provide a preliminary analysis showing that the whole concept is robust and is worth further study. The spatial structure of the LCLS x-ray pulse at the location of the attenuator is shown in Fig. 1. The central high-intensity component, due to the FEL, has a FWHM of {approx}100 {micro}m. A second component, due to the undulator's broad band spontaneous radiation is seen as a much lower intensity ''halo'' with a FWHM of 1 mm. We discuss two versions of the attenuation cell. The first is directed towards a controlled attenuation of the FEL up to the 4 orders of magnitude in the intensity, with the spontaneous radiation halo being eliminated by collimators. In the second version, the spontaneous radiation is not sacrificed but the FEL component (as well as the first harmonic of the spontaneous radiation) gets attenuated by a more modest factor up to 100. We will make all the estimates assuming that the gas used in the attenuator is Xenon and that the energy of the FEL is 8.25 keV. At

  8. Attenuation in silica-based optical fibers

    DEFF Research Database (Denmark)

    Wandel, Marie Emilie


    In this thesis on attenuation in silica based optical fibers results within three main topics are reported. Spectral attenuation measurements on transmission fibers are performed in the wide wavelength range 290 nm – 1700 nm. The measured spectral attenuation is analyzed with special emphasis...... on absorption peaks in order to investigate the cause of an unusual high attenuation in a series of transmission fibers. Strong indications point to Ni2+ in octahedral coordination as being the cause of the high attenuation. The attenuation of fibers having a high core refractive index is analyzed and the cause...... of the high attenuation measured in such fibers is described as being due to scattering of light on fluctuations of the core diameter. A novel semi-empirical model for predicting the attenuation of high index fibers is presented. The model is shown to be able to predict the attenuation of high index fibers...

  9. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.


    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc bias...

  10. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon


    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  11. Stormwater Attenuation by Green Roofs (United States)

    Sims, A.; O'Carroll, D. M.; Robinson, C. E.; Smart, C. C.


    Innovative municipal stormwater management technologies are urgently required in urban centers. Inadequate stormwater management can lead to excessive flooding, channel erosion, decreased stream baseflows, and degraded water quality. A major source of urban stormwater is unused roof space. Green roofs can be used as a stormwater management tool to reduce roof generated stormwater and generally improve the quality of runoff. With recent legislation in some North American cities, including Toronto, requiring the installation of green roofs on large buildings, research on the effectiveness of green roofs for stormwater management is important. This study aims to assess the hydrologic response of an extensive sedum green roof in London, Ontario, with emphasis on the response to large precipitation events that stress municipal stormwater infrastructure. A green roof rapidly reaches field capacity during large storm events and can show significantly different behavior before and after field capacity. At field capacity a green roof has no capillary storage left for retention of stormwater, but may still be an effective tool to attenuate peak runoff rates by transport through the green roof substrate. The attenuation of green roofs after field capacity is linked to gravity storage, where gravity storage is the water that is temporarily stored and can drain freely over time after field capacity has been established. Stormwater attenuation of a modular experimental green roof is determined from water balance calculations at 1-minute intervals. Data is used to evaluate green roof attenuation and the impact of field capacity on peak flow rates and gravity storage. In addition, a numerical model is used to simulate event based stormwater attenuation. This model is based off of the Richards equation and supporting theory of multiphase flow through porous media.

  12. Ferrite attenuator modulation improves antenna performance (United States)

    Hooks, J. C.; Larson, S. G.; Shorkley, F. H.; Williams, B. T.


    Ferrite attenuator inserted into appropriate waveguide reduces the gain of the antenna element which is causing interference. Modulating the ferrite attenuator to change the antenna gain at the receive frequency permits ground tracking until the antenna is no longer needed.


    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O


    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  14. Chlorine signal attenuation in concrete. (United States)

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


    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.

  15. Mechanisms of geometrical seismic attenuation

    Directory of Open Access Journals (Sweden)

    Igor B. Morozov


    Full Text Available In several recent reports, we have explained the frequency dependence of the apparent seismic quality-factor (Q observed in many studies according to the effects of geometrical attenuation, which was defined as the zero-frequency limit of the temporal attenuation coefficient. In particular, geometrical attenuation was found to be positive for most waves traveling within the lithosphere. Here, we present three theoretical models that illustrate the origin of this geometrical attenuation, and we investigate the causes of its preferential positive values. In addition, we discuss the physical basis and limitations of both the conventional and new attenuation models. For waves in media with slowly varying properties, geometrical attenuation is caused by variations in the wavefront curvature, which can be both positive (for defocusing and negative (for focusing. In media with velocity/density contrasts, incoherent reflectivity leads to geometrical-attenuation coefficients which are proportional to the mean squared reflectivity and are always positive. For «coherent» reflectivity, the geometrical attenuation is approximately zero, and the attenuation process can be described according to the concept of «scattering Q». However, the true meaning of this parameter is in describing the mean reflectivity within the medium, and not that of the traditional resonator quality factor known in mechanics. The general conclusion from these models is that non-zero and often positive levels of geometrical attenuation are common in realistic, heterogeneous media, both observationally and theoretically. When transformed into the conventional Q-factor form, this positive geometrical attenuation leads to Q values that quickly increase with frequency. These predictions show that the positive frequency-dependent Q observed in many datasets might represent artifacts of the transformations of the attenuation coefficients into Q.

  1. Optimal ultrasonic array focusing in attenuative media. (United States)

    Ganguli, A; Gao, R X; Liang, K; Jundt, J


    This paper presents a parametric study on the efficiency of ultrasound focusing in an attenuative medium, using phased arrays. Specifically, an analytical model of ultrasound wave focusing in a homogeneous, isotropic and attenuative fluid with point sources is presented. Calculations based on the model have shown that in an attenuative medium, an optimum frequency exists for the best focusing performance for a particular size of aperture and focal distance. The effect of different f numbers on the focusing performance in the attenuative medium is further investigated. The information obtained from the analytical model provides insights into the design and installation of a phased transducer array for energy efficient wave focusing.

  2. Wideband, 50 dB Attenuation Range Liquid Crystal Based Variable Optical Attenuator

    Institute of Scientific and Technical Information of China (English)

    J.J.; Pan; Henry; He; Eric; Zhang


    A compact variable optical attenuator, covering C and L bands with over 50 dB attenuation range, is realized using a single liquid crystal cell with a tilted fused silica coating compensating the cell's small residual birefringence.

  3. Ultrasonic attenuation in cuprate superconductors

    Indian Academy of Sciences (India)

    T Gupta; D M Gaitonde


    We calculate the longitudinal ultrasonic attenuation rate (UAR) in clean d-wave superconductors in the Meissner and the mixed phases. In the Meissner phase we calculate the contribution of previously ignored processes involving the excitation of a pair of quasi-holes or quasi-particles. There is a contribution ∝ in the regime B ≪ F ≪ 0 and a contribution ∝ 1/ in the regime F ≪ B ≪ 0. We find that these contributions to the UAR are large and cannot be ignored. In the mixed phase, using a semi-classical description, we calculate the electronic quasi-particle contribution to the UAR which at very low , has a independent term proportional to $\\sqrt{H}$.


    Directory of Open Access Journals (Sweden)

    Eduardo Fonseca-Pedrero


    Full Text Available Psychotic syndrome includes several devastating mental disorders characterized by a rupture of higher mental functions. The signs and symptoms of psychosis begin in adolescence or early adulthood and usually begin gradually and progress over time. Attenuated psychosis syndrome is a new DSM-5 diagnostic proposal which deals with identifying people at high-risk mental state (ARMS/UHR which may be a predictor of conversion to psychosis. The potential benefit would be that if psychotic disorder is treated more effectively in its early stages, it could produce a lasting beneficial effect that probably could not be achieved with later intervention. This syndrome has generated intense discussion in specialized scientific and professional forums, crisscrossing arguments in favor and against its inclusion. HRMS is preferentially evaluated in the adolescent or young adult population. HRMS evolution is associated with a higher rate of transition toward nonaffective psychosis, although it can evolve toward other mental disorders, remain stable or remit over time. Empirical evidence shows that early intervention seems to have a certain beneficial effect, although for now the results are still insufficient and contradictory. The lack of specificity of symptoms in predicting psychosis, presence of certain limitations (e.g., stigmatization, results found in early interventions and lack of empirical evidence, have led to include the attenuated psychosis syndrome in the DSM-5 Appendix III. The main benefits and limitations of including this supposed category, possible lessons learned from this type of study and future lines of action are discussed in the light of these findings.

  5. Attenuation characteristics of a light attenuator combined by polarizers with different extinction ratios

    Institute of Scientific and Technical Information of China (English)

    Huang Chong; Deng Peng; Zhao Shuang; Chen Hai-Qing


    This paper deals with a systematical analysis and an algorithm of attenuation characteristics of a light attenuator combined by n pieces of polarizers(n-LACP)whose extinction ratios are different from each other.The attenuation ratio expression of a two-LACP is deduced. We find that the monotonic attenuation interval depends on the first polarizer and that the attenuation range depends on the second one.For the three-LACP,a method for obtaining a monotonic attenuation interval is proposed.Moreover,the attenuation ratio expression is demonstrated.Analysis and experiment show that when the initial status of the three-LACP is at the maximum output,if the second or third polarizer rotates alone,the minimum attenuation ratios can reach K2-1and K3-1,respectively,and if the first polarizer rotates,a minimum attenuation ratio of K2-1K3-1can be obtained(K1,K2 and K3 represent the extinction ratios of the three polarizers in turn).Furthermore,the attenuation ratio expression of n-LACP and the relevant attenuation characteristics are proposed.The minimum attenuation ratio of an n-LACP is(K2K3...Kn)-1.


    Institute of Scientific and Technical Information of China (English)

    BI Weiping; MU Xiaowu; SUN Yuqiang


    In present paper, the disturbance attenuation problem of uncertain nonlinear cascaded systems is studied. Based on the adding one power integrator technique and recursive design, a feedback controller that solves the disturbance attenuation problem is constructed for uncertain nonlinear cascaded systems with internal stability.

  7. Light attenuation on Chlorella vulgaris cells (United States)

    Krol, Tadeusz; Lotocka, Maria


    The laboratory measurements of spectrum of light attenuation on phytoplankton particles i.e. monoculture of unicellural green algae Chlorella vulgaris are presented. The measurements were carried out for alive culture and the cultures subjected to chemical (NaOH) or physical (ultrasounds) modification. The distinct changes in the light attenuation spectrum were a result of modification of the internal cell structures.

  8. Attenuation coefficients for water quality trading. (United States)

    Keller, Arturo A; Chen, Xiaoli; Fox, Jessica; Fulda, Matt; Dorsey, Rebecca; Seapy, Briana; Glenday, Julia; Bray, Erin


    Water quality trading has been proposed as a cost-effective approach for reducing nutrient loads through credit generation from agricultural or point source reductions sold to buyers facing costly options. We present a systematic approach to determine attenuation coefficients and their uncertainty. Using a process-based model, we determine attenuation with safety margins at many watersheds for total nitrogen (TN) and total phosphorus (TP) loads as they transport from point of load reduction to the credit buyer. TN and TP in-stream attenuation generally increases with decreasing mean river flow; smaller rivers in the modeled region of the Ohio River Basin had TN attenuation factors per km, including safety margins, of 0.19-1.6%, medium rivers of 0.14-1.2%, large rivers of 0.13-1.1%, and very large rivers of 0.04-0.42%. Attenuation in ditches transporting nutrients from farms to receiving rivers is 0.4%/km for TN, while for TP attenuation in ditches can be up to 2%/km. A 95 percentile safety margin of 30-40% for TN and 6-10% for TP, applied to the attenuation per km factors, was determined from the in-stream sensitivity of load reductions to watershed model parameters. For perspective, over 50 km a 1% per km factor would result in 50% attenuation = 2:1 trading ratio.

  9. Ultrasound fields in an attenuating medium

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.


    Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...... the spatial impulse response, whereas the field cannot readily be found for an attenuating medium. In this paper we present a simulation program capable of calculating the field in a homogeneous attenuating medium. The program splits the aperture into rectangles and uses a far-field approximation for each...... of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...

  10. Attenuation of diacylglycerol second messengers

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, W.R.; Ganong, B.R.; Bell, R.M.


    Diacylglycerol(DAG) derived from phosphatidylinositol activates protein kinase C in agonist-stimulated cells. At least two pathways may contribute to the attenuation of the DAG signal: (1) phosphorylation to phosphatidic acid(PA) by DAG kinase(DGK), and (2) deacylation by DAG and monoacylglycerol lipases. A number of DAG analogs were tested as substrates and inhibitors of partially purified pig brain DGK. Two analogs were potent inhibitors in vitro, 1-monooleoylglycerol(MOG,K/sub I/ = 91 and diotanoylethyleneglycol (diC/sub 8/EG, K/sub I/ = 58 These compounds were tested in human platelets. DiC/sub 8/EG inhibited (70 - 100%) (/sup 32/P/sub i/) incorporation into PA in thrombin-stimulated platelets. Under these conditions the DAG signal was somewhat long-lived but was still metabolized, presumably by the lipase pathway. MOG treatment elevated DAG levels up to 4-fold in unstimulated platelets. The DAG formed was in a pool where it did not activate protein kinase C. Thrombin-stimulation of MOG-treated platelets resulted in DAG levels 10-fold higher than control platelets. This appears to be due to the inability of these platelets to metabolize agonist-linked DAG via the lipase pathway. The development of specific inhibitors of DAG kinase and DAG lipase, in conjunction with mass quantification of DAG levels as used here, will provide further insights into the regulation of DAG second messengers.

  11. Live attenuated intranasal influenza vaccine. (United States)

    Esposito, Susanna; Montinaro, Valentina; Groppali, Elena; Tenconi, Rossana; Semino, Margherita; Principi, Nicola


    Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

  12. Graphene-based Electronically Tuneable Microstrip Attenuator

    Directory of Open Access Journals (Sweden)

    L. Pierantoni


    Full Text Available This paper presents the design of a graphene- based electronically tuneable microstrip attenuator operating at a frequency of 5 GHz. The use of graphene as a variable resistor is discussed and the modelling of its electromagnetic properties at microwave frequencies is fully addressed. The design of the graphene-based attenuator is described. The structure integrates a patch of graphene, whose characteristics can range from being a fairly good conductor to a highly lossy material, depending on the applied voltage. By applying the proper voltage through two high-impedance bias lines, the surface resistivity of graphene can be modified, thereby changing the insertion loss of the microstrip attenuator.

  13. Precision Model for Microwave Rotary Vane Attenuator

    DEFF Research Database (Denmark)

    Guldbrandsen, Tom


    A model for a rotary vane attenuator is developed to describe the attenuator reflection and transmission coefficients in detail. All the parameters of the model can be measured in situ, i.e., without diassembling any part. The tranmission errors caused by internal reflections are calculated from ...... measurements of the much larger reflection parameters, hence commonly used nonprecision instruments can be used to determine the transmission errors with sufficient accuracy for the highest precision obtainable in standard laboratories....

  14. Wave attenuation charcteristics of tethered float system

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.

    and transmitted wave powers, transmission coefficients are computed. The results show that transmission coefficient does not vary with changes in wave height or water depth. When depth of submergence of float increases, wave attenuation decreases, showing... that the system performs well when it is just submerged. As float velocity decreases with increase in float size, transmission coefficient increases with increase in float size. The influence of wave period on wave attenuation is remarkable compared to other...


    DEFF Research Database (Denmark)

    Brunskog, Jonas; Lhomond, Alice; Ohlrich, Mogens


    In this paper the attenuation and flanking transmissions of impact noise in lightweight building structures is studied using a modal approach. The structural field is mainly analysed, putting the main attention to the parts being important in the modelling. The amount of attenuation produced...... by the periodically reinforcing beams used in lightweight building structures is analysed. The consequence of these factors in modelling flanking transmission is also discussed....

  16. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Yanxi [Department of Biology, Lakehead University, Thunder Bay (Canada); College of Life Science, Shanxi University, Taiyuan (China); Wu, Bo [Department of Biology, Lakehead University, Thunder Bay (Canada); Department of Pathophysiology, Harbin Medical University, Harbin (China); Cao, Qiuhui [Department of Biology, Lakehead University, Thunder Bay (Canada); Wu, Lingyun [Department of Pathophysiology, Harbin Medical University, Harbin (China); Department of Pharmacology, University of Saskatchewan, Saskatoon (Canada); Yang, Guangdong, E-mail: [The School of Kinesiology, Lakehead University, Thunder Bay (Canada)


    Hydrogen sulfide (H{sub 2}S) is a novel gasotransmitter that regulates cell proliferation and other cellular functions. Sulforaphane (SFN) is a sulfur-containing compound that exhibits anticancer properties, and young sprouts of broccoli are particularly rich in SFN. There is consistent epidemiological evidence that the consumption of sulfur-containing vegetables, such as garlic and cruciferous vegetables, may help reduce the occurrence of prostate cancer. Here we found that a large amount of H{sub 2}S is released when SFN is added into cell culture medium or mixed with mouse liver homogenates, respectively. Both SFN and NaHS (a H{sub 2}S donor) decreased the viability of PC-3 cells (a human prostate cancer cell line) in a dose-dependent manner, and supplement of methemoglobin or oxidized glutathione (two H{sub 2}S scavengers) reversed SFN-reduced cell viability. We further found both cystathionine gamma-lyase (CSE) and cystathionine beta-synthase are expressed in PC-3 cells and mouse prostate tissues. H{sub 2}S production in prostate tissues from CSE knockout mice was only 20% of that from wild-type mice, suggesting CSE is a major H{sub 2}S-producing enzyme in prostate. CSE overexpression enhanced H{sub 2}S production and inhibited cell viability in PC-3 cells. In addition, both SFN and NaHS activated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinase (JNK). Pre-treatment of PC-3 cells with methemoglobin decreased SFN-stimulated MAPK activities. Suppression of both p38 MAPK and JNK reversed H{sub 2}S- or SFN-reduced viability of PC-3 cells. Our results demonstrated that H{sub 2}S mediates the inhibitory effect of SFN on the proliferation of PC-3 cells, which suggests that H{sub 2}S-releasing diet or drug might be beneficial in the treatment of prostate cancer. Highlights: Black-Right-Pointing-Pointer A large amount of H{sub 2}S is released from sulforaphane. Black-Right-Pointing-Pointer H{sub 2}S mediates the anti-survival effect of sulforaphane on human prostate cancer cells. Black-Right-Pointing-Pointer Cystathionine gamma-lyase is a major H{sub 2}S-producing enzyme in prostate tissues. Black-Right-Pointing-Pointer p38 MAPK and JNK contribute to H{sub 2}S and sulforaphane-reduced viability in prostate cancer cells.

  17. Light attenuation in estuarine mangrove lakes (United States)

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


    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 (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.

  18. Maximum likelihood estimation of the attenuated ultrasound pulse

    DEFF Research Database (Denmark)

    Rasmussen, Klaus Bolding


    The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

  19. Comparison of non-attenuation corrected and attenuation corrected myocardial perfusion SPE

    Directory of Open Access Journals (Sweden)

    Hasan Raza


    Conclusion: This study demonstrates that CT based attenuation corrected Tc-99mm sestamibi SPECT myocardial perfusion imaging significantly improved the specificity of the RCA territory compared with non-attenuation corrected Tc-99mm sestamibi SPECT myocardial perfusion imaging in both genders irrespective of BMI.

  20. Attenuation tomography in West Bohemia/Vogtland (United States)

    Mousavi, Sima; Haberland, Christian; Bauer, Klaus; Hejrani, Babak; Korn, Michael


    We present a three-dimensional (3-D) P-wave attenuation (Qp) model for the geodynamically active swarm earthquake area of West Bohemia/Vogtland in the Czech/German border region. Path-averaged attenuation t* is calculated from amplitude spectra of time windows around the P-wave arrivals of local earthquakes. Average t/t* value or Qp for stations close to Nový Kostel are very low (focal zone (increases up to 500 within 80 km distance). The SIMUL2000 tomography scheme is used to invert the t* for P-wave attenuation perturbation. Analysis of resolution shows that our model is well-resolved in the vicinity of earthquake swarm hypocenters. The prominent features of the model are located around Nový Kostel focal zone and its northern vicinity. Beneath Nový Kostel a vertically stretched (down to depth of 11 km) and a highly attenuating body is observed. We believe that this is due to fracturing and high density of cracks inside the weak earthquake swarm zone in conjunction with presence of free gas/fluid. Further north of Nový Kostel two highly attenuating bodies are imaged which could represent fluid channels toward the surface. The eastern anomaly shows a good correlation with the fluid accumulation area which was suggested in 9HR seismic profile.

  1. Live attenuated vaccines for invasive Salmonella infections. (United States)

    Tennant, Sharon M; Levine, Myron M


    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  2. Research on Nanosecond Pulse Corona Discharge Attenuation

    Institute of Scientific and Technical Information of China (English)

    HE Zheng-hao; XU Huai-li; BAI Jing; YU Fu-sheng; HU Feng; LI Jin


    A line-to-plate reactor was set-up in the experimental study on the application of nanosecond pulsed corona discharge plasma technology in environmental pollution control.Investigation on the attenuation and distortion of the amplitude of the pulse wave front and the discharge image as well as the waveform along the corona wire was conducted.The results show that the wave front decreases sharply during the corona discharge along the corona wire.The higher the amplitude of the applied pulse is,the more the amplitude of the wave front decreased.The wave attenuation responds in a lower corona discharge inversely.To get a higher efficiency of the line-to-plate reactor a sharp attenuation of the corona has to be considered in practical design.

  3. Is there seismic attenuation in the mantle? (United States)

    Ricard, Y.; Durand, S.; Montagner, J.-P.; Chambat, F.


    The small scale heterogeneity of the mantle is mostly due to the mixing of petrological heterogeneities by a smooth but chaotic convection and should consist in a laminated structure (marble cake) with a power spectrum S(k) varying as 1/k, where k is the wavenumber of the anomalies. This distribution of heterogeneities during convective stirring with negligible diffusion, called Batchelor regime is documented by fluid dynamic experiments and corresponds to what can be inferred from geochemistry and seismic tomography. This laminated structure imposes density, seismic velocity and potentially, anisotropic heterogeneities with similar 1/k spectra. A seismic wave of wavenumber k0 crossing such a medium is partly reflected by the heterogeneities and we show that the scattered energy is proportional to k0S(2k0). The reduction of energy for the propagating wave appears therefore equivalent to a quality factor 1/Q∝k0S(2k0). With the specific 1/k spectrum of the mantle, the resulting apparent attenuation should therefore be frequency independent. We show that the total contribution of 6-9% RMS density, velocity and anisotropy would explain the observed S and P attenuation of the mantle. Although these values are large, they are not unreasonable and we discuss how they depend on the range of frequencies over which the attenuation is explained. If such a level of heterogeneity were present, most of the attenuation of the Earth would be due to small scale scattering by laminations, not by intrinsic dissipation. Intrinsic dissipation must certainly exist but might correspond to a larger, yet unobserved Q. This provocative result would explain the very weak frequency dependence of the attenuation, and the fact that bulk attenuation seems negligible, two observations that have been difficult to explain for 50 years.

  4. Ultrasound transmission attenuation tomography using energy-scaled amplitude ratios (United States)

    Chen, Ting; Shin, Junseob; Huang, Lianjie


    Ultrasound attenuation of breast tumors is related to their types and pathological states, and can be used to detect and characterize breast cancer. Particularly, ultrasound scattering attenuation can infer the margin properties of breast tumors. Ultrasound attenuation tomography quantitatively reconstructs the attenuation properties of the breast. Our synthetic-aperture breast ultrasound tomography system with two parallel transducer arrays records both ultrasound reflection and transmission signals. We develop an ultrasound attenuation tomography method using ultrasound energy-scaled amplitude decays of ultrasound transmission signals and conduct ultrasound attenuation tomography using a known sound-speed model. We apply our ultrasound transmission attenuation tomography method to a breast phantom dataset, and compare the ultrasound attenuation tomography results with conventional beamforming ultrasound images obtained using reflection signals. We show that ultrasound transmission attenuation tomography complements beamforming images in identifying breast lesions.

  5. Touch Attenuates Infants' Physiological Reactivity to Stress (United States)

    Feldman, Ruth; Singer, Magi; Zagoory, Orna


    Animal studies demonstrate that maternal touch and contact regulate infant stress, and handling during periods of maternal deprivation attenuates the stress response. To measure the effects of touch on infant stress reactivity during simulated maternal deprivation, 53 dyads were tested in two paradigms: still-face (SF) and still-face with maternal…

  6. Microwave attenuation with composite of copper microwires

    Energy Technology Data Exchange (ETDEWEB)

    Gorriti, A.G.; Marin, P. [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Cortina, D. [Micromag S.L., Las Rozas, Madrid 28230 (Spain); Hernando, A., E-mail: antonio.hernando@adif.e [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Micromag S.L., Las Rozas, Madrid 28230 (Spain)


    It is shown that copper microwires composite media attenuates microwave reflection of metallic surfaces. We show how the distance to the metallic surface, as well as the length and volume fraction of microwires, determine the frequency of maximum absorption and the return loss level. Furthermore, we were able to fit the experimental results with a theoretical model based on Maxwell-Garnett mixing formula.

  7. GPR measurements of attenuation in concrete

    Energy Technology Data Exchange (ETDEWEB)

    Eisenmann, David, E-mail:; Margetan, Frank J., E-mail:; Pavel, Brittney, E-mail: [Center for Nondestructive Evaluation, Iowa State University, 1915 Scholl Road, Ames, IA 50011-3042 (United States)


    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. Sizes of mantle heteogeneities and seismic attenuation (United States)

    Ricard, Y. R.; durand, S.; Chambat, F.; Montagner, J.


    The small scale heterogeneity of the mantle, being mostly due to the mixing of petrological heterogeneities by a smooth but chaotic convection should consist in a laminated structure (marble cake) with a power spectrum S(k) varying as 1/k, where k is the wavenumber of the anomalies. This distribution of heterogeneities during convective stirring with negligible diffusion, called Batchelor regime is documented by fluid dynamic experiments and corresponds to what can be inferred from geochemistry and seismic tomography. This laminated structure imposes density, seismic velocity and potentially, anisotropic heterogeneities with similar 1/k spectrums. We show that a seismic wave of wavenumber k_0 crossing such medium is partly reflected by the heterogeneities and the scattered energy has an energy found proportional to k_0 S(2k_0). The reduction of energy for the propagating wave appears therefore equivalent to a quality factor 1/Q proportional to k_0 S(2k_0). With the specific 1/k spectrum of the mantle, the resulting apparent attenuation should therefore be frequency independent. We show that the total contribution of 6-9% RMS density, velocity and anisotropy would explain the observed S and P attenuation of the mantle. Although these values are large there are not unreasonable and we discuss how they are likely overestimated. In this case, most of the attenuation of the Earth would be due to small scale scattering by laminations not by intrinsic dissipation. Intrinsic dissipation must certainly exists but might correspond to a larger, yet unobserved Q. This provocative result would explain the observed very weak frequency dependence of the attenuation, and the fact that bulk attenuation seems negligeable, two observations that have been difficult to explain for 50 years.

  9. Attenuation of seismic waves in Central Egypt

    Directory of Open Access Journals (Sweden)

    Mamdouh Abbas Morsy


    Full Text Available Attenuation of seismic waves in central Egypt had never been studied before. The results of the research on the seismic attenuation are based upon the information collected by the seismological network from 1998 to 2011. 855 earthquakes were selected from the Egyptian seismological catalog, with their epicenter distances between 15 and 150 km, their magnitudes ranging from 2 and 4.1 and focal depths reaching up to 30 km. The first systematic study of attenuation derived from the P-, S- and coda wave in the frequency range 1–24 Hz is presented. In the interpretation of the results both single and multiple scattering in a half space are considered. The single scattering model proposed by Sato (1977 was used. Two methods, the coda (Qc and the Multiple Lapse Time Window (MLTW method are used. The aim of this study is to validate these interpretations in the region and to try to identify the effects of attenuation due to intrinsic (Qi and scattering attenuation (Qsc. The mean Qc value calculated was Qc = (39 ± 1f1.0±0.009. The average Qc at 1.5 Hz is (53 ± 6 and Qc = (900 ± 195 at 24 Hz with Qo ranging between 23 and 107, where η ranging between 0.9 and 1.3. The quality factor (Q was estimated from spectra of P- and S-waves by applying a spectral ratio technique. The results show variations in Qp and QS as a function of frequency, according to the power law Q = 56η1.1. The seismic albedo is 0.7 at all stations and it mean that the earthquake activity is due to tectonic origin. The attenuation and frequency dependency for different paths and the correlation of the results with the geotectonic of the region are presented. The Qc values were calculated and correlated with the geology and tectonics of the area. The relatively low Qo and the high frequency dependency agree with the values of a region characterized by a low tectonic activity and vise versa.

  10. Frequency Dependence of Attenuation Constant of Dielectric Materials

    Directory of Open Access Journals (Sweden)

    A. S. Zadgaonkar


    Full Text Available Different dielectric materials have been studied for frequency dependence of attenuation constant. The sensitive cathode ray oscillograph method has been used to evaluate to the dielectric constant and loss factor, and from these attenuation constants have been calculated. The temperature remaining constant, a regular increase has been observed in attenuation constant, at higher frequencies of electro-magnetic propagating wave.

  11. On the excess attenuation of sound in the atmosphere (United States)

    Deloach, R.


    The attenuation suffered by an acoustic plane wave propagating from an elevated source to the ground, in excess of absorption losses, was studied. Reported discrepancies between attenuation measurements made in the field and theories which only account for absorption losses are discussed. It was concluded that the scattering of sound by turbulence results in a nonnegligible contribution to the total attenuation.

  12. Attenuation of microwaves by poly-disperse small spheroid particles (United States)

    Zhang, Peichang; Wang, Zhenhui


    Expressions for calculating the attenuation cross sections of poly-disperse, small spheroids, whose rotatory axes are in specific status, have been derived from a universal formula for calculating the attenuation cross section of a particle of arbitrary shape. Attenuation cross sections of liquid, ice, and spongy spheroidal droplets in different size and eccentricity at different wave lengths have been computed and analyzed.

  13. Attenuated partial internal reflection infrared spectroscopy. (United States)

    Zhang, Zhenfeng; Ewing, George E


    A new method for the spectroscopic study of absorbing films is proposed. In contrast to the well-established methods that take advantage of the attenuation of total internal reflection (ATR) to obtain spectra, we intentionally arrange the optics to permit partial internal reflection from the sampling prism face. Attenuated partial internal reflection (APR) spectroscopy is introduced through theoretical calculations and experimental demonstrations. The calculated APR spectra in the infrared region were generated from the Fresnel and Airy equations. Experimentally, APR spectra of water films on a NaCl prism were obtained. APR is more sensitive than ATR, and can easily distinguish water films at the monolayer level (310 pm). The determination of film thickness from interference fringes in APR spectra is also illustrated. It is shown that APR can be used for film thickness measurements that can span 6 orders of magnitude. The limitations of APR are also discussed.

  14. Particle size characterization by ultrasonic attenuation spectra

    Institute of Scientific and Technical Information of China (English)

    Mingxu Su; Minghua Xue; Xiaoshu Cai; Zhitao Shang; Feng Xu


    This paper contributes to extracting information from signals of broadband ultrasonic attenuation spectrum for effective utilization in particle size characterization. The single particle scattering model and the coupled-phase model are formulated simultaneously, the relationship between particle size distribution and ultrasonic spectrum is established, and a convergence criterion for calculation is quantified. Demonsa'ation inversion by the optimum regularization factor method is carded out to yield typical numerical results for discussion. With the experimental set-up developed by the Institute of Particle and Two-Phase Flow Measurement (IPTFM) at the University of Shanghai for Science and Technology, sand sediment particle size is measured by attenuation spectrum and analyzed using the above inversion algorithm and theoretical models. To validate the proposed ultrasonic spectrum particle sizing method, results are compared with those obtained by microscopy.

  15. Attenuated psychosis syndrome: benefits of explicit recognition (United States)

    SCHIFFMAN, Jason; CARPENTER, William T


    Summary Given the unique characteristics of people who meet criteria for attenuated psychosis syndrome (APS) and the growing literature on the clinical benefits of providing services to individuals who meet these criteria, the APS diagnosis serves an important, and previously missing, role in psychiatry. The promotion of the APS diagnosis should help reduce the over-diagnosis and over-treatment of individuals with prodromal psychotic conditions and it should also encourage expanded training about attenuated psychosis among clinicians who primarily provide services to youth (a primary group who are diagnosed with APS). Only some of the individuals with APS subsequently develop psychosis, but all have existing clinical needs – regardless of subsequent conversion. The formal recognition of APS in DSM-5 will facilitate the research needed to identify and meet those needs. PMID:25852257

  16. Carcinoma cervix with fat attenuating skull metastases

    Institute of Scientific and Technical Information of China (English)

    Anuradha Kapali; Atmakuri Sateesh Kumar; Mukunda Malathi; S D Shamsundar


    Skeletal metastasis in carcinoma cervix occurs in about 0.8-23% of cases. These lesions are usually radiographically lytic. Very few cases of metastases to the skull have been identiifed, about 5 cases to the best of our knowledge. We present a case of adenosquamous cell carcinoma of cervix with fat attenuating skull metastases in a 38-year-old lady that is not reported till date. The lesion was lytic, expansile and with negative attenuation of -15 to -30 Hounsifeld units corresponding to fat.Metastases must be included in the differentials of scalp lesions. A history of recent onset of swelling and associated lytic areas in calvarium on contrast enhanced computed tomography with multiplicity can give a clue to metastatic nature of disease.

  17. LCLS XTOD Attenuator System System Concept Report

    Energy Technology Data Exchange (ETDEWEB)

    Kishiyama, K; Roeben, M; Trent, J; Ryutov, D; Shen, S


    The attenuator system for the Linac Coherent Light Source (LCLS) X-ray Transport, Optics and Diagnostics (XTOD) system has been configured and analyzed by the Lawrence Livermore National Laboratory's New Technologies Engineering Division (NTED) as requested by the SLAC/LCLS program. The system layout, performance analyses and selection of the vacuum components are presented in this System Conceptual Review (SCR) report. Also included are the plans for prototype, procurement, mechanical integration, and the cost estimates.

  18. Narrow terahertz attenuation signatures in Bacillus thuringiensis. (United States)

    Zhang, Weidong; Brown, Elliott R; Viveros, Leamon; Burris, Kellie P; Stewart, C Neal


    Terahertz absorption signatures from culture-cultivated Bacillus thuringiensis were measured with a THz photomixing spectrometer operating from 400 to 1200 GHz. We observe two distinct signatures centered at ∼955 and 1015 GHz, and attribute them to the optically coupled particle vibrational resonance (surface phonon-polariton) of Bacillus spores. This demonstrates the potential of the THz attenuation signatures as "fingerprints" for label-free biomolecular detection.

  19. Molecular Characterization of Attenuated Junin Virus Variants. (United States)


    No. DAMD17-89-Z-9024 Area de Quimica Biologica y Biologia Molecular Facultad de Ciencias Exactas Universidad Nacional de La Plata Calles 47 y 115, 1900...MONITORING ORGANIZATION Area de Quimica Biologica (If applicable) y Biologia Molecular I 6c. ADDRESS (City, State, and ZIPCode) 7b. ADDRESS (City, State...AD-A260 128 AD____ MOLECULAR CHARACTERIZATION OF ATTENUATED JUNIN VIRUS VARIANTS FINAL REPORT VICTOR ROMANOWSKI PABLO D. GHIRINGHELLI CESAR G

  20. Novel Intriguing Strategies Attenuating to Sarcopenia

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma


    Full Text Available 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.

  1. Natural Biological Attenuation of Benzene in Groundwater

    Institute of Scientific and Technical Information of China (English)


    Benzene has been found in subsurface unsaturated soil and groundwater beneath a petro-chemical plant. Although the groundwater contained several mg/L of benzene in the area immediately beneath the source, benzene was not detected in monitoring wells approximately 800m down stream. All kinds of physical processes such as adsorption and advection/dispersion are considered to account for the observed attenuation. The results indicated that the attenuation was primarily due to natural biological processes occurring within the aquifer. The evidence for the natural bioremediation of benzene from the groundwater included: (1) analysis of groundwater chemistry, (2) laboratory studies demonstrating benzene biodegradation in aquifer samples, and (3) computer simulations examining benzene transport. Laboratory experiments indicated that for conditions similar to those in the plume, the aerobic degradation of benzene by the naturally occurring microorganisms in the polluted groundwater samples was quite rapid with a half-life time of from 5 to 15 days. In situ analyses indicated the level of dissolved oxygen in the groundwater was over 2mg/L. Thus, oxygen should not limit the biodegradation. In fact, the benzene was also shown to degrade under anaerobic conditions. The results from the modeling simulations indicate that biodegradation is the dominant process influencing attenuation of the benzene.

  2. Seismic Attenuation Inversion with t* Using tstarTomog.

    Energy Technology Data Exchange (ETDEWEB)

    Preston, Leiph


    Seismic attenuation is defined as the loss of the seismic wave amplitude as the wave propagates excluding losses strictly due to geometric spreading. Information gleaned from seismic waves can be utilized to solve for the attenuation properties of the earth. One method of solving for earth attenuation properties is called t*. This report will start by introducing the basic theory behind t* and delve into inverse theory as it pertains to how the algorithm called tstarTomog inverts for attenuation properties using t* observations. This report also describes how to use the tstarTomog package to go from observed data to a 3-D model of attenuation structure in the earth.

  3. Measuring the attenuation length in liquid scintillators

    Energy Technology Data Exchange (ETDEWEB)

    Hellgartner, Dominikus; Oberauer, Lothar; Prummer, Sabrina; Sawatzki, Julia; Zimmer, Vincenz [Technische Universitaet Muenchen, Physik Departement E15, James Franck Strasse, 85748 Garching (Germany); Ulrich, Andreas [Technische Universitaet Muenchen, Physik Departement E12, James Franck Strasse, 85748 Garching (Germany)


    The next generation of liquid scintillator detectors like the proposed LENA detector or the planned JUNO detector will feature diameters of order 30 m. Due to this vast size, the optical quality of the scintillator is of crucial importance. To determine the attenuation length of liquid scintillators, an experiment with a 5 m long measurement section was set-up in the underground laboratory in Garching. The current set-up of the experiment is presented along with a discussion of the results of the first measurements. Additionally, there is an outlook towards possible upgrades of the experiment in the future.

  4. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)


    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  5. Towards a Global Upper Mantle Attenuation Model (United States)

    Karaoglu, Haydar; Romanowicz, Barbara


    Global anelastic tomography is crucial for addressing the nature of heterogeneity in the Earth's interior. The intrinsic attenuation manifests itself through dispersion and amplitude decay. These are contaminated by elastic effects such as (de)focusing and scattering. Therefore, mapping anelasticity accurately requires separation of elastic effects from the anelastic ones. To achieve this, a possible approach is to try and first predict elastic effects through the computation of seismic waveforms in a high resolution 3D elastic model, which can now be achieved accurately using numerical wavefield computations. Building upon the recent construction of such a whole mantle elastic and radially anisotropic shear velocity model (SEMUCB_WM1, French and Romanowicz, 2014), which will be used as starting model, our goal is to develop a higher resolution 3D attenuation model of the upper mantle based on full waveform inversion. As in the development of SEMUCB_WM1, forward modeling will be performed using the spectral element method, while the inverse problem will be treated approximately, using normal mode asymptotics. Both fundamental and overtone time domain long period waveforms (T>60s) will be used from a dataset of over 200 events observed at several hundred stations globally. Here we present preliminary results of synthetic tests, exploring different iterative inversion strategies.

  6. Live attenuated influenza vaccine--a review. (United States)

    Gasparini, R; Amicizia, D; Lai, P L; Panatto, D


    Owing to the variability of influenza viruses, vaccine composition needs to be up-dated annually. As many variables can influence their efficacy, vaccines are still considered "sub-optimal". Many studies have been carried out in recent years to improve vaccines. In particular, researchers and vaccine-producing corporations have focused on developing a live vaccine. Among the candidate vaccines, the strain developed by Maassab has recently been licensed in the USA and Europe, after extensive investigation. This vaccine is safe and well tolerated, and has shown very good genetic stability. Although vaccine recipients are able to spread the virus, transmission to close contacts is practically non-existent. Studies on cold-adapted attenuated influenza vaccines have demonstrated that such vaccines are effective, and sometimes more effective than inactivated influenza vaccines. Cold-adapted attenuated influenza vaccines therefore appear to be an important weapon against influenza. However, a more widespread use of these vaccines is to be recommended, especially in children, as the more acceptable way of administration can favour parental compliance.

  7. Surface Wave Attenuation in the Tibetan Plateau from Ambient Noise (United States)


    R. Weaver, and X.N. Yang, Surface wave attenuation in Tibetan Plateau from ambient noise, Monitoring Research Review, Albuquerque, NM, 2012...AFRL-RV-PS- TR-2015-0150 AFRL-RV-PS- TR-2015-0150 SURFACE WAVE ATTENUATION IN THE TIBETAN PLATEAU FROM AMBIENT NOISE University of Illinois at...DATES COVERED (From - To) 01 May 2012 to 31 Aug 2015 4. TITLE AND SUBTITLE Surface Wave Attenuation in the Tibetan Plateau from Ambient Noise 5a

  8. A wideband IM3 cancellation technique for CMOS attenuators

    NARCIS (Netherlands)

    Cheng, W.; Oude Alink, M.S.; Annema, A.J.; Wienk, G.J.M.; Nauta, B.


    A highly linear P attenuator system using a wideband IM3 cancellation technique is presented that provides 4 discrete attenuation levels with 6dB spacing for DC-5GHz. For the whole band, S11<-14dB, attenuation flatness<1.6dB, +10dBm input P1dB and +26dBm IIP3 are achieved. For the TV band (0.1Gz-1.2

  9. Importance of Attenuation Correction (AC for Small Animal PET Imaging

    Directory of Open Access Journals (Sweden)

    Henrik H. El Ali


    Full Text Available The purpose of this study was to investigate whether a correction for annihilation photon attenuation in small objects such as mice is necessary. The attenuation recovery for specific organs and subcutaneous tumors was investigated. A comparison between different attenuation correction methods was performed. Methods: Ten NMRI nude mice with subcutaneous implantation of human breast cancer cells (MCF-7 were scanned consecutively in small animal PET and CT scanners (MicroPETTM Focus 120 and ImTek’s MicroCATTM II. CT-based AC, PET-based AC and uniform AC methods were compared. Results: The activity concentration in the same organ with and without AC revealed an overall attenuation recovery of 9–21% for MAP reconstructed images, i.e., SUV without AC could underestimate the true activity at this level. For subcutaneous tumors, the attenuation was 13 ± 4% (9–17%, for kidneys 20 ± 1% (19–21%, and for bladder 18 ± 3% (15–21%. The FBP reconstructed images showed almost the same attenuation levels as the MAP reconstructed images for all organs. Conclusions: The annihilation photons are suffering attenuation even in small subjects. Both PET-based and CT-based are adequate as AC methods. The amplitude of the AC recovery could be overestimated using the uniform map. Therefore, application of a global attenuation factor on PET data might not be accurate for attenuation correction.

  10. Attenuation characteristics of ground motions in northern China

    Institute of Scientific and Technical Information of China (English)

    黄玉龙; 赵兴权; 罗奇峰


    Four recently developed attenuation models are calibrated by using a very limited amount of strong motion data recorded in China. The research shows that the attenuation characteristics of the earthquake shaking in northern China are similar to those in the western US. The supporting evidence includes Q factors, preliminary results of kappa values, stress drop,shear wave velocity profile in the shallow earth crust, areas enclosed by the isoseismals of Modified Mercalli Intensity V. From these comparisons of different attenuation models, it is recommended that the Crouse and McGuire spectral attenuation model could possibly be used for northern China.

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

    Energy Technology Data Exchange (ETDEWEB)

    Manago, Takashi, E-mail: [Department of Applied Physics, Fukuoka University, 8-19-1 Nanakuma, Jonan, Fukuoka 814-0180 (Japan); Yamanoi, Kazuto [Department of Physics, Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581 (Japan); Kasai, Shinya; Mitani, Seiji [National Institute for Materials Science (NIMS), Tsukuba, Ibaraki 305-0047 (Japan)


    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 spin waves attenuation can be useful tool for ferromagnetic thin films.

  12. [Usefulness of attenuation correction with transmission source in myocardial SPECT]. (United States)

    Murakawa, Keizo; Katafuchi, Tetsuro; Nishimura, Yoshihiro; Enomoto, Naoyuki; Sago, Masayoshi; Oka, Hisashi


    Attenuation correction in SPECT has been used for uniformly absorptive objects like the head. On the other hand, it has seldom been applied to nonuniform absorptive objects like the heart and surrounding lungs because of the difficulty and inaccuracy of data processing. However, since attenuation correction using a transmission source recently became practical, we were able to apply this method to a nonuniform absorptive object. Therefore, we evaluated the usefulness of this attenuation correction system with a transmission source in myocardial SPECT. The dose linearity, defect/normal ratio using a myocardial phantom, and myocardial count distribution in clinical cases was examined with and without the attenuation correction system. We found that all data processed with attenuation correction were better than those without attenuation correction. For example, in myocardial count distribution, while there was a difference between men and women without attenuation correction, which was considered to be caused by differences in body shape, after processing with attenuation correction, myocardial count distribution was almost the same in all cases. In conclusion, these results suggested that attenuation correction with a transmission source was useful in myocardial SPECT.

  13. Enhanced Attenuation Technologies: Passive Soil Vapor Extraction

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K.; Looney, B.; Kamath, R.; Adamson, D.; Newell, C.


    Passive soil vapor extraction (PSVE) is an enhanced attenuation (EA) approach that removes volatile contaminants from soil. The extraction is driven by natural pressure gradients between the subsurface and atmosphere (Barometric Pumping), or by renewable sources of energy such as wind or solar power (Assisted PSVE). The technology is applicable for remediating sites with low levels of contamination and for transitioning sites from active source technologies such as active soil vapor extraction (ASVE) to natural attenuation. PSVE systems are simple to design and operate and are more cost effective than active systems in many scenarios. Thus, PSVE is often appropriate as an interim-remedial or polishing strategy. Over the past decade, PSVE has been demonstrated in the U.S. and in Europe. These demonstrations provide practical information to assist in selecting, designing and implementing the technology. These demonstrations indicate that the technology can be effective in achieving remedial objectives in a timely fashion. The keys to success include: (1) Application at sites where the residual source quantities, and associated fluxes to groundwater, are relatively low; (2) Selection of the appropriate passive energy source - barometric pumping in cases with a deep vadose zone and barrier (e.g., clay) layers that separate the subsurface from the atmosphere and renewable energy assisted PSVE in other settings and where higher flow rates are required. (3) Provision of sufficient access to the contaminated vadose zones through the spacing and number of extraction wells. This PSVE technology report provides a summary of the relevant technical background, real-world case study performance, key design and cost considerations, and a scenario-based cost evaluation. The key design and cost considerations are organized into a flowchart that dovetails with the Enhanced Attenuation: Chlorinated Organics Guidance of the Interstate Technology and Regulatory Council (ITRC). The PSVE

  14. Gas sensor with attenuated drift characteristic (United States)

    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


    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

  15. Attenuation of ultrasonic waves in rolled metals (United States)

    Yang, Liyong; Turner, Joseph A.


    Scattering of ultrasonic waves in polycrystals with texture is studied in this article. The attenuations of the three wave modes are determined as a function of dimensionless frequency and propagation direction, respectively, for given orientation distribution coefficients (ODCs). The calculation is done in the case of a statistically orthorhombic sample made up of cubic crystallites. The wave propagation and scattering model is formulated by the Dyson equation using an anisotropic Green's function approach. Within the limits of the first-order smoothing approximation, the Dyson equation is solved in the spatial Fourier transform domain. The results presented are shown to be directional dependent, frequency dependent, and especially dependent on the texture coefficients (ODCs) for the quasilongitudinal and two quasishear waves. The theoretical results presented may be used to improve the understanding of the microstructure during recrystallization processes. .

  16. Hollow antiresonant fibers with reduced attenuation. (United States)

    Belardi, Walter; Knight, Jonathan C


    An improved design for hollow antiresonant fibers (HAFs) is presented. It consists of adding extra antiresonant glass elements within the air cladding region of an antiresonant hollow-core fiber. We use numerical simulations to compare fiber structures with and without the additional cladding elements in the near- and mid-IR regimes. We show that realizable fiber structures can provide greatly improved performance in terms of leakage and bending losses compared to previously reported antiresonant fibers. At mid-IR wavelengths, the adoption of this novel fiber design will lead to HAFs with reduced bending losses. In the near-IR, this design could lead to the fabrication of HAFs with very low attenuation.

  17. Evidence of oxidative attenuation of auxin signalling. (United States)

    Peer, Wendy Ann; Cheng, Yan; Murphy, Angus S


    Indole-3-acetic acid (IAA) is the principle auxin in Arabidopsis and is synthesized primarily in meristems and nodes. Auxin is transported to distal parts of the plant in response to developmental programming or environmental stimuli to activate cell-specific responses. As with any signalling event, the signal must be attenuated to allow the system to reset. Local auxin accumulations are thus reduced by conjugation or catabolism when downstream responses have reached their optima. In most cell types, localized auxin accumulation increases both reactive oxygen species (ROS) and an irreversible catabolic product 2-oxindole-3-acid acid (oxIAA). oxIAA is inactive and does not induce expression of the auxin-responsive reporters DR5 or 2XD0. Here it is shown that oxIAA is not transported from cell to cell, although it appears to be a substrate for the ATP-binding cassette subfamily G (ABCG) transporters that are positioned primarily on the outer lateral surface of the root epidermis. However, oxIAA and oxIAA-Glc levels are higher in ABCB mutants that accumulate auxin due to defective cellular export. Auxin-induced ROS production appears to be at least partially mediated by the NAD(P)H oxidase RbohD. oxIAA levels are higher in mutants that lack ROS-scavenging flavonoids (tt4) and are lower in mutants that accumulate excess flavonols (tt3). These data suggest a model where IAA signalling is attenuated by IAA catabolism to oxIAA. Flavonoids appear to buffer ROS accumulations that occur with localized increases in IAA. This buffering of IAA oxidation would explain some growth responses observed in flavonoid-deficient mutants that cannot be explained by their established role in partially inhibiting auxin transport.

  18. A miniaturized reconfigurable broadband attenuator based on RF MEMS switches (United States)

    Guo, Xin; Gong, Zhuhao; Zhong, Qi; Liang, Xiaotong; Liu, Zewen


    Reconfigurable attenuators are widely used in microwave measurement instruments. Development of miniaturized attenuation devices with high precision and broadband performance is required for state-of-the-art applications. In this paper, a compact 3-bit microwave attenuator based on radio frequency micro-electro-mechanical system (RF MEMS) switches and polysilicon attenuation modules is presented. The device comprises 12 ohmic contact MEMS switches, π-type polysilicon resistive attenuation modules and microwave compensate structures. Special attention was paid to the design of the resistive network, compensate structures and system simulation. The device was fabricated using micromachining processes compatible with traditional integrated circuit fabrication processes. The reconfigurable attenuator integrated with RF MEMS switches and resistive attenuation modules was successfully fabricated with dimensions of 2.45  ×  4.34  ×  0.5 mm3, which is 1/1000th of the size of a conventional step attenuator. The measured RF performance revealed that the attenuator provides 10-70 dB attenuation at 10 dB intervals from 0.1-20 GHz with an accuracy better than  ±1.88 dB at 60 dB and an error of less than 2.22 dB at 10 dB. The return loss of each state of the 3-bit attenuator was better than 11.95 dB (VSWR  <  1.71) over the entire operating band.

  19. Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice


    Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi


    The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

  20. 16 CFR 1203.17 - Impact attenuation test. (United States)


    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Impact attenuation test. 1203.17 Section... SAFETY STANDARD FOR BICYCLE HELMETS The Standard § 1203.17 Impact attenuation test. (a) Impact test... the acceleration of the test headform during impact. Acceleration is measured with a...

  1. The attenuation anisotropy of mudstones and shales in subsurface formations

    Institute of Scientific and Technical Information of China (English)

    SHI Ge; DENG Jixin


    We have measured the relationships in the laboratorial condition between the attenuation in three samples of mudstones and shales as well as two samples of layered sandstones and the alteration in direction, confining pressure and pore fluid. The relative contributions of different attenuation mechanisms are also discussed. Studies show that the attenuation in dry and saturated samples is strongly related to pressure and direction. The attenuation coefficient of P-wave propagating parallel to bedding (PH) is less than that of P-wave propagating vertical to bedding (PV), while the attenuation coefficient of S-wave both propagating and vibrating parallel to bedding (SH) and that of S-wave propagating vertical to bedding while vibrating parallel to bedding (SV1) are less than that of S-wave propagating parallel to bedding while vibrating vertical to bedding (SV). Under oil saturated conditions, the Biot flow attenuation acts as the dominant mechanism for waves propagating parallel to bedding, while the frame anelastic attenuation and squirt flow attenuation seem to play important roles in condition of propagation vertical to bedding.

  2. Wave attenuation in mangroves; a quantitative approach to field observations

    NARCIS (Netherlands)

    Horstman, E.M.; Dohmen-Janssen, C.M.; Narra, P.M.F.; Berg, van den N.J.F.; Siemerink, M.; Hulscher, S.J.M.H.


    Coastal mangroves, dwelling at the interface between land and sea, provide an important contribution to reducing risk from coastal hazards by attenuating incident waves and by trapping and stabilizing sediments. This paper focusses on relations between vegetation densities, wave attenuation rates, s

  3. Light attenuation characteristics of glacially-fed lakes (United States)

    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


    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.

  4. Ultrasonic velocity and attenuation anisotropy of shales, Whitby, United Kingdom

    NARCIS (Netherlands)

    Zhubayev, A.; Houben, M.E.; Smeulders, D.M.J.; Barnhoorn, A.


    We have conducted ultrasonic experiments, between 0.3 and 1 MHz, to measure velocity and attenuation (Q−1) anisotropy of P- and S-waves in dry Whitby Mudstone samples as a function of stress. We found the degree of anisotropy to be as large as 70% for velocity and attenuation. The sensitivity of P-w

  5. Ultrasonic velocity and attenuation anisotropy of shales, Whitby, United Kingdom

    NARCIS (Netherlands)

    Zhubayev, Alimzhan; Houben, M.E.; Smeulders, David; Barnhoorn, A.


    We have conducted ultrasonic experiments, between 0.3 and 1 MHz, to measure velocity and attenuation (Q−1) anisotropy of P- and S-waves in dry Whitby Mudstone samples as a function of stress. We found the degree of anisotropy to be as large as 70% for velocity and attenuation. The sensitivity of P-w

  6. Attenuated radon transform: theory and application in medicine and biology

    Energy Technology Data Exchange (ETDEWEB)

    Gullberg, G.T.


    A detailed analysis is given of the properties of the attenuated Radon transform and of how increases in photon attenuation influence the numerical accuracy and computation efficiency of iterative and convolution algorithms used to determine its inversion. The practical applications for this work involve quantitative assessment of the distribution of injected radiopharmaceuticals and radionuclides in man and animals for basic physiological and biochemical studies as well as clinical studies in nuclear medicine. A mathematical structure is developed using function theory and the theory of linear operators on Hilbert spaces which lends itself to better understanding the spectral properties of the attenuated Radon transform. The continuous attenuated Radon transform reduces to a matrix operator for discrete angular and lateral sampling, and the reconstruction problem reduces to a system of linear equations. For the situation of variable attenuation coefficient frequently found in nuclear medicine applications of imaging the heart and chest, the procedure developed in this thesis involves iterative techniques of performing the generalized inverse. For constant attenuation coefficient less than 0.15 cm/sup -1/, convolution methods can reliably reconstruct a 30 cm object with 0.5 cm resolution. However, for high attenuation coefficients or for the situation where there is variable attenuation such as reconstruction of distribution of isotopes in the heart, iterative techniques developed in this thesis give the best results. (ERB)

  7. Flux attenuation at NREL's High-Flux Solar Furnace (United States)

    Bingham, Carl E.; Scholl, Kent L.; Lewandowski, Allan A.


    The High-Flux Solar Furnace (HFSF) at the National Renewable Energy Laboratory (NREL) has a faceted primary concentrator and a long focal-length-to-diameter ratio (due to its off-axis design). Each primary facet can be aimed individually to produce different flux distributions at the target plane. Two different types of attenuators are used depending on the flux distribution. A sliding-plate attenuator is used primarily when the facets are aimed at the same target point. The alternate attenuator resembles a venetian blind. Both attenuators are located between the concentrator and the focal point. The venetian-blind attenuator is primarily used to control the levels of sunlight failing on a target when the primary concentrators are not focused to a single point. This paper will demonstrate the problem of using the sliding-plate attenuator with a faceted concentrator when the facets are not aimed at the same target point. We will show that although the alternate attenuator necessarily blocks a certain amount of incoming sunlight, even when fully open, it provides a more even attenuation of the flux for alternate aiming strategies.

  8. Ultrasound attenuation dependence on air compression or expansion processes

    NARCIS (Netherlands)

    Jakevicius, L.; Demcenko, A.; Mardosaite, R.


    In this work variation of ultrasonic attenuation coefficient is analyzed in terms of air compression or expansion processes. In closed spaces changing air volume, the ultrasound attenuation coefficient depends on thermodynamic processes which occur during the air volume change. Two limiting cases ar

  9. Excess attenuation of an acoustic beam by turbulence. (United States)

    Pan, Naixian


    A theory based on the concept of a spatial sinusoidal diffraction grating is presented for the estimation of the excess attenuation in an acoustic beam. The equation of the excess attenuation coefficient shows that the excess attenuation of acoustic beam not only depends on the turbulence but also depends on the application parameters such as the beam width, the beam orientation and whether for forward propagation or back scatter propagation. Analysis shows that the excess attenuation appears to have a frequency dependence of cube-root. The expression for the excess attenuation coefficient has been used in the estimations of the temperature structure coefficient, C(T)2, in sodar sounding. The correction of C(T)2 values for excess attenuation reduces their errors greatly. Published profiles of temperature structure coefficient and the velocity structure coefficient in convective conditions are used to test our theory, which is compared with the theory by Brown and Clifford. The excess attenuation due to scattering from turbulence and atmospheric absorption are both taken into account in sodar data processing for deducing the contribution of the lower atmosphere to seeing, which is the sharpness of a telescope image determined by the degree of turbulence in the Earth's atmosphere. The comparison between the contributions of the lowest 300-m layer to seeing with that of the whole atmosphere supports the reasonableness of our estimation of excess attenuation.

  10. Periportal low-attenuation: a CT sign of lymphatic obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Kim, Chong Soo; Yang, Doo Hyun; Lee, Sang Yong; Lee, Young Whan; Chung, Gyung Ho; Han, Young Min; Sohn, Myung Hee; Choi, Ki Chul [Chonbuk National University College of Medicine, Jeonju (Korea, Republic of)


    Periportal low attenuation, defined as a low attenuation rim around the portal vein and its branches which is seen on contrast material-enhanced CT scans, has been described in a variety of conditions. We tried to document that lymphatic obstruction is one of the major cause of periportal low attenuation. We retrospectively analyzed 57 cases of periportal low attenuation of abdominal CT scans and also reviewed the surgical records in 32 cases. Lymph node enlargement in the hepatoduodenal ligament which is a main lymphatic channel from the liver were analyzed the calculated the ratio of the transeverse diameter between the inferior vena cava and the aorta at the level of right adrenal gland. After complete surgical interruption of the lymphatic drainage from the liver in a dog, follow up CT scans were obtained and correlated with pathologic findings. Fifty patients (88%) had underlying disease which could cause impairment of lymphatic drainage. Periportal low attenuation was identified in several clinical conditions, including surgical lymph node dissection, lymphadenopathy in the hepatoduodenal ligament, blunt trauma. In animal model, CT scan showed prominent periportal low attenuation at 5 days after surgery. Histologic examination revealed numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches. One of the major cause of periportal low attenuation was impaired lymphatic drainage and periportal low attenuation corresponding to the numerous dilated lymphatic vessels and a marked lymphedema in the connective tissues surrounding the portal vein and its major branches.

  11. A Precision Variable, Double Prism Attenuator for CO(2) Lasers. (United States)

    Oseki, T; Saito, S


    A precision, double prism attenuator for CO(2) lasers, calibrated by its gap capacitance, was constructed to evaluate its possible use as a standard for attenuation measurements. It was found that the accuracy was about 0.1 dB with a dynamic range of about 40 dB.

  12. Effect of lead attenuators on dose in homogeneous phantoms

    Energy Technology Data Exchange (ETDEWEB)

    El-Khatib, E.E.; Podgorsak, E.B.; Pla, C.


    In radiotherapy, the radiation beam is sometimes shaped so as to deliver different doses to different organs or give a homogeneous dose to structures of different densities. This objective is achieved by the use of attenuating materials introduced into the beam. These attenuators alter the primary as well as the scattered radiation components of the beam. There is at present no accurate method of dose calculation for these situations. Most calculations are performed considering only the effect of the attenuators on the primary radiation beam and can produce large errors in dosimetry. In the present study, the broad beam attenuation is investigated in homogeneous phantoms for various radiation field sizes, photon beam energies, and depths in phantom. A calculational method taking account of primary as well as first scatter radiation is developed. This method predicts reasonably well the transmission through lead attenuators for the various experimental conditions investigated.


    Directory of Open Access Journals (Sweden)

    G. N. Ezeh


    Full Text Available Rain attenuation is a major challenge to microwave satellite communication especially at frequencies above 10 GHz, causing unavailability of signals most of the time. Rain attenuation predictions have become one of the vital considerations while setting up a satellite communication link. In this study, rain attenuation models, cumulative distribution curves and other analytical tools for successful prediction of rain attenuation are presented. A three year Rain rate data was obtained from the Nigeria Meteorological Agency (NIMET database in addition to experimental data. Of the three prediction models used in the study, Ajayi model gave the range of values closest to the experimental data. A correctional factor was determined as 1.0988 and used to modify the Ajayi model. This modification to Ajayi’s model enabled its rain attenuation values conform more closely to the experimental result.

  14. Seismic attenuation of the inner core: Viscoelastic or stratigraphic? (United States)

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


    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. Agmatine attenuates silica-induced pulmonary fibrosis. (United States)

    El-Agamy, D S; Sharawy, M H; Ammar, E M


    There is a large body of evidence that nitric oxide (NO) formation is implicated in mediating silica-induced pulmonary fibrosis. As a reactive free radical, NO may not only contribute to lung parenchymal tissue injury but also has the ability to combine with superoxide and form a highly reactive toxic species peroxynitrite that can induce extensive cellular toxicity in the lung tissues. This study aimed to explore the effect of agmatine, a known NO synthase inhibitor, on silica-induced pulmonary fibrosis in rats. Male Sprague Dawley rats were treated with agmatine for 60 days following a single intranasal instillation of silica suspension (50 mg in 0.1 ml saline/rat). The results revealed that agmatine attenuated silica-induced lung inflammation as it decreased the lung wet/dry weight ratio, protein concentration, and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid. Agmatine showed antifibrotic activity as it decreased total hydroxyproline content of the lung and reduced silica-mediated lung inflammation and fibrosis in lung histopathological specimen. In addition, agmatine significantly increased superoxide dismutase (p pulmonary nitrite/nitrate as well as tumor necrosis factor α. Collectively, these results demonstrate the protective effects of agmatine against the silica-induced lung fibrosis that may be attributed to its ability to counteract the NO production, lipid peroxidation, and regulate cytokine effects.

  16. Photoacoustic imaging taking into account thermodynamic attenuation (United States)

    Acosta, Sebastián; Montalto, Carlos


    In this paper we consider a mathematical model for photoacoustic imaging which takes into account attenuation due to thermodynamic dissipation. The propagation of acoustic (compressional) waves is governed by a scalar wave equation coupled to the heat equation for the excess temperature. We seek to recover the initial acoustic profile from knowledge of acoustic measurements at the boundary. We recognize that this inverse problem is a special case of boundary observability for a thermoelastic system. This leads to the use of control/observability tools to prove the unique and stable recovery of the initial acoustic profile in the weak thermoelastic coupling regime. This approach is constructive, yielding a solvable equation for the unknown acoustic profile. Moreover, the solution to this reconstruction equation can be approximated numerically using the conjugate gradient method. If certain geometrical conditions for the wave speed are satisfied, this approach is well-suited for variable media and for measurements on a subset of the boundary. We also present a numerical implementation of the proposed reconstruction algorithm.

  17. Ultrasonic attenuation in rare-earth monoarsenides

    Indian Academy of Sciences (India)



    The present paper deals with the theoretical calculation of mechanical and thermophysical properties of rare-earth monoarsenides, XAs (X: Np, Pu, Th and U) using elastic constants as the input parameters. These second- and third-order elastic constants (SOECs and TOECs) are determinedin the temperature range 100–500K using Coulomb and Born–Mayer potential upto second nearest neighbours. In order to provide the link between mechanical and dynamical behaviour of crystals, parameters such as Young’s modulus, bulk modulus, Poisson’s ratio etc. are also calculated.In addition, the Cauchy relationship is obeyed by the chosen monoarsenides and are fairly anisotropic, which results in the measurement of longitudinal and shear wave velocities along $\\langle100 \\rangle$, $\\langle110\\rangle$ and $\\langle 111\\rangle$ directions. The toughness/fracture $(G/BT)$ ratio is greater than 0.60, which implies that XAs compounds are brittle at room temperature. Further, the Debye temperature is computed using Debye average velocity as the input parameter. It helps in the characterization of lattice vibrations of a solid. In this work, ultrasonic attenuation due to phonon–phonon interaction$\\alpha/f^2_{\\rm p−p}$ and thermoelastic loss $\\alpha/f ^{2}$th are computed for XAs from 100 to 500K using Mason’s theory. It further helps in evaluating the microstructural properties of the chosen materials. The obtained results indicate that XAs is mechanically stable and are compared with data availablein the literature.

  18. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J


    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  19. Atorvastatin attenuates oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Cai Zhiyou; Yan Yong; Wang Yonglong


    Objective: To investigate serum level of SOD, MDA, ox-LDL, AchE and Ach in AD, to study atorvastatin influence on serum level of SOD, MDA, ox-LDL, AchE and Acb in AD and its neuroprotection mechanisms. Methods Subjects were divided into: normal blood lipid level group with Alzheimer's disease (A), higher blood lipid level group with Alzheimer's disease (AH), normal blood lipid level Alzheimer's disease group with atorvastatin treeatment (AT),higher blood lipid level Alzheimer's disease group with atorvastatin treeatment(AHT). Ox-LDL was measured by enzyme linked immunosorbent assay; SOD, MDA, ox-LDL, AchE, Ach and blood lipid level in AD was measured by biochemistry. Results: The serum level of MDA, AchE in AH group after atorvastatin treatment is lower ;The serum level of SOD, Ach in AH group is more increased than that of in A group; The serum level of ox-LDL in AH, A groups is lower than that of in A group; The dementia degree is lower after atorvastatin treatment. Conclusion: Atorvastatin can decrease serum level of MDA, AchE and ox-LDL, and increase that of SOD, Acb, and attenuate dementia symptom in AD, especially, with hyperlipemia. The hypothesis of atorvastatin neuroprotection is concluded that atorvastatin may restrain free radical reaction and retard oxidation in AD.

  20. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)


    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  1. A prototype piecewise-linear dynamic attenuator (United States)

    Hsieh, Scott S.; Peng, Mark V.; May, Christopher A.; Shunhavanich, Picha; Fleischmann, Dominik; Pelc, Norbert J.


    The piecewise-linear dynamic attenuator has been proposed as a mechanism in CT scanning for personalizing the x-ray illumination on a patient- and application-specific basis. Previous simulations have shown benefits in image quality, scatter, and dose objectives. We report on the first prototype implementation. This prototype is reduced in scale and speed and is integrated into a tabletop CT system with a smaller field of view (25 cm) and longer scan time (42 s) compared to a clinical system. Stainless steel wedges were machined and affixed to linear actuators, which were in turn held secure by a frame built using rapid prototyping technologies. The actuators were computer-controlled, with characteristic noise of about 100 microns. Simulations suggest that in a clinical setting, the impact of actuator noise could lead to artifacts of only 1 HU. Ring artifacts were minimized by careful design of the wedges. A water beam hardening correction was applied and the scan was collimated to reduce scatter. We scanned a 16 cm water cylinder phantom as well as an anthropomorphic pediatric phantom. The artifacts present in reconstructed images are comparable to artifacts normally seen with this tabletop system. Compared to a flat-field reference scan, increased detectability at reduced dose is shown and streaking is reduced. Artifacts are modest in our images and further refinement is possible. Issues of mechanical speed and stability in the challenging clinical CT environment will be addressed in a future design.

  2. Broadband Lg Attenuation Modeling in the Middle East

    Energy Technology Data Exchange (ETDEWEB)

    Pasyanos, M E; Matzel, E M; Walter, W R; Rodgers, A J


    We present a broadband tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. A conjugate gradient method is used to tomographically invert the amplitude dataset of over 8000 paths over a 45{sup o} x 40{sup o} region of the Middle East. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5-10 Hz. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, while tectonic regions have high attenuation, with the highest attenuation at 1 Hz is found in eastern Turkey. The results also compare favorably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency-dependence of attenuation is not compatible with the power law representation of Q(f), an assumption that is often made.

  3. Rain Attenuation Prediction for Terrestrial Microwave Link in Bangladesh

    Directory of Open Access Journals (Sweden)

    HOSSAIN Sakir


    Full Text Available Rain attenuation is a major shortcoming of microwave transmission. As a subtropical country, Bangladesh is one of the highest rainy areas of the world. Thus, designing a terrestrial microwave link is a serious challenge to the engineers. In this paper, the annual rain rate and monthly variation of rate are predicted for different percentage of time of the year from the measured rainfall data. Using ITU rain model for terrestrial microwave communication, the rain attenuation is predicted for five major cities of Bangladesh, namely Dhaka, Chittagong, Rajshahi, Sylhet, and Khulna. It is found that rain attenuation is the most severe in Sylhet and least in Rajshahi. The attenuation is estimated for different frequency and polarization. A horizontally polarized signal encounters 15% more rain attenuation than that of vertically polarized signal. It is also found that attenuation in Rajshahi is about 20% lesser than that in Sylhet. Thus, the horizontally polarized transmission in Rajshahi experiences about 5% less attenuation than the vertically polarized transmission in Sylhet.

  4. Molecular basis of live-attenuated influenza virus.

    Directory of Open Access Journals (Sweden)

    Wen He

    Full Text Available Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular response that represents a naturally occurring transient infection. The cold-adapted (ca influenza A/AA/6/60 (H2N2 (AA ca virus is the backbone for the live attenuated trivalent seasonal influenza vaccine licensed in the United States. Similarly, the influenza A components of live-attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17 and A/Leningrad/134/47/57-ca (Len/47 along with virulent epidemic strains. However, the mechanism of temperature-sensitive attenuation is largely elusive. To understand how modification at genetic level of influenza virus would result in attenuation of human influenza virus A/PR/8/34 (H1N1,A/PR8, we investigated the involvement of key mutations in the PB1 and/or PB2 genes in attenuation of influenza virus in vitro and in vivo. We have demonstrated that a few of residues in PB1 and PB2 are critical for the phenotypes of live attenuated, temperature sensitive influenza viruses by minigenome assay and real-time PCR. The information of these mutation loci could be used for elucidation of mechanism of temperature-sensitive attenuation and as a new strategy for influenza vaccine development.

  5. Rain attenuation statistics over millimeter wave bands in South Korea (United States)

    Shrestha, Sujan; Choi, Dong-You


    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.

  6. FSO and radio link attenuation: meteorological models verified by experiment (United States)

    Brazda, Vladimir; Fiser, Ondrej; Svoboda, Jaroslav


    Institute of Atmospheric Physics of Czech Academy measures atmospheric attenuation on 60 m experimental FSO link on 830 and 1550 nm for more than three years. Visibility sensors and two 3D sonic anemometers on both transmitting and receiving site, rain gauge and many sensors enabling the refractivity index computation are spaced along the optical link. Meteorological visibility, wind turbulent energy, sonic temperature, structure index and rain rate are correlated with measured attenuation. FSO link attenuation dependence on the above mentioned parameters is analyzed. The paper shows also basic statistical behavior of the long-term FSO signal level and also the simulation of hybrid link techniques.

  7. Designing attenuators for total-body irradiation using virtual simulation. (United States)

    Corns, R; Evans, M; Olivares, M; Dyke, L; Podgorsak, E B; Freeman, C R


    In total-body photon irradiation, the lungs are the most commonly shielded organ. Lung compensators are often designed by using high-energy portal films. Other organs, such as the kidneys and liver, are poorly visualized in portal films due to their unit-density composition. A computed tomography-based technique to design kidney and liver attenuators involves outlining these organs in a virtual simulation. The position and the shape of the attenuator are then determined from a digitally-reconstructed radiograph. Appropriate attenuator thickness is determined from measured transmission curves. This article provides a summary of this technique for total-body photon irradiation in a 4-MV photon beam.

  8. MNAtoolbox: A Monitored Natural Attenuation Site Screening Program

    Energy Technology Data Exchange (ETDEWEB)

    Borns, David J.; Brady, Patrick V.; Brady, Warren D.; Krupka, Kenneth M.; Spalding, Brian P.; Waters, Robert D.; Zhang, Pengchu


    Screening of sites for the potential application and reliance upon monitored natural attenuation (MNA) can be done using MNAtoolbox, a web-based tool for estimating extent of biodegradation, chemical transformation, and dilution. MNAtoolbox uses site-specific input data, where available (default parameters are taken from the literature), to roughly quantify the nature and extent of attenuation at a particular site. Use of MNAtoolbox provides 3 important elements of site evaluation: (1) Identifies likely attenuation pathways, (2) Clearly identifies sites where MNA is inappropriate, and (3) Evaluates data requirements for subsequent reliance on MNA as a sole or partial corrective action.

  9. Photon attenuation properties of some thorium, uranium and plutonium compounds

    Energy Technology Data Exchange (ETDEWEB)

    Singh, V. P.; Badiger, N. M. [Karnatak University, Department of Physics, Dharwad-580003, Karnataka (India); Vega C, H. R., E-mail: [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)


    Mass attenuation coefficients, effective atomic numbers, effective electron densities for nuclear materials; thorium, uranium and plutonium compounds have been studied. The photon attenuation properties for the compounds have been investigated for partial photon interaction processes by photoelectric effect, Compton scattering and pair production. The values of these parameters have been found to change with photon energy and interaction process. The variations of mass attenuation coefficients, effective atomic number and electron density with energy are shown graphically. Moreover, results have shown that these compounds are better shielding and suggesting smaller dimensions. The study would be useful for applications of these materials for gamma ray shielding requirement. (Author)

  10. Elemental analysis by means of X-ray attenuation measurements (United States)

    Cesareo, Roberto; Giannini, Marino


    Radioactive sources of 109Cd, 241Am and 57Co were employed to measure the attenuation coefficient of biological materials such as whole blood, red blood cells, plasma, urine, water and of materials of interest for computed tomography, such as plexiglas, polyethylene, nylon, teflon, etc. The experimental errors range between 0.3% and 1%. A method is also presented which allows quantitative analysis of materials by measuring their attenuation coefficient at various monoenergetic X-ray energies. As an example, attenuation measurements at 60 keV and 122 keV were employed in order to determine the concentration of lead and copper in silver alloys.

  11. Ultrasonic attenuation measurements determine onset, degree, and completion of recrystallization (United States)

    Generazio, E. R.


    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.

  12. Cystathionine-γ lyase-derived hydrogen sulfide mediates the cardiovascular protective effects of moxonidine in diabetic rats. (United States)

    El-Sayed, Shaimaa S; Zakaria, Mohamed N M; Abdel-Ghany, Rasha H; Abdel-Rahman, Abdel A


    Blunted cystathionine-γ lyase (CSE) activity (reduced endogenous H2S-level) is implicated in hypertension and myocardial dysfunction in diabetes. Here, we tested the hypothesis that CSE derived H2S mediates the cardiovascular protection conferred by the imidazoline I1 receptor agonist moxonidine in a diabetic rat model. We utilized streptozotocin (STZ; 55mg/kg i.p) to induce diabetes in male Wistar rats. Four weeks later, STZ-treated rats received vehicle, moxonidine (2 or 6mg/kg; gavage), CSE inhibitor DL-propargylglycine, (37.5mg/kg i.p) or DL-propargylglycine with moxonidine (6mg/kg) for 3 weeks. Moxonidine improved the glycemic state, and reversed myocardial hypertrophy, hypertension and baroreflex dysfunction in STZ-treated rats. Ex vivo studies revealed that STZ caused reductions in CSE expression/activity, H2S and nitric oxide (NO) levels and serum adiponectin and elevations in myocardial imidazoline I1 receptor expression, p38 and extracellular signal-regulated kinase, ERK1/2, phosphorylation and lipid peroxidation (expressed as malondialdehyde). Moxonidine reversed these biochemical responses, and suppressed the expression of death associated protein kinase-3. Finally, pharmacologic CSE inhibition (DL-propargylglycine) abrogated the favorable cardiovascular, glycemic and biochemical responses elicited by moxonidine. These findings present the first evidence for a mechanistic role for CSE derived H2S in the glycemic control and in the favorable cardiovascular effects conferred by imidazoline I1 receptor activation (moxonidine) in a diabetic rat model.

  13. Licking microstructure reveals rapid attenuation of neophobia. (United States)

    Monk, Kevin J; Rubin, Benjamin D; Keene, Jennifer C; Katz, Donald B


    Many animals hesitate when initially consuming a novel food and increase their consumption of that food between the first and second sessions of access-a process termed attenuation of neophobia (AN). AN has received attention as a model of learning and memory; it has been suggested that plasticity resulting from an association of the novel tastant with "safe outcome" results in a change in the neural response to the tastant during the second session, such that consumption increases. Most studies have reported that AN emerges only an hour or more after the end of the first exposure to the tastant, consistent with what is known of learning-related plasticity. But these studies have typically measured consumption, rather than real-time behavior, and thus the possibility exists that a more rapidly developing AN remains to be discovered. Here, we tested this possibility, examining both consumption and individual lick times in a novel variant of a brief-access task (BAT). When quantified in terms of consumption, data from the BAT accorded well with the results of a classic one-bottle task-both revealed neophobia/AN specific to higher concentrations (for instance, 28mM) of saccharin. An analysis of licking microstructure, however, additionally revealed a real-time correlate of neophobia-an explicit tendency, similarly specific for 28-mM saccharin, to cut short the initial bout of licks in a single trial (compared with water). This relative hesitancy (i.e., the shortness of the first lick bout to 28-mM saccharin compared with water) that constitutes neophobia not only disappeared between sessions but also gradually declined in magnitude across session 1. These data demonstrate that the BAT accurately measures AN, and that aspects of AN-and the processes underlying familiarization-begin within minutes of the very first taste.

  14. Attenuation of Landfill Leachate In Unsaturated Sandstone (United States)

    Butler, A. P.; Brook, C.; Godley, A.; Lewin, K.; Young, C. P.

    Landfill leachate emanating from old "dilute and disperse" sites represents a potential (and in many cases actual) threat to the integrity of groundwater. Indeed, this concern has been included in EU legislation (80/86/EEC), where key contaminants (e.g. ammonia, various toxic organic compounds and heavy metals) are explicitly highlighted in terms of their impact on groundwater. In the UK, whilst there are a substantial number of unlined landfills sited on major aquifers, many of these are in locations where there is a substantial unsaturated zone. Thus, there exists the opportunity for the modification and attenuation of contaminants prior to it encountering the water table. An understanding of likely changes in leachate content and concentrations at such sites will enable a more comprehensive assessment of the potential risks and liabilities posed by such sites to be evaluated. The Burntstump landfill, situated 8 km north of Nottingham (UK), is sited on an outcrop of Sherwood sandstone. The fine friable sand has been quarried since the 1960s and the excavated volume used to store municipal waste. Filling at the site commenced in the mid 1970s and originally was unlined. In 1978 the first of what was to become a series of boreholes was installed within an area of roughly 5 m radius over one of the original waste cells. Cores of the waste and underlying sandstone were extracted and analysed for a range of physical and chemical parameters. The most recent set of analyses were obtained in 2000. The series of investigations therefore provide an important record of leachate migration and modification through the unsaturated zone for over twenty years. The progression of the leachate front is clearly delineated by the chloride concentration profile with an average velocity of around 1.6 m.yr-1. Combining this value with an average (and reasonably uniform) measured moisture content of about 7% gives a mean inter-granular specific discharge of 110 mm.yr-1. An interesting

  15. Psychoneuroendocrine interventions aimed at attenuating immunosenescence: a review

    NARCIS (Netherlands)

    Bauer, M.E.; Muller, G.C.; Correa, B.L.; Vianna, P.; Turner, J.E.; Bosch, J.A.


    There is evidence suggesting that immunosenescence can be accelerated by external factors such as chronic stress. Here we review potential psychoneuroendocrine determinants of premature aging of the immune system and discuss available interventions aimed at attenuating immunosenescence. Chronic stre

  16. Biochanin-A attenuates neuropathic pain in diabetic rats

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Chundi


    Conclusion: Biochanin-A demonstrated better efficacy in reversing mechanical allodynia than mechanical hyperalgesia. Biochanin-A could be a good drug candidate for further studies to establish the mechanism of attenuation of neuropathic pain.


    A natural attenuation model that simulates the aerobic and anaerobic biodegradation of fuel hydrocarbons was developed. The resulting model, BIOPLUME III, demonstrates the importance of biodegradation in reducing contaminant concentrations in ground water. In hypothetical simulat...


    Institute of Scientific and Technical Information of China (English)

    Zhang Qing-he; Onyx W.H. Wai; Joseph H. W. Lee


    A two-layer model, with the upper layer being the perfect fluid and the lower layer being the pseudo-plastic fluid describing water wave attenuation over mud bed, was established. A simplified method based on the principle of equivalent work was applied to solve the boundary value problems. The computational results of the model show that the two-layer perfect fluid model and the perfect-viscous fluid model are all special cases of the present model. The complex nonlinear properties of wave attenuation over mud bed, can be explained by the present model, e.g., the wave dissipation rate decreases with the wave height in certain cases, while the small wave propagates over mud bed with less energy dissipation and large wave attenuates rapidly in other cases. Other factors influencing the wave attenuation were also discussed.

  19. Earth/Mars Landing Impact Attenuation Using Foam Project (United States)

    National Aeronautics and Space Administration — On a previous ICA, a test correlated excel based software tool was developed using the innovative Stress?Energy method to better model impact attenuation using...

  20. 49 CFR 227.117 - Hearing protector attenuation. (United States)


    ... exposure to an 8-hour TWA of 90 decibels or lower, as required by § 227.115. (c) For employees who have...-weighted average of 85 decibels or lower. (d) The adequacy of hearing protector attenuation shall be...

  1. Dose reduction using a dynamic, piecewise-linear attenuator

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Fleischmann, Dominik [Department of Radiology, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)


    Purpose: The authors recently proposed a dynamic, prepatient x-ray attenuator capable of producing a piecewise-linear attenuation profile customized to each patient and viewing angle. This attenuator was intended to reduce scatter-to-primary ratio (SPR), dynamic range, and dose by redistributing flux. In this work the authors tested the ability of the attenuator to reduce dose and SPR in simulations. Methods: The authors selected four clinical applications, including routine full field-of-view scans of the thorax and abdomen, and targeted reconstruction tasks for an abdominal aortic aneurysm and the pancreas. Raw data were estimated by forward projection of the image volume datasets. The dynamic attenuator was controlled to reduce dose while maintaining peak variance by solving a convex optimization problem, assuminga priori knowledge of the patient anatomy. In targeted reconstruction tasks, the noise in specific regions was given increased weighting. A system with a standard attenuator (or “bowtie filter”) was used as a reference, and used either convex optimized tube current modulation (TCM) or a standard TCM heuristic. The noise of the scan was determined analytically while the dose was estimated using Monte Carlo simulations. Scatter was also estimated using Monte Carlo simulations. The sensitivity of the dynamic attenuator to patient centering was also examined by shifting the abdomen in 2 cm intervals. Results: Compared to a reference system with optimized TCM, use of the dynamic attenuator reduced dose by about 30% in routine scans and 50% in targeted scans. Compared to the TCM heuristics which are typically used withouta priori knowledge, the dose reduction is about 50% for routine scans. The dynamic attenuator gives the ability to redistribute noise and variance and produces more uniform noise profiles than systems with a conventional bowtie filter. The SPR was also modestly reduced by 10% in the thorax and 24% in the abdomen. Imaging with the dynamic

  2. Attenuation of 3CM Microwaves Due to Artificial Rain

    Directory of Open Access Journals (Sweden)

    J. K. Singh


    Full Text Available Observations to study the variation of attenuation of 3cm waves due to falling of water or artificial rain are confined to the high rates of precipitation and short distance between the transmitter and receiver, due to low power of the microwave generator. A comparison of these observations and those recorded by others shows that the attenuation increases nonlinearly with the intensity of artificial rainfall which is generally assumed to be linear for the observations at lower rates of precipitation.

  3. An analysis of seismic attenuation in random porous media

    Institute of Scientific and Technical Information of China (English)


    The attenuation of seismic wave in rocks has been one of the interesting research topics, but till now no poroelasticity models can thoroughly explain the strong attenuation of wave in rocks. In this paper, a random porous medium model is designed to study the law of wave propagation in complex rocks based on the theory of Biot poroelasticity and the general theory of stochastic process. This model sets the density of grain, porosity, permeability and modulus of frame as random parameters in space, and only one fluid infiltrates in rocks for the sake of better simulation effect in line with real rocks in earth strata. Numerical simulations are implemented. Two different inverse quality factors of fast P-wave are obtained by different methods to assess attenuation through records of virtual detectors in wave field (One is amplitude decay method in time domain and the other is spectral ratio method in frequency domain). Comparing the attenuation results of random porous medium with those of homogeneous porous medium, we conclude that the attenuation of seismic wave of homogeneous porous medium is far weaker than that of random porous medium. In random porous media, the higher heterogeneous level is, the stronger the attenuation becomes, and when heterogeneity σ = 0.15 in simulation, the attenuation result is consistent with that by actual observation. Since the central frequency (50 Hz) of source in numerical simulation is in earthquake band, the numerical results prove that heterogeneous porous structure is one of the important factors causing strong attenuation in real stratum at intermediate and low frequency.

  4. Characterizing X-ray Attenuation of Containerized Cargo

    Energy Technology Data Exchange (ETDEWEB)

    Birrer, N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Divin, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Glenn, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Martz, H. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wang, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    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.

  5. Kramers-Kronig relationship between ultrasonic attenuation and phase velocity (United States)

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


    Kramers-Kronig relations linking the attenuation and dispersion are presented for a linear acoustic system. These expressions are used as a starting point to derive approximate, nearly local expressions relating the ultrasonic attenuation at a specific frequency to the local frequency derivative of the phase velocity (i.e., dispersion). The validity of these approximate relationships is demonstrated in several acoustic systems exhibiting substantially different physical properties.

  6. Impact of Scattering Model on Disdrometer Derived Attenuation Scaling (United States)

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


    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.

  7. Attenuation of Scalar Fluxes Measured with Spatially-displaced Sensors (United States)

    Horst, T. W.; Lenschow, D. H.


    Observations from the Horizontal Array Turbulence Study (HATS) field program are used to examine the attenuation of measured scalar fluxes caused by spatial separation between the vertical velocity and scalar sensors. The HATS data show that flux attenuation for streamwise, crosswind, and vertical sensor displacements are each a function of a dimensionless, stability-dependent parameter n m multiplied by the ratio of sensor displacement to measurement height. The scalar flux decays more rapidly with crosswind displacements than for streamwise displacements and decays more rapidly for stable stratification than for unstable stratification. The cospectral flux attenuation model of Kristensen et al. agrees well with the HATS data for streamwise sensor displacements, although it is necessary to include a neglected quadrature spectrum term to explain the observation that flux attenuation is often less with the scalar sensor downwind of the anemometer than for the opposite configuration. A simpler exponential decay model provides good estimates for crosswind sensor displacements, as well as for streamwise sensor displacements with stable stratification. A model similar to that of Lee and Black correctly predicts flux attenuation for a combination of streamwise and crosswind displacements, i.e. as a function of wind direction relative to the sensor displacement. The HATS data for vertical sensor displacements extend the near-neutral results of Kristensen et al. to diabatic stratification and confirm their finding that flux attenuation is less with the scalar sensor located below the anemometer than if the scalar sensor is displaced an equal distance either horizontally or above the anemometer.

  8. Characterizing Dust Attenuation in Local Star Forming Galaxies (United States)

    Battisti, Andrew; Calzetti, Daniela; Chary, Ranga-Ram


    The dust attenuation for a sample of ~10000 local (z ≤ 0.1) star forming galaxies is constrained as a function of their physical properties. We utilize aperture-matched multi-wavelength data from the UV-to-NIR, available from the Galaxy Evolution Explorer, the Sloan Digital Sky Survey, the United Kingdom Infrared Telescope, and the Two Micron All-Sky Survey, to ensure that regions of comparable size in each galaxy are being analyzed. We characterize the dust attenuation through the slope of the UV flux density and the Balmer decrement (Hα/Hβ). The observed relationship between these quantities is similar to the local starburst relation and is not seen to vary strongly with galactic properties. We derive the total attenuation curve over the range 1250 Å < λ < 28500 Å and find that a single attenuation curve is effective for characterizing the majority of galaxies in our sample. This attenuation curve is slightly lower in the far-UV than local starburst galaxies, by roughly 15%, but appears similar at longer wavelengths and has a normalization of RV = 3.7±0.4 (V-band). This indicates that a single attenuation curve is reasonable for wide application in the local Universe.

  9. Proteomic Analysis of Pathogenic and Attenuated Alcelaphine Herpesvirus 1▿ (United States)

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


    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

  10. Novel point mutations attenuate autotaxin activity

    Directory of Open Access Journals (Sweden)

    Stracke Mary L


    Full Text Available Abstract Background The secreted enzyme autotaxin (ATX stimulates tumor cell migration, tumorigenesis, angiogenesis, and metastasis. ATX hydrolyzes nucleotides, but its hydrolysis of lysophospholipids to produce lysophosphatidic acid (LPA accounts for its biological activities. ATX has been identified only as a constitutively active enzyme, and regulation of its activity is largely unexplored. In spite of its presence in plasma along with abundant putative substrate LPC, the product LPA is found in plasma at unexpectedly low concentrations. It is plausible that the LPA-producing activity of ATX is regulated by its expression and by access to substrate(s. For this reason studying the interaction of enzyme with substrate is paramount to understanding the regulation of LPA production. Results In this study we determine ATX hydrolytic activities toward several artificial and natural substrates. Two novel point mutations near the enzyme active site (H226Q and H434Q confer attenuated activity toward all substrates tested. The Vmax for LPC compounds depends upon chain length and saturation; but this order does not differ among wild type and mutants. However the mutant forms show disproportionately low activity toward two artificial substrates, pNpTMP and FS-3. The mutant forms did not significantly stimulate migration responses at concentrations that produced a maximum response for WT-ATX, but this defect could be rescued by inclusion of exogenous LPC. Conclusion H226Q-ATX and H434Q-ATX are the first point mutations of ATX/NPP2 demonstrated to differentially impair substrate hydrolysis, with hydrolysis of artificial substrates being disproportionately lower than that of LPC. This implies that H226 and H434 are important for substrate interaction. Assays that rely on hydrolyses of artificial substrates (FS-3 and pNpTMP, or that rely on hydrolysis of cell-derived substrate, might fail to detect certain mutated forms of ATX that are nonetheless capable of

  11. Carbon nanotubes attenuate cancer and improve healing (United States)

    Wailes, Elizabeth Marguerite

    Breast cancer is the most common cancer in American women and the second largest cause of their cancer mortality. Resection of the primary tumor can greatly improve the prognosis, but if any of the cancerous cells remain, the patient is still at risk. This work investigates the ability of high aspect ratio nanoparticles to both heal injured tissue and attenuate cancer cells' aggression. To assess different particles' utility, carbon nanoparticles were evaluated in a fibroblast and collagen gel model of wound contraction, then polymeric nanoparticles were synthesized and tested similarly. The carbon particles, multi-walled nanotubes (MWNT) in particular, performed the best, strongly inhibiting pathological wound contraction, increasing cell viability, and decreasing reactive oxygen species. Later, carbon nanoparticle coatings with or without collagen were tested with breast cancer cells to assess adhesion, migration, and E-cadherin expression of the cells. The collagen-MWNT coatings were able to increase cancer cell adhesion to their substrate, decrease migration, increase E-cadherin expression, and also increase autophagy. The coatings effected all these changes without increasing proliferation of the cancer cells or affecting non-tumorigenic breast cells. To examine how these two sets of results might act together, co-cultures were then created with both fibroblasts and cancer cells in collagen gels with or without MWNT. The cells' movement and matrix metalloproteinase (MMP) expression were measured to gauge the cells' interaction in that environment, as fibroblasts can encourage or suppress metastasis depending on their behavior. The MWNT were able to decrease cancer cell movement, particularly their invasion into the gel, and selectively promote cancer cell death without harming the non-tumorigenic cells. They also decreased MMP expression. Finally, early in vivo work was undertaken to determine how the collagen-nanoparticle gels are able to control cancer in

  12. Patient position alters attenuation effects in multipinhole cardiac SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn, E-mail: [Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7 (Canada)


    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 and 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. The

  13. Imaging the attenuation coefficients of positron beams in matter: positron attenuation tomography

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Charles [Siemens Healthcare, Knoxville, TN (United States)


    A new positron annihilation imaging modality is described that enables nondestructive measurement of the linear attenuation coefficients (LACs) of positron beams in heterogeneous materials. This positron attenuation tomography (PAT) technique utilizes a positron emission tomography (PET) system embedded within a uniform static magnetic field, such as is found in integrated PET/MRI scanners. A Ga68-generated positron beam constrained by a 3T magnetic field penetrates objects placed within the scanner. The positrons slow down and annihilate within the object. The resulting annihilation distribution is tomographically imaged by the PET camera. This image may be interpreted as a map of the product of the positron beam's flux and its LAC at each point in the volume. It is shown that under certain easily achieved conditions this image can be decomposed into separate maps of the flux and the LACs, without need for auxiliary measurements. Although these LACs may depend on both beam and material properties, a beam softening correction is demonstrated that effectively removes the dependence on beam variation, leaving a relative LAC that is characteristic of the material. Unlike x-ray, gamma-ray or other transmission techniques, PAT does not require the penetration of the beam entirely through the object. High resolution and high contrast images of positron beam LACs in objects may be produced over nearly the full range of the positron beam, which for Ga68 beta-rays in a 3T field is about 0.5 g/cm{sup 2}. The first examples of PAT images and an initial characterization of performance will be presented.

  14. Brunenders: a partially attenuated historic poliovirus type I vaccine strain. (United States)

    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


    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.

  15. Characteristics of coda wave attenuation in Yunnan area

    Institute of Scientific and Technical Information of China (English)


    The characteristic of seismic coda wave attenuation in Yunnan area in 7 frequency-bands range from 1 Hz to 20 Hz was estimated by using the local earthquake's waveform data recorded from 22 Yunnan digital seismic stations.Coda attenuation Q-c1 of each station was firstly calculated by single scattering method. Then, mean free path Le and seismic albedo Bo of each station were calculated, and scattering attenuation Q-1s and intrinsic attenuation Q-1i were separated from total attenuation Q-1t by multiple lapse time window analysis based on the multiple scattering model in uniform random isotropic scattering medium. The attenuating characteristics in Yunnan show that most value of Le are in 10~30 km, with maximal within 2~6 Hz;Bo are about 0.5 at 1~2 Hz, but less than 0.5at other frequency-bands, which means Q-1i is comparable with Q-1s at 1~2 Hz, and after 1~2 Hz, Q-1i is greater than Q-1s and dominates the attenuation process. Q-1c is close to Q-1i at other frequency bands except 1~2 Hz.Results show that Q-1 especially Qs-1 varies spatially, Q-1 in eastern Yunnan zone is a bit higher than in northwestern Yunnan zone;northwestern Yunnan zone higher than southwestern Yunnan zone. Comparing with other results in global, Qs-1 in Yunnan is lower than the global average value among these results, Q-1i is higher than the global average value, and Q-1t lies the middle among these results.

  16. Attenuation correction effects on SPECT/CT procedures: phantoms studies. (United States)

    Oliveira, M L; Seren, M E G; Rocha, F C; Brunetto, S Q; Ramos, C D; Button, V L S N


    Attenuation correction is widely used in SPECT/CT (Single Photon Emission Computed Tomography) procedures, especially for imaging of the thorax region. Different compensation methods have been developed and introduced into clinical practice. Most of them use attenuation maps obtained using transmission scanning systems. However, this gives extra dose of radiation to the patient. The purpose of this study was to identify when attenuation correction is really important during SPECT/CT procedures.For this purpose, we used Jaszczak phantom and phantom with three line sources, filled with technetium ((99m)-Tc), with scattering materials, like air, water and acrylic, in different detectors configurations. In all images acquired were applied analytic and iterative reconstruction algorithms; the last one with or without attenuation correction. We analyzed parameters such as eccentricity, contrast and spatial resolution in the images.The best reconstruction algorithm on average was iterative, for images with 128 × 128 and 64 × 64 matrixes. The analytical algorithm was effective only to improve eccentricity in 64 × 64 matrix and matrix in contrast 128 × 128 with low statistics. Turning to the clinical routine examinations, on average, for 128 × 128 matrix and low statistics counting, the best algorithm was the iterative, without attenuation correction,improving in 150% the three parameters analyzed and, for the same matrix size, but with high statistical counting, iterative algorithm with attenuation correction was 25% better than that without correction. We can conclude that using the iterative algorithm with attenuation correction in the water, and its extra dose given, is not justified for the procedures of low statistic counting, being relevant only if the intention is to prioritize contrast in acquisitions with high statistic counting.

  17. Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

    KAUST Repository

    Werner, Craig M.


    Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

  18. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Minicucci, Marcos; Oliveira, Fernando; Santos, Priscila; Polegato, Bertha; Roscani, Meliza; Fernandes, Ana Angelica; Lustosa, Beatriz; Paiva, Sergio; Zornoff, Leonardo; Azevedo, Paula, E-mail: [Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, São Paulo, SP (Brazil)


    Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  19. Frequency-Dependent Attenuation of Blasting Vibration Waves (United States)

    Zhou, Junru; Lu, Wenbo; Yan, Peng; Chen, Ming; Wang, Gaohui


    The dominant frequency, in addition to the peak particle velocity, is a critical factor for assessing adverse effects of the blasting vibration on surrounding structures; however, it has not been fully considered in blasting design. Therefore, the dominant frequency-dependent attenuation mechanism of blast-induced vibration is investigated in the present research. Starting with blasting vibration induced by a spherical charge propagating in an infinite viscoelastic medium, a modified expression of the vibration amplitude spectrum was derived to reveal the frequency dependency of attenuation. Then, ground vibration induced by more complex and more commonly used cylindrical charge that propagates in a semi-infinite viscoelastic medium was analyzed by numerical simulation. Results demonstrate that the absorptive property of the medium results in the frequency attenuation versus distance, whereas a rapid drop or fluctuation occurs during the attenuation of ground vibration. Fluctuation usually appears at moderate to far field, and the dominant frequency generally decreases to half the original value when rapid drop occurs. The decay rate discrepancy between different frequency components and the multimodal structure of vibration spectrum lead to the unsmooth frequency-dependent attenuation. The above research is verified by two field experiments. Furthermore, according to frequency-based vibration standards, frequency drop and fluctuation should be considered when evaluating blast safety. An optimized piecewise assessment is proposed for more accurate evaluation: With the frequency drop point as the breakpoint, the assessment is divided into two independent sections along the propagating path.

  20. Wild type measles virus attenuation independent of type I IFN

    Directory of Open Access Journals (Sweden)

    Horvat Branka


    Full Text Available Abstract 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.

  1. Seismic motion attenuation relations in Sichuan and adjacent areas

    Institute of Scientific and Technical Information of China (English)

    LEI Jian-cheng; GAO Meng-tan; YU Yan-xiang


    The Sichuan and adjacent areas is divided into southwest China region (SWCR) and Sichuan Basin region (SCBR) according to tectonic backgrounds and seismic damage distribution features. 96 modern destructive earthquakes in SWCR and 40 in SCBR are gathered respectively. All their magnitude parameters are checked. Based on the statistic relations between epicentral intensity and magnitude as well as relation between sensible radius and magnitude, the near and far field seismic intensity attenuation features are represented and controlled. And then the seismic intensity attenuation relations along major axis, minor axis and mean axis are established separately. The systematic deviations of surface wave magnitude between China seismograph network and U.S. seismograph network are considered in this paper. By making use of the new attenuation relations of bedrock horizontal ground acceleration response spectrum in west U.S., the attenuation relations of bedrock horizontal ground acceleration response spectrum in SWCR and SCBR are digital transformed based on the attenuation model considering acceleration saturation of distance and magnitude in near field.

  2. Radar attenuation and temperature within the Greenland Ice Sheet (United States)

    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


    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.


    Directory of Open Access Journals (Sweden)

    K. Ferria


    Full Text Available The light intensity control of a luminous source is a very important operation in many optical applications. Several types of light attenuator exploiting different optical phenomena like diffraction, absorption, and reflection exist and they differ principally in the maximum attenuation rate, the control range, the sensitivity and the spectral band. In the presented work, we have developed and designed a light attenuator based on the progressive decrease of the transmitted light intensity, when it undergoes multiple vitreous reflections across eight plates glasses arranged in a roof shape. Several tests were carried out using a laser light as a source. We have shown that the attenuation rate can be controlled by the choice of the incidence angle on the glasses slides, in addition we have confirmed, for the case of perpendicular polarization of the laser light, that the attenuation obeys to a linear function. The obtained results are very close to those predicted theoretically.

  4. Consideration of natural attenuation. In remedation contaminated sites

    Energy Technology Data Exchange (ETDEWEB)



    Upon the proposal submitted by ist Standing committee 5 (Contaminated Sites Committee - ALA) the Federal / State Working Group on Soil protection employed an ad hoc subcommittee dealing with considering natural attenuation in remediating contaminated sites and preparing an inter-State position paper. In the present position paper the way how to consider natural attenuation in practical remediation of contaminated sites is described. The systematic approach outlined allows an understandable decision-finding. A way is shown how the competent soil protection authorities may exercise discretion and in the framework of checking the appropriateness of measures may decide on the implementation of MNA based on a MNA concept (MNA = monitored natural attenuation). It is, however, also explained that when carrying out MNA a decision always made in an individual case is concerned which should be made in a close agreement between the obligated party and the authority.

  5. Smart structures for shock wave attenuation using ER inserts (United States)

    Kim, Jaehwan; Kim, Jung-Yup; Choi, Seung-Bok; Kim, Kyung-Su


    This Paper demonstrates the possibility of shock wave attenuation propagating through a smart structure that incorporates ER insert. The wave transmission of ER inserted beam is theoretically derived using Mead & Markus model and the theoretical results are compared with the finite element analysis results. To experimentally verify the shock wave attenuation, ER insert in an aluminum plate is made and two piezoceramic disks are used as transmitter and receiver of the wave. The transmitter sends a sine pulse signal such that a component of shock wave travels through the plate structure and the receiver gets the transmitted wave signal. Wave propagation of the ER insert can be adjusted by changing the applied electric field on the ER insert. Details of the experiment are addressed and the possibility of shock wave attenuation is experimentally verified. This kind of smart structure can be used for warship and submarine hull structures to protect fragile and important equipment.

  6. Broadband fractal acoustic metamaterials for low-frequency sound attenuation (United States)

    Song, Gang Yong; Cheng, Qiang; Huang, Bei; Dong, Hui Yuan; Cui, Tie Jun


    We fabricate and experimentally characterize a broadband fractal acoustic metamaterial that can serve to attenuate the low-frequency sounds at selective frequencies ranging from 225 to 1175 Hz. The proposed metamaterials are constructed by the periodic Hilbert fractal elements made of photosensitive resin via 3D printing. In analogy to electromagnetic fractal structures, it is shown that multiple resonances can also be excited in the acoustic counterpart due to their self-similar properties, which help to attenuate the acoustic energy in a wide spectrum. The confinement of sound waves in such subwavelength element is evidenced by both numerical and experimental results. The proposed metamaterial may provide possible alternative for various applications such as the noise attenuation and the anechoic materials.

  7. Fiber movements and sound attenuation in glass wool

    DEFF Research Database (Denmark)

    Tarnow, Viggo


    Propagation of a plane harmonic sound wave in fiber materials such as glass wool is studied theoretically and experimentally. Wave equations are set up that take into account the movement of the fiber skeleton. The attenuation of the sound wave in slabs of glass wool was calculated and measured....... The main new result is that the experimental attenuation at low-frequency propagating wave is lower when the fibers move. For wave with frequency 100 Hz in glass wool of density 20 kg/m3, the attenuation of a layer of thickness 0.20 m is 4 dB if the fibers move, and 12 dB if they do not move...

  8. Correction for hydrometeor attenuation of C band radar data

    Institute of Scientific and Technical Information of China (English)


    C band digital weather radar observed data, collected from the Huaihe River Basin Energy and Water Cycle Experiment (HUBEX), are used for the study of correction of hydrometeor attenuation in the Fuyang region. An iterative algorithm is used for the correction scheme. The preliminary study shows that there may be a big difference between the radar observed reflectivity and the corresponding corrected one. Based upon the hourly precipitation data derived by the radar data sampled from the observations at intervals of 10 min and rain-gauge-recorded hourly precipitation data, it is found that the attenuation correction algorithm gives better results than those from the direct observation. It is also shown that the temperature of hydrometeors may strongly affect the results derived from the attenuation algorithm.

  9. Monte Carlo simulation of laser attenuation characteristics in fog (United States)

    Wang, Hong-Xia; Sun, Chao; Zhu, You-zhang; Sun, Hong-hui; Li, Pan-shi


    Based on the Mie scattering theory and the gamma size distribution model, the scattering extinction parameter of spherical fog-drop is calculated. For the transmission attenuation of the laser in the fog, a Monte Carlo simulation model is established, and the impact of attenuation ratio on visibility and field angle is computed and analysed using the program developed by MATLAB language. The results of the Monte Carlo method in this paper are compared with the results of single scattering method. The results show that the influence of multiple scattering need to be considered when the visibility is low, and single scattering calculations have larger errors. The phenomenon of multiple scattering can be interpreted more better when the Monte Carlo is used to calculate the attenuation ratio of the laser transmitting in the fog.

  10. Long term attenuation measurements on optical ground wires

    Energy Technology Data Exchange (ETDEWEB)

    Lamarche, L.; Gagnon, D.; Miron, M. [Hydro-Quebec, Varennes, Quebec1 (Canada)


    The attenuation stability of optical fibers integrated in optical ground wires (OPGW) cables over temperature and time is of paramount importance in the planning of long distance links. The authors report here a mean thermal attenuation dependence of 5.5{center_dot}10{sup {minus}5} dB/(km{center_dot}C) at 1,550 nm, on a 220 km span of dispersion shifted (DS) fibers of an installed OPGW cable. This optical link is installed in the James Bay region over a 735 kV power line where temperature varies from {minus}40 C to +30 C annually. The data sample presented covers 1.5 year starting December 1993. The data sample presented covers 1.5 year starting December 1993. During that period, the authors also observed a temporal evolution of the attenuation described by the empirical relation A = A{sub 0} (t{minus}t{sub 0}){sup 0.00394}.

  11. Ultrasonic attenuation of CdSe at low temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, B.J., E-mail: braulio@ula.v [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Calderon, E.; Bracho, D.B. [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Perez, J.F. [Laboratorio de Instrumentacion Cientifica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of)


    The ultrasonic attenuation of a single crystal of CdSe has been investigated over the temperature range from 1.2 to 300 K at frequencies of 10, 30 and 90 MHz. We report here the temperature dependence of the attenuation in the range 1.2-30 K for piezoactive and non-piezoactive acoustic waves. A temperature-induced relaxation for two piezoactive waves, which scale with frequency towards higher temperatures, was found. A modified Hutson and White model with a new parameter {gamma} is proposed to explain the relaxation maxima of our data and others in the literature. In this model the parameter {gamma}, which seems to be closely related to the compensation, takes into account the impurities-sound wave piezoelectric coupling. By inverting the proposed expression for the sound attenuation to obtain the electrical conductivity from the relaxation, it is found that impurity conductivity of the hopping type is the dominant conduction process at low temperatures.

  12. Homogeneous Magnetic Field Source For Attenuated Total Reflection

    Directory of Open Access Journals (Sweden)

    Lesňák Michal


    Full Text Available The paper is focused on the study of two-dimensional magnetic field distribution used for an analysis of samples containing magnetically active films by means of the Attenuated Total Reflection (ATR method. The design of a proposed electromagnet and the magnetic field model computation are presented together with the results obtained from magnetic field distribution measurement. The ATR method can provide information about a thin film thickness, refractive index, and attenuation in addition to the perfunctory coupling of an optical wave into and off a waveguide [1, 2]. The prism coupling conditions are determined for magnetic structures with induced anisotropy.

  13. Sound attenuation using microelectromechanical systems fabricated acoustic metamaterials (United States)

    Yunker, William N.; Stevens, Colin B.; Flowers, George T.; Dean, Robert N.


    Unlike traditional rotational gyroscopes, microelectromechanical systems (MEMS) gyroscopes use a vibrating proof mass rather than a rotational mass to sense changes in angular rate. They are also smaller and less expensive than traditional gyroscopes. MEMS gyroscopes are known to be susceptible to the effects of acoustic noise, in particular high frequency and high power acoustic noise. Most notably, this has been proven true in aerospace applications where the noise can reach levels in excess of 120 dB and the noise frequency can exceed 20 kHz. The typical resonant frequency for the proof mass of a MEMS gyroscope is between 3 and 20 kHz. High power, high frequency acoustic noise can disrupt the output signal of the gyroscope to the point that the output becomes unreliable. In recent years, considerable research has focused on the fascinating properties found in metamaterials. A metamaterial is an artificially fabricated device or structure that is engineered to produce desired material responses that can either mimic known behaviors or produce responses that do not occur naturally in materials found in nature. Acoustic metamaterials, in particular, have shown great promise in the field of sound attenuation. This paper proposes a method to mitigate the performance degradation of the MEMS gyroscope in the presence of high power, high frequency acoustic noise by using a new acoustic metamaterial in the form of a two-dimensional array of micromachined Helmholtz resonators. The Helmholtz resonators are fabricated in a silicon wafer using standard MEMS manufacturing techniques and are designed to attenuate sound at the resonant frequency of the gyroscope proof mass. The resonator arrays were diced from the silicon wafer in one inch squares and assembled into a box open on one end in a manner to attenuate sound on all sides of the gyroscope, and to seal the gyroscope inside the box. The resulting acoustic metamaterial device was evaluated in an acoustic chamber and was

  14. Heat radiative characteristics of ultra-attenuated materials

    Institute of Scientific and Technical Information of China (English)

    Dehong Xia; Yonghong Wu


    From the microstructure of heat radiation, the interaction between the incident heat radiative wave and the electromagnetism syntonic wave is analyzed to reveal the emission, absorption, transmission and reflection mechanisms of the incident heat radiative wave in materials. Based on Lorentz dispersion theory, the effect of optical parameters on heat radiative characteristics is also analyzed. The method of ultra-attenuation and nanocrystallization improving the heat radiative characteristics of the material and the emissivity dispersion of the ultra-attenuated materials are brought to light.

  15. Attenuating water hammer pressure by means of gas storage tank

    Institute of Scientific and Technical Information of China (English)


    The basic equations for computing the volume of gas storage tank were derived from the principles of attenuating water hammer pressure. Verifications using experiments indicate that the proposed equation can provide a fare precision in the predictions. By using the model of solid-liquid two-phase flow, the gas storage tank, pressure-relief valves and slow-closure reverse-control valves were compared with practical engineering problems, and the functions of gas storage tank in attenuating water hammer pressure were further investigated.

  16. Quasi-optical attenuators for ALMA band 10 receiver (United States)

    Gonzalez, A.; Fujii, Y.; Kaneko, K.; Uzawa, Y.


    Simple quasi-optical attenuators based on beam truncation have been designed, fabricated and tried on ALMA band 10 receivers (787-950 GHz) with optimal results. The design is based on physical-optics simulations considering effects of diffraction. The use of these attenuators allows flexibility in the design of the local oscillator (LO) quasi-optical injection scheme depending on the specific performance of components for each of the 73 ALMA band 10 receivers. In particular, they have proven very effective to keep system noise within the stringent ALMA requirements (230 K at 80% of 787-950 GHz band).

  17. Continental Fog Attenuation Empirical Relationship from Measured Visibility Data

    Directory of Open Access Journals (Sweden)

    F. Nadeem


    Full Text Available Free Space Optics (FSO has the great potential for future communication applications. However, weather influenced reduced availability had been the main cause for its restricted growth. Among different weather influences fog plays the major role. A new model generalized for all FSO wavelengths, has been proposed for the prediction of continental fog attenuation using visibility data. The performance of the proposed model has been compared with well known models for measured attenuation data of Continental fog. The comparison has been performed in terms of Root Mean Square Error (RMSE.

  18. Research on attenuation characteristic of sound wave in coal or rock body

    Institute of Scientific and Technical Information of China (English)

    NIE Bai-sheng; HE Xue-qiu; LI Xiang-chun; GAO Hong


    In order to using power sound wave increase permeability of coal, rules of attenuation of sound wave in coal should be studied. In this paper, characteristic and mechanism of attenuation of sound wave in coal was researched according to acoustic theory and attenuation coefficients was estimated by acoustic parameter of coal. The research results show that the main attenuation mechanism of sound wave in coal is absorption attenuation and scattering attenuation. The absorption attenuation includes viscous absorption, thermal conduction absorption and relaxation absorption. Attenuation coefficient of sound wave in gaseous coal is 38.5 Np/m. Researches on attenuation characteristic of sound wave will provide the theoretical basis for power sound wave improving permeability of coal and accelerating desorption of coal bed gas.

  19. A CMOS Wideband Linear Current Attenuator with Electronically Variable Gain

    NARCIS (Netherlands)

    Wiegerink, Remco J.


    A CMOS highly linear current attenuator is described. The circuit is suited for both differential and single input currents. The current gain is electronically variable between -1 and +1 by means of two controlling currents. A simple additional circuit is described to obtain a gain that is linearly

  20. Low-energy gamma ray attenuation characteristics of aviation fuels (United States)

    Singh, Jag J.; Shen, Chih-Ping; Sprinkle, Danny R.


    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.

  1. Novel monohydroxamate drugs attenuate myocardial reperfusion-induced arrhythmias

    DEFF Research Database (Denmark)

    Collis, C S; Rice-Evans, C; Davies, Michael Jonathan


    The novel monohydroxamates N-methyl hexanoylhydroxamic acid, N-methyl acetohydroxamic acid, and N-methyl butyrohydroxamic acid have antioxidant and iron chelating properties. They attenuated reperfusion-induced contractile dysfunction following long periods of ischaemia (50 min) in the isolated r...

  2. On the effectiveness of mangroves in attenuating cyclone induced waves

    NARCIS (Netherlands)

    Narayan, S.; Suzuki, T.; Stive, M.J.F.; Verhagen, H.J.; Ursem, W.N.J.; Ranasinghe, R.


    A study of the effectiveness of mangroves in attenuating cyclone- induced waves was done using the SWAN 40.81 numerical model. Hydraulic parameters during extreme events and local mangrove vegetation parameters were estimated for the Kanika Sands mangrove island near the upcoming Dhamra Port in Oris

  3. Measurement of acoustic attenuation in South Pole ice

    NARCIS (Netherlands)

    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.; Alba, J.L.B.; 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.; Boser, 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.; Clercq, C. De; Demirors, L.; Depaepe, O.; Descamps, F.; Desiati, P.; Vries-Uiterweerd, G. de; DeYoung, T.; Diaz-Velez, J.C.; Dreyer, J.; Dumm, J.P.; Duvoort, M.R.; Ehrlich, R.; Eisch, J.; Ellsworth, R.W.; Engdegard, 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.; Glusenkamp, 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.; Lafebre, S.J.


    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

  4. Outdoor FSO Communications Under Fog: Attenuation Modeling and Performance Evaluation

    KAUST Repository

    Esmail, Maged Abdullah


    Fog is considered to be a primary challenge for free space optics (FSO) systems. It may cause attenuation that is up to hundreds of decibels per kilometer. Hence, accurate modeling of fog attenuation will help telecommunication operators to engineer and appropriately manage their networks. In this paper, we examine fog measurement data coming from several locations in Europe and the United States and derive a unified channel attenuation model. Compared with existing attenuation models, our proposed model achieves a minimum of 9 dB, which is lower than the average root-mean-square error (RMSE). Moreover, we have investigated the statistical behavior of the channel and developed a probabilistic model under stochastic fog conditions. Furthermore, we studied the performance of the FSO system addressing various performance metrics, including signal-to-noise ratio (SNR), bit-error rate (BER), and channel capacity. Our results show that in communication environments with frequent fog, FSO is typically a short-range data transmission technology. Therefore, FSO will have its preferred market segment in future wireless fifth-generation/sixth-generation (5G/6G) networks having cell sizes that are lower than a 1-km diameter. Moreover, the results of our modeling and analysis can be applied in determining the switching/thresholding conditions in highly reliable hybrid FSO/radio-frequency (RF) networks.

  5. Attenuation of Rayleigh Surface Waves in a Porous Material

    Institute of Scientific and Technical Information of China (English)



    Using acoustic microscopy at higher frequency,we show the velocity evolutions of surface acoustic waves,in particular Rayleigh waves that depend on porosity for a mesoporous silicon layer.The velocities are obtained from different V(z) curves,which are determined experimentally at a frequency of 600MHz.The analysis of V(z) data yields attenuation that is directly dependent on porosity.On the other hand,αN attenuation has been modeled and allows us to investigate its influence on the velocity VR of the propagation for Rayleigh waves.%Using acoustic microscopy at higher frequency, we show the velocity evolutions of surface acoustic waves, in particular Rayleigh waves that depend on porosity for a mesoporous silicon layer. The velocities are obtained from different V(z) curves, which are determined experimentally at a frequency of 600 MHz. The analysis of V(z) data yields attenuation that is directly dependent on porosity. On the other hand, αN attenuation has been modeled and allows us to investigate its influence on the velocity VR of the propagation for Rayleigh waves.

  6. Simultaneous amplification and attenuation in isotropic chiral materials

    CERN Document Server

    Mackay, Tom G


    The electromagnetic field phasors in an isotropic chiral material (ICM) are superpositions of two Beltrami fields of different handedness. Application of the Bruggeman homogenization formalism to two-component composite materials delivers ICMs wherein Beltrami fields of one handedness attenuate whereas Beltrami waves of the other handedness amplify. One component material is a dissipative ICM, the other an active dielectric material.

  7. Closed-Loop Control of MEMS Variable Optical Attenuator (VOA)

    Institute of Scientific and Technical Information of China (English)

    H.Cai; X.; M.; Zhang; A.; Q.; Liu; Y.; X.; Wang; C.; Lu


    This paper reports the development of an optical power regulator based on surface-micromachined variable optical attenuators (VOAs). By use of closed-loop control circuits, each VOA module implements the functions of power setpoint tracking, disturbance rejection and ripple suppression.

  8. Gamma ray attenuation coefficient measurement for neutron-absorbent materials

    Energy Technology Data Exchange (ETDEWEB)

    Jalali, Majid [Isfahan Nuclear Science and Technology Research Institute (NSTRT), Reactor and Accelerators Research and Development School, Atomic Energy Organization (Iran, Islamic Republic of)], E-mail:; Mohammadi, Ali [Faculty of Science, Department of Physics, University of Kashan, Km. 6, Ravand Road, Kashan (Iran, Islamic Republic of)


    The compounds Na{sub 2}B{sub 4}O{sub 7}, H{sub 3}BO{sub 3}, CdCl{sub 2} and NaCl and their solutions attenuate gamma rays in addition to neutron absorption. These compounds are widely used in the shielding of neutron sources, reactor control and neutron converters. Mass attenuation coefficients of gamma related to the four compounds aforementioned, in energies 662, 778.9, 867.38, 964.1, 1085.9, 1173, 1212.9, 1299.1,1332 and 1408 keV, have been determined by the {gamma} rays transmission method in a good geometry setup; also, these coefficients were calculated by MCNP code. A comparison between experiments, simulations and Xcom code has shown that the study has potential application for determining the attenuation coefficient of various compound materials. Experiment and computation show that H{sub 3}BO{sub 3} with the lowest average Z has the highest gamma ray attenuation coefficient among the aforementioned compounds.

  9. Engineering attenuated virulence of a Theileria annulata-infected macrophage.

    Directory of Open Access Journals (Sweden)

    Nadia Echebli

    Full Text Available Live attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuated lines lose their vaccine potential. To circumvent this we engineered the rapid ablation of the host cell transcription factor c-Jun, and within only 3 weeks the line engineered for loss of c-Jun activation displayed in vitro correlates of attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and diminished capacity to traverse Matrigel. Specific ablation of a single infected host cell virulence trait (c-Jun induced a complete failure of Theileria annulata-transformed macrophages to disseminate, whereas virulent macrophages disseminated to the kidneys, spleen, and lungs of Rag2/γC mice. Thus, in this heterologous mouse model loss of c-Jun expression led to ablation of dissemination of T. annulata-infected and transformed macrophages. The generation of Theileria-infected macrophages genetically engineered for ablation of a specific host cell virulence trait now makes possible experimental vaccination of calves to address how loss of macrophage dissemination impacts the disease pathology of tropical theileriosis.

  10. Variable optical attenuator fabricated by direct UV writing

    DEFF Research Database (Denmark)

    Svalgaard, Mikael; Færch, Kjartan Ullitz; Andersen, L.U.


    It is demonstrated that direct ultraviolet writing of waveguides is a method suitable for mass production of compact variable optical attenuators with low insertion loss, low polarization-dependent loss, and high dynamic range. The fabrication setup is shown to be robust, providing good device...

  11. PAUT inspection of copper canister: Structural attenuation and POD formulation (United States)

    Gianneo, A.; Carboni, M.; Mueller, C.; Ronneteg, U.


    For inspection of thick-walled (50mm) copper canisters for final disposal of spent nuclear fuel in Sweden, ultrasonic inspection using phased array technique (PAUT) is applied. Because thick-walled copper is not commonly used as a structural material, previous experience on Phased Array Ultrasonic Testing for this type of application is limited. The paper presents the progress in understanding the amplitudes and attenuation changes acting on the Phased Array Ultrasonic Testing inspection of copper canisters. Previous studies showed the existence of a low pass filtering effect and a heterogeneous grain size distribution along the depth, thus affecting both the detectability of defects and their "Probability of Detection" determination. Consequently, the difference between the first and second back wall echoes were not sufficient to determine the local attenuation (within the inspection range), which affects the signal response for each individual defect. Experimental evaluation of structural attenuation was carried out onto step-wedge samples cut from full-size, extruded and pierced & drawn, copper canisters. Effective attenuation values has been implemented in numerical simulations to achieve a Multi Parameter Probability of Detection and to formulate a Model Assisted Probability of Detection through a Monte-Carlo extraction model.

  12. Adaptive disturbance attenuation via logic-based switching

    NARCIS (Netherlands)

    Battistelli, Giorgio; Mari, Daniele; Selvi, Daniela; Tesi, Alberto; Tesi, Pietro


    The problem of attenuating unknown and possibly time-varying disturbances acting on a linear time-invariant dynamical system is addressed by means of an adaptive switching control approach. Given a family of pre-designed stabilizing controllers, a supervisory unit infers in real-time the potential b

  13. Timing attention : Cuing target onset interval attenuates the attentional blink

    NARCIS (Netherlands)

    Martens, S; Johnson, A


    Three experiments tested whether the attentional blink (AB; a deficit in reporting the second of two targets when it occurs 200-500 msec after the first) can be attenuated by providing information about the target onset asynchrony (TOA) of the second target relative to the first. Blocking the TOA di

  14. Lg Attenuation Characteristic of Gujarat Region (Western India) (United States)

    Jaiswal, Namrata; Singh, Chandrani


    We estimate the Lg attenuation characteristics of the Gujarat Region in Western India by using a reliable two-station method. This region comes under the V, IV and III seismicity zone. So, in India this is the seismic active region other than Himalayas, which shows high seismicity. Lg is typically the most prominent short-period seismic phase on high frequency seismogram observed over the continental paths from regional to teleseimic distance. We use data from 15 earthquakes with magnitude > 5 mb and focal depth Lg Q (Q0) values between many pairs of stations. Finally, 5 events with 70 high-quality inter-station paths were selected from 117 possible pairs of stations that are (1) aligned approximately with the source and (2) separated enough to permit the use of the standard two-station method for Lg Q measurement. Spatial variations in Q0 have been noticed across the Gujarat region. Low Q0 ( 300) value. These observations are consistent with the results of the body wave attenuation structure reported for the region. The variations in the attenuation characteristics may be caused due to both the intrinsic and scattering contributions caused by thermal effects, sedimentary layer thickness as well as heterogeneities present below the study region. Our results are found to be comparable with the previous studies of the attenuation characteristics of the Gujarat region.

  15. Attenuation of ground vibrations due to different technical sources

    Institute of Scientific and Technical Information of China (English)

    L. Auersch; S. Said


    The attenuation of technically induced surface waves is studied theoretically and experimentally. In this paper, nineteen measurements of ground vibrations induced by eight different technical sources including road and rail traffic, vibratory and impulsive construction work or pile driving, explosions, hammer impulses and mass drops are described, and it is shown that the technically induced ground vibrations exhibit a power-law attenuation v ~ r where the exponents q are in the range of 0.5 to 2.0 and depend on the source types. Comparisons performed demonstrate that the measured exponents are considerably higher than theoretically expected. Some potential effects on ground vibration attenuation are theoretically analyzed. The most important effect is due to the material or scattering damping. Each frequency component is attenuated exponentially as exp(-kr), but for a broad-band excitation, the sum of the exponential laws also yields a power law but with a high exponent. Additional effects are discussed, for example the dispersion of the Rayleigh wave due to soil layering, which yields an additional exponent of 0.5 in cases of impulsive loading.

  16. Pyrrolidine Dithiocarbamate Attenuates Paraquat-Induced Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xiuli Chang


    PQ+PDTC-treated groups than that of PQ-treated groups (P<.05. The histopathological changes in the PQ+PDTC-treated groups were milder than those of PQ groups. Our results suggested that PDTC treatment significantly attenuated paraquat-induced pulmonary damage.

  17. Body Wave Crustal Attenuation Characteristics in the Garhwal Himalaya, India (United States)

    Negi, Sanjay S.; Paul, Ajay; Joshi, Anand; Kamal


    We estimate frequency-dependent attenuation of P and S waves in Garhwal Himalaya using the extended coda normalization method for the central frequencies 1.5, 2, 3, 4, 6, 8, 10, 12, and 16 Hz, with earthquake hypocentral distance ranging from 27 to 200 km. Forty well-located local earthquake waveforms were used to study the seismic attenuation characteristics of the Garhwal Himalaya, India, as recorded by eight stations operated by Wadia Institute of Himalayan Geology, Dehradun, India, from 2007 to 2012. We find frequency-dependent P and S wave quality factors as defined by the relations Q P = 56 ± 8 f 0.91±0.002 and Q S = 151 ± 8 f 0.84±0.002 by fitting a power-law frequency dependence model for the estimated values over the whole region. Both the Q P and Q S values indicate strong attenuation in the crust of Garhwal Himalaya. The ratio of Q S/ Q P > 1 obtained for the entire analyzed frequency range suggests that the scattering loss is due to a random and high degree of heterogeneities in the earth medium, playing an important role in seismic wave attenuation in the Himalayan crust.

  18. The Ultraviolet Attenuation Law in Backlit Spiral Galaxies

    CERN Document Server

    Keel, William C; Holwerda, Benne W; Lintott, Chris J; Schawinski, Kevin


    (Abridged) The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet 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 GALEX, XMM Optical Monitor, and HST data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with candidates provided by Galaxy Zoo participants. 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 close to the Calzetti et al. (1994) form; the UV slope for the overall sample is substantially shallower than found by Wild et al. (2011), 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 accuracy almost equal ...

  19. Laboratory measurements of seismic attenuation in partially saturated rocks (United States)

    Chapman, Samuel; Tisato, Nicola; Quintal, Beatriz; Holliger, Klaus


    Laboratory measurements of seismic attenuation and transient pore fluid pressure are performed on partially saturated Berea sandstone and synthetic borosilicate samples. Various degrees of water (liquid) and nitrogen (gas) saturation are considered. These measurements are carried out at room temperature and under confining pressures varying from ambient conditions up to 25 MPa. The cylindrical samples are 25 cm long and have a diameter of 7.6 cm. In the context of the experimental setup, the solid frames of both the Berea sandstone and the borosilicate samples can be considered homogenous, which in turn allows for isolating and exploring the effects of partial saturation on seismic attenuation. We employ the sub-resonance method, which is based on the application of a time-harmonic vertical stress to the top of the sample and the measurement of the thus resulting strain. For any given frequency, the attenuation is then inferred as the tangent of the phase shift between the applied stress and the observed strain. Using five equally spaced sensors along the central axis of the cylindrical sample, we measure the transient fluid pressure induced by the application of a step-function-type vertical stress to the top of the sample. Both the sensors and the sample are sealed off with the regard to the confining environment. Together with the numerical results from corresponding compressibility tests based on the quasi-static poroelastic equations, these transient fluid pressure measurements are then used to assist the interpretation of the seismic attenuation measurements.

  20. Bioavailability of jarosite for stimulating acid mine drainage attenuation (United States)

    Coggon, Matthew; Becerra, Caryl Ann; Nüsslein, Klaus; Miller, Karen; Yuretich, Richard; Ergas, Sarina J.


    Biological reduction of iron-sulfate minerals, such as jarosite, has the potential to contribute to the natural attenuation of acid mine drainage (AMD) sites. Previous studies of AMD attenuation at Davis Mine, an abandoned pyrite mine in Rowe Massachusetts, provided evidence of iron and sulfate reduction by indigenous bacteria. Jarosite is a large component of the sediment at Davis Mine and may play a role in AMD attenuation. In this study, microcosms were constructed with groundwater and sediment from Davis Mine and amended with glycerol, nitrogen and phosphorus (GNP) and naturally formed natrojarosite. Over time, higher total iron, sulfate, pH and sodium concentrations and lower oxidation-reduction potentials were observed in microcosms amended with GNP and jarosite, compared with unamended microcosms and killed controls. Geochemical modeling predicted jarosite precipitation under microcosm conditions, suggesting that abiotic processes were unlikely contributors to jarosite dissolution. SEM imaging at the jarosite surface showed microbial attachment. Microbial community composition analysis revealed a shift to higher populations of Clostridia, which are known to reduce both iron and sulfate. The results show that jarosite may be utilized as an electron acceptor by iron and/or sulfate reducing bacteria at Davis Mine and its presence may aid in the attenuation of AMD.

  1. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen


    Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal...

  2. Attenuated familial adenomatous polyposis (AFAP). A review of the literature

    DEFF Research Database (Denmark)

    Knudsen, Anne Lyster; Bisgaard, Marie Luise; Bülow, Steffen


    Over the last decade, a subset of familial adenomatous polyposis (FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity - the reports on AFAP are largely casuistic or only deal with a ...

  3. Seismic wave attenuation and velocity dispersion in UAE carbonates (United States)

    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

  4. Modeling transmission and scatter for photon beam attenuators. (United States)

    Ahnesjö, A; Weber, L; Nilsson, P


    The development of treatment planning methods in radiation therapy requires dose calculation methods that are both accurate and general enough to provide a dose per unit monitor setting for a broad variety of fields and beam modifiers. The purpose of this work was to develop models for calculation of scatter and transmission for photon beam attenuators such as compensating filters, wedges, and block trays. The attenuation of the beam is calculated using a spectrum of the beam, and a correction factor based on attenuation measurements. Small angle coherent scatter and electron binding effects on scattering cross sections are considered by use of a correction factor. Quality changes in beam penetrability and energy fluence to dose conversion are modeled by use of the calculated primary beam spectrum after passage through the attenuator. The beam spectra are derived by the depth dose effective method, i.e., by minimizing the difference between measured and calculated depth dose distributions, where the calculated distributions are derived by superposing data from a database for monoenergetic photons. The attenuator scatter is integrated over the area viewed from the calculation point of view using first scatter theory. Calculations are simplified by replacing the energy and angular-dependent cross-section formulas with the forward scatter constant r2(0) and a set of parametrized correction functions. The set of corrections include functions for the Compton energy loss, scatter attenuation, and secondary bremsstrahlung production. The effect of charged particle contamination is bypassed by avoiding use of dmax for absolute dose calibrations. The results of the model are compared with scatter measurements in air for copper and lead filters and with dose to a water phantom for lead filters for 4 and 18 MV. For attenuated beams, downstream of the buildup region, the calculated results agree with measurements on the 1.5% level. The accuracy was slightly less in situations

  5. Cement-based materials' characterization using ultrasonic attenuation (United States)

    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

  6. Signal attenuation as a rat model of obsessive compulsive disorder. (United States)

    Goltseker, Koral; Yankelevitch-Yahav, Roni; Albelda, Noa S; Joel, Daphna


    In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

  7. CT-based attenuation and scatter correction compared with uniform attenuation correction in brain perfusion SPECT imaging for dementia (United States)

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


    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.


    Laboratory experiments show that amorphous and poorly crystallized ferric iron hydroxides have much greater capacity to attenuate arsenic compared to clays and other aluminosilicate minerals. Studies (e.g., Lin and Qvarfort, 1996) showed that a sudden change in geochemical condit...

  9. Monitored Natural Attenuation For Inorganic Contaminants In Ground Water - Technical Issues (United States)

    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. Estimation of compressional seismic wave attenuation of carbonate rocks in Abu Dhabi, United Arab Emirates (United States)

    Bouchaala, Fateh; Ali, Mohammed Y.; Farid, Asam


    The subsurface geology of Abu Dhabi in the United Arab Emirates is primarily composed of carbonate rocks. Such media are known to be highly heterogeneous. Very few studies have attempted to estimate attenuation in carbonate rocks. In Abu Dhabi no attenuation profile has been published. This study provides the first seismic wave attenuation profiles in Abu Dhabi using dense array of VSP data. We estimated three attenuation profiles: the apparent, the scattering, and the intrinsic attenuations. The apparent attenuation profile was computed using amplitude decay and spectral-ratio methods. The scattering attenuation profile was estimated using a generalized reflection-transmission matrix forward model. It is usually estimated from the sonic log, but to be more consistent with the apparent attenuation, we succeeded in this paper to estimate it from the VSP data. We subtracted the scattering attenuation from the apparent attenuation to deduce the intrinsic attenuation. The results of the study indicate that the scattering attenuation is significant compared to the published studies that are mainly based on clastic rocks. The high scattering attenuation can reach up to 0.02. It can be explained by the strong heterogeneity of the carbonate rocks. This study demonstrates that the Simsima and Rus Formations have considerable scattering and intrinsic attenuations. These formations are considered aquifers in Abu Dhabi; we therefore interpreted this high intrinsic attenuation zones to be due to the heterogeneity and to the fluids contained in these formations. The Umm-Er-Radhuma Formation is a more homogenous formation with limited aquifer potential. Hence, scattering and intrinsic attenuations of the Umm-Er-Radhuma Formation are low.

  11. Physiological and Antigenic Characteristics of Virulent and Attenuated Strains of Legionella pneumophila (Philadelphia 3) (United States)


    CHARACTERISTICS OF I, VIRULENT AND ATTENUATED5TRAINS OF LEGIONELLA Interim PNEUMOPHILA (PHILADELPHIA 3) 6 . PERFORMING ORG. REPORT NUMBER 70 AUTHOR(*) B...number) Several methods were used to cJvrtcterize selected virulent and attenuated strains of Legionella pneumophila serogroup 1. The cultural...Antigenic Characteristics of Virulent and Attenuated Strains of Legionella pneumophila (Philadelphia 3) JOSEPH D. RISTROPH, KENNETH W. HEDLUND, AND

  12. Effects of Hearing Protection Device Attenuation on Unmanned Aerial Vehicle (UAV) Audio Signatures (United States)


    ARL-TR-7639 ● MAR 2016 US Army Research Laboratory Effects of Hearing Protection Device Attenuation on Unmanned Aerial Vehicle ...Research Laboratory Effects of Hearing Protection Device Attenuation on Unmanned Aerial Vehicle (UAV) Audio Signatures by Melissa Bezandry...further study. In the future, the work could aid in the development of a filter to attenuate unmanned aerial vehicle noise in different environmental

  13. Earth-To-Space Improved Model for Rain Attenuation Prediction at Ku-Band

    Directory of Open Access Journals (Sweden)

    Mandeep S.J. Singh


    Full Text Available A model for predicting rain attenuation on earth-to-space was developed by using the measurement data obtained from tropical and equatorial region. The proposed rain attenuation model uses the complete rainfall rate cumulative distribution as input data. It was shown that significant improvements in terms of prediction error over existing attenuation model obtained.

  14. Attenuation correction for X-ray emission computed tomography of laser-produced plasma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yen-Wei; Nakao, Zensho [Ryukyus Univ., Nishihara, Okinawa (Japan). Faculty of Engineering; Tamura, Shinichi


    An attenuation correction method was proposed for laser-produced plasma emission computed tomography (ECT), which is based on a relation of the attenuation coefficient and the emission coefficient in plasma. Simulation results show that the reconstructed images are dramatically improved in comparison to the reconstructions without attenuation correction. (J.P.N.)

  15. Velocity and attenuation of sound in arterial tissues (United States)

    Rooney, J. A.; Gammell, P. M.; Hestenes, J. D.; Chin, H. P.; Blankenhorn, D. H.


    The velocity of sound in excised human and canine arterial tissues is measured in order to serve as a basis for the development and application of ultrasonic techniques for the diagnosis of atherosclerotic lesions. Measurements of sound velocity at different regions of 11 human and six canine aortas were made by a time delay spectrometer technique at frequencies from 2 to 10 MHz, and compared with ultrasonic attenuation parameters and the results of biochemical assays. Sound velocity is found to increase with increasing attenuation at all frequencies, and with increasing collagen content. A strong dependence of sound velocity on cholesterol content or low calcium contents is not observed, although velocities of up to 2000 m/sec are observed in highly organized calcified lesions. A decrease in velocity with decreasing temperature is also noted. It is thus concluded that it is principally the differences in tissue collagen levels that contribute to image formation according to sound velocity.

  16. Wave attenuation model for dephasing and measurement of conditional times

    Indian Academy of Sciences (India)

    A M Jayannavar; Colin Benjamin


    Inelastic scattering induces dephasing in mesoscopic systems. An analysis of previous models to simulate inelastic scattering in such systems is presented and a relatively new model based on wave attenuation is introduced. The problem of Aharonov–Bohm (AB) oscillations in conductance of a mesoscopic ring is studied. We show that the conductance is symmetric under flux reversal and the visibility of AB oscillations decays to zero as a function of the incoherence parameter, signaling dephasing. Further the wave attenuation model is applied to a fundamental problem in quantum mechanics, that of the conditional (reflection/transmission) times spent in a given region of space by a quantum particle before scattering off from that region.

  17. Numerical support of laboratory experiments: Attenuation and velocity estimations (United States)

    Saenger, Erik; Madonna, Claudio; Frehner, Marcel; Almqvist, Bjarne


    We show that numerical support of laboratory experiments can significantly increase the understanding and simplify the interpretation of the obtained laboratory results. First we perform simulations of the Seismic Wave Attenuation Module to measure seismic attenuation of reservoir rocks. Our findings confirm the accuracy of this system. However, precision can be further improved by optimizing the sensor positions. Second, we model wave propagation for an ultrasonic pulse transmission experiment used to determine pressure- and temperature-dependent seismic velocities in the rock. Multiple waves are identified in our computer experiment, including bar waves. The metal jacket that houses the sample assembly needs to be taken into account for a proper estimation of the ultrasonic velocities. This influence is frequency-dependent.

  18. Electroacupuncture attenuates neuropathic pain after brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Shenyu Zhang; Hailiang Tang; Junming Zhou; Yudong Gu


    Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root (associated with upper-limb chronic neuropathic pain) were given electroacu-puncture stimulation at bilateralQuchi(LI11),Hegu(LI04),Zusanli(ST36) andYanglingquan (GB34). After electroacupuncture therapy, chronic neuropathic pain in the rats’ upper limbs was signiifcantly attenuated. Immunolfuorescence staining showed that the expression of β-endorphins in the arcuate nucleus was signiifcantly increased after therapy. Thus, experimental ifndings indi-cate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulatingβ-endorphin expression.

  19. Random seismic noise attenuation using the Wavelet Transform (United States)

    Aliouane, L.; Ouadfeul, S.; Boudella, A.; Eladj, S.


    In this paper we propose a technique of random noises attenuation from seismic data using the discrete and continuous wavelet transforms. Firstly the discrete wavelet transform (DWT) is applied to denoise seismic data. This last is based on the threshold method applied at the modulus of the DWT. After we calculate the continuous wavelet transform of the denoised seismic seismogram, the final denoised seismic seismogram is the continuous wavelet transform coefficients at the low scale. Application at a synthetic seismic seismogram shows the robustness of the proposed tool for random noises attenuation. We have applied this idea at a real seismic data of a vertical seismic profile realized in Algeria. Keywords: Seismic data, denoising, DWT, CWT, random noise.

  20. A novel live-attenuated vaccine candidate for mayaro Fever.

    Directory of Open Access Journals (Sweden)

    William J Weise


    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  1. Attenuation of rare earth elements in a boreal estuary (United States)

    Åström, Mats E.; Österholm, Peter; Gustafsson, Jon Petter; Nystrand, Miriam; Peltola, Pasi; Nordmyr, Linda; Boman, Anton


    This study focuses on attenuation of rare earth elements (REE) when a boreal creek, acidified and loaded with REE and other metals as a result of wetland drainage, empties into a brackish-water estuary (salinity MINTEQ version 3.0 and the Stockholm Humic Model after revision and updating, predicted that the dissolved (<0.45 μm) REE pool in the estuary is bound almost entirely to humic substances. Acid sulphate soils, the source of the REE and other metals in the creek water, are widespread on coastal plains worldwide and therefore the REE attenuation patterns and mechanisms identified in the studied estuary are relevant for recognition of similar geochemical processes and conditions in a variety of coastal locations.

  2. Depolarization and attenuation effects of radomes at 20 GHz (United States)

    Hendrix, Charles E.; McNally, James E.; Monzingo, Robert A.


    The problem of describing the attenuation and depolarization effects of a wet radome on a transmitted signal is considered by experiments carried out with two commonly used radome materials, ESSCOLAM-6 and ESSCOLAM-8. The results suggest that a two-component model of depolarization is required to account for the observed results. Predictions for the behavior of a complete radome are obtained, but full-scale testing with an operating radome to compare predicted and actual results remains to be done. An important conclusion is that, while highly water-repellent radome materials are desirable from the point of view of attenuation, they are not so desirable in terms of the degree of depolarization introduced between orthogonally polarized signal components in frequency-reuse systems.

  3. Experimental and theoretical studies on visible light attenuation in water

    CERN Document Server

    Simpson, A; Cho, H J; Liu, H


    In this study we describe lab experiments on determining the above water reflectance Rrs coefficient, and the water attenuation coefficient Kd for fresh water. Different types of screens (totally absorbent, gray, etc.) were submerged in water (0-0.6 m) and illuminated from outside. The spectral density of the water leaving radiance was measured for different depths. The results were ran by a code which took into account the geometry of the incident irradiation, the geometry of the screen under water, and boundary conditions at the water surface provided by the radiation transfer theory. From the experimental data and our model we obtain the spectral distribution of the attenuation coefficient for fresh water and compared it with other data in literature. These experiments, performed in the Nonlinear Wave Lab at ERAU# represent just a preliminary calibration of the experimental protocol. More tests with water of different degrees of turbidity, and possibly wave filed at the water surface are in progress and wi...

  4. Propagation and Attenuation Characteristics of Diesel Particulate Filter

    Institute of Scientific and Technical Information of China (English)

    GAO Wenzhi; SONG Chonglin; LIU Jianguo; GUAN Shunji


    Diesel particulate filter (DPF) is an important factor which influences the sound from exhaust system of an engine. In order to understand the propagation law of sound wave and predict the insertion loss in DPF, based on the general aero-dynamic equations and Darcy′s law, an acoustic property calculation model of DPF is constructed. Propagation and attenuation characteristics of the forward and backward propagating acoustic waves in the close and open pipe of the filter are investigated. The theoretical model is combined with experiment to investigate sound attenuation property of DPF. The insertion loss obtained from the experiment is compared with that computed for a DPF. The results from the experiment and theoretical calculation agree well.

  5. A novel live-attenuated vaccine candidate for mayaro Fever. (United States)

    Weise, William J; Hermance, Meghan E; Forrester, Naomi; Adams, A Paige; Langsjoen, Rose; Gorchakov, Rodion; Wang, Eryu; Alcorn, Maria D H; Tsetsarkin, Konstantin; Weaver, Scott C


    Mayaro virus (MAYV) is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  6. Attenuation measurements of vacuum ultraviolet light in liquid argon revisited

    Energy Technology Data Exchange (ETDEWEB)

    Neumeier, A. [Physik-Department E15, Technische Universität München, James-Franck-Straße 1, 85748 Garching (Germany); Dandl, T.; Himpsl, A. [Physik-Department E12, Technische Universität München, James-Franck-Straße 1, 85748 Garching (Germany); Hofmann, M. [Physik-Department E15, Technische Universität München, James-Franck-Straße 1, 85748 Garching (Germany); KETEK GmbH, Hofer Straße 3, 81737 München (Germany); Oberauer, L.; Potzel, W.; Schönert, S. [Physik-Department E15, Technische Universität München, James-Franck-Straße 1, 85748 Garching (Germany); Ulrich, A., E-mail: [Physik-Department E12, Technische Universität München, James-Franck-Straße 1, 85748 Garching (Germany)


    The attenuation of vacuum ultraviolet light in liquid argon in the context of its application in large liquid noble gas detectors has been studied. Compared to a previous publication several technical issues concerning transmission measurements in general are addressed and several systematic effects were quantitatively measured. Wavelength-resolved transmission measurements have been performed from the vacuum ultraviolet to the near-infrared region. On the current level of sensitivity with a length of the optical path of 11.6 cm, no xenon-related absorption effects could be observed, and pure liquid argon is fully transparent down to the short wavelength cut-off of the experimental setup at 118 nm. A lower limit for the attenuation length of pure liquid argon for its own scintillation light has been estimated to be 1.10 m based on a very conservative approach.

  7. Attenuation of vacuum ultraviolet light in liquid argon

    CERN Document Server

    Neumeier, A; Oberauer, L; Potzel, W; Schönert, S; Dandl, T; Heindl, T; Ulrich, A; Wieser, J


    The transmission of liquid argon has been measured, wavelength resolved, for a wavelength interval from 118 to 250 nm. The wavelength dependent attenuation length is presented for pure argon. It is shown that no universal wavelength independent attenuation length can be assigned to liquid argon for its own fluorescence light due to the interplay between the wavelength dependent emission and absorption. A decreasing transmission is observed below 130 nm in both chemically cleaned and distilled liquid argon and assigned to absorption by the analogue of the first argon excimer continuum. For not perfectly cleaned argon a strong influence of impurities on the transmission is observed. Two strong absorption bands at 126.5 and 141.0 nm with approximately 2 and 4 nm width, respectively, are assigned to traces of xenon in argon. A broad absorption region below 180 nm is found for unpurified argon and tentatively attributed to the presence of water in the argon sample.

  8. Nutrient attenuation in rivers and streams, Puget Sound Basin, Washington (United States)

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


    Nutrients such as nitrogen and phosphorus are important for aquatic ecosystem health. Excessive amounts of nutrients, however, can make aquatic ecosystems harmful for biota because enhanced growth and decay cycles of aquatic algae can reduce dissolved oxygen in the water. In Puget Sound marine waters, low dissolved oxygen concentrations are observed in a number of marine nearshore areas, and nutrients have been identified as a major stressor to the local ecosystem. Delivery of nutrients from major rivers in the Puget Sound Basin to the marine environment can be large. Therefore, it is important to identify factors related to how nutrients are retained (attenuated) within streams and rivers in the Puget Sound Basin. Physical, chemical, and biological factors related to nutrient attenuation were identified through a review of related scientific literature.

  9. Dust Attenuation in Hydrodynamic Simulations of Spiral Galaxies

    CERN Document Server

    Rocha, M; Primack, J R; Cox, T J; Rocha, Miguel; Jonsson, Patrik; Primack, Joel R.


    We study the effects of dust in hydrodynamic simulations of spiral galaxies when different radial metallicity gradients are assumed. SUNRISE, a Monte-Carlo radiative-transfer code, is used to make detailed calculations of the internal extinction of disk galaxies caused by their dust content. SUNRISE is used on eight different Smooth Particle Hydrodynamics (SPH) simulations of isolated spiral galaxies. These galaxies vary mainly in mass and hence luminosity, spanning a range in luminosities from -16 to -22 magnitudes in the B band. We focus on the attenuation in different wavelength bands as a function of the disk inclination and the luminosity of the models, and compare this to observations. Observations suggest different metallicity gradients for galaxies of different luminosities. These metallicity gradients were explored in our different models, finding that the resulting dust attenuation matches observations for edge-on galaxies, but do not show a linear behaviour in log axis ratio as some observations ha...

  10. Attenuation measurements of vacuum ultraviolet light in liquid argon revisited

    CERN Document Server

    Neumeier, A; Himpsl, A; Hofmann, M; Oberauer, L; Potzel, W; Schönert, S; Ulrich, A


    The attenuation of vacuum ultraviolet light in liquid argon in the context of its application in large liquid noble gas detectors has been studied. Compared to a previous publication several technical issues concerning transmission measurements in general are addressed and several systematic effects were quantitatively measured. Wavelength-resolved transmission measurements have been performed from the vacuum ultraviolet to the near-infrared region. On the current level of sensitivity with a length of the optical path of 11.6 cm, no xenon-related absorption effects could be observed, and pure liquid argon is fully transparent down to the short wavelength cut-off of the experimental setup at 118 nm. A lower limit for the attenuation length of pure liquid argon for its own scintillation light has been estimated to be 1.10 m based on a very conservative approach.


    Energy Technology Data Exchange (ETDEWEB)

    Van der Lelie, D.; Reid-Green, J. D.; Stern, E. A.


    We have investigated the feasibility of using natural attenuation methods for ecosystem restoration in New York/New Jersey Harbor. Measurements were made of the most probable number of sulfate-reducing bacteria (SRB) in native sediments and in samples, which had been supplemented with an appropriate electron donor and electron acceptor. The results showed that the activity of the endogenous microbial population in the native sediment was high enough to make possible adequate chemical transformation rates. The bioavailability of the zinc in the sediments was measured using the BIOMET biosensor technique. The bioavailability of the zinc was effectively eliminated following the microbial activities. We concluded that natural attenuation could be used effectively in treating sediments from Newark Bay and surrounding waters and that the resultant materials could likely be used in environmental restoration projects of the type proposed for construction in South Kearny, NJ.

  12. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury


    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi


    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  13. Advanced reconstruction of attenuation maps using SPECT emission data only (United States)

    Salomon, André; Goedicke, Andreas; Aach, Til


    Today, attenuation corrected SPECT, typically performed using CT or Gadolinium line source based transmission scans, is more and more becoming standard in many medical applications. Moreover, the information about the material density distribution provided by these scans is key for other artifact compensation approaches in advanced SPECT reconstruction. Major drawbacks of these approaches are the additional patient radiation and hardware/maintenance costs as well as the additional workflow effort, e.g. if the CT scans are not performed on a hybrid scanner. It has been investigated in the past, whether it is possible to recover this structural information solely from the SPECT scan data. However, the investigated methods often result in noticeable image artifacts due to cross-dependences between attenuation and activity distribution estimation. With the simultaneous reconstruction method presented in this paper, we aim to effectively prevent these typical cross-talk artifacts using a-priori known atlas information of a human body. At first, an initial 3D shape model is coarsely registered to the SPECT data using anatomical landmarks and each organ structure within the model is identified with its typical attenuation coefficient. During the iterative reconstruction based on a modified ML-EM scheme, the algorithm simultaneously adapts both, the local activity estimation and the 3D shape model in order to improve the overall consistency between measured and estimated sinogram data. By explicitly avoiding topology modifications resulting in a non-anatomical state, we ensure that the estimated attenuation map remains realistic. Several tests with simulated as well as real patient SPECT data were performed to test the proposed algorithm, which demonstrated reliable convergence behaviour in both cases. Comparing the achieved results with available reference data, an overall good agreement for both cold as well as hot activity regions could be observed (mean deviation: -5.98%).

  14. Genetically attenuated Trypanosoma cruzi parasites as a potential vaccination tool



    Chagas disease is the clinical manifestation of the infection produced by the parasite Trypanosoma cruzi. Currently there is no vaccine to prevent this disease and the protection attained with vaccines containing non-replicating parasites is limited. Genetically attenuated trypanosomatid parasites can be obtained by deletion of selected genes. Gene deletion takes advantage of the fact that this parasite can undergo homologous recombination between endogenous and foreign DNA sequences artifici...

  15. Mesenchymal dental pulp cells attenuate dentin resorption in homeostasis. (United States)

    Zheng, Y; Chen, M; He, L; Marão, H F; Sun, D M; Zhou, J; Kim, S G; Song, S; Wang, S L; Mao, J J


    Dentin in permanent teeth rarely undergoes resorption in development, homeostasis, or aging, in contrast to bone that undergoes periodic resorption/remodeling. The authors hypothesized that cells in the mesenchymal compartment of dental pulp attenuate osteoclastogenesis. Mononucleated and adherent cells from donor-matched rat dental pulp (dental pulp cells [DPCs]) and alveolar bone (alveolar bone cells [ABCs]) were isolated and separately cocultured with primary rat splenocytes. Primary splenocytes readily aggregated and formed osteoclast-like cells in chemically defined osteoclastogenesis medium with 20 ng/mL of macrophage colony-stimulating factor (M-CSF) and 50 ng/mL of receptor activator of nuclear factor κB ligand (RANKL). Strikingly, DPCs attenuated osteoclastogenesis when cocultured with primary splenocytes, whereas ABCs slightly but significantly promoted osteoclastogenesis. DPCs yielded ~20-fold lower RANKL expression but >2-fold higher osteoprotegerin (OPG) expression than donor-matched ABCs, yielding a RANKL/OPG ratio of 41:1 (ABCs:DPCs). Vitamin D3 significantly promoted RANKL expression in ABCs and OPG in DPCs. In vivo, rat maxillary incisors were atraumatically extracted (without any tooth fractures), followed by retrograde pulpectomy to remove DPCs and immediate replantation into the extraction sockets to allow repopulation of the surgically treated root canal with periodontal and alveolar bone-derived cells. After 8 wk, multiple dentin/root resorption lacunae were present in root dentin with robust RANKL and OPG expression. There were areas of dentin resoprtion alternating with areas of osteodentin formation in root dentin surface in the observed 8 wk. These findings suggest that DPCs of the mesenchymal compartment have an innate ability to attenuate osteoclastogenesis and that this innate ability may be responsible for the absence of dentin resorption in homeostasis. Mesenchymal attenuation of dentin resorption may have implications in internal

  16. The Attribute for Hydrocarbon Prediction Based on Attenuation (United States)

    Hermana, Maman; Harith, Z. Z. T.; Sum, C. W.; Ghosh, D. P.


    Hydrocarbon prediction is a crucial issue in the oil and gas industry. Currently, the prediction of pore fluid and lithology are based on amplitude interpretation which has the potential to produce pitfalls in certain conditions of reservoir. Motivated by this fact, this work is directed to find out other attributes that can be used to reduce the pitfalls in the amplitude interpretation. Some seismic attributes were examined and studies showed that the attenuation attribute is a better attribute for hydrocarbon prediction. Theoretically, the attenuation mechanism of wave propagation is associated with the movement of fluid in the pore; hence the existence of hydrocarbon in the pore will be represented by attenuation attribute directly. In this paper we evaluated the feasibility of the quality factor ratio of P-wave and S-wave (Qp/Qs) as hydrocarbon indicator using well data and also we developed a new attribute based on attenuation for hydrocarbon prediction -- Normalized Energy Reduction Stack (NERS). To achieve these goals, this work was divided into 3 main parts; estimating the Qp/Qs on well log data, testing the new attribute in the synthetic data and applying the new attribute on real data in Malay Basin data. The result show that the Qp/Qs is better than Poisson's ratio and Lamda over Mu as hydrocarbon indicator. The curve, trend analysis and contrast of Qp/Qs is more powerful at distinguishing pore fluid than Poisson ratio and Lamda over Mu. The NERS attribute was successful in distinguishing the hydrocarbon from brine on synthetic data. Applying this attribute on real data on Malay basin, the NERS attribute is qualitatively conformable with the structure and location where the gas is predicted. The quantitative interpretation of this attribute for hydrocarbon prediction needs to be investigated further.

  17. Arsenic cycling in hydrocarbon plumes: secondary effects of natural attenuation (United States)

    Cozzarelli, Isabelle M.; Schreiber, Madeline E.; Erickson, Melinda L.; Ziegler, Brady A.


    Monitored natural attenuation is widely applied as a remediation strategy at hydrocarbon spill sites. Natural attenuation relies on biodegradation of hydrocarbons coupled with reduction of electron acceptors, including solid phase ferric iron (Fe(III)). Because arsenic (As) adsorbs to Fe-hydroxides, a potential secondary effect of natural attenuation of hydrocarbons coupled with Fe(III) reduction is a release of naturally occurring As to groundwater. At a crude-oil-contaminated aquifer near Bemidji, Minnesota, anaerobic biodegradation of hydrocarbons coupled to Fe(III) reduction has been well documented. We collected groundwater samples at the site annually from 2009 to 2013 to examine if As is released to groundwater and, if so, to document relationships between As and Fe inside and outside of the dissolved hydrocarbon plume. Arsenic concentrations in groundwater in the plume reached 230 µg/L, whereas groundwater outside the plume contained less than 5 µg/L As. Combined with previous data from the Bemidji site, our results suggest that (1) naturally occurring As is associated with Fe-hydroxides present in the glacially derived aquifer sediments; (2) introduction of hydrocarbons results in reduction of Fe-hydroxides, releasing As and Fe to groundwater; (3) at the leading edge of the plume, As and Fe are removed from groundwater and retained on sediments; and (4) downgradient from the plume, patterns of As and Fe in groundwater are similar to background. We develop a conceptual model of secondary As release due to natural attenuation of hydrocarbons that can be applied to other sites where an influx of biodegradable organic carbon promotes Fe(III) reduction.

  18. Evaluation of satellite derived spectral diffuse attenuation coefficients

    Digital Repository Service at National Institute of Oceanography (India)

    Suresh, T.; Talaulikar, M.; Desa, E.; Mascarenhas, A.A.M.Q.; Matondkar, S.G.P.

    Conference on Harbour and Ocean Engineering, 12-14, Dec. 2007, at NITK, Surathkal 116 EVALUATION OF SATELLITE DERIVED SPECTRAL DIFFUSE ATTENUATION COEFFICIENTS T.Suresh, Madhubala Talaulikar, Elgar Desa, Antonio Mascaranhas, S.G. Prabhu Matondkar... evaluated the satellite-derived values using the Root mean Squared Error (RMSE), mean of the absolute percentage difference (apd) (Lee, 2005), mean percent deviation (MPD) and coefficient of determination (r 2 ). The RMSE and apd provide information about...

  19. Interlaboratory comparison of radiation-induced attenuation in optical fibers

    Energy Technology Data Exchange (ETDEWEB)

    Friebele, E.J.; Lyons, P.B.; Blackburn, J.C.; Henschel, H.; Johan, A.; Krinsky, J.A.; Robinson, A.; Schneider, W.; Smith, D.; Taylor, E.W. (Naval Research Lab., Washington, DC (USA); Los Alamos National Lab., NM (USA); Harry Diamond Labs., Adelphi, MD (USA); Fraunhofer-Institut fuer Naturwissenschaftlich-Technische Trendanalysen (INT), Euskirchen (Germany, F.R.); Direction des Recherches, Etudes et Techni


    A comparison of the losses induced in step index multimode, graded index multimode and single mode fibers by pulsed radiation exposure has been made among 12 laboratories over a period of 5 years. The recoveries of the incremental attenuations from 10{sup -9} to 10{sup 1} s are reported. Although a standard set of measurement parameters was attempted, differences between the laboratories are evident; possible origins for these are discussed. 18 refs., 18 figs., 7 tabs.

  20. Synthetic Chemicals with Potential for Natural Attenuation (Postprint) (United States)


    Distribution Code 20: JOURNAL ARTICLES; DTIC USERS ONLY. Document contains color images. Published in Bioremediation Journal 1 (1): 1-9 (1997...Natural attenuation of petroleum hydrocarbons is predictable and self-sustaining because bacteria able to use the contaminants as growth substrates are...petroleum hydrocarbons is predictable and self-sustaining because bacteria able to use the contaminants as growth substrates are widely distributed. In

  1. Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus. (United States)

    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


    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.

  2. Attenuation Analysis and Acoustic Pressure Levels for Combined Absorptive Mufflers

    Directory of Open Access Journals (Sweden)

    Ovidiu Vasile


    Full Text Available The paper describes the pressure-wave propagation in a muffler for an internal combustion engine in case of two combined mufflers geometry. The approach is generally applicable to analyzing the damping of propagation of harmonic pressure waves. The paper purpose is to show finite elements analysis of both inductive and resistive damping in pressure acoustics. The main output is the attenuation and acoustic pressure levels for the frequency range 50 Hz–3000 Hz.

  3. Mode-dependent attenuation of optical fibers: excess loss. (United States)

    Olshansky, R; Nolan, D A


    A theory is presented for calculating the excess loss produced by random perturbations of optical fibers. The theory is applicable to perturbations whose longitudinal spatial frequencies are below the range required for mode coupling. To illustrate the method, losses due to diameter variations are calculated for the case of a step-index optical fiber. The diameter variations are found to produce a strong attenuation of the higher order modes. The total excess loss is approximately wavelength independent.

  4. Deduction of static surface roughness from complex excess attenuation. (United States)

    Nichols, Andrew; Attenborough, Keith; Taherzadeh, Shahram


    Data for complex excess attenuation have been used to determine the effective surface admittance and hence characteristic roughness size of a surface comprising a random distribution of semi-cylindrical rods on an acoustically hard plane. The inversion for roughness size is based on a simplified boss model. The technique is shown to be effective to within 4%, up to a threshold roughness packing density of 32%, above which the interaction between scattering elements appears to exceed that allowed by the model.

  5. Towards ISS disturbance attenuation for randomly switched systems

    CERN Document Server

    Chatterjee, Debasish


    We are concerned with input-to-state stability (ISS) of randomly switched systems. We provide preliminary results dealing with sufficient conditions for stochastic versions of ISS for randomly switched systems without control inputs, and with the aid of universal formulae we design controllers for ISS-disturbance attenuation when control inputs are present. Two types of switching signals are considered: the first is characterized by a statistically slow-switching condition, and the second by a class of semi-Markov processes.

  6. Peripheral δ-opioid receptors attenuate the exercise pressor reflex. (United States)

    Leal, Anna K; Yamauchi, Katsuya; Kim, Joyce; Ruiz-Velasco, Victor; Kaufman, Marc P


    In rats with ligated femoral arteries, the exercise pressor reflex is exaggerated, an effect that is attenuated by stimulation of peripheral μ-opioid receptors on group IV metabosensitive afferents. In contrast, δ-opioid receptors are expressed mostly on group III mechanosensitive afferents, a finding that prompted us to determine whether stimulation of these opioid receptors could also attenuate the exaggerated exercise pressor reflex in "ligated" rats. We found femoral arterial injection of [D-Pen2,D-Pen5]enkephalin (DPDPE; 1.0 μg), a δ-opioid agonist, significantly attenuated the pressor and cardioaccelerator components of the exercise pressor reflex evoked by hindlimb muscle contraction in both rats with ligated and patent femoral arteries. DPDPE significantly decreased the pressor responses to muscle mechanoreflex activation, evoked by tendon stretch, in ligated rats only. DPDPE (1.0 μg) had no effect in either group on the pressor and cardioaccelerator responses to capsaicin (0.2 μg), which primarily stimulates group IV afferents. DPDPE (1.0 μg) had no effect on the pressor and cardioaccelerator responses to lactic acid (24 mM), which stimulates group III and IV afferents, in rats with patent femoral arteries but significantly decreased the pressor response in ligated rats. Western blots revealed the amount of protein comprising the δ-opioid receptor was greater in dorsal root ganglia innervating hindlimbs with ligated femoral arteries than in dorsal root ganglia innervating hindlimbs with patent femoral arteries. Our findings support the hypothesis that stimulation of δ-opioid receptors on group III afferents attenuated the exercise pressor reflex.

  7. Caffeine attenuates scopolamine-induced memory impairment in humans. (United States)

    Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J


    Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

  8. Simulating atmospheric free-space optical propagation: rainfall attenuation (United States)

    Achour, Maha


    With recent advances and interest in Free-Space Optics (FSO) for commercial deployments, more attention has been placed on FSO weather effects and the availability of global weather databases. The Meteorological Visual Range (Visibility) is considered one of the main weather parameters necessary to estimate FSO attenuation due to haze, fog and low clouds. Proper understanding of visibility measurements conducted throughout the years is essential. Unfortunately, such information is missing from most of the databases, leaving FSO players no choice but to use the standard visibility equation based on 2% contrast and other assumptions on the source luminance and its background. Another challenge is that visibility is measured using the visual wavelength of 550 nm. Extrapolating the measured attenuations to longer infrared wavelengths is not trivial and involves extensive experimentations. Scattering of electromagnetic waves by spherical droplets of different sizes is considered to simulate FSO scattering effects. This paper serves as an introduction to a series of publications regarding simulation of FSO atmospheric propagation. This first part focuses on attenuation due to rainfall. Additional weather parameters, such as rainfall rate, temperature and relative humidity are considered to effectively build the rain model. Comparison with already published experimental measurement is performed to validate the model. The scattering cross section due to rain is derived from the density of different raindrop sizes and the raindrops fall velocity is derived from the overall rainfall rate. Absorption due the presence of water vapor is computed using the temperature and relative humidity measurements.

  9. Gender differences in real-world hearing protector attenuation. (United States)

    Abel, S M; Alberti, P W; Rokas, D


    This research investigated the possibility of differences in real-world attenuation attributable to gender. A total of 160 subjects, 80 males and 80 females, under the age of 45 years, and with normal hearing, were tested. Subjects were assigned to four hearing protector categories with the restriction that there were 20 males and 20 females in each group. The devices chosen for study were the E-A-R expandable foam plug, the Willson Sound Silencer premolded vinyl plug with double flange, the Bilsom Soft polyethylene encapsulated glass fiber plug, and the MSA Ear Defender (V-51R) premolded vinyl plug with single flange. Binaural headphone detection thresholds were measured in quiet with the open ear, and subsequently with protectors fitted binaurally for one-third octave noise bands centered at 250, 500, 1000, 3150 and 6300 Hz. The results indicated that attenuation scores achieved by females were less than those observed for males when the device was sold in only one size. Apart from the question of adequate sizing, for two of the insert protectors studied, mean achieved attenuation fell short of the manufacturer's specifications by as much as 18 dB, for particular frequencies tested. The relatively wide variation in scores observed for all four protectors in spite of experimenter-fit could not be accounted for by differences in either hearing threshold across subjects or by size of plug fit, for those devices available in several sizes.

  10. Ultrasound attenuation as a quantitative measure of fracture healing (United States)

    Gheduzzi, Sabina; Humphrey, Victor F.; Dodd, Simon P.; Cunningham, James L.; Miles, Anthony W.


    The monitoring of fracture healing still relies upon the judgment of callus formation and on the manual assessment of the stiffness of the fracture. A diagnostic tool capable of quantitatively measuring healing progression of a fracture would allow the fine-tuning of the treatment regime. Ultrasound attenuation measurements were adopted as a possible method of assessing the healing process in human long bones. The method involves exciting ultrasonic waves at 200 kHz in the bone and measuring the reradiation along the bone and across the fracture zone. Seven cadaveric femora were tested in vitro in intact form and after creating a transverse fracture by sawing through the cortex. The effects of five different fracture types were investigated. A partial fracture, corresponding to a 50% cut through the cortex, a closed fracture, and fractures of widths varying between 1, 2, and 4 mm were investigated. The introduction of a fracture was found to produce a dramatic effect on the amplitude of the signal. Ultrasound attenuation was found to be sensitive to the presence of a fracture, even when the fracture was well reduced. It would therefore appear feasible to adopt attenuation across a fracture as a quantitative measurement of fracture healing.

  11. Genetically attenuated Trypanosoma cruzi parasites as a potential vaccination tool. (United States)

    Pérez Brandan, Cecilia; Basombrío, Miguel Ángel


    Chagas disease is the clinical manifestation of the infection produced by the parasite Trypanosoma cruzi. Currently there is no vaccine to prevent this disease and the protection attained with vaccines containing non-replicating parasites is limited. Genetically attenuated trypanosomatid parasites can be obtained by deletion of selected genes. Gene deletion takes advantage of the fact that this parasite can undergo homologous recombination between endogenous and foreign DNA sequences artificially introduced in the cells. This approach facilitated the discovery of several unknown gene functions, as well as allowing us to speculate about the potential for genetically attenuated live organisms as experimental immunogens. Vaccination with live attenuated parasites has been used effectively in mice to reduce parasitemia and histological damage, and in dogs, to prevent vector-delivered infection in the field. However, the use of live parasites as immunogens is controversial due to the risk of reversion to a virulent phenotype. Herein, we present our results from experiments on genetic manipulation of two T. cruzi strains to produce parasites with impaired replication and infectivity, and using the mutation of the dhfr-ts gene as a safety device against reversion to virulence.

  12. Frequency dependent Lg attenuation in south-central Alaska (United States)

    McNamara, D.E.


    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.

  13. Creating a collimated ultrasound beam in highly attenuating fluids. (United States)

    Raeymaekers, Bart; Pantea, Cristian; Sinha, Dipen N


    We have devised a method, based on a parametric array concept, to create a low-frequency (300-500 kHz) collimated ultrasound beam in fluids highly attenuating to sound. This collimated beam serves as the basis for designing an ultrasound visualization system that can be used in the oil exploration industry for down-hole imaging in drilling fluids. We present the results of two different approaches to generating a collimated beam in three types of highly attenuating drilling mud. In the first approach, the drilling mud itself was used as a nonlinear mixing medium to create a parametric array. However, the short absorption length in mud limits the mixing length and, consequently, the resulting beam is weak and broad. In the second improved approach, the beam generation process was confined to a separate "frequency mixing tube" that contained an acoustically non-linear, low attenuation medium (e.g., water) that allowed establishing a usable parametric array in the mixing tube. A low-frequency collimated beam was thus created prior to its propagation into the drilling fluid. Using the latter technique, the penetration depth of the low frequency ultrasound beam in the drilling fluid was significantly extended. We also present measurements of acoustic nonlinearity in various types of drilling mud.

  14. Attenuation of S wave in the crust of Ordos massif

    Institute of Scientific and Technical Information of China (English)

    LIU Hong-gui; CHUO Yong-qing; CHEN Shu-qing; JIN Chun-hua


    We presented attenuation characteristics of S waves in the crust of Ordos massif. Using 487 pieces of digital oscillograms of 19 seismic events recorded by 32 seismologic stations located on Ordos massif and its surroundings, we have calculated the parameter of three-segment geometric attenuation and give the relation of inelastic attenuation Q value with frequency in the crust of Ordos massif, site responses of 32 stations, and source parameters of 19 events by the genetic algorithm. The results indicate that Q value (at 1 Hz) of S-wave in the crust of Ordos massif is much larger than that in the geologically active tectonic region. The site responses of the 32 stations in the high-frequency section do not show clear amplification effect except one or two stations, while in the low-frequency section, there is difference among the stations. The logarithmic value of seismic moment and the magnitude ML of 19 seismic events has a very good linear relationship.

  15. Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine. (United States)

    Precioso, Alexander Roberto; Palacios, Ricardo; Thomé, Beatriz; Mondini, Gabriella; Braga, Patrícia; Kalil, Jorge


    Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.

  16. Multicomponent seismic noise attenuation with multivariate order statistic filters (United States)

    Wang, Chao; Wang, Yun; Wang, Xiaokai; Xun, Chao


    The vector relationship between multicomponent seismic data is highly important for multicomponent processing and interpretation, but this vector relationship could be damaged when each component is processed individually. To overcome the drawback of standard component-by-component filtering, multivariate order statistic filters are introduced and extended to attenuate the noise of multicomponent seismic data by treating such dataset as a vector wavefield rather than a set of scalar fields. According to the characteristics of seismic signals, we implement this type of multivariate filtering along local events. First, the optimal local events are recognized according to the similarity between the vector signals which are windowed from neighbouring seismic traces with a sliding time window along each trial trajectory. An efficient strategy is used to reduce the computational cost of similarity measurement for vector signals. Next, one vector sample each from the neighbouring traces are extracted along the optimal local event as the input data for a multivariate filter. Different multivariate filters are optimal for different noise. The multichannel modified trimmed mean (MTM) filter, as one of the multivariate order statistic filters, is applied to synthetic and field multicomponent seismic data to test its performance for attenuating white Gaussian noise. The results indicate that the multichannel MTM filter can attenuate noise while preserving the relative amplitude information of multicomponent seismic data more effectively than a single-channel filter.

  17. A robust polynomial principal component analysis for seismic noise attenuation (United States)

    Wang, Yuchen; Lu, Wenkai; Wang, Benfeng; Liu, Lei


    Random and coherent noise attenuation is a significant aspect of seismic data processing, especially for pre-stack seismic data flattened by normal moveout correction or migration. Signal extraction is widely used for pre-stack seismic noise attenuation. Principle component analysis (PCA), one of the multi-channel filters, is a common tool to extract seismic signals, which can be realized by singular value decomposition (SVD). However, when applying the traditional PCA filter to seismic signal extraction, the result is unsatisfactory with some artifacts when the seismic data is contaminated by random and coherent noise. In order to directly extract the desired signal and fix those artifacts at the same time, we take into consideration the amplitude variation with offset (AVO) property and thus propose a robust polynomial PCA algorithm. In this algorithm, a polynomial constraint is used to optimize the coefficient matrix. In order to simplify this complicated problem, a series of sub-optimal problems are designed and solved iteratively. After that, the random and coherent noise can be effectively attenuated simultaneously. Applications on synthetic and real data sets note that our proposed algorithm can better suppress random and coherent noise and have a better performance on protecting the desired signals, compared with the local polynomial fitting, conventional PCA and a L1-norm based PCA method.

  18. Dust Attenuation in High Redshift Galaxies -- 'Diamonds in the Sky'

    CERN Document Server

    Scoville, Nick; Capak, Peter; Kakazu, Yuko; Li, Gongjie; Steinhardt, Charles


    We use observed optical to near infrared spectral energy distributions (SEDs) of 266 galaxies in the COSMOS survey to derive the wavelength dependence of the dust attenuation at high redshift. All of the galaxies have spectroscopic redshifts in the range z = 2 to 6.5. The presence of the CIV absorption feature, indicating that the rest-frame UV-optical SED is dominated by OB stars, is used to select objects for which the intrinsic, unattenuated spectrum has a well-established shape. Comparison of this intrinsic spectrum with the observed broadband photometric SED then permits derivation of the wavelength dependence of the dust attenuation. The derived dust attenuation curve is similar in overall shape to the Calzetti curve for local starburst galaxies. We also see the 2175 \\AA~bump feature which is present in the Milky Way and LMC extinction curves but not seen in the Calzetti curve. The bump feature is commonly attributed to graphite or PAHs. No significant dependence is seen with redshift between sub-sample...

  19. High Attenuation Rate for Shallow, Small Earthquakes in Japan (United States)

    Si, Hongjun; Koketsu, Kazuki; Miyake, Hiroe


    We compared the attenuation characteristics of peak ground accelerations (PGAs) and velocities (PGVs) of strong motion from shallow, small earthquakes that occurred in Japan with those predicted by the equations of Si and Midorikawa (J Struct Constr Eng 523:63-70, 1999). The observed PGAs and PGVs at stations far from the seismic source decayed more rapidly than the predicted ones. The same tendencies have been reported for deep, moderate, and large earthquakes, but not for shallow, moderate, and large earthquakes. This indicates that the peak values of ground motion from shallow, small earthquakes attenuate more steeply than those from shallow, moderate or large earthquakes. To investigate the reason for this difference, we numerically simulated strong ground motion for point sources of M w 4 and 6 earthquakes using a 2D finite difference method. The analyses of the synthetic waveforms suggested that the above differences are caused by surface waves, which are predominant at stations far from the seismic source for shallow, moderate earthquakes but not for shallow, small earthquakes. Thus, although loss due to reflection at the boundaries of the discontinuous Earth structure occurs in all shallow earthquakes, the apparent attenuation rate for a moderate or large earthquake is essentially the same as that of body waves propagating in a homogeneous medium due to the dominance of surface waves.

  20. Static tests of excess ground attenuation at Wallops Flight Center (United States)

    Sutherland, L. C.; Brown, R.


    An extensive experimental measurement program which evaluated the attenuation of sound for close to horizontal propagation over the ground was designed to replicate, under static conditions, results of the flight measurements carried out earlier by NASA at the same site (Wallops Flight Center). The program consisted of a total of 41 measurement runs of attenuation, in excess of spreading and air absorption losses, for one third octave bands over a frequency range of 50 to 4000 Hz. Each run consisted of measurements at 10 locations up to 675 m, from a source located at nominal elevations of 2.5, or 10 m over either a grassy surface or an adjacent asphalt concrete runway surface. The tests provided a total of over 8100 measurements of attenuation under conditions of low wind speed averaging about 1 m/s and, for most of the tests, a slightly positive temperature gradient, averaging about 0.3 C/m from 1.2 to 7 m. The results of the measurements are expected to provide useful experimental background for the further development of prediction models of near grazing incidence sound propagation losses.

  1. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis (United States)


    Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan. PMID:28280523

  2. Neuropeptide FF receptors as novel targets for limbic seizure attenuation. (United States)

    Portelli, Jeanelle; Meurs, Alfred; Bihel, Frederic; Hammoud, Hassan; Schmitt, Martine; De Kock, Joery; Utard, Valerie; Humbert, Jean-Paul; Bertin, Isabelle; Buffel, Ine; Coppens, Jessica; Tourwe, Dirk; Maes, Veronique; De Prins, An; Vanhaecke, Tamara; Massie, Ann; Balasubramaniam, Ambikaipakan; Boon, Paul; Bourguignon, Jean-Jacques; Simonin, Frederic; Smolders, Ilse


    Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class antiepileptic neuropeptide. In this study, the controversial role of NPY1 receptors in epilepsy was reassessed by testing two highly selective NPY1 receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat model for limbic seizures. While BIBP3226 significantly attenuated the pilocarpine-induced seizures, neither of the highly selective NPY1 receptor ligands altered the seizure severity. Administration of the NPFF1/NPFF2 receptor antagonist RF9 also significantly attenuated limbic seizure activity. To further prove the involvement of NPFF receptors in these seizure-modulating effects, low and high affinity antagonists for the NPFF receptors were tested. We observed that the low affinity ligand failed to exhibit anticonvulsant properties while the two high affinity ligands significantly attenuated the seizures. Continuous NPFF1 receptor agonist administration also inhibited limbic seizures whereas bolus administration of the NPFF1 receptor agonist was without effect. This suggests that continuous agonist perfusion could result in NPFF1 receptor desensitization and mimic NPFF1 receptor antagonist administration. Our data unveil for the first time the involvement of the NPFF system in the management of limbic seizures.

  3. Adaptation with disturbance attenuation in nonlinear control systems

    Energy Technology Data Exchange (ETDEWEB)

    Basar, T. [Univ. of Illinois, Urbana, IL (United States)


    We present an optimization-based adaptive controller design for nonlinear systems exhibiting parametric as well as functional uncertainty. The approach involves the formulation of an appropriate cost functional that places positive weight on deviations from the achievement of desired objectives (such as tracking of a reference trajectory while the system exhibits good transient performance) and negative weight on the energy of the uncertainty. This cost functional also translates into a disturbance attenuation inequality which quantifies the effect of the presence of uncertainty on the desired objective, which in turn yields an interpretation for the optimizing control as one that optimally attenuates the disturbance, viewed as the collection of unknown parameters and unknown signals entering the system dynamics. In addition to this disturbance attenuation property, the controllers obtained also feature adaptation in the sense that they help with identification of the unknown parameters, even though this has not been set as the primary goal of the design. In spite of this adaptation/identification role, the controllers obtained are not of certainty-equivalent type, which means that the identification and the control phases of the design are not decoupled.

  4. Plasmodium yoelii: induction of attenuated mutants by irradiation

    Energy Technology Data Exchange (ETDEWEB)

    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 of 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.

  5. Attenuation Tomography of Sierra Negra Volcano of the Galapagos Archipelago (United States)

    Rodd, R.; Lees, J. M.


    Following relocation of events with the double-difference location algorithm (HypoDD), we apply tomographic methods to extract 3D attenuation models illuminating the plumbing system of the Sierra Negra Caldera of the Galapagos Archipelago. The dataset consists of 1737 events recorded from July 2009 to June 2011 on the 17-station SIGNET broadband seismic array. We use t* spectral decay methods for both P- and S- phases with the clustered locations to highlight locations where significant variations in Q suggest the presence of magma melt. While the presence of a magma sill, at least 2 km depth, is indicated by InSAR and GPS studies, the delineated magma body has not been explored in detail. The lower bound of the proposed magma accumulation is still under question and thus forms the primary target of this research. Melt replenishment and degassing of the magma sill is believed to cause inflation and/or deflation of the caldera floor. Imaging the extent of the magma sill will provide insight into the feeder system and deformation process of the Sierra Negra caldera. Detailed relocation, Qp and Qs inversion, as well as estimates of the scattering attenuation using coda-normalization technique will be presented. The close relationship between seismic attenuation and the thermal state of the magmatic system suggests we can distinguish melt and/or fluid regions within the Sierra Negra plumbing system.

  6. Natural attenuation software (NAS): Assessing remedial strategies and estimating timeframes (United States)

    Mendez, E.; Widdowson, M.; Chapelle, F.; Casey, C.


    Natural Attenuation Software (NAS) is a screening tool to estimate remediation timeframes for monitored natural attenuation (MNA) and to assist in decision-making on the level of source zone treatment in conjunction with MNA using site-specific remediation objectives. Natural attenuation processes that NAS models include are advection, dispersion, sorption, non-aqueous phase liquid (NAPL) dissolution, and biodegradation of either petroleum hydrocarbons or chlorinated ethylenes. Newly-implemented enhancements to NAS designed to maximize the utility of NAS for site managers were observed. NAS has expanded source contaminant specification options to include chlorinated ethanes and chlorinated methanes, and to allow for the analysis of any other user-defined contaminants that may be subject to microbially-mediated transformations (heavy metals, radioisotopes, etc.). Included is the capability to model co-mingled plumes, with constituents from multiple contaminant categories. To enable comparison of remediation timeframe estimates between MNA and specific engineered remedial actions , NAS was modified to incorporate an estimation technique for timeframes associated with pump-and-treat remediation technology for comparison to MNA. This is an abstract of a paper presented at the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).

  7. A study of the acoustical radiation force considering attenuation (United States)

    Wu, RongRong; Liu, XiaoZhou; Gong, XiuFen


    Acoustical tweezer is a primary application of the radiation force of a sound field. When an ultrasound focused beam passes through a micro-particle, like a cell or living biological specimens, the particle will be manipulated accurately without physical contact and invasion, due to the three-dimensional acoustical trapping force. Based on the Ray acoustics approach in the Mie regime, this work discusses the effects on the particle caused by Gaussian focused ultrasound, studies the acoustical trapping force of spherical Mie particles by ultrasound in any position, and analyzes the numerical calculation on the two-dimensional acoustical radiation force. This article also analyzes the conditions for the acoustical trapping phenomenon, and discusses the impact of the initial position and size of the particle on the magnitude of the acoustical radiation force. Furthermore, this paper considers the ultrasonic attenuation in a particle in the case of two-dimension, studies the attenuation's effects on the acoustical trapping force, and amends the calculation to the ordinary case with attenuation.

  8. An adaptive noise attenuation method for edge and amplitude preservation

    Institute of Scientific and Technical Information of China (English)

    Cai Han-Peng; He Zhen-Hua; Li Ya-Lin; He Guang-Ming; Zou Wen; Zhang Dong-Jun; Liu Pu


    Noise intensity distributed in seismic data varies with different frequencies or frequency bands; thus, noise attenuation on the full-frequency band affects the dynamic properties of the seismic reflection signal and the subsequent seismic data interpretation, reservoir description, hydrocarbon detection, etc. Hence, we propose an adaptive noise attenuation method for edge and amplitude preservation, wherein the wavelet packet transform is used to decompose the full-band seismic signal into multiband data and then process these data using nonlinear anisotropic dip-oriented edge-preservingfi ltering. In the fi ltering, the calculated diffusion tensor from the structure tensor can be exploited to establish the direction of smoothing. In addition, the fault confidence measure and discontinuity operator can be used to preserve the structural and stratigraphic discontinuities and edges, and the decorrelation criteria can be used to establish the number of iterations. These parameters can minimize the intervention and subjectivity of the interpreter, and simplify the application of the proposed method. We applied the proposed method to synthetic and real 3D marine seismic data. We found that the proposed method could be used to attenuate noise in seismic data while preserving the effective discontinuity information and amplitude characteristics in seismic refl ection waves, providing high-quality data for interpretation and analysis such as high-resolution processing, attribute analysis, and inversion.

  9. Empirical Relations for Optical Attenuation Prediction from Liquid Water Content of Fog

    Directory of Open Access Journals (Sweden)

    M. S. Khan


    Full Text Available Simultaneous measurements of the liquid water content (LWC and optical attenuation have been analyzed to predict optical attenuation caused by fog particles. Attenuation has been measured at two different wavelengths, 830 nm and 1550 nm, across co-located links. Five months measured data have been processed to assess power-law empirical models, which estimate optical attenuation from the LWC. The proposed models are compared with other published models and are demonstrated to perform sufficiently well to predict optical attenuation if the LWC values are available.

  10. MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mehranian, Abolfazl; Zaidi, Habib [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland)


    The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA-Salomon in brain TOF-PET/MR imaging.

  11. Forward- vs. Inverse Problems in Modeling Seismic Attenuation (United States)

    Morozov, I. B.


    Seismic attenuation is an important property of wave propagation used in numerous applications. However, the attenuation is also a complex phenomenon, and it is important to differentiate between its two typical uses: 1) in forward problems, to model the amplitudes and spectral contents of waves required for hazard assessment and geotechnical engineering, and 2) in inverse problems, to determine the physical properties of the subsurface. In the forward-problem sense, the attenuation is successfully characterized in terms of empirical parameters of geometric spreading, radiation patterns, scattering amplitudes, t-star, alpha, kappa, or Q. Arguably, the predicted energy losses can be correct even if the underlying attenuation model is phenomenological and not sufficiently based on physics. An example of such phenomenological model is the viscoelasticity based on the correspondence principle and the Q-factor assigned to the material. By contrast, when used to invert for in situ material properties, models addressing the specific physics are required. In many studies (including in this session), a Q-factor is interpreted as a property of a point within the subsurface; however this property is only phenomenological and may be physically insufficient or inconsistent. For example, the bulk or shear Q at the same point can be different when evaluated from different wave modes. The cases of frequency-dependent Q are particularly prone of ambiguities such as trade-off with the assumed background geometric spreading. To rigorously characterize the in situ material properties responsible for seismic-wave attenuation, it is insufficient to only focus on the seismic energy loss. Mechanical models of the material need to be considered. Such models can be constructed by using Lagrangian mechanics. These models should likely contain no Q but will be based on parameters of microstructure such as heterogeneity, fractures, or fluids. I illustrate several such models based on viscosity

  12. Polymerase Mechanism-Based Method of Viral Attenuation (United States)

    Lee, Cheri A.; August, Avery; Arnold, Jamie J.; Cameron, Craig E.


    Vaccines remain the most effective way of preventing infection and spread of infectious diseases. These prophylactics have been used for centuries but still to this day only three main design strategies exist: (1) live attenuated virus (LAV) vaccines, (2) killed or inactivated virus vaccines, (3) and subunit vaccines of the three, the most efficacious vaccines remain LAVs. LAVs replicate in relevant tissues, elicit strong cellular and humoral responses, and often confer lifelong immunity. While this vaccine strategy has produced the majority of successful vaccines in use today, there are also important safety concerns to consider with this approach. In the past, the development of LAVs has been empirical. Blind passage of viruses in various cell types results in the accumulation of multiple attenuating mutations leaving the molecular mechanisms of attenuation unknown. Also, due to the high error rate of RNA viruses and selective pressures of the host environment, these LAVs, derived from such viruses, can potentially revert back to wild-type virulence. This not only puts the vaccinee at risk, but if shed can put those that are unvaccinated at risk as well. While these vaccines have been successful there still remains a need for a rational design strategy by which to create additional LAVs. One approach for rational vaccine design involves increasing the fidelity of the viral RdRp. Increased fidelity decreases the viral mutational frequency thereby reducing the genetic variation the virus needs in order to evade the host imposed bottlenecks to infection. While polymerase mutants exist which decrease viral mutation frequency the mutations are not in conserved regions of the polymerase, which doesn’t lend itself toward using a common mutant approach toward developing a universal vaccine strategy for all RNA viruses. We have identified a conserved lysine residue in the active site of the PV RdRp that acts as a general acid during nucleotide incorporation. Mutation

  13. Comparison of Reg. Guide 1.99 fluence attenuation methods

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.N. [TransWare Enterprises Inc., 1565 Mediterranean Dr., Sycamore, IL 60178 (United States)


    U.S. Regulatory Guide 1.99 Revision 2 (U.S. Nuclear Regulatory Commission, 1988, 'Radiation Embrittlement of Reactor Vessel Materials,' Regulatory Guide 1.99, Revision 2, Washington, D.C.) provides for the use of two substantially different methods for determining through-wall fluence in nuclear reactor pressure vessels. One method is a generic attenuation curve based on a simplistic exponential decay equation. Partly due to the simplicity of its application, the generic attenuation method is predominantly used for licensing calculations. However, it has a limitation in that at increasing distances away from the core belt-line, it becomes increasingly less accurate because it cannot account for neutron streaming effects in the cavity region surrounding the pressure vessel. The other attenuation method is based on a displacement per atom (dpa) calculation specific to the reactor vessel structure. The dpa method provides a more accurate representation of fluence attenuation through the reactor pressure vessel (RPV) wall at all elevations of the pressure vessel because it does account for neutron streaming in the cavity region. A requirement for using the dpa method, however, is an accurate flux solution through the RPV wall. This requirement has limited the use of traditional transport methods, such as discrete ordinates, that are limited by their treatment of cavity regions (i.e., air) outside the pressure vessel wall. TransWare Enterprises, under the sponsorship of EPRI and BWRVIR has developed an advanced three-dimensional transport methodology capable of producing fully converged flux solutions throughout the entire reactor system, including in the cavity region and primary shield structures. This methodology provides an accurate and reliable determination of through-wall fluence in boiling water reactor (BWR) and pressurized water reactor (PWR) pressure vessels, thus allowing the dpa method to be implemented with high reliability. Using this advanced 3

  14. P-wave attenuation anisotropy in TI media and its application in fracture parameters inversion (United States)

    He, Yi-Yuan; Hu, Tian-Yue; He, Chuan; Tan, Yu-Yang


    The existence of aligned fractures in fluid-saturated rocks leads to obvious attenuation anisotropy and velocity anisotropy. Attenuation anisotropy analysis can be applied to estimate fracture density and scale, which provide important information for reservoir identification. This paper derives P-wave attenuation anisotropy in the ATI media where the symmetry axis is in the arbitrary direction theoretically and modifies the spectral ratio method to measure attenuation anisotropy in the ATI media, thus avoiding a large measurement error when applied to wide azimuth or full azimuth data. Fracture dip and azimuth can be estimated through attenuation anisotropy analysis. For small-scale fractures, fracture scale and fracture density can be determined with enhanced convergence if velocity and attenuation information are both used. We also apply the modified spectralratio method to microseismic field data from an oilfield in East China and extract the fracture dip through attenuation anisotropy analysis. The result agrees with the microseismic monitoring.

  15. Derivation of attenuation map for attenuation correction of PET data in the presence of nanoparticulate contrast agents using spectral CT imaging

    NARCIS (Netherlands)

    Ghadiri, Hossein; Shiran, Mohammad Bagher; Soltanian-Zadeh, Hamid; Rahmim, Arman; Zaidi, Habib; Ay, Mohammad Reza


    Uptake value in quantitative PET imaging is biased due to the presence of CT contrast agents when using CT-based attenuation correction. Our aim was to examine spectral CT imaging to suppress inaccuracy of 511 keV attenuation map in the presence of multiple nanoparticulate contrast agents. Using a s

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

    Yamshchikov, Vladimir; 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 analyzed effects of E138K and K279M 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.

  17. Seismic random noise attenuation via 3D block matching (United States)

    Amani, Sajjad; Gholami, Ali; Javaheri Niestanak, Alireza


    The lack of signal to noise ratio increases the final errors of seismic interpretation. In the present study, we apply a new non-local transform domain method called "3 Dimensional Block Matching (3DBM)" for seismic random noise attenuation. Basically, 3DBM uses the similarities through the data for retrieving the amplitude of signal in a specific point in the f-x domain, and because of this, it is able to preserve discontinuities in the data such as fractures and faults. 3DBM considers each seismic profile as an image and thus it can be applied to both pre-stack and post-stack seismic data. It uses the block matching clustering method to gather similar blocks contained in 2D data into 3D groups in order to enhance the level of correlation in each 3D array. By applying a 2D transform and 1D transform (instead of a 3D transform) on each array, we can effectively attenuate the noise by shrinkage of the transform coefficients. The subsequent inverse 2D transform and inverse 1D transform yield estimates of all matched blocks. Finally, the random noise attenuated data is computed using the weighted average of all block estimates. We applied 3DBM on both synthetic and real pre-stack and post-stack seismic data and compared it with a Curvelet transform based denoising method which is one of the most powerful methods in this area. The results show that 3DBM method eventuates in higher signal to noise ratio, lower execution time and higher visual quality.

  18. Attenuation of shock waves in copper and stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, W.B.


    By using shock pins, data were gathered on the trajectories of shock waves in stainless steel (SS-304L) and oxygen-free-high-conductivity copper (OFHC-Cu). Shock pressures were generated in these materials by impacting the appropriate target with thin (approx.1.5 mm) flying plates. The flying plates in these experiments were accelerated to high velocities (approx.4 km/s) by high explosives. Six experiments were conducted, three using SS-304L as the target material and three experiments using OFHC-Cu as the target material. Peak shock pressures generated in the steel experiments were approximately 109, 130, and 147 GPa and in the copper experiments, the peak shock pressures were approximately 111, 132, and 143 GPa. In each experiment, an attenuation of the shock wave by a following release wave was clearly observed. An extensive effort using two characteristic codes (described in this work) to theoretically calculate the attenuation of the shock waves was made. The efficacy of several different constitutive equations to successfully model the experiments was studied by comparing the calculated shock trajectories to the experimental data. Based on such comparisons, the conclusion can be drawn that OFHC-Cu enters a melt phase at about 130 GPa on the principal Hugoniot. There was no sign of phase changes in the stainless-steel experiments. In order to match the observed attenuation of the shock waves in the SS-304L experiments, it was necessary to include strength effects in the calculations. It was found that the values for the parameters in the strength equations were dependent on the equation of state used in the modeling of the experiments. 66 refs., 194 figs., 77 tabs.

  19. Lateral variation of seismic attenuation in Sikkim Himalaya (United States)

    Thirunavukarasu, Ajaay; Kumar, Ajay; Mitra, Supriyo


    We use data from local earthquakes (mb ≥ 3.0) recorded by the Sikkim broad-band seismograph network to study the frequency-dependent attenuation of the crust and uppermost mantle. These events have been relocated using body wave phase data from local and regional seismograms. The decay of coda amplitudes at a range of central frequencies (1 to 12 Hz) has been measured for 74 earthquake-receiver pairs. These measurements are combined to estimate the frequency-dependent coda Q of the form Q( f) = Q0 f η. The estimated Q0 values range from 80 to 200, with an average of 123 ± 29; and η ranges from 0.92 to 1.04, with an average of 0.98 ± 0.04. To study the lateral variation of Q0 and η, we regionalized the measured Q values by combining all the earthquake-receiver path measurements through a back projection algorithm. We consider a single back-scatter model for the coda waves with elliptical sampling and parametrize the sampled area using 0.2° square grids. A nine-point spatial smoothening (similar to spatial Gaussian filter) is applied to stabilize the inversion. This is done at every frequency to observe the spatial variation of Q( f) and subsequently combined to obtain η variations. Results of our study reveal that the Sikkim Himalaya is characterized by low Q0 (80-100) compared to the foreland basin to its south (150-200) and the Nepal Himalaya to its west (140-160). The low Q and high η in Sikkim Himalaya is attributed to extrinsic scattering attenuation from structural heterogeneity and active faults within the crust, and intrinsic attenuation due to anelasticity in the hotter lithosphere beneath the actively deforming mountain belt. Similar low Q and high η values had also been observed in northwest and Garhwal-Kumaun Himalaya.

  20. Hybrid approach for attenuation correction in PET/MR scanners

    Energy Technology Data Exchange (ETDEWEB)

    Santos Ribeiro, A., E-mail: [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, Lisbon (Portugal); Rota Kops, E.; Herzog, H. [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, Juelich (Germany); Almeida, P. [Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, Lisbon (Portugal)


    Aim: Attenuation correction (AC) of PET images is still one of the major limitations of hybrid PET/MR scanners. Different methods have been proposed to obtain the AC map from morphological MR images. Although, segmentation methods normally fail to differentiate air and bone regions, while template or atlas methods usually cannot accurately represent regions anatomically different from the template image. In this study a feed forward neural network (FFNN) algorithm is presented which directly outputs the attenuation coefficients by non-linear regression of the images acquired with an ultrashort echo time (UTE) sequence guided by the template-based AC map (TAC-map). Materials and methods: MR as well as CT data were acquired in four subjects. The UTE images and the TAC-map were the inputs of the presented FFNN algorithm for training as well as classification. The resulting attenuation maps were compared with CT-based, PNN-based and TAC maps. All the AC maps were used to reconstruct the PET emission data which were then compared for the different methods. Results: For each subject dice coefficients D were calculated between each method and the respective CT-based AC maps. The resulting Ds show higher values for all FFNN-based tissues comparatively to both TAC-based and PNN-based methods, particularly for bone tissue (D=0.77, D=0.51 and D=0.71, respectively). The AC-corrected PET images with the FFNN-based map show an overall lower relative difference (RD=3.90%) than those AC-corrected with the PNN-based (RD=4.44%) or template-based (RD=4.43%) methods. Conclusion: Our results show that an enhancement of current methods can be performed by combining both information of new MR image sequence techniques and general information provided from template techniques. Nevertheless, the number of tested subjects is statistically low and current analysis for a larger dataset is being carried out.

  1. Intensive Exercise Training During Bed Rest Attenuates Deconditioning (United States)

    Greenleaf, John E.


    Intensive exercise training during bed rest attenuates deconditioning. Med. Sci. Sports Exerc., Vol. 29, No. 2, pp. 207-215, 1997. A 30-d 6 deg head-down bed rest project was conducted to evaluate variable high-intensity, short-duration, isotonic cycle ergometer exercise (ITE) training and high-intensity intermittent resistive isokinetic exercise (IKE) training regimens designed to maintain peak VO2 and muscle mass, strength, and endurance at ambulatory control levels throughout prolonged bed rest. Other elements of the deconditioning (adaptive) syndrome, such as proprioception, psychological performance, hypovolemia, water balance, body composition, and orthostatic tolerance, were also measured. Major findings are summarized in this paper. Compared with response during bed rest of the no exercise (NOE) control group: the ITE training regimen (a) maintained work capacity (peak VO2), (b) maintained plasma and red cell volumes, (c) induced positive body water balance, (d) decreased quality of sleep and mental concentration, and (e) had no effect on the decrease in orthostatic tolerance; the IKE training regimen (f) attenuated the decrease in peak VO2 by 50%, (g) attenuated loss of red cell volume by 40% but had no effect on loss of plasma volume, (b) induced positive body water balance, (i) had no adverse effect on quality of sleep or concentration, and 0) had no effect on the decrease in orthostatic tolerance. These findings suggest that various elements of the deconditioning syndrome can be manipulated by duration and intensity of ITE or IKE training regimens and that several different training protocols will be required to maintain or restore physiological and psychological performance of individuals confined to prolonged bed rest.

  2. Magnesium nitrate attenuates blood pressure rise in SHR rats. (United States)

    Vilskersts, Reinis; Kuka, Janis; Liepinsh, Edgars; Cirule, Helena; Gulbe, Anita; Kalvinsh, Ivars; Dambrova, Maija


    The administration of magnesium supplements and nitrates/nitrites decreases arterial blood pressure and attenuates the development of hypertension-induced complications. This study was performed to examine the effects of treatment with magnesium nitrate on the development of hypertension and its complications in spontaneously hypertensive (SHR) rats. Male SHR rats with persistent hypertension at the age of 12-13 weeks were allocated to two groups according to their arterial blood pressure. Rats from the control group received purified water, while the experimental animals from the second group received magnesium nitrate dissolved in purified water at a dose of 50 mg/kg. After four weeks of treatment, blood pressure was measured, the anatomical and functional parameters of the heart were recorded using an ultrasonograph, vascular reactivity was assayed in organ bath experiments and the cardioprotective effects of magnesium nitrate administration was assayed in an ex vivo experimental heart infarction model. Treatment with magnesium nitrate significantly increased the nitrate concentration in the plasma (from 62 ± 8 μmol/l to 111 ± 8 μmol/L), and attenuated the increase in the arterial blood pressure. In the control and magnesium nitrate groups, the blood pressure rose by 21 ± 3 mmHg and 6 ± 4 mmHg, respectively. The administration of magnesium nitrate had no effect on the altered vasoreactivity, heart function or the size of the heart infarction. In conclusion, our results demonstrate that magnesium nitrate effectively attenuates the rise in arterial blood pressure. However, a longer period of administration or earlier onset of treatment might be needed to delay the development of complications due to hypertension.

  3. Optical coherence tomography for blood glucose monitoring through signal attenuation (United States)

    De Pretto, Lucas R.; Yoshimura, Tania M.; Ribeiro, Martha S.; de Freitas, Anderson Z.


    Development of non-invasive techniques for glucose monitoring is crucial to improve glucose control and treatment adherence in patients with diabetes. Hereafter, Optical Coherence Tomography (OCT) may offer a good alternative for portable glucometers, since it uses light to probe samples. Changes in the object of interest can alter the intensity of light returning from the sample and, through it, one can estimate the sample's attenuation coefficient (μt) of light. In this work, we aimed to explore the behavior of μt of mouse's blood under increasing glucose concentrations. Different samples were prepared in four glucose concentrations using a mixture of heparinized blood, phosphate buffer saline and glucose. Blood glucose concentrations were measured with a blood glucometer, for reference. We have also prepared other samples diluting the blood in isotonic saline solution to check the effect of a higher multiple-scattering component on the ability of the technique to differentiate glucose levels based on μt. The OCT system used was a commercial Spectral Radar OCT with 930 nm central wavelength and spectral bandwidth (FWHM) of 100 nm. The system proved to be sensitive for all blood glucose concentrations tested, with good correlations with the obtained attenuation coefficients. A linear tendency was observed, with an increase in attenuation with higher values of glucose. Statistical difference was observed between all groups (p<0.001). This work opens the possibility towards a non-invasive diagnostic modality using OCT for glycemic control, which eliminates the use of analytes and/or test strips, as in the case with commercially available glucometers.

  4. Predicting Spectral and PAR Light Attenuation in Greenlandic Coastal Waters

    DEFF Research Database (Denmark)

    Murray, Ciarán; Stedmon, Colin A.; Markager, Stiig

    present models for spectral and PAR (photosynthetically active radiation) attenuation in two contrasting Greenlandic fjords, Godthåbsfjord (SW Greenland) and Young Sound (NE Greenland). The fjords differ in the character and concentrations of optically active components present: dissolved organic material...... (CDOM), phytoplankton pigments and inorganic particles. These differences are due in part to hydrography and to the sources of meltwater: respectively, fjord-terminating and land-terminating glaciers. We present a model to explain the variation in spectral and PAR irradiance in terms of the variation...

  5. Predicting spectral and PAR light attenuation in Greenlandic coastal waters

    DEFF Research Database (Denmark)

    Murray, Ciarán; Markager, Stiig; Stedmon, Colin

    present models for spectral and PAR (photosynthetically active radiation) attenuation in two contrasting Greenlandic fjords, Godthåbsfjord (SW Greenland) and Young Sound (NE Greenland). The fjords differ in the character and concentrations of optically active components present: dissolved organic material...... (CDOM), phytoplankton pigments and inorganic particles. These differences are due in part to hydrography and to the sources of meltwater: respectively, fjord-terminating and land-terminating glaciers. We present a model to explain the variation in spectral and PAR irradiance in terms of the variation...

  6. Secure Communication via a Recycling of Attenuated Classical Signals (United States)

    Smith, A. Matthew


    We describe a simple method of interleaving a classical and quantum signal in a secure communication system at a single wavelength. The system transmits data encrypted via a one-time pad on a classical signal and produces a single-photon reflection of the encrypted signal. This attenuated signal can be used to observe eavesdroppers and produce fresh secret bits. The system can be secured against eavesdroppers, detect simple tampering or classical bit errors, produces more secret bits than it consumes, and does not require any entanglement or complex wavelength division multiplexing, thus, making continuous secure two-way communication via one-time pads practical.

  7. On the attenuation coefficient of monomode periodic waveguides

    CERN Document Server

    Baron, Alexandre; Smigaj, Wojciech; Lalanne, Philippe


    It is widely accepted that, on ensemble average, the transmission T of guided modes decays exponentially with the waveguide length L due to small imperfections, leading to the important figure of merit defined as the attenuation-rate coefficient alpha = -/L. In this letter, we evidence that the exponential-damping law is not valid in general for periodic monomode waveguides, especially as the group velocity decreases. This result that contradicts common beliefs and experimental practices aiming at measuring alpha is supported by a theoretical study of light transport in the limit of very small imperfections, and by numerical results obtained for two waveguide geometries that offer contrasted damping behaviours.

  8. Pharmacologically induced hypothermia attenuates traumatic brain injury in neonatal rats. (United States)

    Gu, Xiaohuan; Wei, Zheng Zachory; Espinera, Alyssa; Lee, Jin Hwan; Ji, Xiaoya; Wei, Ling; Dix, Thomas A; Yu, Shan Ping


    Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3°C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15min or 2h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201

  9. Finite-time disturbance attenuation of nonlinear systems

    Institute of Scientific and Technical Information of China (English)

    MO LiPo; JIA YingMin; ZHENG ZhiMing


    This paper is devoted to the finite-time disturbance attenuation problem of affine nonlinear systems.Based on the finite time Lyapunov stability theory,some finite-time H_∞ performance criterions are derived.Then the state-feedback control law is designed and the structure of such a controller is investigated.Furthermore,it is shown that the H_∞ controller can also make the closed-loop system satisfy finite-time H_∞ performance for nonlinear homogeneous systems.An example is provided to demonstrate the effectiveness of the presented results.

  10. Disturbance Attenuation State-Feedback Control for Uncertain Interconnected Systems

    Institute of Scientific and Technical Information of China (English)


    This paper studies the problem of robust H∞ control design for a class of uncertain interconnected systems viastate feedback. This class of systems are described by a state space model, which contains unknown nonlinear interactionand time-varying norm-bounded parametric uncertainties in state equation. Using the Riccati-equation-based approach wedesign state feedback control laws, which guarantee the decentralized stability with disturbance attenuation for the inter-connected uncertain systems. A simple example of an interconnected uncertain linear system is presented to illustrate theresults.

  11. Live attenuated varicella vaccine in children with leukemia in remission. (United States)

    Gershon, A A; Steinberg, S; Galasso, G; Borkowsky, W; Larussa, P; Ferrara, A; Gelb, L


    One-hundred-ninety-one children with acute leukemia in remission for at least one year were immunized with 1 or more doses of live attenuated varicella vaccine. All were susceptible to varicella prior to vaccination. The only significant side effect was mild to moderate rash, seen especially in children with maintenance chemotherapy temporarily suspended for one week before and one week after vaccination. Children with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact.

  12. Attenuation of allergic contact dermatitis through the endocannabinoid system. (United States)

    Karsak, Meliha; Gaffal, Evelyn; Date, Rahul; Wang-Eckhardt, Lihua; Rehnelt, Jennifer; Petrosino, Stefania; Starowicz, Katarzyna; Steuder, Regina; Schlicker, Eberhard; Cravatt, Benjamin; Mechoulam, Raphael; Buettner, Reinhard; Werner, Sabine; Di Marzo, Vincenzo; Tüting, Thomas; Zimmer, Andreas


    Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase-deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.

  13. Natural attenuation of hydrocarbon polluted soils in Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Linares, L.; Rojas-Avelizapa, N.; Roldan-Carrillo, T.; Islas-Ramirez, M.


    Crude oil and hydrocarbon by-proudcts are the most common pollutants in Mexico. In the last years, the two terms, contamination and remediation have being re-defined; also, based on both the scientific advancement and the human risk, the sustentability of remediation technologies and the definition of cleaning levels has been taking place. In this context, the Natural Attenuation of soils is a viable and low cost remediation choice, defined as the degradation of organic compounds without artificial stimulation, through microbial activity including physical processes, such as volatilization, dilution, sorption, and hydraulic dispersion. (Author)

  14. Mucosal vaccination with an attenuated maedi-visna virus clone. (United States)

    Pétursson, Gudmundur; Matthíasdóttir, Sigrídur; Svansson, Vilhjálmur; Andrésdóttir, Valgerdur; Georgsson, Gudmundur; Martin, Agnes H; Agnarsdóttir, Gudrún; Gísladóttir, Eygló; Arnadóttir, Steinunn; Högnadóttir, Svava; Jónsson, Stefán Ragnar; Andrésson, Olafur S; Torsteinsdóttir, Sigurbjörg


    Four sheep were infected intratracheally with an attenuated molecular clone of maedi-visna virus (MVV). All four became infected. Ten months later these sheep were challenged intratracheally with a genetically similar but pathogenic clone of MVV. Four unvaccinated sheep were infected simultaneously. All sheep became infected by the challenge virus. The vaccinated sheep were not protected against superinfection with the challenge clone. However, virus was isolated more frequently from the blood of the unvaccinated controls than of the vaccinated animals and ten times more frequently from lungs of unvaccinated sheep than from lungs of vaccinated sheep at sacrifice, indicating partial protection.

  15. Regional Lg attenuation for the continental United States (United States)

    Benz, H.M.; Frankel, A.; Boore, D.M.


    Measurements of the Fourier amplitude spectra of Lg phases recorded at high frequency (0.5 to 14.0 Hz) by broadband seismic stations are used to determine regional attenuation relationships for southern California, the Basin and Range Province, the central United States, and the northeastern United States and southeastern Canada. Fourier spectral amplitudes were measured every quarter octave from Lg phases windowed between 3.0 and 3.7 km sec-1 and recorded in the distance range of 150 to 1000 km. Attenuation at each frequency is determined by assuming a geometrical spreading exponent of 0.5 and inverting for Q and source and receiver terms. Both southern California and the Basin and Range Province are well described by low Lg Q and frequency-dependent attenuation. Lg spectral amplitudes in southern California are fit at low frequencies (0.625 to 0.875 Hz) by a constant Lg Q of 224 and by a frequency-dependent Lg Q function Q = 187-7+7 f0.55(??0.03) in the frequency band 1.0 to 7.0 Hz. The Basin and Range Province is characterized by a constant Lg Q of 192 for frequencies of 0.5 to 0.875 Hz and by the frequency-dependent Lg Q function Q = 235-11+11 f0.56(??0.04) in the frequency band 1.0 to 5.0 Hz. A change in frequency dependence above 5.0 Hz is possible due to contamination of the Lg window by Pn and Sn phases. Lg spectral amplitudes in the central United States are fit by a mean frequency-independent Lg Q of 1291 for frequencies of 1.5 to 7.0 Hz, while a frequency-dependent Lg Q of Q = 1052-83+91(f/1.5)0.22(??0.06) fits the Lg spectral amplitudes for the northeastern United States and southeastern Canada over the passband 1.5 to 14.0 Hz. Attenuation measurements for these areas were restricted to frequencies >1.5 Hz due to larger microseismic noise levels at the lower frequencies.

  16. Research progress in live attenuated Brucella vaccine development. (United States)

    Wang, Zhen; Wu, Qingmin


    Brucella spp. are facultative intracellular bacteria that cause brucellosis, which is a globally occurring zoonotic disease that is characterized by abortion in domestic animals and undulant fever, arthritis, endocarditis, and meningitis in humans. There are currently no licensed vaccines against brucellosis for human use, and only a few licensed live Brucella vaccines are available for use in animals. However, the available animal vaccines may cause abortion and are associated with lower protection rates in animals and higher virulence in humans. Much research has been performed recently to develop novel Brucella vaccines for the prevention and control of animal brucellosis. This article discusses the approaches and strategies for novel live attenuated vaccine development.

  17. Attenuation and source properties at the Coso Geothermal area, California (United States)

    Hough, S.E.; Lees, J.M.; Monastero, F.


    We use a multiple-empirical Green's function method to determine source properties of small (M -0.4 to 1.3) earthquakes and P- and S-wave attenuation at the Coso Geothermal Field, California. Source properties of a previously identified set of clustered events from the Coso geothermal region are first analyzed using an empirical Green's function (EGF) method. Stress-drop values of at least 0.5-1 MPa are inferred for all of the events; in many cases, the corner frequency is outside the usable bandwidth, and the stress drop can only be constrained as being higher than 3 MPa. P- and S-wave stress-drop estimates are identical to the resolution limits of the data. These results are indistinguishable from numerous EGF studies of M 2-5 earthquakes, suggesting a similarity in rupture processes that extends to events that are both tiny and induced, providing further support for Byerlee's Law. Whole-path Q estimates for P and S waves are determined using the multiple-empirical Green's function (MEGF) method of Hough (1997), whereby spectra from clusters of colocated events at a given station are inverted for a single attenuation parameter, ??, with source parameters constrained from EGF analysis. The ?? estimates, which we infer to be resolved to within 0.01 sec or better, exhibit almost as much scatter as a function of hypocentral distance as do values from previous single-spectrum studies for which much higher uncertainties in individual ?? estimates are expected. The variability in ?? estimates determined here therefore suggests real lateral variability in Q structure. Although the ray-path coverage is too sparse to yield a complete three-dimensional attenuation tomographic image, we invert the inferred ?? value for three-dimensional structure using a damped least-squares method, and the results do reveal significant lateral variability in Q structure. The inferred attenuation variability corresponds to the heat-flow variations within the geothermal region. A central low

  18. Relationship between normalized light intensity and attenuated total reflection ratio

    Institute of Scientific and Technical Information of China (English)

    Yingcai Wu; Zhengtian Gu


    Attenuated total reflection (ATR) ratio is usually utilized to study the properties of surface plasmon resonance (SPR) sensors. The relationship between normalized light intensity and ATR ratio is investigated, and a modification coefficient is put forward to describe the relationship. A mathematical expression is built up for the coefficient based on Fresnel principle. The result shows that the ATR ratio, which cannot be measured directly in experiments, can be determined with the coefficient and the normalized intensity of light. The characteristic of the coefficient is also discussed.

  19. Multi-resolution inversion algorithm for the attenuated radon transform

    KAUST Repository

    Barbano, Paolo Emilio


    We present a FAST implementation of the Inverse Attenuated Radon Transform which incorporates accurate collimator response, as well as artifact rejection due to statistical noise and data corruption. This new reconstruction procedure is performed by combining a memory-efficient implementation of the analytical inversion formula (AIF [1], [2]) with a wavelet-based version of a recently discovered regularization technique [3]. The paper introduces all the main aspects of the new AIF, as well numerical experiments on real and simulated data. Those display a substantial improvement in reconstruction quality when compared to linear or iterative algorithms. © 2011 IEEE.

  20. The Study of Rain Specific Attenuation for the Prediction of Satellite Propagation in Malaysia (United States)

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


    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.

  1. The new approach of polarimetric attenuation correction for improving radar quantitative precipitation estimation(QPE) (United States)

    Gu, Ji-Young; Suk, Mi-Kyung; Nam, Kyung-Yeub; Ko, Jeong-Seok; Ryzhkov, Alexander


    To obtain high-quality radar quantitative precipitation estimation data, reliable radar calibration and efficient attenuation correction are very important. Because microwave radiation at shorter wavelength experiences strong attenuation in precipitation, accounting for this attenuation is the essential work at shorter wavelength radar. In this study, the performance of different attenuation/differential attenuation correction schemes at C band is tested for two strong rain events which occurred in central Oklahoma. And also, a new attenuation correction scheme (combination of self-consistency and hot-spot concept methodology) that separates relative contributions of strong convective cells and the rest of the storm to the path-integrated total and differential attenuation is among the algorithms explored. A quantitative use of weather radar measurement such as rainfall estimation relies on the reliable attenuation correction. We examined the impact of attenuation correction on estimates of rainfall in heavy rain events by using cross-checking with S-band radar measurements which are much less affected by attenuation and compared the storm rain totals obtained from the corrected Z and KDP and rain gages in these cases. This new approach can be utilized at shorter wavelength radars efficiently. Therefore, it is very useful to Weather Radar Center of Korea Meteorological Administration preparing X-band research dual Pol radar network.

  2. Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging

    Energy Technology Data Exchange (ETDEWEB)

    Aznar, M.C., E-mail: [Department of Oncology, Section of Radiotherapy 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen (Denmark); Sersar, R., E-mail: [DTU Informatics, Technical University of Denmark, Kongens Lyngby (Denmark); Saabye, J., E-mail: [DTU Informatics, Technical University of Denmark, Kongens Lyngby (Denmark); Ladefoged, C.N., E-mail: [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Andersen, F.L., E-mail: [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Rasmussen, J.H., E-mail: [Department of Oncology, Section of Radiotherapy 3994, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen (Denmark); Löfgren, J., E-mail: [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Beyer, T., E-mail: [Centre for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna (Austria)


    Purpose: In combined PET/MRI standard PET attenuation correction (AC) is based on tissue segmentation following dedicated MR sequencing and, typically, bone tissue is not represented. We evaluate PET quantification in whole-body (WB)-PET/MRI following MR-AC without considering bone attenuation and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. Methods: Twenty oncology patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET(/MRI) images were reconstructed (AW-OSEM, 3 iterations, 21 subsets, 4 mm Gaussian) following routine MR-AC and MR-AC based on four modified attenuation maps. These modified attenuation maps were created for each patient by non-linear co-registration of the CT images to the orgMR-AC images, and adding CT bone mask values representing cortical bone: 1200 HU (cortCT), spongiosa bone: 350 HU (spongCT), average CT value (meanCT) and original CT values (orgCT). Relative difference images of the PET following AC using the modified attenuation maps were compared. SUVmean was calculated in anatomical reference regions and for PET-positive lesions. Results: The relative differences in SUVmean across patients following orgMR-AC and orgCT in soft tissue lesions and in bone lesions were similar (range: 0.0% to −22.5%), with an average underestimation of SUVmean of 7.2% and 10.0%, respectively when using orgMR-AC. In bone lesions, spongCT values were closest to orgCT (median bias of 1.3%, range: –9.0% to 13.5%) while the overestimation of SUVmean with respect to orgCT was

  3. An acoustic eikonal equation for attenuating transversely isotropic media with a vertical symmetry axis

    KAUST Repository

    Hao, Qi


    Seismic-wave attenuation is an important component of describing wave propagation. Certain regions, such as gas clouds inside the earth, exert highly localized attenuation. In fact, the anisotropic nature of the earth induces anisotropic attenuation because the quasi P-wave dispersion effect should be profound along the symmetry direction. We have developed a 2D acoustic eikonal equation governing the complex-valued traveltime of quasi P-waves in attenuating, transversely isotropic media with a vertical-symmetry axis (VTI). This equation is derived under the assumption that the complex-valued traveltime of quasi P-waves in attenuating VTI media are independent of the S-wave velocity parameter υS0 in Thomsen\\'s notation and the S-wave attenuation coefficient AS0 in Zhu and Tsvankin\\'s notation. We combine perturbation theory and Shanks transform to develop practical approximations to the acoustic attenuating eikonal equation, capable of admitting an analytical description of the attenuation in homogeneous media. For a horizontal-attenuating VTI layer, we also derive the nonhyperbolic approximations for the real and imaginary parts of the complex-valued reflection traveltime. These equations reveal that (1) the quasi SV-wave velocity and the corresponding quasi SV-wave attenuation coefficient given as part of Thomsen-type notation barely affect the ray velocity and ray attenuation of quasi P-waves in attenuating VTI media; (2) combining the perturbation method and Shanks transform provides an accurate analytic eikonal solution for homogeneous attenuating VTI media; (3) for a horizontal attenuating VTI layer with weak attenuation, the real part of the complex-valued reflection traveltime may still be described by the existing nonhyperbolic approximations developed for nonattenuating VTI media, and the imaginary part of the complex-valued reflection traveltime still has the shape of nonhyperbolic curves. In addition, we have evaluated the possible extension of the

  4. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats. (United States)

    Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina


    Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-κB) p65, promoted the phosphorylation of inhibitor of nuclear factor-κB-α (IκBα) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPKα) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-κB signaling pathway.

  5. Mitragynine attenuates withdrawal syndrome in morphine-withdrawn zebrafish.

    Directory of Open Access Journals (Sweden)

    Beng-Siang Khor

    Full Text Available A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.

  6. Evolutionary history and attenuation of myxoma virus on two continents. (United States)

    Kerr, Peter J; Ghedin, Elodie; DePasse, Jay V; Fitch, Adam; Cattadori, Isabella M; Hudson, Peter J; Tscharke, David C; Read, Andrew F; Holmes, Edward C


    The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.

  7. Evolutionary history and attenuation of myxoma virus on two continents.

    Directory of Open Access Journals (Sweden)

    Peter J Kerr

    Full Text Available The attenuation of myxoma virus (MYXV following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.

  8. Mechanical compression attenuates normal human bronchial epithelial wound healing

    Directory of Open Access Journals (Sweden)

    Malavia Nikita


    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  9. (-)-Epicatechin Attenuates Degradation of Mouse Oxidative Muscle Following Hindlimb Suspension. (United States)

    Lee, Icksoo; Hüttemann, Maik; Malek, Moh H


    The purpose of this study was to conduct a 14-day hindlimb suspension (HS) with and without (-)-epicatechin supplementation to determine whether (-)-epicatechin treatment can attenuate the loss in muscle degradation, angiogenesis, and mitochondrial signaling in oxidative skeletal muscle. Adult mice were randomized into 3 groups: (a) control (C); (b) HS with vehicle (HS-V); and (c) HS with (-)-epicatechin (HS-(-)-Epi). Animals in the HS-(-)-Epi group received (-)-epicatechin (1.0 mg · kg(-1) of body mass) twice daily through oral gavage. For markers related to muscle degradation, the HS-V group had significantly higher protein expression compared with the control and HS-(-)-Epi groups. Moreover, protein expression for myosin heavy chain type I was significantly reduced by approximately 45% in the HS-V group compared with the control and HS-(-)-Epi groups. In addition, capillarity contact and capillary-to-fiber ratio were significantly higher in the HS-(-)-Epi group compared with the HS-V group. Furthermore, protein expression for thrombospondin-1 was significantly higher in HS-V group compared with the control and HS-(-)-Epi groups. Hindlimb suspension also significantly reduced protein expression for mitochondrial signaling compared with the control and HS-(-)-Epi groups. These findings suggest that (-)-epicatechin supplementation attenuates degradation in oxidative muscles after HS.

  10. Attenuation Analysis of Lamb Waves Using the Chirplet Transform

    Directory of Open Access Journals (Sweden)

    Sprenger Helge


    Full Text Available Guided Lamb waves are commonly used in nondestructive evaluation to monitor plate-like structures or to characterize properties of composite or layered materials. However, the dispersive propagation and multimode excitability of Lamb waves complicate their analysis. Advanced signal processing techniques are therefore required to resolve both the time and frequency content of the time-domain wave signals. The chirplet transform (CT has been introduced as a generalized time-frequency representation (TFR incorporating more flexibility to adjust the window function to the group delay of the signal when compared to the more classical short-time Fourier transform (STFT. Exploiting this additional degree of freedom, this paper applies an adaptive algorithm based on the CT to calculate mode displacement ratios and attenuation of Lamb waves in elastic plate structures. The CT-based algorithm has a clear performance advantage when calculating mode displacement ratios and attenuation for numerically-simulated Lamb wave signals. For experimental data, the CT retains an advantage over the STFT although measurement noise and parameter uncertainties lead to larger overall deviations from the theoretically expected solutions.

  11. Extragalactic Background Light and Gamma-Ray Attenuation

    CERN Document Server

    Primack, Joel R; Gilmore, Rudy C; Somerville, Rachel S


    Data from (non-) attenuation of gamma rays from active galactic nuclei (AGN) and gamma ray bursts (GRBs) give upper limits on the extragalactic background light (EBL) from the UV to the mid-IR that are only a little above the lower limits from observed galaxies. These upper limits now rule out some EBL models and purported observations, with improved data likely to provide even stronger constraints. We present EBL calculations both based on multiwavelength observations of thousands of galaxies and also based on semi-analytic models, and show that they are consistent with these lower limits from observed galaxies and with the gamma-ray upper limit constraints. Such comparisons "close the loop" on cosmological galaxy formation models, since they account for all the light, including that from galaxies too faint to see. We compare our results with those of other recent works, and discuss the implications of these new EBL calculations for gamma ray attenuation. Catching a few GRBs with groundbased atmospheric Cher...

  12. The role of mangroves in attenuating storm surges (United States)

    Zhang, Keqi; Liu, Huiqing; Li, Yuepeng; Xu, Hongzhou; Shen, Jian; Rhome, Jamie; Smith, J.


    Field observations and numerical simulations indicate that the 6-to-30-km-wide mangrove forest along the Gulf Coast of South Florida effectively attenuated stormsurges from a Category 3 hurricane, Wilma, and protected the inland wetland by reducing an inundation area of 1800 km2 and restricting surge inundation inside the mangrove zone. The surge amplitude decreases at a rate of 40–50 cm/km across the mangrove forest and at a rate of 20 cm/km across the areas with a mixture of mangrove islands with open water. In contrast, the amplitudes of stormsurges at the front of the mangrove zone increase by about 10–30% because of the "blockage" of mangroves to surge water, which can cause greater impacts on structures at the front of mangroves than the case without mangroves. The mangrove forest can also protect the wetlands behind the mangrove zone against surge inundation from a Category 5 hurricane with a fast forward speed of 11.2 m/s (25 mph). However, the forest cannot fully attenuate stormsurges from a Category 5 hurricane with a slow forward speed of 2.2 m/s (5 mph) and reduced surges can still affect the wetlands behind the mangrove zone. The effects of widths of mangrove zones on reducing surge amplitudes are nonlinear with large reduction rates (15–30%) for initial width increments and small rates (<5%) for subsequent width increments.

  13. Application Progress of Recombinant Attenuated Listeria monocytogenes in Tumor Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Yin Xiaojiao; Bai Lin; Yang Xu


    Much progress of application of bacterial vaccine in treatment and prevention of tumor was acquired,which showed broad prospect in clinical study of animals and humans. Listeria monocytogenes( L. monocytogenes) was considered much important by virtue of its special characteristic of biology and immunology.L. monocytogenes was ingested by professional or part-time phagocytes,survived and proliferated in the phagocytes under synergism of toxic factor secreted by itself,meanwhile,the cellular and humoral immune response was induced. Antigenic gene of specific tumor was loaded in the attenuated L. monocytogenes,which can enhance immune response of host cells. Effective cell targeted to enter tumor tissue and acted on tumor cells to induce apoptosis of tumor cells. Tumor degenerated not easy to reappear. Therefore,recombinant attenuated L. monocytogenes was a safe and effective anti-cancer vaccine vector. Now the work of researchers mainly focuses on solving practical problem in clinical application. Biological characteristics of L. monocytogenes,feasibility and superiority of L. monocytogenes as targeted vaccine vector,problem and prospect of L. monocytogenes in clinical application of anti-tumor were reviewed in this paper.

  14. Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus (United States)

    Ljungberg, Karl; Kümmerer, Beate M.; Gosse, Leslie; Dereuddre-Bosquet, Nathalie; Tchitchek, Nicolas; Hallengärd, David; García-Arriaza, Juan; Meinke, Andreas; Esteban, Mariano; Merits, Andres


    Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this virus is a serious threat to public health, but at present, there is no vaccine against this debilitating disease. We have recently developed a number of vaccine candidates, and here we have evaluated 3 of them in a nonhuman primate model. A single immunization with an attenuated strain of CHIKV (Δ5nsP3), a homologous prime-boost immunization with a DNA-launched RNA replicon encoding CHIKV envelope proteins (DREP-E), and a DREP-E prime followed by a recombinant modified vaccinia virus Ankara encoding CHIKV capsid and envelope (MVA-CE) boost all induced protection against WT CHIKV infection. The attenuated Δ5nsP3 virus proved to be safe and did not show any clinical signs typically associated with WT CHIKV infections such as fever, skin rash, lymphopenia, or joint swelling. These vaccines are based on an East/Central/South African strain of Indian Ocean lineage, but they also generated neutralizing antibodies against an isolate of the Asian genotype that now is rapidly spreading across the Americas. These results form the basis for clinical development of an efficacious CHIKV vaccine that generates both humoral and cellular immunity with long-term immunological memory. PMID:28352649

  15. Browning attenuates murine white adipose tissue expansion during postnatal development. (United States)

    Lasar, D; Julius, A; Fromme, T; Klingenspor, M


    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  16. The contribution of scattering to near-surface attenuation (United States)

    Pilz, Marco; Fäh, Donat


    The rapid decrease of the acceleration spectral amplitude at high frequencies has widely been modeled by the spectral decay factor kappa (κ). Usually, the path-corrected component of κ, often called κ0, is believed to be a local and frequency-independent site characteristic, in turn representing attenuation related to waves propagating vertically through the very shallow layers beneath the study site. Despite the known relevance of κ0 in a wide range of seismological applications, most methods for its calculation do not fully consider the influence of the scattering component. To account for the scattering component, we present a summary of statistical observations of the seismic wavefield at sites of the Swiss seismic networks. The intrinsic properties of the wavefield show a clear dependency on the local shallow subsoil conditions with differences in the structural heterogeneity of the shallow subsoil layers producing different scattering regimes. Such deviations from the ballistic behavior (i.e., direct waves that sample only distinct directions) are indicative for local structural heterogeneities and the associated level of scatter. Albeit the attenuation term related to scattering depends nonlinearly on the intrinsic term, the results indicate that the commonly used explanation for the high-frequency decay spectrum might not be appropriate but involving the amount of scattering might allow better constrained estimates of κ0.

  17. Nitrite attenuated peroxynitrite and hypochlorite generation in activated neutrophils. (United States)

    Ren, Xiaoming; Ding, Yun; Lu, Naihao


    Oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Peroxynitrite (ONOO(-)) and hypochlorite (OCl(-)) are formed in immune cells as a part of the innate host defense system, but excessive reactive oxygen species generation can cause progressive inflammation and tissue damage. It has been proven that through mediating nitric oxide (NO) homeostasis, inorganic nitrite (NO2(-)) shows organ-protective effects on oxidative stress and inflammation. However, the effects of NO2(-) on the function of immune cells were still not clear. The potential role of NO2(-) in modulating ONOO(-) and OCl(-) generation in neutrophil cells was investigated in this study. As an immune cell activator, lipopolysaccharide (LPS) increased both ONOO(-) and OCl(-) production in neutrophils, which was significantly attenuated by NO2(-). NO2(-) reduced superoxide (O2(·-)) generation via a NO-dependent mechanism and increased NO formation in activated neutrophils, suggesting a crucial role of O2(·-) in NO2(-)-mediated reduction of ONOO(-). Moreover, the reduced effect of NO2(-) on OCl(-) production was attributed to that NO2(-) reduced H2O2 production in activated neutrophils without influencing the release of myeloperoxidase (MPO), thus limiting OCl(-) production by MPO/H2O2 system. Therefore, NO2(-) attenuates ONOO(-) and OCl(-) formation in activated neutrophils, opening a new direction to modulate the inflammatory response.

  18. Galacto-oligosaccharides attenuate renal injury with microbiota modification. (United States)

    Furuse, Satoshi U; Ohse, Takamoto; Jo-Watanabe, Airi; Shigehisa, Akira; Kawakami, Koji; Matsuki, Takahiro; Chonan, Osamu; Nangaku, Masaomi


    Tubulointerstitial injury is central to the progression of end-stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto-oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham-operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS-treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury.

  19. Photon counting spectroscopic CT with dynamic beam attenuator

    CERN Document Server

    Atak, Haluk


    Purpose: Photon counting (PC) computed tomography (CT) can provide material selective CT imaging at lowest patient dose but it suffers from suboptimal count rate. A dynamic beam attenuator (DBA) can help with count rate by modulating x-ray beam intensity such that the low attenuating areas of the patient receive lower exposure, and detector behind these areas is not overexposed. However, DBA may harden the beam and cause artifacts and errors. This work investigates positive and negative effects of using DBA in PCCT. Methods: A simple PCCT with single energy bin, spectroscopic PCCT with 2 and 5 energy bins, and conventional energy integrating CT with and without DBA were simulated and investigated using 120kVp tube voltage and 14mGy air dose. The DBAs were modeled as made from soft tissue (ST) equivalent material, iron (Fe), and holmium (Ho) K-edge material. A cylindrical CT phantom and chest phantom with iodine and CaCO3 contrast elements were used. Image artifacts and quantification errors in general and mat...

  20. Attenuation of cryocooler induced vibration in spaceborne infrared payloads (United States)

    Veprik, A.; Twitto, A.


    Recent advancement of operational responsive space programs calls for a development of compact, reliable, low power and vibration free cryogenic cooling for sophisticated infrared payloads. The refrigeration in a typical closed cycle split Stirling linear cryocooler is achieved by a cyclic compression and expansion of a gaseous working agent due to a synchronized reciprocation of electro-dynamically and pneumatically actuated compressor and expander pistons. Attenuation of the cryocooler induced vibration usually relies on the concept of actively assisted momentum cancellation. In a typical dual-piston compressor this objective is achieved by actively synchronizing the motion of oppositely moving piston assemblies; a typical single-piston expander may be counterbalanced by a motorized counter-balancer. The above approach produces complexity, weight, size, high incurred costs and affects reliability. The authors analyze the case of passive attenuation the vibration export induced by the split Stirling linear cryocooler comprised of inline mounted single-piston compressor and expander. Placement of all the moving components onto a common axis results in a single axis consolidation of vibration export and enables use of single tuned dynamic absorber and low frequency vibration mount. From theoretical analysis and full-scale testing, the performance of such vibration protection arrangement is similar to known systems of active vibration cancellation.

  1. Recruitment-of-loudness effects of attenuative noise reduction algorithms (United States)

    Whitmal, Nathaniel; Vosoughi, Azadeh


    Hearing-impaired listeners have greater difficulty understanding speech in noise than normal-hearing listeners do. As a result, hearing aid users are often challenged by the inability of their hearing aids to improve intelligibility in noise. Several investigators have addressed this problem by using well-known signal processing methods (e.g., spectral subtraction, Wiener filtering) to enhance noise-corrupted speech. Unfortunately, these methods have failed to provide significant improvements in intelligibility. One possible explanation is the level-dependent nature of the attenuation that the algorithms impose on the speech. In the cases described above, this attenuation resembles the piecewise-linear input-output characteristic observed in certain recruitment-of-loudness simulators. The purpose of this study was to compare the intelligibility of processed speech with that expected for recruitment-of-loudness simulation. Trials of the CUNY Nonsense Syllable Test were conducted with 12 normal-hearing listeners, using syllables that were mixed with additive noise at SNRs of 6, 12, and 18 dB. Input-output characteristics for the signals were measured and used to determine the effective threshold shift imposed by the algorithms. Comparisons of measured intelligibility scores with articulation index-based intelligibility predictions indicate that the behavior of such noise reduction algorithms can be successfully modeled as a form of mild sensorineural hearing loss.

  2. Dispersion analysis of velocity and attenuation in Berea sandstone (United States)

    Winkler, Kenneth W.


    Ultrasonic velocity and attenuation measurements were made on dry, brine- and oil-saturated Berea sandstone and fused glass beads. The results for fused glass beads are consistent with the predictions of Biot theory. They indicate that as predicted, the Biot absorption/dispersion mechanism shifts to higher frequencies as the fluid viscosity increases. Similar data for Berea sandstone are not consistent with Biot theory, since observed velocities are generally higher than predicted. Using the Biot theory, we calculate low- and high-frequency velocities for the liquid-saturated samples. "Biot dispersion" is then defined as the percent difference between the low- and high-frequency limits. "Apparent dispersion" is defined as the percent difference between the measured ultrasonic velocity and the low-frequency Biot limit. Comparison of these two measures of dispersion gives insight into the presence of a non-Biot absorption/dispersion mechanism. Whenever the apparent dispersion is larger than the Biot dispersion, the extra dispersion is interpreted as being caused by a local flow relaxation. To be consistent with attenuation data, this relaxation must be distributed over at least five to six decades in frequency.

  3. Shock propagation and attenuation in high-power excimer lasers (United States)

    Holzwarth, Achim; Berger, Peter; Huegel, Helmut


    Theoretical and experimental investigations on the propagation, reflection, and attenuation of shock waves as they occur in excimer lasers have been performed. The numerical simulations have been carried out using a two-dimensional, unsteady finite difference scheme. The experimental setup is a piston driven shock tube with a rectangular cross section working in air at atmospheric pressure. The shocks were detected interferometrically as well as by means of pressure transducers. This shock tube allows us to investigate basic phenomena of shock diffraction which can be used to confirm the computational results in the range of weak shock waves. In particular, the influence of the shape of the wall contour on the reflection of shock waves has been investigated theoretically. The decay time of pressure and density perturbations differs for various wall configurations in such a way that short electrodes accelerate the attenuation as well as does a strong area increase in the vicinity of them. After each laser pulse there is a shock travelling into the laser channel. Experiments have been carried out on the reflection of this shock at a specially formed bend that is able to focus the shock into a muffling element.

  4. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice. (United States)

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard


    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial.

  5. Seismic attenuation due to wave-induced flow

    Energy Technology Data Exchange (ETDEWEB)

    Pride, S.R.; Berryman, J.G.; Harris, J.M.


    Analytical expressions for three P-wave attenuation mechanisms in sedimentary rocks are given a unified theoretical framework. Two of the models concern wave-induced flow due to heterogeneity in the elastic moduli at mesoscopic scales (scales greater than grain sizes but smaller than wavelengths). In the first model, the heterogeneity is due to lithological variations (e.g., mixtures of sands and clays) with a single fluid saturating all the pores. In the second model, a single uniform lithology is saturated in mesoscopic ''patches'' by two immiscible fluids (e.g., air and water). In the third model, the heterogeneity is at ''microscopic'' grain scales (broken grain contacts and/or micro-cracks in the grains) and the associated fluid response corresponds to ''squirt flow''. The model of squirt flow derived here reduces to proper limits as any of the fluid bulk modulus, crack porosity, and/or frequency is reduced to zero. It is shown that squirt flow is incapable of explaining the measured level of loss (10{sup -2} < Q{sup -1} < 10{sup -1}) within the seismic band of frequencies (1 to 10{sup 4} Hz); however, either of the two mesoscopic scale models easily produce enough attenuation to explain the field data.

  6. AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress. (United States)

    Ma, Yuedong; Huang, Huiling; Jiang, Jingzhou; Wu, Lingling; Lin, Chunxi; Tang, Anli; Dai, Gang; He, Jiangui; Chen, Yili


    AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.

  7. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin (United States)

    Borovikova, Lyudmila V.; Ivanova, Svetlana; Zhang, Minghuang; Yang, Huan; Botchkina, Galina I.; Watkins, Linda R.; Wang, Haichao; Abumrad, Naji; Eaton, John W.; Tracey, Kevin J.


    Vertebrates achieve internal homeostasis during infection or injury by balancing the activities of proinflammatory and anti-inflammatory pathways. Endotoxin (lipopolysaccharide), produced by all gram-negative bacteria, activates macrophages to release cytokines that are potentially lethal. The central nervous system regulates systemic inflammatory responses to endotoxin through humoral mechanisms. Activation of afferent vagus nerve fibres by endotoxin or cytokines stimulates hypothalamic-pituitary-adrenal anti-inflammatory responses. However, comparatively little is known about the role of efferent vagus nerve signalling in modulating inflammation. Here, we describe a previously unrecognized, parasympathetic anti-inflammatory pathway by which the brain modulates systemic inflammatory responses to endotoxin. Acetylcholine, the principle vagal neurotransmitter, significantly attenuated the release of cytokines (tumour necrosis factor (TNF), interleukin (IL)-1β, IL-6 and IL-18), but not the anti-inflammatory cytokine IL-10, in lipopolysaccharide-stimulated human macrophage cultures. Direct electrical stimulation of the peripheral vagus nerve in vivo during lethal endotoxaemia in rats inhibited TNF synthesis in liver, attenuated peak serum TNF amounts, and prevented the development of shock.

  8. Desferrioxamine attenuates minor lung injury following surgical acute liver failure. (United States)

    Kostopanagiotou, G G; Kalimeris, K A; Arkadopoulos, N P; Pafiti, A; Panagopoulos, D; Smyrniotis, V; Vlahakos, D; Routsi, C; Lekka, M E; Nakos, G


    Acute liver failure (ALF) can be complicated by lung dysfunction. The aim of this study was to test the hypothesis that inhibition of oxidative stress through iron chelation with desferrioxamine (DFX) attenuates pulmonary injury caused by ALF. 14 adult female domestic pigs were subjected to surgical devascularisation of the liver and were randomised to a study group (DFX group, n = 7), which received post-operative intravenous infusion of DFX (14.5 mg x kg(-1) x h(-1) for the first 6 h post-operatively and 2.4 mg x kg(-1) x h(-1) until completion of 24 h), and a control group (n = 7). Post-operative lung damage was evaluated by histological and bronchoalveolar lavage fluid (BALF) analysis. DFX resulted in reduced BALF protein levels and tissue phospholipase (PL)A(2) activity. Plasma malondialdehyde and BALF nitrate and nitrite concentrations were lower, while catalase activity in the lung was higher after DFX treatment. PLA(2), platelet-activating factor acetylhydrolase and total cell counts in BALF did not differ between groups. Histological examination revealed reduced alveolar collapse, pneumonocyte necrosis and total lung injury in the DFX-treated animals. DFX reduced systemic and pulmonary oxidative stress during ALF. The limited activity of PLA(2) and the attenuation of pneumonocyte necrosis could represent beneficial mechanisms by which DFX improves alveolar-capillary membrane permeability and prevents alveolar space collapse.

  9. Calculation of dose in homogeneous phantoms for partially attenuated photon beams

    Energy Technology Data Exchange (ETDEWEB)

    El-Khatib, E.; Podgorsak, E.B.; Pla, C.


    Measured and calculated dose distributions under attenuators, which are of smaller cross-sectional dimensions than the radiation field, are presented. The study was performed on a 4-MV linac at a source--surface distance of 120 cm on the beam central axis in a water phantom for several thicknesses and cross sections of lead attenuators. Dose correction factors, which are used to multiply the open beam data to get dose distributions under partial attenuators, depend strongly on attenuator parameters and on depths in phantom. A method to calculate dose correction factors for any combination of attenuator parameters and any phantom depth is presented. The calculated dose distributions under partial attenuators agree well with measured data, which indicates that the method can be applied in clinical situations.

  10. On the Attenuation of Neutrons and Photons in a Duct Filled with a Helical Plug

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, E.; Krell, Aa.


    Neutron and gamma ray attenuation has been studied in a cylindrical duct, length/diam. ratio 7, partly (36 vol.%) filled by a helical (screw-like) plug with adjustable number of turns. The total neutron leakage through the duct decreased by a factor of six from zero to 0.5 turn, and by an additional factor of three from 0.5 to 2 turns (saturation value). The leakage with less than 0.5 turn is governed by fast flux and above 0.5 turn by epithermal flux. It is observed that the attenuation calculation in a homogenized, infinite material combined with the predicted attenuation in a duct give the measured saturation attenuation. The length coordinates used must be slightly modified in this case. The attenuation of gamma in the saturation case (3 turns) equals that predicted without the duct attenuation in a homogenized infinite material.

  11. Influence of attenuation on acoustic emission signals in carbon fiber reinforced polymer panels. (United States)

    Asamene, Kassahun; Hudson, Larry; Sundaresan, Mannur


    Influence of attenuation on acoustic emission (AE) signals in Carbon Fiber Reinforced Polymer (CFRP) crossply and quasi-isotropic panels is examined in this paper. Attenuation coefficients of the fundamental antisymmetric (A0) and symmetric (S0) wave modes were determined experimentally along different directions for the two types of CFRP panels. In the frequency range from 100 kHz to 500 kHz, the A0 mode undergoes significantly greater changes due to material related attenuation compared to the S0 mode. Moderate to strong changes in the attenuation levels were noted with propagation directions. Such mode and frequency dependent attenuation introduces major changes in the characteristics of AE signals depending on the position of the AE sensor relative to the source. Results from finite element simulations of a microscopic damage event in the composite laminates are used to illustrate attenuation related changes in modal and frequency components of AE signals.

  12. Properties of sound attenuation around a two-dimensional underwater vehicle with a large cavitation number (United States)

    Ye, Peng-Cheng; Pan, Guang


    Due to the high speed of underwater vehicles, cavitation is generated inevitably along with the sound attenuation when the sound signal traverses through the cavity region around the underwater vehicle. The linear wave propagation is studied to obtain the influence of bubbly liquid on the acoustic wave propagation in the cavity region. The sound attenuation coefficient and the sound speed formula of the bubbly liquid are presented. Based on the sound attenuation coefficients with various vapor volume fractions, the attenuation of sound intensity is calculated under large cavitation number conditions. The result shows that the sound intensity attenuation is fairly small in a certain condition. Consequently, the intensity attenuation can be neglected in engineering. Project supported by the National Natural Science Foundation of China (Grant Nos. 51279165 and 51479170) and the National Defense Basic Scientific Research Program of China (Grant No. B2720133014).


    Institute of Scientific and Technical Information of China (English)

    ChengJiulong; LiLi; LiuTianfang; LiDechun


    Proceeding from wave equations, the paper strictly deduced the dispersion relation equation of Love-type channel waves in Standard Linear Solid model. The equation is a complex one with its real part signifying the dispersion characteristics of the channel wave while the imaginary part, the attenuation characteristics. In calculating the attenuation value, the author has set up a mathematical model of a horizontal symmetric sequence (a three layer sequence of rock-coal-rock), given out some physical parameters, and adopted the dichotomy method that is more often used inroot resolving of an equation. The calculation indicates that the influence of nonelastic absorption on the attenuation of the propagation of channel wave varies with thefrequency. In the frequency band of the Airy phase, the attenuation increases steeplike, which is unfavorable for the channel wave seismic prospecting. The study ofchannel wave attenuation has provided a theoretical basis for the compensation of attenuation.

  14. A depolarization and attenuation experiment using the COMSTAR and CTS satellites (United States)

    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.


    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.

  15. The Gas Flow from the Gas Attenuator to the Beam Line

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D.D.


    The gas leak from the gas attenuator to the main beam line of the Linac Coherent Light Source has been evaluated, with the effect of the Knudsen molecular beam included. It has been found that the gas leak from the gas attenuator of the present design, with nitrogen as a working gas, does not exceed 10{sup -5} torr x l/s even at the highest pressure in the main attenuation cell (20 torr).

  16. An experimental model of ice floe induced attenuation of ocean waves

    CERN Document Server

    Toffoli, Alessandro; Bennetts, Luke G; Meylan, Michael H; Cavaliere, Claudio; Babanin, Alexandr


    An experimental model of ocean wave attenuation due to interactions with an ice floe is presented. Evolution of mechanically-generated, regular waves is monitored in front and in the lee of a solitary, square floe, made of a synthetic material. Results confirm dependence of attenuation on the period of the incident wave. Results also indicate dependence of attenuation on the depth of wave overwash on the floe.

  17. On the attenuation of x-rays and gamma-rays in dilute solutions

    DEFF Research Database (Denmark)

    Gerward, Leif


    The theory of X-ray and gamma-ray attenuation in solutions is developed. The rule of mixture for the calculation of mass and linear attenuation coefficients is elaborated in the general case as well as in the limit of extreme dilution. The validity of the latter approximation is illustrated...... by the attenuation of 17.443 keV X-rays in aqueous solutions of NaCl. Copyright (C) 1996 Elsevier Science Ltd...

  18. Whole-body PET/MRI: The effect of bone attenuation during MR-based attenuation correction in oncology imaging

    DEFF Research Database (Denmark)

    Aznar, M.C.; Sersar, Rachida; Saabye, J.;


    and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. Methods: Twenty oncology...... patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET......(/MRI) images were reconstructed (AW-OSEM, 3 iterations, 21 subsets, 4mm Gaussian) following routine MR-AC and MR-AC based on four modified attenuation maps. These modified attenuation maps were created for each patient by non-linear co-registration of the CT images to the orgMR-AC images, and adding CT bone...

  19. Different atmospheric effects causing FSO link attenuation: experimental results and modelling in Czech Republic (United States)

    Fiser, Ondrej; Brazda, Vladimir; Wilfert, Otakar


    The four year FSO link attenuation measurement concurrently with most important meteorological parameters was performed at our mountain observatory Milesovka. In this contribution we summarize and classify different atmospheric phenomena after the FSO link attenuation quantity. For all particular phenomena the CD curves, typical events and simple dependences on relevant atmospheric parameter(s) are presented. We consider the following phenomena (approximate specific attenuation in dB/km in brackets): 1. Fog and cloud (hundreds dB/km) 2. Rain and snow (tens dB/km) 3. Atmospheric turbulence (unit dB) 4. Clear air attenuation due to water vapour (unit dB or less)

  20. Attenuation coefficient determination of printed ABS and PLA samples in diagnostic radiology standard beams (United States)

    Veneziani, G. R.; Corrêa, E. L.; Potiens, M. P. A.; Campos, L. L.


    IAEA code of practice TRS-457 states that standard phantoms should offer the same primary attenuation and scatter production as relevant body section of a representative patient. Material cost, availability and dimensional stability must also be considered. The goal of this study is to determine the attenuation coefficient of printed ABS and PLA samples in standard X-ray beams, verifying if phantoms printed with these materials could be an easier-handle substitute for PMMA, enabling the creation of different designs in an easier and cheaper way. Results show that PMMA presents higher attenuation coefficient, followed by PLA and ABS, which means that thinner PMMA layer creates higher radiation attenuation.

  1. Adjustable character of microwave attenuation in BaTiO3 electrorheological fluids

    Institute of Scientific and Technical Information of China (English)


    The behavior of microwave attenuation in BaTiO3 electrorheological fluids is studied when considering microwave propagation in the directions perpendicular and parallel to the particle chains, respectively. In the former case, the microwave attenuation increases with field strength when the particle concentration is low, and the increase of the particle concentration can also increase the microwave attenuation. However, when the particle concentration exceeds a critical value, the attenuation will first increase then decrease with field strength. At the same time, the higher the field strength, the greater the change of microwave attenuation. Moreover, there is a saturation field strength. When the field strength is lower than the saturated one, the change of microwave attenuation is fast. On the other hand, in the case of microwave propagation parallel to the particle chains, the microwave attenuation increases with the field strength monotonously. In addition, the variation of microwave attenuation with the field strength shows relaxation effect. The adjustable character of microwave attenuation in BaTiO3 ER fluids can be attributed to the dielectric changes resulting from the field-induced-structural transformation and the polarization of BaTiO3.

  2. Attenuation coefficient determination of printed ABS and PLA samples in diagnostic radiology standard beams

    Energy Technology Data Exchange (ETDEWEB)

    Veneziani, G.R.; Correa, E.L.; Potiens, M.P.A.; Campos, L.L., E-mail: [Instituto de Pesquisas Energeticas e Nucleres (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)


    IAEA code of practice TRS-457 states that standard phantoms should offer the same primary attenuation and scatter production as relevant body section of a representative patient. Material cost, availability and dimensional stability must also be considered. The goal of this study is to determine the attenuation coefficient of printed ABS and PLA in standard X-ray beams, verifying if phantoms printed with these materials could be an easier-handle substitute for PMMA, enabling the creation of different designs in an easier and cheaper way. Results show that PMMA presents higher attenuation coefficient, followed by PLA and ABS, which means that thinner PMMA layer creates higher radiation attenuation. (author)

  3. Silicon-on-Insulator Based Electro-optic Variable Optical Attenuator with a Series Structure

    Institute of Scientific and Technical Information of China (English)

    HE Yue-Jiao; LI Fang; LIU Yu-Liang


    An electro-optic variable optical attenuator in silicon-on-insulator is designed and fabricated. A series structure is used to improve the device efficiency. Compared to the attenuator in the single p-i-n diode structure in the same modulating length, the attenuation range of the device in the series structure improves 2-3 times in the same injecting current density, while the insertion loss is not affected. The maximum dynamic attenuation of the device is greater than 30dB. The response frequency is obtained to be about 2MHz.

  4. Results of 11.7-GHz CTS rain attenuation measurements at Waltham, Massachusetts (United States)

    Nackoney, O. G.; Davidson, D.


    Satellite-to-earth rain attenuation at 11.7 GHz was measured at Waltham, Massachusetts (42.4 deg N, 71.3 deg W; elevation angle 25 deg), utilizing the Communications Technology Satellite beacon signal. This paper summarizes 29 months of measurements by presenting attenuation and rain rate distributions, fade duration distributions, fading rate distributions, and statistical relationships between attenuation and rain rate. For a two-year statistical base, rain attenuation exceeded 9.7 dB for 0.01 percent of the time and 2.0 dB for 0.1 percent of the time.

  5. Robust Stabilization, Robust Performance, and Disturbance Attenuation for Uncertain Linear Systems (United States)


    the following Riccati equation: [ - ] B Tp+!I+ 1 CTC+Q=O. (7) Then, a disturbance-attenuation robust- stabilizing control law is given by u(t) = K z(t...disturbance-attenuation robust- stabilizing control law with the attenuation constant 6 is given by u(t) = K x(t), where K = -- BT P with 7> 1/2... stabilizing control law with the attenuation constant 6 is given by u(t) = K z(t), where K = -7 BT P with 7> - 1/2. Furthermore, the state-feedback

  6. Natural attenuation of mining pollutants in the transboundary Save River (United States)

    Meck, M. L.; Masamba, W. R. L.; Atlhopheng, J.; Ringrose, S.

    The objective of the study was to investigate the role played by the natural environment in protecting the transboundary Save River from the impacts of metals derived from phosphate mining at Dorowa. The study is a follow up study from a previous one that noted that there is natural attenuation at Dorowa. Water and sediment samples were collected in the Save River and the streams that drain the Dorowa dumps. Inductively coupled plasma mass spectrometry (ICP-MS) was used to analyze the cations (Na +, K +, Ca 2+, Mg 2+, Cu 2+, Co 2+, Fe 2+, Ni 2+, Zn 2+, Pb 2+, Sn 2+, Mn 2+, Cd 2+) in the samples. Major anions Cl -, SO42- and NO3- were analyzed by standard chromatography whilst CO32- and HCO3- were determined by titration. pH was measured on site. Geochemical modeling of the water composition was conducted with Visual Minteq. The results show that natural attenuation is being achieved through precipitation of solids from the water and subsequent deposition onto the sediments. Six of the metals are almost completely precipitated (Cu 99.99%, Fe 99.39%, Ni 91.24%, Pb 99.87%, Sn 99.99% and Zn 88.66%). However Mn, Co and Cd remain in solution. Thus the natural environment is protecting the Save River which is a transboundary river from the impacts of mining through precipitation of the metals. Users downstream of Dorowa mine are therefore not being affected by mining pollution. This study demonstrates that besides being a legitimate and important user of water, the natural environment can also play a significant role in protecting water quality by attenuating metals naturally. By analyzing costs incurred in several places where alternative methods are employed to remediate metal related pollution the study concludes that natural remediation at Dorowa is saving the nation in environmental costs. Therefore the paper advocates for appreciation of the role that the natural environment plays in protecting ecosystems from the impact of human developments and environmental costs

  7. Oxymatrine liposome attenuates hepatic fibrosis via targeting hepatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    Ning-Li Chai; Qiang Fu; Hui Shi; Chang-Hao Cai; Jun Wan; Shi-Ping Xu; Ben-Yan Wu


    AIM:To investigate the potential mechanism of ArgGly-Asp (RGD) peptide-labeled liposome loading oxymatrine (OM) therapy in CCl4-induced hepatic fibrosis in METHODS:We constructed a rat model of CCl4-induced hepatic fibrosis and treated the rats with different formulations of OM.To evaluate the antifibrotic effect of OM,we detected levels of alkaline phosphatase,hepatic histopathology (hematoxylin and eosin stain and Masson staining) and fibrosis-related gene expression of matrix metallopeptidase (MMP)-2,tissue inhibitor of metalloproteinase (TIMP)-1 as well as type Ⅰ procollagen via quantitative real-time polymerase chain reaction.To detect cell viability and apoptosis of hepatic stellate cells (HSCs),we performed 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay and flow cytometry.To reinforce the combination of oxymatrine with HSCs,we constructed fluorescein-isothiocyanate-conjugated Arg-Gly-Asp peptide-labeled liposomes loading OM,and its targeting of HSCs was examined by fluorescent microscopy.RESULTS:OM attenuated CCl4-induced hepatic fibrosis,as defined by reducing serum alkaline phosphatase (344.47 ± 27.52 U/L vs 550.69 ± 43.78 U/L,P < 0.05),attenuating liver injury and improving collagen deposits (2.36% ± 0.09% vs 7.70% ± 0.60%,P < 0.05) and downregulating fibrosis-related gene expression,that is,MMP-2,TIMP-1 and type Ⅰ procollagen (P < 0.05).OM inhibited cell viability and induced apoptosis of HSCs in vitro.RGD promoted OM targeting of HSCs and enhanced the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51 ± 19.55 U/L vs 344.47 ± 27.52 U/L,P < 0.05),liver injury,collagen deposits (0.26% ± 0.09% vs 2.36% ± 0.09%,P < 0.05) and downregulating fibrosis-related gene expression,that is,MMP-2,TIMP-1 and type Ⅰ procollagen (P < 0.05).Moreover,in vitro assay demonstrated that RGD enhanced the effect of OM on HSC viability and apoptosis.CONCLUSION:OM attenuated hepatic fibrosis by

  8. Inhalation of hydrogen gas attenuates ouabaininduced auditory neuropathy in gerbils

    Institute of Scientific and Technical Information of China (English)

    Juan QU; Yun-na GAN; Ke-liang XIE; Wen-bo LIU; Ya-fei WANG; Ren-yi HEI; Wen-juan MI; Jian-hua QIU


    Aim:Auditory neuropathy (AN)is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells.This study was designed to investigate whether treatment with molecular hydrogen (H2),which can remedy damage in various organs via reducing oxidative stress,inflammation and apoptosis,is beneficial to ouabain-induced AN in gerbils.Methods:AN model was made by local application of ouabain (1 mmoVL,20 mL)to the round window membrane in male Mongolian gerbils.H2 treatment was given twice by exposing the animals to H2 (1%,2%,and 4%)for 60 min at 1 h and 6 h after ouabain application.Before and 7 d after ouabain application,the hearing status of the animals was evaluated using the auditory brainstem response (ABR)approach,the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE).Seven days after ouabain application,the changes in the cochleae,especially the spiral ganglion neurons (SGNs),were morphologically studied.TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs.Results:Treatment with H2 (2% and 4%)markedly attenuated the click and tone burst-evoked ABR threshold shift at 4,8,and 16 kHz in ouabain-exposed animals.Neither local ouabain application,nor H2 treatment changed the amplitude of DPOAE at 4,8,and 16 kHz.Morphological study showed that treatment with H2 (2%)significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals.Furthermore,ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea,which was significantly attenuated by the H2 treatment.However,ouabain did not change the morphology of cochlear hair cells.Conclusion:The results demonstrate that H2 treatment is beneficial to ouabain-induced AN via reducing apoptosis.Thus,H2 might be a potential agent for treating hearing impairment in AN patients.

  9. Developing active noise control systems for noise attenuation in ducts (United States)

    Campos, Rosely V.; Ivo, Rodrigo C.; Medeiros, Eduardo B.


    The present work describes some of the research effort on Active Noise Control (ANC) being jointly developed by the Catholic University of Minas Gerais (PUC-MINAS) and the Federal University of Minas Gerais (UFMG). Considerations about the implementation of Digital Signal Processing for noise control in ducts has been presented. The objective is to establish a study on Active Noise Control in ducts combining geometry and acoustic parameters modification together with adaptive digital filtering implementation. Both algorithm and digital signal processing details are also discussed. The main results for a typical application where real attenuation has been obtained are presented and considered according to their use in developing real applications. The authors also believe that the present text should provide an interesting overview for both designers and students concerned about Active Noise Control in ducts. (To be presented in Portuguese.)

  10. Shock Wave Attenuation Using Foam Obstacles: Does Geometry Matter?

    Directory of Open Access Journals (Sweden)

    Hongjoo Jeon


    Full Text Available A shock wave impact study on open and closed cell foam obstacles was completed to assess attenuation effects with respect to different front face geometries of the foam obstacles. Five different types of geometries were investigated, while keeping the mass of the foam obstacle constant. The front face, i.e., the side where the incident shock wave impacts, were cut in geometries with one, two, three or four convergent shapes, and the results were compared to a foam block with a flat front face. Results were obtained by pressure sensors located upstream and downstream of the foam obstacle, in addition to high-speed schlieren photography. Results from the experiments show no significant difference between the five geometries, nor the two types of foam.

  11. Nitrite attenuated hypochlorous acid-mediated heme degradation in hemoglobin. (United States)

    Lu, Naihao; Li, Jiayu; Ren, Xiaoming; Tian, Rong; Peng, Yi-Yuan


    Hypochlorous acid (HOCl) is elevated in many inflammatory diseases and causes the accumulation of free iron. Through the Fenton reaction, free iron has the ability to generate free radicals and subsequently is toxic. Recent studies have demonstrated that HOCl participates in heme destruction of hemoglobin (Hb) and free iron release. In this study, it was showed that nitrite (NO2(-)) could prevent HOCl-mediated Hb heme destruction and free iron release. Also, NO2(-) prevented HOCl-mediated loss of Hb peroxidase activity. After the NO2(-)/HOCl treatment, Tyr 42 in α-chain was found to be nitrated in Hb, attenuating the electron transferring abilities of phenolic compounds. The protective effects of NO2(-) on HOCl-induced heme destruction were attributed to its reduction of ferryl Hb and/or direct scavenging of HOCl. Therefore, NO2(-) could show protective effects in some inflammatory diseases by preventing HOCl-mediated heme destruction of hemoproteins and free iron release.

  12. Attenuation Coefficient of Single-Mode Periodic Waveguides (United States)

    Baron, A.; Mazoyer, S.; Smigaj, W.; Lalanne, P.


    It is widely accepted that, on ensemble average, the transmission T of guided modes decays exponentially with the waveguide length L due to small imperfections, leading to the important figure of merit defined as the attenuation-rate coefficient α=-⟨ln⁡(T)⟩/L. In this Letter, we evidence that the exponential-damping law is not valid in general for periodic monomode waveguides, especially as the group velocity decreases. This result, that contradicts common beliefs and experimental practices aiming at measuring α, is supported by a theoretical study of light transport in the limit of very small imperfections, and by numerical results obtained for two waveguide geometries that offer contrasted damping behaviors.

  13. A quasi-unidimensional granular chain to attenuate impact. (United States)

    Machado, L P; Rosas, A; Lindenberg, K


    We study via numerical simulations a granular chain not only with decreasing radii (forward tapering) in geometric progression, but also decorated with grains positioned on the top and bottom of the chain, without altering its original length. The decorating grains act as an auxiliary chain which traps part of the energy and linear momentum, both propagating as a pulse due to disturbances produced at the end of the chain. Thus, this configuration optimizes the impact attenuation and aligns the chain naturally (by symmetry) which facilitates the construction of the experimental setup. Furtheremore, since the decorating grain radii increase along the chain, this new type of chain is necessarily short in order to avoid precompression. Nevertheless, even with short chains, it is possible to mitigate impacts almost completely.

  14. Variants of Sporothrix schenckii with attenuated virulence for mice. (United States)

    de Lima, Renata Ferretti; Schäffer, Guido Vidal; Borba, Cintia de Moraes


    Strains of Sporothrix schenckii preserved under mineral oil were examined for virulence in BALB/c mice. The mice were inoculated with S. schenckii conidia and development of cutaneous lesions, signs of inactivity, weight loss, survival rates, number of viable yeast cells in lung and spleen, splenomegaly and organ lesions were evaluated. After intravenous injection of 7.5 x 10(6) conidia, two of five S. schenckii strains were unable to induce systemic disease and to kill the mice, only producing cord-like lesions on the tail that regressed with mouse maturation. Very small numbers of viable cells isolated from the spleen confirmed the lower invasive ability of these strains when compared with other strains studied here. These results suggest a relationship between the attenuation of virulence and the storage method under mineral oil after long periods of time.

  15. Temperature dependence of radiation-induced attenuation of optical fibers

    Institute of Scientific and Technical Information of China (English)

    Jingming Song; Jianhua Guo; Xueqin Wang; Jing Jin


    We investigate the temperature dependence of radiation-induced attenuation (RIA) at 1 310 nm for a Ge/P co-doped fiber after a steady-state γ-ray irradiation.A γ irradiation facility 60Co source is used to irradiate the fiber at a dose rate of 0.5 Gy/min,satisfying a total dose of 100 Gy.The test temperature ranges from-40 to 60 ℃ by 20 ℃,and the RIA of the fiber is obtained using a power measuring device.The experimental result demonstrates that RIA exhibits a steady,monotonic,and remarkable temperature dependence after approximately 48 h of accelerated annealing at 70 ℃.The optical fiber irradiated with a high dose and annealed sufficiently can be used as a temperature sensor.

  16. Live attenuated varicella vaccine use in immunocompromised children and adults. (United States)

    Gershon, A A; Steinberg, S P; Gelb, L


    Live attenuated varicella vaccine has been administered to 307 children with leukemia in remission and to 86 healthy adults. The vaccine was well tolerated and immunogenic. The major side effect in leukemic children receiving maintenance chemotherapy was development of a vaccine-associated rash. Vaccinees in whom a rash developed were potentially somewhat infectious to others about 1 month after immunization. Vaccination was not associated with an increase in the incidence of herpes zoster or in relapse of leukemia. Vaccination provided excellent protection against severe varicella. It was associated with a significant decrease in the attack rate of chickenpox following an intimate exposure to varicella-zoster virus, conferring about 80% protection in leukemic children. The cases of breakthrough varicella that occurred were mild. Thus, the vaccine may either prevent or modify varicella in high-risk individuals. It may also have use for prevention of nosocomial varicella.

  17. On the intergalactic attenuation for high-z galaxies (United States)

    Inoue, Akio K.


    Even after the cosmic reionization, neutral hydrogen still remains in the intergalactic space. These intervening hydrogen atoms absorb the radiation from high-z objects and make a numerous absorption lines, the so-called Lyman alpha forest, in the spectra of the objects. To know the absorption amount as a function of redshift is essentially important for studies of the high-z objects, for example, to predict how much reddening occurs in the spectra of the high-z galaxies, which is used as the so-called Lyman break technique. The current standard model for the intergalactic attenuation is Madau (1995). However, the intergalactic absorbers' statistics, which is the ingredient of the model, is largely updated during two decades after Madau (1995). Here, I present an update of this kind model. I also show a preliminary result of the absorption excess in a proto-cluster environment found in a composite spectrum of galaxies behind the proto-cluster.

  18. Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne;


    BACKGROUND: We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role...... and 54, we measured body weight, mean arterial blood pressure (MAP), serum creatinine, whole blood trough CsA, plasma Ang II, haemoglobin and liver function parameters. Magnetic resonance imaging was used to estimate kidney length, volume, relative glomerular filtration rate (rGFR) and renal blood flow...... (RBF). Kidney tissue biopsies were used for conventional histological examination. RESULTS: Plasma Ang II levels were significantly higher during telmisartan treatment. Interstitial fibrosis and glomerulosclerosis occurred in both groups, but were attenuated in the telmisartan-treated pigs (P = 0...

  19. Antioxidant treatment attenuates lactate production in diabetic nephropathy

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Nielsen, Per Mose; Stokholm Nørlinger, Thomas


    The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying......-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2......-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels...

  20. Vibration Attenuation in Rotating Machines Using Smart Spring Mechanism

    Directory of Open Access Journals (Sweden)

    Aldemir Ap. Cavalini


    Full Text Available This paper proposes a semiactive vibration control technique dedicated to a rotating machine passing by its critical speed during the transient rotation, by using a Smart Spring Mechanism (SSM. SSM is a patented concept that, using an indirect piezoelectric (PZT stack actuation, changes the stiffness characteristics of one or more rotating machine bearings to suppress high vibration amplitudes. A Genetic Algorithm (GA optimization technique is used to determine the best design of the SSM parameters with respect to performance indexes associated with the control efficiency. Additionally, the concept of ecologically correct systems is incorporated to this work including the PZT stack energy consumption in the indexes considered for the optimization process. Simulation carried out on Finite Element Method (FEM model suggested the feasibility of the SSM for vibration attenuation of rotors for different operating conditions and demonstrated the possibility of incorporating SSM devices to develop high-performance ecologic control systems.

  1. Memory effects in attenuation and amplification quantum processes (United States)

    Lupo, Cosmo; Giovannetti, Vittorio; Mancini, Stefano


    With increasing communication rates via quantum channels, memory effects become unavoidable whenever the use rate of the channel is comparable to the typical relaxation time of the channel environment. We introduce a model of a bosonic memory channel, describing correlated noise effects in quantum-optical processes via attenuating or amplifying media. To study such a channel model, we make use of a proper set of collective field variables, which allows us to unravel the memory effects, mapping the n-fold concatenation of the memory channel to a unitarily equivalent, direct product of n single-mode bosonic channels. We hence estimate the channel capacities by relying on known results for the memoryless setting. Our findings show that the model is characterized by two different regimes, in which the cross correlations induced by the noise among different channel uses are either exponentially enhanced or exponentially reduced.

  2. Memory effects in attenuation and amplification quantum processes

    CERN Document Server

    Lupo, Cosmo; Mancini, Stefano


    With increasing communication rates via quantum channels, memory effects become unavoidable whenever the use rate of the channel is comparable with the typical relaxation time of the channel environment. We then introduce a model of bosonic memory channel, describing correlated noise effects in quantum optical processes via attenuating or amplifying media. To study such a channel model we make use of a proper set of collective field variables, which allows us to unravel the memory effects, mapping the n-fold concatenation of the memory channel to a, unitarily equivalent, direct product of n single-mode bosonic channels. We hence estimate the channel capacities by relying on known results for the memoryless setting. Our findings show that the model is characterized by two different regimes, in which the cross-correlations induced by the noise among different channel uses are either exponentially enhanced or exponentially reduced.

  3. Melatonin attenuates β-amyloid-induced inhibition of neurofilament expression

    Institute of Scientific and Technical Information of China (English)

    Ying-chun ZHANG; Ze-fen WANG; Qun WANG; Yi-peng WANG; Jian-zhi WANG


    AIM: To explore the effect of β-amyloid (Aβ) on metabolism of cytoskeletal protein neurofilament, and search for effective cure to the lesion. METHODS: Wild type murine neuroblastoma N2a (N2awt) and N2a stably transfected with wild type amyloid precursor protein (N2aAPP) were cultured. Sandwich ELISA, immunocytochemistry, and Western blot were used respectively to measure the level of Aβ, the expression and phosphorylation of neurofilament proteins. RESULTS: The immunoreactivity of neurofilament protein was almost abolished in N2aAPP, which beard a significantly higher level of Aβ. Melatonin effectively decreased the level of Aβ, and restored partially the level of phosphorylated and non-phosphorylated neurofilament in N2aAPP. CONCLUSION: Overproduction of Aβ inhibits neurofilament expression, and melatonin attenuates the Aβ-induced lesion in cytoskeletal protein.

  4. Modeling classic attenuation regulation of gene expression in bacteria. (United States)

    Lyubetsky, Vassily A; Pirogov, Sergey A; Rubanov, Lev I; Seliverstov, Alexander V


    A model is proposed primarily for the classical RNA attenuation regulation of gene expression through premature transcription termination. The model is based on the concept of the RNA secondary structure macrostate within the regulatory region between the ribosome and RNA-polymerase, on hypothetical equation describing deceleration of RNA-polymerase by a macrostate and on views of transcription and translation initiation and elongation, under different values of the four basic model parameters which were varied. A special effort was made to select adequate model parameters. We first discuss kinetics of RNA folding and define the concept of the macrostate as a specific parentheses structure used to construct a conventional set of hairpins. The originally developed software that realizes the proposed model offers functionality to fully model RNA secondary folding kinetics. Its performance is compared to that of a public server described in Ref. 1. We then describe the delay in RNA-polymerase shifting to the next base or its premature termination caused by an RNA secondary structure or, herefrom, a macrostate. In this description, essential concepts are the basic and excited states of the polymerase first introduced in Ref. 2: the polymerase shifting to the next base can occur only in the basic state, and its detachment from DNA strand - only in excited state. As to the authors' knowledge, such a model incorporating the above-mentioned attenuation characteristics is not published elsewhere. The model was implemented in an application with command line interface for running in batch mode in Windows and Linux environments, as well as a public web server.(3) The model was tested with a conventional Monte Carlo procedure. In these simulations, the estimate of correlation between the premature transcription termination probability p and concentration c of charged amino acyl-tRNA was obtained as function p(c) for many regulatory regions in many bacterial genomes, as well as

  5. Galacto‐oligosaccharides attenuate renal injury with microbiota modification (United States)

    Furuse, Satoshi U.; Ohse, Takamoto; Jo‐Watanabe, Airi; Shigehisa, Akira; Kawakami, Koji; Matsuki, Takahiro; Chonan, Osamu; Nangaku, Masaomi


    Abstracts Tubulointerstitial injury is central to the progression of end‐stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto‐oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham‐operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS‐treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury. PMID:24994892

  6. Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis (United States)

    Lin, Yen-You; Jean, Yen-Hsuan; Lee, Hsin-Pai; Lin, Sung-Chun; Pan, Chieh-Yu; Chen, Wu-Fu; Wu, Shu-Fen; Su, Jui-Hsin; Tsui, Kuan-Hao; Sheu, Jyh-Horng; Sung, Ping-Jyun; Wen, Zhi-Hong


    Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA. PMID:28067799

  7. Attenuated response to repeated daily ozone exposures in asthmatic subjects

    Energy Technology Data Exchange (ETDEWEB)

    Gong, H. Jr.; Linn, W.S. [Rancho Low Amigos Medical Center, Downey, CA (United States); McManus, M.S. [Univ. of California, Los Angeles, CA (United States)


    The development of attenuated response ({open_quotes}tolerance{close_quotes}) to daily ozone (O{sub 3}) exposures in the laboratory is well established in healthy adult volunteers. However, the capability of asthmatics to develop tolerance during multiday ozone exposures in unclear. We exposed 10 adult volunteers with mild asthma to 0.4 ppm O{sub 3} in filtered air for 3 h/d on 5 consecutive d. Two similar filtered-air exposures during the preceding week served as controls. Follow-up O{sub 3} exposures were performed 4 and 7 d after the most recent consecutive exposure. All exposures were performed in an environmental chamber at 31 {degrees}C and 35% relative humidity. The subjects performed moderate exercise (mean ventilation rate of 32 l/min) for 15 min of each half-hour. Responses were measured with spirometry and symptom evaluations before and after each exposure, and a bronchial reactivity test (methacholine challenge) was conducted after each exposure. All response measurements showed clinically and statistically significant day-to-day variation. Symptom and forced-expiratory-volume-in-1-s responses were similarly large on the 1st and 2nd O{sub 3} exposure days, after which they diminished progressively, approaching filtered air response levels by the 5th consecutive O{sub 3} day. This tolerance was partially lost 4 and 7 d later. Bronchial reactivity peaked after the first O{sub 3} exposure and remained somewhat elevated after all subsequent O{sub 3} exposures, relative to its control level following filtered-air exposures. Individual responses varied widely; more severe initial responses to O{sub 3} predicted less rapid attenuation. We concluded that asthmatics can develop tolerance to frequent high-level O{sub 3} exposures in much the same manner as normal subjects, although the process may be slower and less fully effective in asthmatics. 27 refs., 3 figs., 4 tabs.

  8. An attenuation Layer for Electromagnetic Shielding in X- Band Frequency

    Directory of Open Access Journals (Sweden)

    vida Zaroushani


    Full Text Available Uncontrolled exposure to X-band frequency leads to health damage. One of the principles of radiation protection is shielding. But, conventional shielding materials have disadvantages. Therefore, studies of novel materials, as an alternative to conventional shielding materials, are required to obtain new electromagnetic shielding material. Therefore, this study investigated the electromagnetic shielding of two component epoxy thermosetting resin for the X - band frequency with workplace approach. Two components of epoxy resin mixed according to manufacturing instruction with the weight ratio that was 100:10 .Epoxy plates fabricated in three different thicknesses (2, 4 and 6mm and shielding effectiveness measured by Vector Network Analyzer. Then, shielding effectiveness measured by the scattering parameters.The results showed that 6mm thickness of epoxy had the highest and 2mm had the lowest average of shielding effectiveness in X-band frequency that is 4.48 and 1.9 dB, respectively. Also, shielding effectiveness increased by increasing the thickness. But this increasing is useful up to 4mm. Percentage shielding effectiveness of attenuation for 6, 4 and 2mm thicknesses is 64.35%, 63.31% and 35.40%. Also, attenuation values for 4mm and 6mm thicknesses at 8.53 GHz and 8.52 GHz frequency are 77.15% and 82.95%, respectively, and can be used as favourite shields for the above frequency. 4mm-Epoxy is a suitable candidate for shielding application in X-band frequency range but, in the lower section, 6mm thickness is recommended. Finely, the shielding matrix can be used for selecting the proper thickness for electromagnetic shielding in X- Band frequency.

  9. Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice

    Institute of Scientific and Technical Information of China (English)

    OU Xue-mei; FENG Yu-lin; WEN Fu-qiang; HUANG Xiang-yang; XIAO Jun; WANG Ke; WANG Tao


    Background Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.Methods Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days.We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.Results Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (Ⅰand Ⅲ) mRNA expression induced by bleomycin. Moreover,simvastatin down-regulated the increased expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-(] (TNF-a) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore,the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.Conclusions Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-βI and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.

  10. Attenuation of high-frequency seismic waves in northeast India (United States)

    Padhy, Simanchal; Subhadra, N.


    We studied attenuation of S and coda waves, their frequency and lapse time dependencies in northeast India in the frequency range of 1-24 Hz. We adopted theories of both single and multiple scattering to bandpass-filtered seismograms to fit coda envelopes to estimate Q for coda waves (QC) and Q for S-waves (QS) at five central frequencies of 1.5, 3, 6, 12 and 24 Hz. The selected data set consists of 182 seismograms recorded at ten seismic stations within epicentral distance of 22-300 km in the local magnitude range of 2.5-5.2. We found that with the increase in lapse time window from 40 to 60 s, Q0 (QC at 1 Hz) increases from 213 to 278, while the frequency dependent coefficient n decreases from 0.89 to 0.79. Both QC and QS increase with frequency. The average value of QS obtained by using coda normalization method for NE India has the power law form of (96.8 +/- 21.5)f(1.03+/-0.04) in 1-24 Hz. We adopted energy flux model (EFM) and diffusion model for the multiple scattered wave energy in three-dimensions. The results show that the contribution of multiple scattering dominates for longer lapse time close to or larger than mean free time of about 60 s. The estimates of QC are overestimated at longer lapse time by neglecting the effects of multiple scattering. Some discrepancies have been observed between the theoretical predictions and the observations, the difference could be due to the approximation of the uniform medium especially at large hypocentral distances. Increase in QC with lapse time can be explained as the result of the depth dependent attenuation properties and multiple scattering effect.

  11. Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination. (United States)

    Evonuk, Kirsten S; Baker, Brandi J; Doyle, Ryan E; Moseley, Carson E; Sestero, Christine M; Johnston, Bryce P; De Sarno, Patrizia; Tang, Andrew; Gembitsky, Igor; Hewett, Sandra J; Weaver, Casey T; Raman, Chander; DeSilva, Tara M


    T cell infiltration into the CNS is a significant underlying pathogenesis in autoimmune inflammatory demyelinating diseases. Several lines of evidence suggest that glutamate dysregulation in the CNS is an important consequence of immune cell infiltration in neuroinflammatory demyelinating diseases; yet, the causal link between inflammation and glutamate dysregulation is not well understood. A major source of glutamate release during oxidative stress is the system Xc(-) transporter; however, this mechanism has not been tested in animal models of autoimmune inflammatory demyelination. We find that pharmacological and genetic inhibition of system Xc(-) attenuates chronic and relapsing-remitting experimental autoimmune encephalomyelitis (EAE). Remarkably, pharmacological blockade of system Xc(-) 7 d after induction of EAE attenuated T cell infiltration into the CNS, but not T cell activation in the periphery. Mice harboring a Slc7a11 (xCT) mutation that inactivated system Xc(-) were resistant to EAE, corroborating a central role for system Xc(-) in mediating immune cell infiltration. We next examined the role of the system Xc(-) transporter in the CNS after immune cell infiltration. Pharmacological inhibitors of the system Xc(-) transporter administered during the first relapse in a SJL animal model of relapsing-remitting EAE abrogated clinical disease, inflammation, and myelin loss. Primary coculture studies demonstrate that myelin-specific CD4(+) Th1 cells provoke microglia to release glutamate via the system Xc(-) transporter, causing excitotoxic death to mature myelin-producing oligodendrocytes. Taken together, these studies support a novel role for the system Xc(-) transporter in mediating T cell infiltration into the CNS as well as promoting myelin destruction after immune cell infiltration in EAE.

  12. Production of cloned pigs with targeted attenuation of gene expression.

    Directory of Open Access Journals (Sweden)

    Vilceu Bordignon

    Full Text Available The objective of this study was to demonstrate that RNA interference (RNAi and somatic cell nuclear transfer (SCNT technologies can be used to attenuate the expression of specific genes in tissues of swine, a large animal species. Apolipoprotein E (apoE, a secreted glycoprotein known for its major role in lipid and lipoprotein metabolism and transport, was selected as the target gene for this study. Three synthetic small interfering RNAs (siRNA targeting the porcine apoE mRNA were tested in porcine granulosa cells in primary culture and reduced apoE mRNA abundance ranging from 45-82% compared to control cells. The most effective sequence was selected for cloning into a short hairpin RNA (shRNA expression vector under the control of RNA polymerase III (U6 promoter. Stably transfected fetal porcine fibroblast cells were generated and used to produce embryos with in vitro matured porcine oocytes, which were then transferred into the uterus of surrogate gilts. Seven live and one stillborn piglet were born from three gilts that became pregnant. Integration of the shRNA expression vector into the genome of clone piglets was confirmed by PCR and expression of the GFP transgene linked to the expression vector. Analysis showed that apoE protein levels in the liver and plasma of the clone pigs bearing the shRNA expression vector targeting the apoE mRNA was significantly reduced compared to control pigs cloned from non-transfected fibroblasts of the same cell line. These results demonstrate the feasibility of applying RNAi and SCNT technologies for introducing stable genetic modifications in somatic cells for eventual attenuation of gene expression in vivo in large animal species.

  13. Multidrug Efflux Pumps Attenuate the Effect of MGMT Inhibitors. (United States)

    Tomaszowski, Karl-Heinz; Schirrmacher, Ralf; Kaina, Bernd


    Various mechanisms of drug resistance attenuate the effectiveness of cancer therapeutics, including drug transport and DNA repair. The DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) is a key factor determining the resistance against alkylating anticancer drugs inducing the genotoxic DNA lesions O(6)-methylguanine and O(6)-chloroethylguanine, and MGMT inactivation or depletion renders cells more susceptible to treatment with methylating and chloroethylating agents. Highly specific and efficient inhibitors of the repair protein MGMT were designed, including O(6)-benzylguanine (O(6)BG) and O(6)-(4-bromothenyl)guanine (O(6)BTG) that are nontoxic on their own. Unfortunately, these inhibitors do not select between MGMT in normal and cancer cells, causing nontarget effects in the healthy tissue. Therefore, a targeting strategy for MGMT inhibitors is required. Here, we used O(6)BG and O(6)BTG conjugated to β-d-glucose (O(6)BG-Glu and O(6)BTG-Glu, respectively) in order to selectively inhibit MGMT in tumors, harnessing their high demand for glucose. Both glucose conjugates efficiently inhibited MGMT in several cancer cell lines, but with different extents of sensitization to DNA alkylating agents, with lomustine being more effective than temozolomide. We further show that the glucose conjugates are subject to ATP-binding cassette (ABC) transporter mediated efflux, involving P-glycoprotein, MRP1, and BCRP, which impacts the efficiency of MGMT inhibition. Surprisingly, also O(6)BG and O(6)BTG were subject to an active transport out of the cell. We also show that pharmacological inhibition of efflux transporters increases the induction of cell death following treatment with these MGMT inhibitors and temozolomide. We conclude that strategies of attenuating the efflux by ABC transporters are required for achieving successful MGMT targeting.

  14. A Novel Strategy for Attenuating Opioid Withdrawal in Neonates (United States)

    Santoro, Giovanni C; Shukla, Samarth; Patel, Krishna; Kaczmarzyk, Jakub; Agorastos, Stergiani; Scherrer, Sandra; Choi, Yoon Young; Veith, Christina; Carrion, Joseph; Silverman, Rebecca; Mullin, Danielle; Ahmed, Mohamed; Schiffer, Wynne K; Brodie, Jonathan D; Dewey, Stephen L


    The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence. Pregnant Sprague-Dawley rats were treated in one of four ways: 1) saline; 2) morphine alone; 3) morphine+GVG at 25 mg/kg; 4) morphine+GVG at 50 mg/kg. Morphine was administered throughout gestation, while GVG administration occurred only during the last 5 days of gestation. On post-natal day 1, naloxone-induced withdrawal behaviours were recorded in order to obtain a gross behaviour score. Approximately 28 days following birth, 18FDG microPET scans were obtained on these same animals (Groups 1, 2, and 4). Morphine-treated neonates demonstrated significantly higher withdrawal scores than saline controls. However, GVG at 50 but not 25 mg/kg/day significantly attenuated them. Upon reaching adolescence, morphine treated animals showed regionally specific changes in 18FDG uptake. Again, prenatal GVG exposure blocked them. These data demonstrate that low-dose, short-term prenatal GVG administration blocks naloxone-induced withdrawal in neonates. Taken together, these preliminary findings suggest that GVG may provide an alternative and long-lasting pharmacologic approach for the management of neonatal and adolescent symptoms associated with NAS. PMID:28078167

  15. Conventional housing conditions attenuate the development of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Andreas Arndt

    Full Text Available BACKGROUND: The etiology of multiple sclerosis (MS has remained unclear, but a causative contribution of factors outside the central nervous system (CNS is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease. METHODS: C57BL/6 (B6 mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP-proteolipid protein (PLP fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice. RESULTS: In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH reaction in ear swelling assays. CONCLUSIONS: The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics.

  16. Improving live attenuated bacterial carriers for vaccination and therapy. (United States)

    Loessner, Holger; Endmann, Anne; Leschner, Sara; Bauer, Heike; Zelmer, Andrea; zur Lage, Susanne; Westphal, Kathrin; Weiss, Siegfried


    Live attenuated bacteria are well established as vaccines. Thus, their use as carriers for prophylactic and therapeutic macromolecules is a logical consequence. Here we describe several experimental applications of bacteria to carry heterologous macromolecules into the murine host. First, Listeria monocytogenes are described that are able to transfer eukaryotic expression plasmids into host cells for gene therapy. High multiplicities of infection are still required for efficient gene transfer and we point out some of the bottlenecks that counteract a more efficient transfer and application in vivo. Then, we describe Salmonella enterica serovar Typhimurium (S. typhimurium) as an expression plasmid transfer vehicle for oral DNA vaccination of mice. We demonstrate that the stabilization of the plasmid transformants results in an improved immune response. Stabilization was achieved by replacing the origin of replication of the original high-copy-number plasmid by a low-copy-number origin. Finally, we describe Salmonella carriers for the improved expression of heterologous proteins. We introduce a system in which the plasmid is carried as a single copy during cultivation but is amplified several fold upon infection of the host. Using the same in vivo inducible promoter for both protein expression and plasmid amplification, a substantial increase in antigen expression in vivo can be achieved. A modification of this approach is the introduction of inducible gene expression in vivo with a low-molecular-weight compound. Using P(BAD) promoter and L-arabinose as inducer we were able to deliberately activate genes in the bacterial carrier. No background activity could be observed with P(BAD) such that an inducible suicide gene could be introduced. This is adding an important safety feature to such live attenuated carrier bacteria.

  17. Impact attenuation of protective boxing and taekwondo headgear. (United States)

    O'Sullivan, David M; Fife, Gabriel P


    This study aimed to compare the impact attenuation performance of boxing and taekwondo headgear in terms of peak linear and rotational acceleration. To measure the impact attenuation of headgear, a standardized (American Society for Testing and Materials (ASTM) F-2397) martial arts headgear striker was used to impart impacts to a 50th Percentile Male Hybrid III Crash Test Dummy head and neck complex. Two boxing (Adidas and Greenhill) and two taekwondo (Adidas and Nike) headgear, approved by the Association Internationale de Boxe Amateur and the World Taekwondo Federation (WTF), were selected. Each of the selected headgear was fitted to the Hybrid III head and subsequently subjected to five impacts at the front and side with a maximum impact interim time of 60 seconds by the rotating striker at 8 ± 0.3 m/s. Linear and rotational acceleration were recorded at 10,000 Hz. There were significant interactions of the impact location and brand on the rotational acceleration, F(3,40) = 6.7, p < .05. There were significant main effects of both impact location F(1,40) = 9.07, p < .05 and headgear brand F(3,40) = 9.9, p < .05 on the linear acceleration. Pairwise comparisons show significant differences between the front and side for both linear and rotational acceleration. The headgear tested failed the ASTM high impact test requirement to reduce the linear acceleration to below a threshold of 150 g. Further development of headgear to reduce impact linear and rotational acceleration magnitudes should be called for by the relevant sport governing bodies and initiated by headgear manufactures.

  18. Analysis of multiscale scattering and poroelastic attenuation in a real sedimentary rock sequence (United States)

    Hackert; Parra


    Compressional waves in heterogeneous permeable media experience attenuation from both scattering and induced pore scale flow of the viscous saturating fluid. For a real, finely sampled sedimentary sequence consisting of 255 layers and covering 30 meters of depth, elastic and poroelastic computer models are applied to investigate the relative importance of scattering and fluid-flow attenuation. The computer models incorporate the known porosity, permeability, and elastic properties of the sand/shale sequence in a binary medium, plane layered structure. The modeled elastic scattering attenuation is well described by stochastic medium theory if two-length scale statistics are applied to reflect the relative thickness of the shale layers when compared to the sand layers. Under the poroelastic Biot/squirt flow model, fluid-flow attenuation from the moderate permeability (10(-14) m2) sands may be separated in the frequency domain from the attenuation due to the low permeability (5 x 10(-17) m2) shale layers. Based on these models, the overall attenuation is well approximated by the sum of the scattering attenuation from stochastic medium theory and the volume weighted average of the attenuations of the sequence member rocks. These results suggest that a high permeability network of sediments or fractures in a lower permeability host rock may have a distinct separable attenuation signature, even if the overall volume of high permeability material is low. Depending on the viscosity of the saturating fluid, the magnitude of the flow-based attenuation can dominate or be dominated by the scattering attenuation at typical sonic logging frequencies (approximately 10 kHz).

  19. Combination of balanced ultrafiltration with modified ultrafiltration attenu-ates pulmonary injury in patients undergoing open heart surgery

    Institute of Scientific and Technical Information of China (English)

    黄惠民; 姚廷俊; 王伟; 朱德明; 张蔚; 陈虹; 付维定


    Objective To explore the effects of ultrafiltration technique in preventing and relieving pulmonary injury in children undergoing open heart surgery and cardiopulmonary bypass (CPB).Methods Thirty cases with congenital heart defects were divided into a control group and an experimental group. In the control group, conventional cardiopulmonary bypass was used without ultrafiltration; while in the experimental group, cardiopulmonary bypass with balanced ultrafiltration and modified ultrafiltration were used. Pulmonary static compliance (Cstat), airway resistance (Raw), alveolar-arterial oxygen difference (A-a DO2), hematocrit (HCT), serum albumin (Alb), interleukin-6 (IL-6), endothelia-1 (ET-1) and thromboxane (TXB2) were measured. Results The pulmonary function was improved, HCT and serum albumin concentrations were increased, and some harmful medium-size solutes were decreased in the experimental groups compared with the control group.Conclusions Combination of balanced ultrafiltration with modified ultrafiltration can effectively concentrate blood, exclude harmful inflammatory mediators, and attenuate lung edema and inflammatory responsive pulmonary injury.

  20. Multiple Lines Of Evidence Supporting Natural Attenuation: Lines Of Inquiry Supporting Monitored Natural Attenuation And Enhanced Attenuatin Of Chlorinated Solvents

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, Karen; Widemeirer, T. H.; Barden, M.J.; Dickson, W. Z.; Major, David


    The Department of Energy (DOE) is sponsoring an initiative to facilitate efficient, effective and responsible use of Monitored Natural Attenuation (MNA) and Enhanced Attenuation (EA) for chlorinated solvents. This Office of Environmental Management (EM) ''Alternative Project,'' focuses on providing scientific and policy support for MNA/EA. A broadly representative working group of scientists supports the project along with partnerships with regulatory organizations such as the Interstate Technology Regulatory Council (ITRC) and the United States Environmental Protection Agency (USEPA). The initial product of the technical working group was a summary report that articulated the conceptual approach and central scientific tenants of the project, and that identified a prioritized listing of technical targets for field research. This report documented the process in which: (1) scientific ground rules were developed, (2) lines of inquiry were identified and then critically evaluated, (3) promising applied research topics were highlighted in the various lines of inquiry, and (4) these were discussed and prioritized. The summary report will serve as a resource to guide management and decision making throughout the period of the subject MNA/EA Alternative Project. To support and more fully document the information presented in the summary report, the DOE is publishing a series of supplemental documents that present the full texts from the technical analyses within the various lines of inquiry (see listing). The following report--documenting our evaluation of the state of the science for the lines of evidence for supporting decision-making for MNA--is one of those supplemental documents.

  1. A New Approach for Quantitative Evaluation of Ultrasonic Wave Attenuation in Composites (United States)

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


    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.

  2. Study on Attenuation Characteristics of Biocontrol Strain Anti-8098A, Bacillus cereus, against Ralstoniasolanacearum

    Institute of Scientific and Technical Information of China (English)

    BoLIU; Ying-ZhiLIN; Yu-JingZHU; Ci-BinGE; YiCAO


    The present study dealt with the attenuation characteristics of bacterial-wilt-disease biocontrol strain Anti-8098A, Bacillus cereus, againstpathogeny Ralstonia solanacearum (RS). In order to distinguish the pathogenicity of RS, the attenuation index (radius of the center red ring/radius of the whole mycelium ring, on TTC culture medium) was established (Hayward, 1976), companying with the mortality of tomato

  3. Uncovering the genetic basis of attenuation in Marek’s disease virus (United States)

    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...

  4. Flux attenuation at NREL`s High-Flux Solar Furnace

    Energy Technology Data Exchange (ETDEWEB)

    Bingham, C E; Scholl, K L; Lewandowski, A A


    The High-Flux Solar Furnace (HFSF) at the National Renewable Energy Laboratory (NREL) has a faceted primary concentrator and a long focal-length-to-diameter ratio (due to its off-axis design). Each primary facet can be aimed individually to produce different flux distributions at the target plane. Two different types of attenuators are used depending on the flux distribution. A sliding-plate attenuator is used primarily when the facets are aimed at the same target point. The alternate attenuator resembles a venetian blind. Both attenuators are located between the concentrator and the focal point. The venetian-blind attenuator is primarily used to control the levels of sunlight failing on a target when the primary concentrators are not focused to a single point. This paper will demonstrate the problem of using the sliding-plate attenuator with a faceted concentrator when the facets are not aimed at the same target point. We will show that although the alternate attenuator necessarily blocks a certain amount of incoming sunlight, even when fully open, it provides a more even attenuation of the flux for alternate aiming strategies.

  5. The behavioural depression of hippocampal kindled rats is attenuated by subcutaneous and intracerebroventricular naltrexone

    NARCIS (Netherlands)

    Cottrell, G.A.; Nyakas, C.; Bohus, B.


    1. Two questions were asked: Does naltrexone attenuate the behavioural depression (BD) in other models of limbic epilepsy besides amygdala kindling? Does intracerebroventricular (ICV) administration produce the same effects as subcutaneous injection i.e., attenuation of the BD. 2. Male wistar rats

  6. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect? (United States)

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco


    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.

  7. Impact shock frequency components and attenuation in rearfoot and forefoot running

    Directory of Open Access Journals (Sweden)

    Allison H. Gruber


    Conclusion: The difference in impact shock frequency content between footfall patterns suggests that the primary mechanisms for attenuation may differ. The relationship between shock attenuation mechanisms and injury is not clear but given the differences in impact frequency content, neither footfall pattern may be more beneficial for injury, rather the type of injury sustained may vary with footfall pattern preference.

  8. Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); De Amorim Bernstein, Karen [Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Francis H Burr Proton Therapy Center, Boston, MA (United States); Halpern, Elkan F. [Massachusetts General Hospital and Harvard Medical School, Institute of Technology Assessment, Boston, MA (United States)


    To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

  9. Live-attenuated measles virus vaccine targets dendritic cells and macrophages in muscle of nonhuman primates

    NARCIS (Netherlands)

    L.J. Rennick (Linda); R.D. de Vries (Rory); T.J. Carsillo (Thomas J.); K. Lemon (Ken); G. van Amerongen (Geert); M. Ludlow (Martin); D.T. Nguyen (Tien); S. Yüksel (Selma); R.J. Verbugh (Joyce); P. Haddock (Paula); S. McQuaid (Stephen); W.P. Duprex (Paul); R.L. de Swart (Rik)


    textabstractAlthough live-attenuated measles virus (MV) vaccines have been used successfully for over 50 years, the target cells that sustain virus replication in vivo are still unknown. We generated a reverse genetics system for the live-attenuated MV vaccine strain Edmonston- Zagreb (EZ), allowing

  10. Quantitative multi-pinhole small-animal SPECT : uniform versus non-uniform Chang attenuation correction

    NARCIS (Netherlands)

    Wu, C.; de Jong, J. R.; van Andel, H. A. Gratama; van der Have, F.; Vastenhouw, B.; Laverman, P.; Boerman, O. C.; Dierckx, R. A. J. O.; Beekman, F. J.


    Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusi

  11. Quantitative multi-pinhole small-animal SPECT: uniform versus non-uniform Chang attenuation correction

    NARCIS (Netherlands)

    Wu, C.; Jong, J.R. de; Gratama van Andel, H.A.; Have, F. van der; Vastenhouw, B.; Laverman, P.; Boerman, O.C.; Dierckx, R.A.; Beekman, F.J.


    Attenuation of photon flux on trajectories between the source and pinhole apertures affects the quantitative accuracy of reconstructed single-photon emission computed tomography (SPECT) images. We propose a Chang-based non-uniform attenuation correction (NUA-CT) for small-animal SPECT/CT with focusi

  12. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents : Is there an age effect?

    NARCIS (Netherlands)

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco


    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 l

  13. Hippocampal volume correlates with attenuated negative psychotic symptoms irrespective of antidepressant medication

    Directory of Open Access Journals (Sweden)

    Raffaele Bernasconi


    Conclusion: Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.

  14. Seismic attenuation in partially saturated Berea sandstone submitted to a range of confining pressures (United States)

    Chapman, Samuel; Tisato, Nicola; Quintal, Beatriz; Holliger, Klaus


    Using the forced oscillation method, we measure the extensional-mode attenuation and Young's modulus of a Berea sandstone sample at seismic frequencies (0.5-50 Hz) for varying levels of water saturation (~0-100%) and confining pressures (2-25 MPa). Attenuation is negligible for dry conditions and saturation levels <80%. For saturation levels between ~91% and ~100%, attenuation is significant and frequency dependent in the form of distinct bell-shaped curves having their maxima between 1 and 20 Hz. Increasing saturation causes an increase of the overall attenuation magnitude and a shift of its peak to lower frequencies. On the other hand, increasing the confining pressure causes a reduction in the attenuation magnitude and a shift of its peak to higher frequencies. For saturation levels above ~98%, the fluid pressure increases with increasing confining pressure. When the fluid pressure is high enough to ensure full water saturation of the sample, attenuation becomes negligible. A second series of comparable experiments reproduces these results satisfactorily. Based on a qualitative analysis of the data, the frequency-dependent attenuation meets the theoretical predictions of mesoscopic wave-induced fluid flow (WIFF) in response to a heterogeneous water distribution in the pore space, so-called patchy saturation. These results show that mesoscopic WIFF can be an important source of seismic attenuation at reservoir conditions.

  15. House attenuation of aircraft and street traffic noise in relation to annoyance: A pilot study (United States)

    Kryter, Karl D.


    House barrier sound attenuation was measured as differences between the levels of street traffic and aircraft noise found outdoors near the front (street facing) and rear façades, and in rooms of two one-story houses. Also, attenuation of street traffic and aircraft noise between the front and rear façades of similar one-story houses was calculated in accordance with acoustical models. Findings: (1) relative to levels measured near the front façade, street traffic noise near the rear façade, and in rooms inside the houses, was, on average, 9 max dB and 8 SEL dB more attenuated than was aircraft noise. (2) When attenuation of street traffic noise was measured relative to its level near the front façade, and attenuation for aircraft noise was measured relative to its level near the rear façade, street traffic noise was, on average, 7 max dB and 6 SEL dB more attenuated than aircraft noise. (3) Calculated barrier attenuation of street traffic noise was, on average, 1.3 max dB less than measured; calculated barrier attenuation of aircraft noise differed from measured by ~0.4 max dB. Implications of the findings for guidelines for assessing impact of these noises on communities and land-use zoning are discussed.

  16. Experimental Study and Numerical Modeling of Wave Induced Pore Pressure Attenuation Inside a Rubble Mound Breakwater

    DEFF Research Database (Denmark)

    Troch, Peter; Rouck, Julien De; Burcharth, Hans Falk


    The main objective of this paper is to study the attenuation of the wave induced pore pressures inside the core of a rubble mound breakwater. The knowledge of the distribution and the attenuation of the pore pressures is important for the design of a stable and safe breakwater. The pore pressure...

  17. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

    Directory of Open Access Journals (Sweden)

    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  18. Monitoring the catalytic synthesis of glycerol carbonate by real-time attenuated total reflection FTIR spectroscopy

    NARCIS (Netherlands)

    Calvino-Casilda, V.; Mul, G.; Fernandez, J.F.; Rubio-Marcos, F.; Banares, M.A.


    In situ Attenuated Total Reflectance FTIR spectroscopy was used to study the carbonylation of glycerol with urea. Cobalt oxide nanoparticles, Co3O4, hierarchically dispersed on zinc oxide microparticles, ZnO, were used as catalysts. The present work demonstrates that in situ real-time attenuated tot

  19. Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in Iberian rivers. (United States)

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


    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.

  20. Detailed Study of Seismic Wave Attenuation in Carbonate Rocks: Application on Abu Dhabi Oil Fields (United States)

    Bouchaala, F.; Ali, M. Y.; Matsushima, J.


    Seismic wave attenuation is a promising attribute for the petroleum exploration, thanks to its high sensitivity to physical properties of subsurface. It can be used to enhance the seismic imaging and improve the geophysical interpretation which is crucial for reservoir characterization. However getting an accurate attenuation profile is not an easy task, this is due to complex mechanism of this parameter, although that many studies were carried out to understand it. The degree of difficulty increases for the media composed of carbonate rocks, known to be highly heterogeneous and with complex lithology. That is why few attenuation studies were done successfully in carbonate rocks. The main objectives of this study are, Getting an accurate and high resolution attenuation profiles from several oil fields. The resolution is very important target for us, because many reservoirs in Abu Dhabi oil fields are tight.Separation between different modes of wave attenuation (scattering and intrinsic attenuations).Correlation between the attenuation profiles and other logs (Porosity, resistivity, oil saturation…), in order to establish a relationship which can be used to detect the reservoir properties from the attenuation profiles.Comparison of attenuation estimated from VSP and sonic waveforms. Provide spatial distribution of attenuation in Abu Dhabi oil fields.To reach these objectives we implemented a robust processing flow and new methodology to estimate the attenuation from the downgoing waves of the compressional VSP data and waveforms acquired from several wells drilled in Abu Dhabi. The subsurface geology of this area is primarily composed of carbonate rocks and it is known to be highly fractured which complicates more the situation, then we separated successfully the intrinsic attenuation from the scattering. The results show that the scattering is significant and cannot be ignored. We found also a very interesting correlation between the attenuation profiles and the